Article

Effect of mouth cleaning with hinokitiol-containing gel on oral malodor: A randomized, open-label pilot study

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Abstract

The aim of the study was to evaluate the effect of mouth cleaning with hinokitiol-containing gel on oral malodor. An open-label, randomized, controlled trial was conducted to assess oral malodor and clinical parameters related to oral malodor before and after mouth cleaning with hinokitiol-containing gel (n = 9) or with gel not including hinokitiol (n = 9). Mouth cleaning included the teeth, gingiva, and tongue and was carried out 3 times per day for 4 weeks. Organoleptic test (OLT) scores (P = .021), levels of hydrogen sulfide (P = .008) and methyl mercaptan (P = .020), frequency of bleeding on probing, average probing pocket depth, and plaque index significantly improved in the group using hinokitiol. In contrast, only the OLT score (P = .031) significantly improved in the control group after the treatment regimen. Mouth cleaning with hinokitiol-containing gel may be effective for reduction of oral malodor.

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... Suzuki et al. [30] 26 Lactobaccilus Salivarius WB21 Tablets Daily consumption of tablets decreased malodor I Iha et al. [31] 18 Hinokitiol Gel Significant reduction in malodor and plaque scores II Tian et al. [32] 15 ...
... [25,27] Triclosan is a compound that is often added to toothpastes for its effect in preventing the formation of calculus. [30][31][32] Sharma et al. have shown that triclosan can produce better breath odor scores 12 h after use in comparison to control. [28] This is also supported by the findings of Hu et al. who showed that 0.3% triclosan/2.0% ...
... [33] Level II evidence existed for products such as hinokitiol. [31] Abrasive microcapsules (Breezy candy) [35] and tablets containing bovine lactoferrin and lactoperoxidase. ...
Article
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Halitosis is a common problem. There are many assessment methods in the literature as well as treatment modalities. The objective of this systematic review is to evaluate the level of evidence for each treatment modality of halitosis. Electronic databases were searched in a systematic method according to preferred reporting items for systematic reviews and meta-analyses guidelines. The review included human clinical trials with or without randomization and excluded case reports and case series. Only articles written in English were included in the review. Forty-three articles were included in this review. It was found that treatment modalities can be classified into chemical compounds in mouthwashes, chemical compounds in dentifrices, chemical compounds in other products, herbal products and combinations of chemical and physical methods. The level of evidence ranged from I to IV for each class. This review suggests that mouthwashes and dentifrices are the best ways to combat halitosis. There is currently insufficient amount of level I evidence to support the efficacy of herbal products or mechanical modifications to oral hygiene practices and there is a need for a greater number of randomized controlled trials to study the efficacy of these methods.
... β-thujaplicin (4-isopropyltropolone), isolated from the essential oil of the Japanese cypress, is a tropolone-based phenolic compound [40,41]. This compound has a safety profile and has been approved for use in both clinical practice and health care products [42][43][44]. It exerts a wide variety of biologic activities, including antimicrobial, antioxidant, and antitumor activities [45]. ...
... β-thujaplicin is an antimicrobial agent with an established good safety profile, it is known to be of fairly low cytotoxicity and teratogenic effects, and has minimal side effects in animal models [49,50]. Thus, β-thujaplicin has been widely used as a preservative in toothpastes, skin lotions, body soaps and other health care products [42][43][44]. Likewise, techniques have been established to improve the yield of β-thujaplicin production [51]. ...
Article
Investigation of natural products is an attractive strategy to identify novel compounds for cancer prevention and treatment. Numerous studies have shown the efficacy and safety of natural products, and they have been widely used as alternative treatments for a wide range of illnesses, including cancers. However, it remains unknown whether natural products affect homologous recombination (HR)-mediated DNA repair and whether these compounds can be used as sensitizers with minimal toxicity to improve patients' responses to radiation therapy, a mainstay of treatment for many human cancers. In this study, in order to systematically identify natural products with an inhibitory effect on HR repair, we developed a high-throughput image-based HR repair screening assay and screened a chemical library containing natural products. Among the most interesting of the candidate compounds identified from the screen was β-thujaplicin, a bioactive compound isolated from the heart wood of plants in the Cupressaceae family, can significantly inhibit HR repair. We further demonstrated that β-thujaplicin inhibits HR repair by reducing the recruitment of a key HR repair protein, Rad51, to DNA double-strand breaks. More importantly, our results showed that β-thujaplicin can radiosensitize cancer cells. Additionally, β-thujaplicin sensitizes cancer cells to PARP inhibitor in different cancer cell lines. Collectively, our findings for the first time identify natural compound β-thujaplicin, which has a good biosafety profile, as a novel HR repair inhibitor with great potential to be translated into clinical applications as a sensitizer to DNA-damage-inducing treatment such as radiation and PARP inhibitor. In addition, our study provides proof of the principle that our robust high-throughput functional HR repair assay can be used for a large-scale screening system to identify novel natural products that regulate DNA repair and cellular responses to DNA damage-inducing treatments such as radiation therapy.
... En la actualidad es sabido que el origen de la halitosis puede ser de carácter intraoral o extraoral. En el primer caso las causas que se describen en la literatura son 51 numerosas, tales como caries, cubierta del dorso lingual, pobre higiene oral, lesiones endodónticas, restauraciones inadecuadas, prótesis fijas o removibles mal higienizadas, úlceras en la mucosa oral, flujo salival disminuido, respiradores orales y problemas periodontales, aunque con respecto a éste último no hay consenso ya que no todos los pacientes que padecen periodontitis presentan halitosis y no todos aquéllos que sufren de halitosis tienen periodontitis 107,108,118 . Si el origen es de causa extraoral puede deberse a diferentes patologías, destacando las de tipo hepático, renal, metabólico como la diabetes y trimetilaminuria (síndrome del olor a pescado), rinitis, sinusitis crónica, bronquitis, algunas medicaciones y carcinoma de pulmón 119,120 . ...
... Otras pruebas diagnósticas que se han descrito son el test de la ß-galactosidasa que cuantifica el número de enzimas involucradas en la degradación de la mucina oral, el test colorimétrico que se basa en la detección de aminas en al saliva, el uso de sensores químicos cuyo propósito es medir los CSV en lengua y bolsas periodontales, la incubación salival, la monitorización del amonio, el método de la ninhidrina y el estudio de reacción en cadena de la polimerasa (PCR) 15 Muchos autores 117,118,[129][130][131][132][133][134][135][136][137] han descrito diferentes opciones terapéuticas para tratar la halitosis, todos ellos remarcan la importancia de una buena higiene oral (HO) ya que es indispensable para cualquier tipo de halitosis ya sea fisiológica, patológica o incluso de origen psicólogico. Se indican diferentes pautas, las cuales pasan por cepillado del dorso lingual, cepillado dental, enjuagues, pasta dentífrica, exámenes periodontales y tratamiento del mismo. ...
Thesis
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The aim of the present PhD thesis was to study the relationship between the volatile sulphur compounds and the evolution of the periodontitis after having performed a non surgical periodontal treatment, without antimicrobial therapy, as well as its relationship with different variables.
... A potential "natural therapy" could also modify the applicability of the treatment, not only as curative but also as a preventive therapy, both in pediatric and old-aged patients. Natural derivatives such as propolis, cranberry, tea, Galla chinensis, grapes, coffee, and cacao-containing polyphenols have already demonstrated their activity against oral biofilms [20,[25][26][27][28]. Similarly, hinokitiol, green tea powder, and eucalyptus extract have been beneficially used against oral malodor [19,[29][30][31]. ...
Article
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Streptococcus mutans and Fusobacterium nucleatum are two key bacteria of the oral microbiota. Due to their ability to form biofilms on oral tissues, they are both involved in the onset of the most common oral diseases. F. nucleatum is also the principal producer of hydrogen sulfide (H2S), causative of the awkward bad breath of halitosis. In this study, the oral product Vea® Oris, made by vitamin E and capric/caprylic acid only, was evaluated as a potential treatment for the most common oral diseases. Different concentrations of the product were tested against both S. mutans and F. nucleatum. The effect on planktonic and biofilm growth was investigated for both strains, and for F. nucleatum, the influence on H2S production was evaluated. From our data, the product did not relevantly reduce the planktonic growth of both strains, whereas it validly counteracted biofilm assemblage. Moreover, an interesting trend of H2S reduction was highlighted. Overall, these results suggested, on the one hand, a synergistic antimicrobial–antibiofilm action of two Vea® Oris components and, together, potential modulation activity on H2S production. However, the study should be implemented to confirm these only preliminary findings, certainly extending the panel of tested bacteria and using alternative methods of detection.
... Hinokitiol exhibits antibacterial, antifungal, antiviral, and insecticidal activities [4][5][6] and no developmental toxicity or carcinogenic effects have been observed [7,8]. Hinokitiol inhibits oral bacteria but exhibits low cytotoxicity to normal oral cells [9,10], and has been used in toothpaste and oral-care gel to improve the oral lichen planus and reduce halitosis [11][12][13]. Hypoxia-inducible factor-1a (HIF-1a), prostaglandins, and tumor necrosis factor-a (TNF-a) mediated inflammatory response have also been inhibited by hinokitiol [14][15][16]. ...
Article
Full-text available
Hinokitiol displays potent antimicrobial activity. It has been used in toothpaste and oral-care gel to improve the oral lichen planus and reduce halitosis. The aim of this study was to evaluate the antimicrobial activity of 3 different dental root canal sealers with hinokitiol (sealers+H) and their physical and biological effects. AH Plus (epoxy amine resin-based, AH), Apexit Plus (calcium-hydroxide-based, AP), and Canals (zinc-oxide-eugenol-based, CA), were used in this study. The original AH and CA exhibited strong anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activity, but AP did not. The setting time, working time, flowability, film thickness, and solubility of each sealer+0.2%H complied with ISO 6876:2001. CA+0.2%H exhibited high cytotoxicity, but the others sealers+0.2%H did not. Because hinokitiol combined with Zn2+ in CA creates a synergistic effect. The physical tests of AP+0.5%-1%H complied with ISO 6876:2001, improved antimicrobial activity, inhibited inflammation genes cyclooxygenase-2 (COX-2) and hypoxia-inducible factor-1α (HIF-1α) mRNA in MG-63 cells and human gingival fibroblasts (HGF), and down-regulated lysyl oxidase (LOX) mRNA of HGF. In summary, AH and CA demonstrated strong antimicrobial activity, but AP did not. Application of hinokitiol increases AH anti-MRSA activity should less than 0.2% for keep well flowability. AP+0.5%-1% hinokitiol exhibited strong physical, antibacterial, and anti-inflammation potentials, and inhibited S. aureus abscess formation. Applying an appreciable proportion of hinokitiol to epoxy-amine-resin-based and calcium-hydroxide-based root canal sealers is warranted, but the enhanced cytotoxicity and synergistic effect must be considered.
... In the 20th century the antimicrobial effect of hinokitiol is applied in daily living products for disease prevention, and for extension of the expiration date of goods. In mouth cleaning gels, it lowers the incidence of periodontal disease and tooth decay (Iha, Suzuki, Yoneda, Takeshita, & Hirofuji, 2013). In cosmetics, it inhibits the melanin synthesis by reducing tyrosinase protein expession (Choi et al., 2006). ...
... There is no information on clinical investigations or human use of tropolone as a food product. Similar to other phytochelators, considerations of risk/benefit assessment could also apply to tropolone or naturally occurring biologically active homologues of tropolone like hinokitiol and purpurogallin which have shown iron chelating, antioxidant and other biological activities [111][112][113][114]. ...
Article
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Iron chelating drugs are primarily and widely used in the treatment of transfusional iron overload in thalassaemia and similar conditions. Recent in vivo and clinical studies have also shown that chelators, and in particular deferiprone, can be used effectively in many conditions involving free radical damage and pathology including neurodegenerative, renal, hepatic, cardiac conditions and cancer. Many classes of phytochelators (Greek: phyto (φυτό)-plant, chele (χηλή)-claw of the crab) with differing chelating properties, including plant polyphenols resembling chelating drugs, can be developed for clinical use. The phytochelators mimosine and tropolone have been identified to be orally active and effective in animal models for the treatment of iron overload and maltol for the treatment of iron deficiency anaemia. Many critical parameters are required for the development of phytochelators for clinical use including the characterization of the therapeutic targets, ADMET, identification of the therapeutic index and risk/benefit assessment by comparison to existing therapies. Phytochelators can be developed and used as main, alternative or adjuvant therapies including combination therapies with synthetic chelators for synergistic and or complimentary therapeutic effects. The development of phytochelators is a challenging area for the introduction of new pharmaceuticals which can be used in many diseases and also in ageing. The commercial and other considerations for such development have great advantages in comparison to synthetic drugs and could also benefit millions of patients in developing countries.
... Hinokitiol, found in hiba or Taiwanese hinoki, has a high level of antibacterial activity through the inhibition of bacterial tricarboxylic acid cycles. [18][19][20] The antifungal effect of liquid moisturizer "a" is attributed to the presence of protamine as an antimicrobial agent. Protamine is a testis-derived protein in salmon and herring that has a broad antimicrobial spectrum. ...
Article
Purpose: To examine the impact of oral moisturizer type and application time on antifungal effects. Materials and methods: Seventeen oral moisturizers (7 liquids, 10 gels) and amphotericin B (AMPH-B) were tested. Antifungal effects were evaluated with newly opened moisturizer samples (0 hour) and with samples incubated for 8 hours to simulate contact during sleep. Candida albicans samples (10(8) cells/ml) were placed into cylindrical holes in 50% trypticase soy agar plates. Antifungal effects were evaluated based on growth-inhibitory zones after 24 hours. Equal quantities of moisturizers showing growth-inhibitory zones were mixed as additional samples. The effects of moisturizer type and application time on growth-inhibitory zones were evaluated with ANOVA. Growth-inhibitory zone sizes were compared with multiple comparisons. Results: Growth-inhibitory zones were found with two liquids, one gel, moisturizer mixtures, and AMPH-B. Significant differences in antifungal effects were found among different moisturizer types and between the 0- and 8-hour groups. The growth-inhibitory zones of the 8-hour group were significantly smaller than those of the 0-hour group. In both the 0- and 8-hour groups, the growth-inhibitory zones of the liquid-gel mixtures were significantly larger than those of other moisturizer types, and were the same size as those of AMPH-B at two concentrations (1.25 and 2.5 μg/ml). Growth-inhibitory zones of individual moisturizers and liquid-liquid mixtures were the same size as those of lower AMPH-B concentrations (0.16, 0.31, and 0.63 μg/ml). Conclusion: Our findings suggest that mixing liquid and gel moisturizers improves their antifungal efficiency.
... Klorheksidin, triklosan, ketilpridinyum klorid, klorin dioksit, çinko ve hidrojen peroksit içerikli gargaralar ağız kokusunu gidermede kullanılır. 18 Fakat uzun süre kullanılması oral mikroflora dengesini bozabileceği, dişlerde ve yumuşak dokuda renklenmelere neden olabileceği ve tat bozukluklarına yol açabileceği için belli bir aşamadan sonra tavsiye edilmez. Alkol içeren ağız gargaraları ağız kuruluğuna yol açtığı için günümüzde alkol içermeyen gargaraların kullanımı artmaktadır. ...
... Hinokitiol has already been used in a mouth cleaning gel [55] and root canal sealer [29]. Liquid and vaporous hinokitiol had the best antibacterial activity, stability, and long-term effects in this study. ...
Article
Full-text available
The aim of the present study was to determine the antibacterial activities of the phenolic essential oil (EO) compounds hinokitiol, carvacrol, thymol, and menthol against oral pathogens. Aggregatibacter actinomycetemcomitans, Streptococcus mutans, Methicillin-resistant Staphylococcus aureus (MRSA), and Escherichia. coli were used in this study. The minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs), bacterial growth curves, temperature and pH stabilities, and synergistic effects of the liquid and vapor EO compounds were tested. The MIC/MBC of the EO compounds, ranging from the strongest to weakest, were hinokitiol (40–60 μg/mL/40-100 μg/mL), thymol (100–200 μg/mL/200-400 μg/mL), carvacrol (200–400 μg/mL/200-600 μg/mL), and menthol (500-more than 2500 μg/mL/1000-more than 2500 μg/mL). The antibacterial activities of the four EO phenolic compound based on the agar diffusion test and bacterial growth curves showed that the four EO phenolic compounds were stable under different temperatures for 24 h, but the thymol activity decreased when the temperature was higher than 80°C. The combination of liquid carvacrol with thymol did not show any synergistic effects. The activities of the vaporous carvacrol and thymol were inhibited by the presence of water. Continual violent shaking during culture enhanced the activity of menthol. Both liquid and vaporous hinokitiol were stable at different temperatures and pH conditions. The combination of vaporous hinokitiol with zinc oxide did not show synergistic effects. These results showed that the liquid and vapor phases of hinokitiol have strong anti-oral bacteria abilities. Hinokitiol has the potential to be applied in oral health care products, dental materials, and infection controls to exert antimicrobial activity.
... The progressive colonization of the internal implant cavity and the screw access channel by mostly anaerobic proteolytic microorganisms, which also produce malodor, leads to the formation of a bacterial reservoir 8,[18][19][20] . Malodor -usually caused by the presence of gram-negative oral bacteria-is the result of microbial metabolism of amino acids in the oral cavity 21,22) . Streptococci and other gram-positive oral bacteria may also lead to malodor due to the production of a volatile sulfur compound (VSC) 23,24) . ...
Article
Full-text available
Unsuccessfully sealed screw access channels of prosthetic implant abutments may lead to malodor or peri-implant diseases in gingival tissues adjacent to implant-supported restorations. Therefore, 72 sets of screw channel analogs with six different materials incorporated (Polytetrafluoroethylene (PTFE), wax, gutta-percha, cavit, endofrost-pellets and cotton pellets) were exposed (2.5 h, 37°C) to Streptococcus mutans, oralis and Candida albicans suspensions. Bacterial adherence was quantified by using the fluorescence dye, Alamar Blue/resazurin, and an automated multifunctional reader. For quantification of fungal adherence the ATP-based bioluminescence approach was used. High relative fluorescence and luminescence intensities (>10,000), indicating high adhesion of streptococci and fungi were found for cotton and endofrost-pellets and low intensities (<5,000) for wax, gutta-percha, cavit and PTFE. The quantity of bacterial and fungal adhesion differed significantly between the assessed various sealing materials. In conclusion and within the limitations of this study, wax, gutta-percha, cavit and PTFE should be preferred as sealing materials.
... The level of VSCs and organoleptic score were measured at 3 PM. Organoleptic test scores were estimated by 1 evaluator using scale 0-5 (0, absence of odor; 1, questionable odor; 2, slight malodor; 3, moderate malodor; 4, strong malodor; 5, severe malodor) 14 . ...
Article
Burahol [Stelechocarpus burahol (Blume) Hook.f. & Thomson] fruit is well known as food and used traditionally as bad deodorization. The objective of this study was to examine mouth bad deodorization activity of burahol mouthwash. Firstly, methyl mercaptan capturing activity of the burahol fruit extracts was evaluated using gas chromatography. The antibacterial activity against Porphyromonas ginggivalis, a volatile sulfide compound (VSC)-producing Gram-negative anaerobic bacterium was tested. The mouthwash mouth bad deodorization activity was performed with cross over design in healthy subjects, randomized controlled trial. Subjects were treated by the burahol mouth wash, as positive control was used commercial mouth wash containing green tea extract. The burahol fruits extract captured 97.5% methyl mercaptan. The burahol mouthwash demonstrated no antibacterial activity against P. ginggivalis. The treatment of the burahol mouthwash on the subjects reduced the volatile sulfur compounds (VSCs) concentration. The burahol mouthwash mouth bad deodorization activity is not different statistically compared with that positive control (P < 0.05). This study showed that S. burahol fruits demonstrated the mouth bad odor reducing activity.
... The use of higher concentrations is also warranted by the fact that several studies have suggested the use of hinokitiol as a therapeutic agent and, thereby, basically the safety (LD50 mouse, 85 mg/kg) and solubility of hinokitiol are the limitations. Hinokitiol has been used, for example, in gels for mouth cleaning in concentration of 2% (appr 12 mM) [40]. Thus, concentrations (µM scale) used in our study fit in these limitations and allow also the use of higher concentrations in further studies. ...
Article
Full-text available
Background: Hinokitiol (β-thujaplicin), isolated from the wood of Chamaecyparis taiwanensis, has a wide variety of biological properties including anti-inflammatory, anti-microbial, and anti-tumor effects. Therefore, hinokitiol has become a frequent additive in oral and other healthcare products. Objectives: Our goal was to determine the anti-tumor activity of hinokitiol on human papillomavirus (HPV) positive (n = 3) and negative (n = 2) cell lines derived from cervical or head and neck squamous cell carcinoma (HNSCC) and keratinocyte cell lines (n = 3) transformed spontaneously or with HPV16E6 and E7 oncogenes. Methods: The cell-lines were exposed to hinokitiol at different concentrations (0–200 µM) for 24 h. Cell metabolism, proliferation, and the cell cycle distribution were assessed by MTT- and 3H-thymidine incorporation and flow cytometry. Expressions of p21 and on HPV16E6 and E7 oncogenes were assessed by qPCR. Results: In all carcinoma cell lines, hinokitiol treatment declined the metabolic activity irrespective of the HPV status. This decline was statistically significant, however, only in HPV-positive cell lines CaSki and UD-SCC-2 when exposed to hinokitiol concentrations at 100 and 200 µM, respectively (p < 0.05). Immortalized cell lines, HMK and HPV-positive IHGK, were more sensitive as a similar metabolic effect was achieved at lower hinokitiol concentrations of 3.1, 6.25, and 50 µM, respectively. Hinokitiol blocked DNA synthesis of all carcinoma cell lines without evident association with HPV status. G1 cell cycle arrest and p21 upregulation was found in all cell lines after hinokitiol treatment at higher concentration. However, when the p21 results of all HPV-positive cells were pooled together, the increase in p21 expression was statistically significantly higher in HPV-positive than in HPV-negative cell lines (p = 0.03), but only at the highest hinokitiol concentration (200 µM). In HPV-positive cell lines hinokitiol declined the expression of HPV16E7 and E6 along the increase of p21 expression. The dose-dependent inverse correlation between p21 and E7 was statistically significant in SiHa cells (r = −0.975, p-value = 0.03) and borderline in UD-SCC-2 cells (r = −0.944, p-value = 0.06), in which p21 and E6 were also inversely correlated (r = −0.989). Conclusions: Our results indicate that hinokitiol might have potential in preventing the progress of immortalized cells toward malignancy and the growth of malignant lesions. Hinokitiol can also influence on the progression of HPV-associated lesions by downregulating the E6 and E7 expression.
... Chlorine dioxide has also been shown to reduce oral malodor by chemically neutralizing VSCs 12 . Natural ingredients, such as hinokitiol, green tea powder, and Eucalyptus extract, also reduce oral malodor through various antibacterial mechanisms 7,11,22 . ...
Article
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Objectives The aim of this study was to reveal the mechanisms by which zinc ions inhibit oral malodor. Material and Methods The direct binding of zinc ions to gaseous hydrogen sulfide (H2S) was assessed in comparison with other metal ions. Nine metal chlorides and six metal acetates were examined. To understand the strength of H2S volatilization inhibition, the minimum concentration needed to inhibit H2S volatilization was determined using serial dilution methods. Subsequently, the inhibitory activities of zinc ions on the growth of six oral bacterial strains related to volatile sulfur compound (VSC) production and three strains not related to VSC production were evaluated. Results Aqueous solutions of ZnCl2, CdCl2, CuCl2, (CH3COO)2Zn, (CH3COO)2Cd, (CH3COO)2Cu, and CH3COOAg inhibited H2S volatilization almost entirely. The strengths of H2S volatilization inhibition were in the order Ag+ > Cd2+ > Cu2+ > Zn2+. The effect of zinc ions on the growth of oral bacteria was strain-dependent. Fusobacterium nucleatum ATCC 25586 was the most sensitive, as it was suppressed by medium containing 0.001% zinc ions. Conclusions Zinc ions have an inhibitory effect on oral malodor involving the two mechanisms of direct binding with gaseous H2S and suppressing the growth of VSC-producing oral bacteria.
... β-Thujaplicin, a natural tropolone derivative, has been identified to exhibit a variety of biological properties, including antibacterial, antifungal, antiviral, anti-inflammatory, and anticancer potential [6][7][8][9][10][11][12][13] . β-Thujaplicin has been used in some health-care products, such as cosmetics, toothpastes, and body soaps 14 . Recent data suggested that β-Thujaplicin inhibited tumor formation of human colon cancer cells through the S-phase arrest and DNA demethylation 6,8 . ...
Article
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Hepatocellular carcinoma (HCC), a common liver malignancy worldwide, has high morbidity and mortality. β-Thujaplicin, a tropolone derivative, has been used in some health-care products and clinical adjuvant drugs, but its use for HCC is unknown. In this study, we found that β-Thujaplicin inhibits the growth of HCC cells, but not normal liver cells, with nanomolar potency. Mechanistically, we found that β-Thujaplicin could induce autophagy, as judged by western blot, confocal microscopy, and transmission electron microscopy. Further using β-Thujaplicin combined with an autophagy blocker or agonist treatment HepG2 cells, we found that β-Thujaplicin induced autophagic cell death (ACD) mediated by ROS caused inhibition of the Akt-mTOR signaling pathway. Moreover, β-Thujaplicin triggered HepG2 apoptosis and increased cleaved PARP1, cleaved caspase-3, and Bax/Bcl-2 ratio, which indicated that β-Thujaplicin induced apoptosis mediated by the mitochondrial-dependent pathway. We also found that increased expression of p21 and decreased expression of CDK7, Cyclin D1, and Cyclin A2 participating in β-Thujaplicin caused the S-phase arrest. It seems that β-Thujaplicin exerts these functions by ROS-mediated p38/ERK MAPK but not by JNK signaling pathway activation. Consistent with in vitro findings, our in vivo study verified that β-Thujaplicin treatment significantly reduced HepG2 tumor xenograft growth. Taken together these findings suggest that β-Thujaplicin have an ability of anti-HCC cells and may conducively promote the development of novel anti-cancer agents.
... [8][9][10] Thus, hinokitiol has been used in oral care products, such as toothpastes and oral-care gels, which are used to prevent and treat oral infectious diseases and halitosis. 11,12 Dental caries and periodontal diseases are common oral infectious diseases caused by bacterial colonization on tooth surfaces. The bacterial species that are considered the most cariogenic are the mutans streptococci, especially S. mutans and Streptococcus sobrinus. ...
Article
Hinokitiol is a component of the essential oil isolated from Cupressaceae. It possesses antibacterial and antifungal activities and has been used in oral care products. In this study, we examined the antibacterial activities of hinokitiol toward various oral, nasal, and nasopharyngeal pathogenic bacteria, including Streptococcus mutans, Streptococcus sobrinus, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Fusobacterium nucleatum, methicillin‐resistant and ‐susceptible Staphylococcus aureus, antibiotic‐resistant and ‐susceptible Streptococcus pneumoniae, and Streptococcus pyogenes. The growth of all bacterial strains was significantly inhibited by hinokitiol. The minimal inhibitory concentrations of hinokitiol against S. mutans, S. sobrinus, P. gingivalis, P. intermedia, A. actinomycetemcomitans, F. nucleatum, methicillin‐resistant S. aureus, methicillin‐susceptible S. aureus, antibiotic‐resistant S. pneumoniae isolates, antibiotic‐susceptible S. pneumoniae, and S. pyogenes were 0.3, 1.0, 1.0, 30, 0.5, 50, 50, 30, 0.3–1.0, 0.5, and 0.3 μg/mL, respectively. Additionally, with the exception of P. gingivalis, hinokitiol exerted bactericidal effects against all bacterial strains at 1 h after exposure. Hinokitiol did not display any significant cytotoxicity toward the human gingival epithelial cell line Ca9‐22, pharyngeal epithelial cell line Detroit 562, human umbilical vein endothelial cells, and human gingival fibroblasts, with the exception of 500 μg/mL hinokitiol treatment, which decreased viable Ca9‐22 cells and gingival fibroblasts by 13% and 12%, respectively. These results suggest that hinokitiol exhibits antibacterial activity against a broad spectrum of pathogenic bacteria and low cytotoxicity towards human epithelial cells. This article is protected by copyright. All rights reserved.
... In addition, Hinokitiol is also considered as a safe zinc ionophore rather than hydroxychloroquine (HCQ) for the treatment of viral infections. Moreover, Hinokitiol has been reported in skin and oral care because of its potent antiviral, anti-inflammatory, and anticancer properties [42,43]. In this study, through qRT-PCR assays and western blotting analysis screening, we found that Hinokitiol could inhibit some of the CSC characteristics of ICC cells by reducing the expression of ERK and P38, thus inhibiting tumor sphere formation. ...
Article
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Aims: Intrahepatic cholangiocarcinoma (ICC) is a highly malignant and heterogeneous cancer with a poor prognosis. At present, there is no optimal treatment except for surgical resection, and recurrence after resection will lead to death due to multidrug resistance. Changes in the redox signal have been found to be closely related to the growth and drug resistance of tumor cells. Therefore, the purpose of this study was to screen small molecule compounds from the redox library to find a drug for anti-ICC and to explore its downstream mechanism. Material and methods: Tumor clone and sphere formation of ICC cell lines, as well as mouse ICC organoid proliferation assays were utilized to screen the candidate drug in the Redox library. Western blotting, quantitative reverse-transcription polymerase chain reaction (qRT-PCR), as well as cell apoptosis and cell cycle flow cytometry assays were used to explore the mechanism. Results: We found that Hinokitiol was a candidate drug through inhibition of tumor clone and sphere formation, and the expression of cancer stem cell (CSC)-related genes. Furthermore, Hinokitiol significantly inhibited the proliferation of ICC cells by downregulating the ERK and P38 pathways. In addition, the combination of Hinokitiol and Palbociclib showed a significant inhibitory effect on human ICC cells and mouse ICC organoids. Conclusion: Hinokitiol may have the potential to be developed as a clinical therapeutic drug for ICC treatment.
... 32,33 Natural ingredients, such as hinokitiol, green tea powder, and Eucalyptus extract, also reduce oral malodor through various antibacterial mechanisms. [34][35][36] While the bactericidal activity of S-PRG eluate is limited, it is able to decrease VSC production by the other means. The results presented here suggest that oral rinsing and tongue cleaning using S-PRG eluate may represent new methods of controlling oral malodor. ...
Article
This study evaluated the effects of a surface pre-reacted glass-ionomer (S-PRG) eluate on oral microbiota and dental biofilms in vitro, and on oral malodor and tongue bacterial loads clinically. The effect of S-PRG eluate on the growth and survival of salivary bacteria was examined under both aerobic and anaerobic conditions; its ability to inhibit new biofilm formation and disrupt mature biofilms was also evaluated. The concentration of volatile sulfur compounds (VSCs) was measured using a portable sulfide monitor before and after rinsing with S-PRG eluate or distilled water. The number of bacteria on the tongue surface was calculated using a portable bacterial counter before and after tongue scraping with S-PRG eluate or distilled water. No zone of inhibition was seen for S-PRG eluate against salivary microbiota under either aerobic or anaerobic conditions; however, treatment with ≥20% S-PRG eluate was sufficient to suppress biofilm formation relative to untreated controls. Mature biofilms were significantly disrupted following treatment with ≥60% S-PRG eluate relative to controls. Rinsing with S-PRG eluate significantly reduced the level of VSCs relative to baseline; this effect was not seen with distilled water alone. Waste fluids collected after oral rinsing with S-PRG eluate contained more bacteria than rinsing with distilled water alone. Finally, tongue scraping using S-PRG eluate was shown to significantly reduce the number of bacteria on the tongue surface. S-PRG eluate inhibits biofilm formation and disrupts mature biofilms, although its antibacterial activity is limited. Oral rinsing and tongue cleaning with S-PRG eluate may reduce oral malodor by effectively removing oral bacteria from the oral cavity.
Article
A synthetic procedure towards 4,6-diisopropyl-3-nitro-1,2-benzoquinone was elaborated. Based on this benzoquinone, a series of novel 5,7-diisopropyl-2-(quinolin-2-yl)-1,3-tropolones and 5,7diisopropyl-2-(quinolin-2-yl)-4-nitro-1,3-tropolones were derived. Molecular structure of 2-(4-chloro-8-methylquinolin-2-yl)-5,7-diisopropyl-1,3-tropolone was established by X-ray diffraction analysis. Energetic and structural characteristics of isomeric 5,7-diisopropyl-2-(quinolin-2yl)-1,3-tropolones and 5,7-diisopropyl-2-(quinolin-2-yl)-4-nitro-1,3-tropolones in the gas phase and in the polar solvent were calculated by quantum chemistry method (PBE0/6-311+G(d,p)).
Article
Volatile sulfur compounds (VSCs) such as hydrogen sulfide (H2S) and methyl mercaptan (CH3SH) are the main components of oral malodor, and are produced as the end products of the proteolytic processes of oral microorganisms. The main pathway of proteolysis is the metabolism of sulfur‐containing amino acids by Gram‐negative anaerobic bacteria. Gram‐positive bacteria may promote VSC production by Gram‐negative anaerobes by cleaving sugar chains from glycoproteins and thus providing proteins. A large variety of bacteria within the oral microbiota are thought to be involved in the complex phenomenon of halitosis. Oral microbiota associated with a lack of oral malodor, oral microbiota associated with severe and H2S‐dominant oral malodor, and oral microbiota associated with severe and CH3SH‐dominant oral malodor have been distinguished through molecular approaches using the 16S rRNA gene. Pathological halitosis may primarily be addressed through treatment of causative diseases. In all cases, plaque control is the basis of oral malodor control, and dentifrices, mouthwashes, and functional foods play a supplementary role in addition to brushing. Recently, the use of natural ingredients in products tends to be preferred for reasons such as preventing increased resistance to antibiotics and the side effects of some chemical agents. In addition, probiotics and vaccines are expected to offer new strategies for improving the oral conditions through mechanisms other than antibacterial agents. This article is protected by copyright. All rights reserved.
Article
Background: Halitosis or bad breath is a symptom in which a noticeably unpleasant breath odour is present due to an underlying oral or systemic disease. 50% to 60% of the world population has experienced this problem which can lead to social stigma and loss of self-confidence. Multiple interventions have been tried to control halitosis ranging from mouthwashes and toothpastes to lasers. This new Cochrane Review incorporates Cochrane Reviews previously published on tongue scraping and mouthrinses for halitosis. Objectives: The objectives of this review were to assess the effects of various interventions used to control halitosis due to oral diseases only. We excluded studies including patients with halitosis secondary to systemic disease and halitosis-masking interventions. Search methods: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 8 April 2019), the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 3) in the Cochrane Library (searched 8 April 2019), MEDLINE Ovid (1946 to 8 April 2019), and Embase Ovid (1980 to 8 April 2019). We also searched LILACS BIREME (1982 to 19 April 2019), the National Database of Indian Medical Journals (1985 to 19 April 2019), OpenGrey (1992 to 19 April 2019), and CINAHL EBSCO (1937 to 19 April 2019). The US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (8 April 2019), the World Health Organization International Clinical Trials Registry Platform (8 April 2019), the ISRCTN Registry (19 April 2019), the Clinical Trials Registry - India (19 April 2019), were searched for ongoing trials. We also searched the cross-references of included studies and systematic reviews published on the topic. No restrictions were placed on the language or date of publication when searching the electronic databases. Selection criteria: We included randomised controlled trials (RCTs) which involved adults over the age of 16, and any intervention for managing halitosis compared to another or placebo, or no intervention. The active interventions or controls were administered over a minimum of one week and with no upper time limit. We excluded quasi-randomised trials, trials comparing the results for less than one week follow-up, and studies including advanced periodontitis. Data collection and analysis: Two pairs of review authors independently selected trials, extracted data, and assessed risk of bias. We estimated mean differences (MDs) for continuous data, with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the GRADE approach. Main results: We included 44 trials in the review with 1809 participants comparing an intervention with a placebo or a control. The age of participants ranged from 17 to 77 years. Most of the trials reported on short-term follow-up (ranging from one week to four weeks). Only one trial reported long-term follow-up (three months). Three studies were at low overall risk of bias, 16 at high overall risk of bias, and the remaining 25 at unclear overall risk of bias. We compared different types of interventions which were categorised as mechanical debridement, chewing gums, systemic deodorising agents, topical agents, toothpastes, mouthrinse/mouthwash, tablets, and combination methods. Mechanical debridement: for mechanical tongue cleaning versus no tongue cleaning, the evidence was very uncertain for the outcome dentist-reported organoleptic test (OLT) scores (MD -0.20, 95% CI -0.34 to -0.07; 2 trials, 46 participants; very low-certainty evidence). No data were reported for patient-reported OLT score or adverse events. Chewing gums: for 0.6% eucalyptus chewing gum versus placebo chewing gum, the evidence was very uncertain for the outcome dentist-reported OLT scores (MD -0.10, 95% CI -0.31 to 0.11; 1 trial, 65 participants; very low-certainty evidence). No data were reported for patient-reported OLT score or adverse events. Systemic deodorising agents: for 1000 mg champignon versus placebo, the evidence was very uncertain for the outcome patient-reported visual analogue scale (VAS) scores (MD -1.07, 95% CI -14.51 to 12.37; 1 trial, 40 participants; very low-certainty evidence). No data were reported for dentist-reported OLT score or adverse events. Topical agents: for hinokitiol gel versus placebo gel, the evidence was very uncertain for the outcome dentist-reported OLT scores (MD -0.27, 95% CI -1.26 to 0.72; 1 trial, 18 participants; very low-certainty evidence). No data were reported for patient-reported OLT score or adverse events. Toothpastes: for 0.3% triclosan toothpaste versus control toothpaste, the evidence was very uncertain for the outcome dentist-reported OLT scores (MD -3.48, 95% CI -3.77 to -3.19; 1 trial, 81 participants; very low-certainty evidence). No data were reported for patient-reported OLT score or adverse events. Mouthrinse/mouthwash: for mouthwash containing chlorhexidine and zinc acetate versus placebo mouthwash, the evidence was very uncertain for the outcome dentist-reported OLT scores (MD -0.20, 95% CI -0.58 to 0.18; 1 trial, 44 participants; very low-certainty evidence). No data were reported for patient-reported OLT score or adverse events. Tablets: no data were reported on key outcomes for this comparison. Combination methods: for brushing plus cetylpyridium mouthwash versus brushing, the evidence was uncertain for the outcome dentist-reported OLT scores (MD -0.48, 95% CI -0.72 to -0.24; 1 trial, 70 participants; low-certainty evidence). No data were reported for patient-reported OLT score or adverse events. Authors' conclusions: We found low- to very low-certainty evidence to support the effectiveness of interventions for managing halitosis compared to placebo or control for the OLT and patient-reported outcomes tested. We were unable to draw any conclusions regarding the superiority of any intervention or concentration. Well-planned RCTs need to be conducted by standardising the interventions and concentrations.
Chapter
Nowadays, natural medicines like honey, clove, miswak, and propolis are a part of dental treatment due to their reduced toxicity, wide availability, and cost effectiveness. This chapter gives an insight to the reader about the potential use of natural products in current dentistry. They are in many forms and include chewing sticks, oils, herbal extracts, minerals, animal products (e.g., honey), herbs, herbal materials, herbal preparations, and finished herbal products that contain parts of plants or other plant materials as active ingredients. Natural medicines hold huge benefits as adjunctive therapeutic uses in dentistry. Use of these techniques with suitable dosage would benefit the general population by preventing various dental problems.
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Focused question: Is there a role for alternative therapies in controlling intra-oral halitosis? Treatments other than tongue cleaning and anti-halitosis products containing zinc, chlorhexidine and cetylpyridinium chloride were considered as alternative therapies. Materials and methods: Four databases were searched (PubMed, EMBASE, Web of Science and The Cochrane Library). Inclusion criteria were: examination of alternative halitosis therapies, study population with oral malodour, a (negative or positive) control group and evaluation of the breath odour via organoleptic and/or instrumental assessment. Data were extracted for descriptive analysis. Results: The screening of 7656 titles led to the inclusion of 26 articles. Analysis showed heterogeneity concerning the population of interest (from cysteine-induced to genuine halitosis), the examined treatment and the reported outcomes. This made a meta-analysis impossible. Essential oils, fluoride containing products and herbal substances were the most studied. Results varied enormously and none of the active ingredients had an unambiguous positive effect on the malodour. The risk of bias was assessed as high in all articles. Conclusion: Given the fact that little evidence was found for each of the investigated treatments, it could be concluded that there is currently insufficient evidence that alternative therapies are of added value in the treatment of halitosis.
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The aim of this study was to evaluate the physicochemical properties of solid dispersion on mixtures of hinokitiol (HT) and γ-cyclodextrin (γ-CD) and of HT and (2-hydroxypropyl)-γ-cyclodextrin (HP-γ-CD). Differential scanning calorimetry revealed that coground HT/γ-CD at a molar ratio of 1:1 and HT and HP-γ-CD at molar ratios of 1:1 and 1:2 lacked an endothermic peak due to melting of HT crystals. Powder x-ray diffraction revealed that HT crystal showed a halo pattern respectively, by mixing and grinding of the CDs and HT. Thus, coground HT/γ-CD and HT/HP-γ-CD at a molar ratio of 1:1 had molecular interaction. Assessment of dissolution revealed that ground mixtures had improved dissolution of HT compared to HT crystals, ground HT alone, and physical mixtures containing HT. 1H-1H NOESY NMR suggested that the 7-membered ring and isopropyl group of HT were located within the cavity of γ-CD and HP-γ-CD. The antimicrobial tests indicated that ground mixtures exhibited a minimum inhibitory concentration (MIC) of 20 μg/mL against Bacillus subtilis, 40 μg/mL against Staphylococcus aureus, and 20 μg/mL against Escherichia coli. GMs were found to have 4 times more antimicrobial activity than HT crystals. Ground mixtures also exhibited MIC of 160 μg/mL against Pseudomonas aeruginosa and they were found to 2 times more antimicrobial activity than HT crystals. Improvement in antimicrobial activity with the formation of inclusion complexes is presumably due to increase the solubility of HT as a result of the formation of HT/CD inclusion complexes.
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Many hydrogel-based crosslinking membranes have been designed and tailored to meet the needs of different applications. The aim of this research is to design a bifunctional hydrogel membrane with antibacterial and osteoconducting properties to guide different tissues. The membrane uses gelatin and hyaluronic acid as the main structure, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride as the crosslinker, hinokitiol as the antibacterial agent, and dicalcium phosphate anhydrous (DCPA) micron particles for osteoconduction. Results show that the hydrogel membrane with added DCPA and impregnated hinokitiol has a fixation index higher than 88%. When only a small amount of DCPA is added, the tensile strength does not decrease significantly. The tensile strength decreases considerably when a large amount of modified DCPA is added. The stress–strain curve shows that the presence of a large amount of hinokitiol in hydrogel membranes results in considerably improved deformation and toughness properties. Each group impregnated with hinokitiol exhibits obvious antibacterial capabilities. Furthermore, the addition of DCPA and impregnation with hinokitiol does not exert cytotoxicity on cells in vitro, indicating that the designed amount of DCPA and hinokitiol in this study is appropriate. After a 14-day cell culture, the hydrogel membrane still maintains a good shape because the cells adhere and proliferate well, thus delaying degradation. In addition, the hydrogel containing a small amount of DCPA has the best cell mineralization effect. The developed hydrogel has a certain degree of flexibility, degradability, and bifunctionality and is superficial. It can be used in guided tissue regeneration in clinical surgery.
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Oral diseases are among the most common human diseases yet less studied. These diseases affect both the physical, mental, and social health of the patients resulting in poor quality of life. They affect all ages, although severe stages are mostly observed in older individuals. Poor oral hygiene, genetics, and environmental factors contribute enormously to the development and progression of these diseases. Although there are available treatment options for these diseases, the recurrence of the diseases hinders their efficiency. Oral volatile sulfur compounds (VSCs) are highly produced in oral cavity as a result of bacteria activities. Together with bacteria components such as lipopolysaccharides, VSCs participate in the progression of oral diseases by regulating cellular activities and interfering with the immune response. Hydrogen sulfide (H2S) is a gaseous neurotransmitter primarily produced endogenously and is involved in the regulation of cellular activities. The gas is also among the VSCs produced by oral bacteria. In numerous diseases, H2S have been reported to have dual effects depending on the cell, concentration, and donor used. In oral diseases, high production and subsequent utilization of this gas have been reported. Also, this high production is associated with the progression of oral diseases. In this review, we will discuss the production of H2S in oral cavity, its interaction with cellular activities, and most importantly its role in oral diseases.
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Supragingival plaque is permanently in contact with saliva. However, the extent to which the microbiota contributes to the salivary bacterial population remains unclear. We compared the compositional shift in the salivary bacterial population with that in supragingival plaque following periodontal therapy. Samples were collected from 19 patients with periodontitis before and after periodontal therapy (mean sample collection interval, 25.8 ± 2.6 months), and their bacterial composition was investigated using barcoded pyrosequencing analysis of the 16S rRNA gene. Phylogenetic community analysis using the UniFrac distance metric revealed that the overall bacterial community composition of saliva is distinct from that of supragingival plaque, both pre- and post-therapy. Temporal variation following therapy in the salivary bacterial population was significantly smaller than in the plaque microbiota, and the post-therapy saliva sample was significantly more similar to that pre-therapy from the same individual than to those from other subjects. Following periodontal therapy, microbial richness and biodiversity were significantly decreased in the plaque microbiota, but not in the salivary bacterial population. The operational taxonomic units whose relative abundances changed significantly after therapy were not common to the two microbiotae. These results reveal the compositional stability of salivary bacterial populations against shifts in the supragingival microbiota, suggesting that the effect of the supragingival plaque microbiota on salivary bacterial population composition is limited.
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Oral lichen planus (OLP) decreases the quality of life because it can cause spontaneous pain during eating and tooth-brushing and an uncomfortable feeling in the mouth. In addition, OLP may be associated with HCV-related liver disease.We investigated the visual analogue scale (VAS) and effects of oral care gel, REFRECARE-H®, on patients with OLP associated with HCV infection. Nine OLP patients (mean age 67.9 ± 7.6 years) with HCV-related liver diseases were recruited and their VAS score determined along with a biochemical examination of the blood. Types of OLP included erosive (6 patients) and reticular (3). REFRECARE-H®, an oral care gel (therapeutic dentifrice) containing hinokitiol, was applied by each patient as a thin layer on the oral membrane, after each meal and at bedtime for 30 days. Application of REFRECARE-H® improved the quality of life in all terms of dry mouth, breath odor, oral freshness, oral pain during rest, oral pain at a mealtimes, taste disorder, loss of appetite, sleep disorder, depressive mood and jitteriness. VAS scores of dry mouth, breath odor, oral freshness, and sleep disorder were significantly increased 30 days after application of REFRECARE-H® (P = 0.01, P = 0.05, P = 0.03, P = 0.04). VAS scores of oral pain at a mealtimes and taste disorder were increased 30 days after application of REFRECARE-H® (P = 0.06). There was an absence of side effects. REFRECARE-H® improved the quality of life for OLP. It is necessary for the hepatologist to educate patients regarding oral hygiene, as well as provide treatment of liver disease.
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Using common alcohol consumption categories, to conduct a pooled analysis of six ongoing large-scale cohort studies in Japan in order to produce concrete estimates of the quantitative contribution of alcohol consumption to all-cause and major causes of mortality in the Japanese population. Of the 309 082 subjects, there were 35 801 deaths during 3 832 285 person-years of follow-up. Using a random-effect model, we conducted a meta-analysis of the HRs of each alcohol consumption category in each study, thereby obtaining pooled estimates for the risk of total and major causes of mortality due to alcohol consumption. There was a J- or U-shaped association for the risk of total and major causes of mortality in men, and the risk of total and heart disease mortality in women. Compared with non-drinkers, there was a significantly lower risk for total mortality at an alcohol consumption level of <69 g/day, cancer mortality at <46 g/day, heart disease mortality at <69 g/day and cerebrovascular disease mortality at <46 g/day in men, and for total mortality at <23 g/day in women. In addition, mortality risk increased linearly with rising alcohol dose among drinkers. It was estimated that 5% of total mortality, 3% of cancer mortality, 2% of heart disease mortality and 9% of cerebrovascular disease mortality in men, but only 0-1% of these risks in women, could be prevented by reducing alcohol consumption to <46 g/day in men and <23 g/day in women. Maintaining alcohol consumption below 46 g/day in men and 23 g/day in women appears to minimise the risks of mortality in the Japanese population.
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Halitosis or bad breath is an oral health condition characterized by unpleasant odors emanating consistently from the oral cavity. The origin of halitosis may be related both to systemic and oral conditions, but a large percentage of cases, about 85%, are generally related to an oral cause. Causes include certain foods, poor oral health care, improper cleaning of dentures, dry mouth, tobacco products and medical conditions. Oral causes are related to deep carious lesions, periodontal disease, oral infections, peri-implant disease, pericoronitis, mucosal ulcerations, impacted food or debris and, mainly, tongue coating. Thus, the aim of the present review was to describe the etiological factors, prevalence data and the therapeutic mechanical and chemical approaches related to halitosis. In general, halitosis most often results from the microbial degradation of oral organic substrates including volatile sulfur compounds (VSC). So far, there are few studies evaluating the prevalence of oral malodor in the world population. These studies reported rates ranging from 22% to more than 50%. The mechanical and chemical treatment of halitosis has been addressed by several studies in the past four decades. Many authors agree that the solution of halitosis problems must include the reduction of the intraoral bacterial load and/or the conversion of VSC to nonvolatile substrates. This could be achieved by therapy procedures that reduce the amount of microorganisms and substrates, especially on the tongue.
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The capacity to form volatile sulfur compounds was tested in bacteria isolated from subgingival microbiotas and in a representative number of reference strains. A majority of the 75 tested oral bacterial species and 7 unnamed bacterial taxa formed significant amounts of hydrogen sulfide from L-cysteine. The most active bacteria were found in the genera Peptostreptococcus, Eubacterium, Selenomonas, Centipeda, Bacteroides and Fusobacterium. Methyl mercaptan from L-methionine was formed by some members of the genera Fusobacterium, Bacteroides, Porphyromonas and Eubacterium. When incubated in serum for 7 d, the most potent producers of hydrogen sulfide were Treponema denticola and the black-pigmented species, Bacteroides intermedius, Bacteroides loescheii, Porphyromonas endodontalis and Porphyromonas gingivalis. P. endodontalis and P. gingivalis also produced significant amounts of methyl mercaptan in serum. No other volatile sulfur compound was detected in serum or in the presence of L-cysteine and L-methionine. These findings significantly increase the list of oral bacteria known to produce volatile sulfur compounds.
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A degree of halitosis (oral malodour or foetor oris) is common in healthy people, particularly after sleep. It seems to originate from the mouth, resulting from the metabolic activity of bacteria present in oral plaque. Halitosis at other times is a distressing complaint from which few people probably escape completely and which is still incompletely understood. The true prevalence is not known, but one recent study suggested that nearly half of a group of young women (dental hygienists) believed that they sometimes had halitosis.1 Halitosis generally has as its basis bacterial putrefaction of food debris, cells, saliva, and blood.2 In particular, proteolysis of proteins to peptides, amino acids, and thence substrates with free thiol groups, such as cysteine and reduced glutathione, gives rise to volatile fluids and sulphides.3 Acetone, acetaldehyde, ethanol, propanol, and diacyl are also important causes of …
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Slow pyrolysis of Eucalyptus grandis wood was performed in an oven laboratory, and smoke was trapped and condensed to yield liquid products. Polycyclic aromatic hydrocarbons (PAHs) and phenolic fractions were isolated from the former liquid products using adsorption column chromatography (ACC) and identified by GC/MS. Concentrations of PAH and phenolic fractions in total pyrolysis liquids were respectively 48.9 μg/g and 8.59% (w/w). Acute toxicity of total samples of pyrolysis liquids and the phenolic fraction was evaluated by means of two bioassays, namely, 24-h immobilization bioassay with Daphnia magna and Microtox™ bioassays, the latter employing the luminescent bacteria Photobacterium phosphoreum. Total pyrolysis liquids and the PAH fraction were evaluated for genotoxicity by the Microtox™ bioassay conducted using rehydrated freeze-dried dark mutant of the luminescent bacteria Vibrio fisheri strain M169. Total pyrolysis liquids and the phenolic fraction, respectively, in concentrations of 170 and 68 mg/L were able to immobilize 50% (EC50) of the D. magna population following 24-h exposure. Concentrations of 19 and 6 mg/L, respectively, for total pyrolysis liquids and phenolic fraction were the effective concentrations that resulted in a 50% (EC50) reduction in light produced by bacteria in the Microtox™ bioassay. Accordingly, the Microtox™ bioassay was more sensitive to toxic effects of both kind of samples than the D. magna bioassay, particularly for the phenolic fraction. Regarding to the genotoxicity evaluation, the results achieved by Microtox™ bioassay showed that total pyrolysis liquids had no genotoxic effects with and without exogenous metabolic activation using rat liver homogenate (S9). However, the PAH fraction showed toxic effects with rat liver activation and had a dose-response number (DRN) equal to 1.6, being in this way suspected genotoxic. The lowest detected concentration (LDC) of the PAH fraction able to cause genotoxic effects was 375 μg/L.
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This study was undertaken to assess patients' response to their treatment at a multidisciplinary oral malodor clinic. In 4 years, a multidisciplinary breath odor clinic in Belgium examined 406 patients. The team consisted of an ear, nose, and throat specialist, a periodontologist, occasionally a specialist in internal medicine, and, more recently, a psychiatrist. After the initial visit, each patient was scheduled for a follow-up appointment 2 to 6 months later; however, only 143 patients (35%) showed up for this control visit. The remaining 65% of the patients answered a mailed questionnaire. About half of the patients who returned no longer had complaints, while 17% reported no improvement. This group was characterized by imaginary bad breath and manifest psychologic problems. There was also disbelief of their cure, although clinical examination (organoleptic evaluation and volatile sulfide measurement by means of a portable monitor) did not reveal any oral malodor. Some also insufficiently performed the recommended oral hygiene measures (tongue brushing and interdental cleaning). Most of the patients who returned the questionnaire were disappointed by the suggestion that their halitosis was the result of insufficient oral hygiene. Better education of both the public and dental professionals as to the most frequent cause of halitosis, insufficient oral hygiene, might elevate the level of compliance by patients.
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The aims of this study were to identify hydrogen sulfide (H2S)-producing bacteria among tongue biofilm microflora and to investigate the relationship between bacterial flora and H2S levels in mouth air. Oral malodour levels in 10 subjects (age 21-56 years) were assessed by gas chromatography, and Breathtron and organoleptic scores. Based on these assessments, subjects were divided into two groups: an odour group and a no/low odour group. Tongue coatings were sampled and spread onto Fastidious Anaerobe Agar plates containing 0.05% cysteine, 0.12% glutathione and 0.02% lead acetate, and were then incubated anaerobically at 37 degrees C for 2 weeks. Bacteria forming black or grey colonies were selected as H2S-producing phenotypes. The numbers of total bacteria (P<0.005) and H2S-producing bacteria (P<0.05) in the odour group were significantly larger than those in the no/low odour group. Bacteria forming black or grey colonies (126 isolates from the odour group; 242 isolates from the no/low odour group) were subcultured, confirmed as producing H2S and identified according to 16S rRNA gene sequencing. Species of Veillonella (38.1% in odour group; 46.3% in no/low odour group), Actinomyces (25.4%; 17.7%) and Prevotella (10.3%; 7.8%) were the predominant H2S-producing bacteria in both the odour and no/low odour groups. These results suggest that an increase in the number of H2S-producing bacteria in the tongue biofilm is responsible for oral malodour, although the bacterial composition of tongue biofilm was similar between the two groups.
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We report a case of oral malodor associated with internal resorption. A 39-year-old male attended our hospital complaining of oral malodor. Utilizing organoleptic measurement, the halimeter test and gas chromatography, it was diagnosed as a strong halitosis caused by oral origin. The pocket probing depth of tooth 21 was 10 mm, and X-ray examination revealed a vertical bone loss around this tooth. The patient had received periodontal treatment at two dental offices previously, but the periodontal conditions and oral malodor persisted. We performed an initial periodontal preparation, however a deep pocket remained. We therefore performed a surgical inspection including flap reflection, and found that the tooth had a large perforating defect in the distal surface. The extracted tooth had multiple perforating defects covered with granulation tissues on all root surfaces including the root apex. Taking into consideration the anamnesis and X-ray examination of the extracted tooth, internal absorption was considered to have been the cause of the multiple perforating defects. After extraction of the causative tooth, oral malodor dramatically decreased. To our knowledge, this is the first report of an oral malodor associated with internal resorption.
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Invasive fungal infection has become a major cause of morbidity and mortality in immunocompromised patients. Rapid identification of pathogenic fungi to species level is critical for disease treatment. A real-time LightCycler assay aiming at rapid detection and species identification of pathogenic fungi from clinical isolates was developed. Template DNAs of different species were amplified and detected in real time by employing SYBR Green fluorescent dye. The target sequences for species-level detection were located between the 18S and 28S rDNA. Seven fungal species encountered frequently in the clinical setting, Candida albicans, Candida glabrata, Candida krusei, Candida parapsilosis, Candida tropicalis, Candida guilliermondii and Cryptococcus neoformans, could be discriminated by species-specific primers and confirmed by melting-curve analyses. The range of linearity was from 1 ng to 1 pg (μl -1 water) and the sensitivity was 1 pg fungal DNA μl -1 . Identification by this real-time PCR method matched biochemical identification for all 58 clinical strains. Therefore, the method is simple, rapid and sensitive enough for detection and identification of several fungal species.
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今回, 歯周疾患治療剤の塗布方法の違いによるプラーク除去効果と歯肉炎改善効果を検討した。被験者は鶴見大学歯学部5年生のうち歯列不正はなく咬合状態は正常で, 歯肉炎の認められた36名で, 被験歯はRamfjordの6歯とした。使用した薬剤は昭和薬品化工(株)社製ヒノポロンTMで, 塗布方法は, (1)試作歯ブラシ群, (2)塗布群(指), (3)塗布群(試作歯ブラシ)の3種類とし, 被験者を12名ずつの3群に振り分けた。試作塗布用歯ブラシの形状は, 毛の直径0.30mm, 毛束の長さ6mm, 3列23毛束のナイロン毛で柄はストレートタイプとした。臨床パラメーターとして, PlI, GI, BOPを用い, 実験開始前と4週間後で診査を行い, その差を改善率で求め, t検定を用い統計処理を行った。改善率は, PlIは試作歯ブラシ群 : 57.3±5.8%, 塗布群(指) : 44.7±14.8%, 塗布群(試作歯ブラシ) : 61.9±6.8%であり, GIは試作歯ブラシ群 : 82.4±3.5%, 塗布群(指) : 78.9±5.0%, 塗布群(試作歯ブラシ) : 66.7±11.3%であり, PlI, GIともに統計学的有意差は認められず, BOPは, 試作歯ブラシ群 : 64.4±12.9%, 塗布群(指) : 85.5±4.6%, 塗布群(試作歯ブラシ) : 87.9±3.1%であり, 試作歯ブラシ群と塗布群(指)間, 試作歯ブラシ群と塗布群(試作歯ブラシ)間で, 統計学的有意差(p<0.05)が認められた。歯周疾患治療剤(ヒノポロンTM)の使用により歯肉出血抑制効果に差が認められ, 試作塗布用歯ブラシを使用することにより, 指で塗布するのと同等の歯肉出血抑制効果があり, また, 試作塗布用歯ブラシにはプラーク除去効果も期待できる。日本歯周病学会会誌(日歯周誌)50: 30-38, 2008
Article
Candida spp. are an opportunistic pathogen causing serious local and systemic infections, especially in immuno-compromised hosts such as the elderly and HIV-positive patients. Hinokitiol C10H12O2 (β-thujaplicin) is a component of the essential oils isolated from Cupressaceae and shows antibacterial activities for various bacteria. The aim of this study was to demonstrate the preventive effects of hinokitiol on the adherence of seven species of Candida to oral epithelial cells and to establish a safe and useful method for oral hygiene. A short-time treatment (30 min) with 0.25 mM hinokitiol showed 30–70% inhibition of adherence of Candida spp. to oral epithelial cells, inhibited about 11% biofilm formation, and did not inhibit the cell growth of Candida spp. Furthermore, short treatment with 0.25 mM hinokitiol was a safe method for oral hygiene against Candida infection because it did not inhibit the cell growth of commensal bacteria, such as oral streptococci existing in normal flora, or damage the epithelial cells. However, long-time treatment and a high concentration of hinokitiol demonstrated both the adherence inhibition of Candida and damage to commensal bacteria and epithelial cells. Our data suggest an appropriate procedure to apply hinokitiol that may be beneficial for the prevention of opportunistic pathogens such as Candida spp. in the oral cavity. The clinical and daily use of hinokitiol under an appropriate procedure may be a preventive and realistic therapy for Candida infection in immune-compromised hosts.
Article
β-thujaplicin, an active constituent from Chamaecyparis obtusa, has been shown to have acaricidal and antimicrobial effects. Very few studies have focused on the potential of the anti-inflammatory effect of β-thujaplicin. Moreover, its capability of inhibiting inflammatory mediators e.g. TNF-α gene transcription, nitric oxide (NO) and prostaglandin E2, remains unknown. Besides those molecular mechanisms behind the anti-inflammatory effect of β-thujaplicin, solid proof of its effectiveness in vivo has not yet been studied. In our study, in vitro effects of β-thujaplicin were verified on RAW 264.7 macrophages which were stimulated by LPS. Indomethacin was used as a positive control. The inducible NO production after stimulation was measured by Griess reagent. PGE2, IL-6 and TNF-α were measured by ELISA methods. Protein expressions of iNOS, COX2, and NF-κB were evaluated by Western blotting. Septic ICR mice were administered 20 mg/kg of LPS and then the mortality rate was monitored. Within the concentration range which was devoid of cytotoxicry, β-thujaplicin exhibited a clear dose-dependent inhibition on LPS-induced NO production. Furthermore, β-thujaplicin inhibited LPS-induced PGE2, IL-6, and TNF-α production as well as iNOS, COX2, and NF-κB protein expression more substantially potent than indomethacin. In agreement with the in vitro study, β-thujaplicin was shown to be effective in vivo for inhibiting LPS-induced NO and TNF-α production and a significant decrease in mortality rate of mice suffering from septic shock was observed. This study demonstrates the potential of β-thujaplicin in treatment of inflammation and sepsis. These effects occur through an efficient blockage of TNF-α and iNOS production. β-thujaplicin efficacy is comparable to that of indomethacin thus it can be a substitution but bear less depletion of PGE2, making this compound very promising in clinical applications.
Article
The objective of this paper is to evaluate the effects of oil drops containing Lactobacillus salivarius WB21 on periodontal health and oral microbiota producing volatile sulfur compounds (VSCs). For this study, 42 subjects were randomly assigned to receive oil samples containing L. salivarius WB21 or a placebo for two weeks. Oral assessment and saliva collection were performed on days 1 and 15. Bacterial analysis was performed using the real-time polymerase chain reaction and terminal restriction fragment length polymorphism (T-RFLP). In both the experimental and placebo groups, the average probing depth, number of periodontal pockets, and the percentage of bleeding on probing (BOP) decreased while stimulated salivary flow increased on day 15. BOP was reduced in the experimental group compared with the placebo group (P = 0.010). In the experimental group, total bacterial numbers decreased, and the number of L. salivarius increased. The number of Prevotella intermedia, which is correlated with hydrogen sulfide concentration in mouth air, increased in the placebo group and did not change in the experimental group. T-RFLP analysis found that the peak area proportions representing Porphyromonas gingivalis, P. intermedia, Tannerella forsythensis, and Fusobacterium nucleatum decreased in the experimental group, although there was no significant change in the bacterial composition. Thus we observed oil drops containing L. salivarius WB21 improved BOP and inhibited the reproduction of total and VSC-producing periodontopathic bacteria compared with the placebo group, but also showed the limit of its efficacy in controlling VSCs producing and periodontal pathogens.
Article
Only a few clinical research studies have assessed different therapeutic approaches to oral malodor in subjects affected by periodontal diseases. The aim of this study was to evaluate the effects of periodontal treatment and tongue cleaning on oral malodor parameters in periodontitis and gingivitis patients. The subjects were 102 periodontitis and 116 gingivitis patients with oral malodor. Oral malodor was measured by organoleptic test and Oral Chroma™. Oral health status, including tooth conditions, periodontal health, tongue coating and proteolytic activity of the BANA test in tongue coating were assessed. Subjects in each periodontal disease group were randomly assigned into two subgroups depending on the sequence of treatment: periodontal treatment and tongue cleaning. Oral malodor and oral health parameters were compared by groups and sequence of treatment. For subjects in the periodontitis group, there were statistically significant reductions in oral malodor after periodontitis treatment or tongue cleaning; however, major reductions were found after periodontitis treatment. For those in the gingivitis group, there were also statistically significant reductions in oral malodor after gingivitis treatment or tongue cleaning, but the most marked reductions were observed after tongue cleaning. At the completion of treatment, all oral malodor parameters fell below the threshold levels in all subgroups. The present study indicated that periodontal treatment played an important role and tongue cleaning contributed to a lesser extent to reduction in oral malodor in periodontitis patients. In contrast, tongue cleaning alone can be the primary approach to reduce oral malodor in gingivitis patients.
Article
Water extract of western red cedar heartwood inhibits growth of a wide variety of bacteria and fungi. Inhibition is due to stasis, not to death, of the organisms. Susceptibility of microorganisms is unrelated to Gram-staining reaction or to morphology.
Article
The objective of this study was to evaluate whether oral administration of lactobacilli alters the degree of halitosis and clinical conditions associated with halitosis. Twenty patients with genuine halitosis were given 2.0 x 10(9)Lactobacillus salivarius WB21 and xylitol in tablet form daily. Oral malodor and clinical parameters were evaluated at the same time of day for each patient after 2 and 4 weeks. All 20 patients were positive for L. salivarius DNA in their saliva at 2 weeks, although 12 patients were negative for this organism at baseline. Oral malodor parameters significantly decreased at 2 weeks in the subjects with physiologic halitosis. The scores of an organoleptic test and bleeding on probing significantly decreased at 4 weeks in the subjects with oral pathologic halitosis. Oral administration of probiotic lactobacilli primarily improved physiologic halitosis and also showed beneficial effects on bleeding on probing from the periodontal pocket.
Article
The aim of this systematic review was to evaluate the effects of 0.12% chlorhexidine (CHX) mouthrinse compared with 0.2% on plaque and periodontal parameters. MEDLINE-PubMed and the Cochrane Central Register of Controlled Trials were searched for (randomized) clinical trials and cohort studies. Plaque scores, parameters of periodontal inflammation and periodontal attachment loss were selected as primary outcome parameters. Screening of 409 titles and abstracts identified eight eligible publications. A meta-analysis of seven studies using the same plaque index showed a significant difference between 0.2% and 0.12% CHX (p=0.008). The Weighted Mean Difference for plaque based on the Quigley & Hein Plaque Index (1968) was 0.10 (95%CI [0.03-0.17]) (heterogeneity I(2)=0%, p=0.87). Three studies that compared 0.12% and 0.2% CHX mouthrinse products provided data on gingival inflammation. No difference in the effect of gingivitis between the two concentrations was found in these studies. No studies could be found that compared the two CHX concentrations and evaluated the probing pocket depth and/or the periodontal attachment level. In comparing 0.12% and 0.2% CHX, information concerning the effect on gingival inflammation was sparse and no studies could be found that compared the two CHX concentrations and evaluated the probing pocket depth and/or the periodontal attachment level. With respect to plaque inhibition, the results showed a small but significant difference in favour of the 0.2% CHX concentration. However, the clinical relevance of this difference is probably negligible.
Article
Eucalyptus extracts were found to possess an antibacterial activity against some oral pathogens that produce oral malodor compounds in vitro; however, the clinical effects with respect to oral malodor in humans remain unproven. In the present investigation, a randomized clinical study was designed to test the hypothesis that eucalyptus-extract chewing gum can reduce oral malodor in the general adult population. Subjects were randomly assigned to the following three groups: a high-concentration (0.6% eucalyptus extract) group (n = 32), a low-concentration (0.4% eucalyptus extract) group (n = 32), and a placebo group (n = 33). The intake period was 12 weeks. The organoleptic score, level of volatile sulfur compounds (VSCs), and tongue-coating score were recorded at baseline and 4, 8, 12, and 14 weeks. Treatment-to-time interactions among groups were evaluated by repeated-measures analysis of variance (ANOVA) followed by the Games-Howell pairwise comparison test. Relative to baseline readings, significant reductions in clinical parameters, including organoleptic and tongue-coating scores in the high- and/or low-concentration groups, occurred at 4, 8, 12, and 14 weeks (P <0.05). In addition, group-time interactions revealed significant reductions in the organoleptic score, VSCs, and tongue-coating score in both concentration groups compared to the placebo group (P <0.05). Eucalyptus-extract chewing gum had long-term effects on the olganoleptic score, levels of VSCs, and tongue-coating score. These findings suggest that eucalyptus-extract chewing gum may reduce oral malodor by decreasing the accumulation of tongue coating.
Article
A multicomponent evaluation of the oxidative consumption of salivary biomolecules by a commercially-available oral rinse preparation containing an admixture of the stable free radical species chlorine dioxide (ClO2.) with chlorite anion (ClO2-) has been investigated using high resolution H-1 NMR spectroscopy. The results obtained demonstrated that ClO2. and/or ClO2- present in this preparation effected the oxidative decarboxylation of salivary pyruvate (to acetate and CO2). Experiments conducted on chemical model systems confirmed the oxidative decarboxylation of pyruvate by this oral rinse, and also demonstrated that urate, thiocyanate anion, and the amino acids cysteine and methionine (precursors to volatile sulphur compounds responsible for oral malodour), were oxidatively consumed. The biochemical, periodontal and therapeutic significance of the results are discussed.
Article
Article Title and Bibliographic Information: Oral malodor and removable complete dentures in the elderly. Nalcaci R, Baran I. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;105(6):e5-9. Reviewer: Neal R. Garrett, PhD. Purpose/Question: Is oral malodor in complete denture wearers related to various sociodemographic factors, medical conditions, and oral hygiene? Does provision of oral hygiene instruction decrease oral malodor? Source of Funding: Information not available. Type of Study/Design: Case series study. Level of Evidence: Level 2: Limited-quality, patient-oriented evidence. Strength of Recommendation Grade: Not applicable.
Article
The amounts of volatile sulfur compounds (VSC) and methyl mercaptan/hydrogen sulfide ratio in mouth air from patients with periodontal involvement were 8 times greater than those of control subjects. Our studies demonstrated that, in patients with periodontal disease: 1) the concentration of disulfide, which is converted to VSC, increased in proportion to the total pocket depth; 2) 60% of the VSC was produced from the tongue surface; 3) the amount of tongue coating was 4 times greater than in control subjects; and 4) VSC production and the methyl mercaptan/hydrogen sulfide ratio of the tongue coating were increased. 2-Ketobutyrate, which is a byproduct of the metabolism of methionine to methyl mercaptan, was higher in the saliva of patients with periodontal disease. This implies that metabolism of methionine to methyl mercaptan increases in the oral cavity of patients with periodontal pockets. Since free L-methionine, rather than protein, is the main source for methyl mercaptan, we estimated the methionine supply from the gingival fluid into the oral cavity of patients with periodontal involvement. The results showed that the ratio of methionine to whole free amino acids was significantly higher than that of cysteine. Our studies suggest that not only microorganisms, but also the tongue coating and gingival fluid are factors which enhance VSC production in patients with periodontal disease.
Article
Plant extracts and their constituents were tested for antibacterial activity against periodontopathic bacteria, including Actinobacillus, Capnocytophaga, Fusobacterium, Eikenella and Bacteroides species. The essential oils of two labiatae plants, Mosla chinensis Maxim. and Pogostemon cablin Benth., and five terpenoids, hinokitiol, thymol, carvacrol, patchoulialcohol and pogostone, showed antibacterial activity. The terpenoids were especially effective against Bacteroides species.
Article
The antimicrobial action of natural substances was investigated in vitro against oral bacteria including Streptococcus sp., Actinomyces sp., Actinobacillus sp., Bacteroides sp., Capnocytophaga sp., Eikenella sp., Fusobacterium sp. and Propionibacterium sp. Among the natural substances tested, hinokitiol was the most inhibitory to oral bacteria. Cinnamon bark oil, papua-mace extracts, and clove bud oil in spice extracts were also inhibitory against many oral bacteria. Egg white lysozyme exhibited antimicrobial action against the periodontitis associated bacteria.
Article
Halitosis originates mainly from the oral cavity, and the volatile sulfur-containing compounds (VSC) are the major contributors of the unpleasant odor. Anaerobic G- bacteria use sulfur-containing amino acids in their production of VSC. Zinc has been shown to inhibit production of odiferous VSC, and the mechanism proposed has been that zinc, with its affinity for sulfur, oxidizes thiol groups and thereby inhibits the precursors of VSC. The aim of the study was to investigate whether, and to what extent, other metal ions with affinity for sulfur exert the same effect and whether a correlation exists between the sulfur affinity and VSC-inhibiting activity of these metals. VSC levels were measured on the 'morning breath' of 10 test subjects, using a portable sulfide monitor. The mouthrinses tested were aqueous solutions of zinc chloride, zinc citrate, stannous fluoride, cuprous gluconate, ferrous gluconate, and silver acetate, and they contained equimolar amounts of metals (1.47 mmol/I). The results showed that the ranking of Zn++ and Sn++ differed in the clinical test compared with sulfur affinity, and likewise with Ag+ and Fe++. It may therefore be concluded that there is no positive correlation between the inhibiting effect of metal ions on VSC and their affinity for sulfur.
Article
Background: Bad breath has a significant impact on our daily social life to those who suffer from it. The majority of bad breath originates within the oral cavity. However, it is also possible that it can come from other sources such as gastric-intestine imbalance. The term "oral malodor" is used to describe a foul or offensive odor emanating from the oral cavity, in which proteolysis, metabolic products of the desquamating cell, and bacterial putrefaction are involved. Recent evidence has demonstrated a link between oral malodor and adult periodontitis. The process of developing bad breath is similar to that noted in the progression of gingivitis/periodontitis. Oral malodor is mainly attributed to volatile sulfur compounds (VSC) such as hydrogen sulfide, methyl mercaptan and dimethyl sulfide. The primary causative microbes are gram-negative, anaerobic bacteria that are similar to the bacteria causing periodontitis. These bacteria produce the VSC by metabolizing different cells/tissues (i.e., epithelial cells, leukocytes, etc.) located in saliva, dental plaque, and gingival crevicular fluid. Tongue surface is composed of blood components, nutrients, large amounts of desquamated epithelial cells and bacteria, suggesting that it has the proteolytic and putrefactive capacity to produce VSC. One of the challenges in dealing with oral malodor is to identify a reliable test for detecting bad breath. Aims: The purposes of this review article were: (1) to correlate the relationship between oral malodor and adult periodontitis; (2) to analyze current malodor tests and discuss available treatment regimens.
Article
Putrefaction of saliva is commonly used as an in-vitro assay in oral malodour investigations. To exam the hypothesis that deglycosylation of salivary glycoproteins promotes oral malodour production. Porphyromonas gingivalis-mediated putrefaction of salivary glycoproteins was tested following preincubation of saliva in the presence of beta-galactosidase with or without glycosidic inhibitor (galactosamine), and in the presence of glucose with or without a non-glycosylated protein (bovine serum albumin). Malodour was determined by two odour judges, and volatile sulphides by using a sulphide monitor. Salivary glycoprotein degradation was measured densitometrically following electrophoresis on SDS-PAGE. The addition of beta-galactosidase promoted salivary glycoprotein degradation and concomitant malodour production, whereas addition of a glycosidic inhibitor (D-galactosamine) inhibited this process. Glucose inhibited salivary glycoproteins putrefaction, but this inhibitory effect was mitigated when a non-glycosylated protein (BSA) was added. Deglycosylation of salivary glycoproteins may be an initial step in oral malodour production. This process exposes the protein core of the glycoprotein, which is then further degraded by Gram-negative microorganisms under anaerobic conditions.
Article
The aim of this double-blind, parallel study was to test the clinical efficacy of a newly developed mouthrinse in the treatment of oral halitosis in patients without periodontitis. Forty volunteers, recruited in two centers, participated in this study. Patients were selected on the basis of (1) halitosis of oral origin, (2) full-mouth organoleptic score>1, using an arbitrary 0-5 scale, (3) level of volatile sulfur compounds (VSC)>170 parts per billion (ppb) and (4) Winkel tongue coating index (WTCI)>4 (0-12). Intervention included gargling with a mouthrinse containing chlorhexidine (0.05%), cetylpyridinium chloride (0.05%) and zinc-lactate (0.14%) or with a placebo mouthrinse without active ingredients. At days 0 and 14 clinical variables were assessed in order of performance: (1) organoleptic assessments, (2) levels of VSC, and (3) WTCI. Treatment with the active mouthrinse resulted in a significant mean reduction in the organoleptic score from 2.8 to 1.5 (p<0.005). In the placebo group, no significant reduction in the mean organoleptic score occurred. Consequently, this resulted, after 2 weeks, in a greater change of the organoleptic scores in the test group in comparison to the placebo group (p<0.005). The mean VSC scores were reduced from 292 to 172 ppb in the test group (p<0.005), whereas no reduction was observed in the placebo group. At the 2-week examination, the mean change of the VSC scores in the test group was significantly greater than the mean change in the placebo group (p<0.005). Neither in the test nor in the placebo group a significant reduction in tongue coating was observed. In conclusion, the tested mouthrinse is effective in the treatment of oral halitosis.
Article
The purpose of this study was to determine whether a reduction of salivary flow would influence the production of methylmercaptan (CH(3)SH) and hydrogen sulfide (H(2)S), which are volatile sulfur compounds (VSCs) known to cause oral malodor. The VSCs in mouth air were measured by means of gas chromatography. Spitting and masticatory (stimulated) methods were used to determine the salivary flow rates of 174 patients. There was no significant correlation between the level of VSCs and salivary flow rate. However, subjects with extremely low resting salivary flow rates had significantly higher CH(3)SH and H(2)S concentrations and tongue-coating scores than those with higher resting salivary flow rates. Moreover, logistic analyses revealed that extremely low resting salivary flow, the increase in tongue coating, and a probing pocket depth greater than 4 mm were strong explanatory factors for the generation of VSCs, which could have caused oral malodor. These findings suggested that an extreme reduction in resting saliva influenced the generation of CH(3)SH and H(2)S in mouth air.
Article
Invasive fungal infection has become a major cause of morbidity and mortality in immunocompromised patients. Rapid identification of pathogenic fungi to species level is critical for disease treatment. A real-time LightCycler assay aiming at rapid detection and species identification of pathogenic fungi from clinical isolates was developed. Template DNAs of different species were amplified and detected in real time by employing SYBR Green fluorescent dye. The target sequences for species-level detection were located between the 18S and 28S rDNA. Seven fungal species encountered frequently in the clinical setting, Candida albicans, Candida glabrata, Candida krusei, Candida parapsilosis, Candida tropicalis, Candida guilliermondii and Cryptococcus neoformans, could be discriminated by species-specific primers and confirmed by melting-curve analyses. The range of linearity was from 1 ng to 1 pg (microl(-1) water) and the sensitivity was 1 pg fungal DNA microl(-1). Identification by this real-time PCR method matched biochemical identification for all 58 clinical strains. Therefore, the method is simple, rapid and sensitive enough for detection and identification of several fungal species.
Article
The objective of this study was to evaluate the developmental toxicity of beta-thujaplicin (TP) in rats. Pregnant rats were given TP by gastric intubation at 15, 45, or 135 mg/kg on days 6-15 of pregnancy. The maternal body weight gain during administration at 45 and 135 mg/kg and after administration at 136 mg/kg and adjusted weight gain at 45 and 135 mg/kg were significantly reduced. A significant decrease in food consumption during and after administration was found at 45 and 135 mg/kg. A significant increase in the incidence of postimplantation loss was found in pregnant rats given TP at 135 mg/kg. A significantly lower weight was found in female fetuses at 45 and 135 mg/kg and in male fetuses at 135 mg/kg. Although a significantly increased incidence of fetuses with skeletal variations and decreased degree of ossification were found at 135 mg/kg, no significant increase in external, skeletal and internal malformations was detected after administration of TP. The data demonstrated that TP had adverse effects on embryonic/fetal survival and growth only at maternal toxic doses. No adverse effects on morphological development were found in rats fetuses. Based on the significant decreases in maternal body weight gain and weight of female fetuses at 45 mg/kg and higher, it is concluded that the no-observed-adverse-effect levels (NOAELs) of TP for both dams and fetuses are considered to be 15 mg/kg in rats.
Article
To compare five different commercial mouth rinses with chlorhexidine (CHX) with respect to their anti-halitosis effect and anti-microbial activity on salivary bacterial counts, following a standardised research protocol. And secondly, to validate the study model proposed in the evaluation of patients suffering from halitosis. Ten volunteers, with a healthy oral status, were enrolled in a double-blind, cross-over design, using sterile saline as negative control and five CHX-containing mouth rinses: 0.12% CHX alone (CHX+NO), plus alcohol (CHX+ALC), plus 0.05% cetylpiridinium chloride (CHX+CPC), plus sodium fluoride (CHX+NaF), and 0.05% CHX plus 0.05% CPC, plus 0.14% zinc lactate (CHX+Zn). The levels of whole-mouth volatile sulphur compounds (VSCs) were measured by means of a sulphide monitor at baseline, 1 and 5 h after rinsing with the assigned product. Baseline measurements also included an organoleptic assessment and the recording of the tongue-coating index. Aerobic and anaerobic salivary bacterial counts were also obtained by collecting unstimulated saliva samples at the same evaluation times, and processed by culturing techniques. Analysis of variance was used to evaluate whether significant differences existed among groups, at each evaluation point, or in changes between evaluations. No significant differences were detected at baseline, with VSC levels ranging between 190 and 227 parts per billion (p.p.b.) After rinsing, VSC levels were reduced with all products (except saline), after 1 h. Significant differences at 1 h were detected (p=0.04), corresponding to a lower amount of p.p.b. (109) in (CHX+Zn) as compared with the other groups (except CHX+NO). At 5 h, VSC levels were lower for CHX+CPC and CHX+Zn (155 and 169, respectively), while the other groups showed levels higher than 220 p.p.b. With respect to aerobic salivary bacterial counts, CHX+CPC demonstrated the lowest percentage of survival (6% after 1 h and 18% after 5 h). For anaerobic bacterial counts, again CHX+CPC demonstrated the lowest percentage of survival (10% at 1 h and 23% at 5 h), together with CHX+ALC (18% of survival at 5 h). However, salivary counts and VSCs were only significantly correlated at baseline, but not after treatment. Important differences can be expected from different CHX formulations, in relation to both their anti-halitosis effect and anti-microbial activity in saliva. Formulations that combine CHX and CPC achieved the best results, and a formulation combining CHX with NaF resulted in the poorest.
Article
To evaluate the ability of Moisture Checker for Mucus (MCM), a device which measures the weight percent of water content in the oral mucosal epithelium, for the diagnosis of dry mouth. Forty-three consecutive patients seen at the Dry Mouth Clinic of Tsurumi University were divided into two groups by the diagnostic criteria of hyposalivation defined by the stimulated salivary flow rate < or =10 ml per 10 min. The MCM values in the buccal, tongue and labial mucosa in each group were compared. The value of the normal salivation group was significantly higher when compared with that of the hyposalivation group both in the buccal and tongue mucosa, P = 0.01 and P = 0.046, respectively. Moisture Checker for Mucus has the potential to be a useful device in the screening of hyposalivation.
Article
Bacterial proliferation and plaque accumulation on the surface of the tongue are major factors contributing to oral malodor. In this research, we used subjective and objective methods to evaluate the breath benefit of a triclosan-containing dentifrice (Blend-a-Med Complete Night) with and without tongue brushing in a randomized, examiner-blinded, three-period crossover clinical trial. Twenty-nine adults (mean age 40.2 years) with morning malodor were randomly assigned to a treatment sequence: triclosan dentifrice, triclosan dentifrice plus tongue brushing, and a control dentifrice (Crest Cavity Protection). The subjects used each product four times in 27 h with a 2-day wash-out period between treatments. Halimeter measurements were taken at baseline and at 3, 24 and 27 h. Subject questionnaire data assessing the breath quality were collected at 24 and 27 h. Both triclosan regimens showed significant improvement in oral malodor (p < 0.03) relative to the control. Significant (p = 0.035) malodor benefit was observed when tooth brushing with triclosan dentifrice was supplemented with tongue brushing. The triclosan dentifrice was associated with significant improvement (p < 0.05) in morning mouth feel and feeling of clean and fresh breath during the day relative to the control. There were no adverse events reported. The triclosan dentifrice was effective against overnight and daytime oral malodor. Supplementing routine brushing with tongue brushing resulted in additional breath improvement and breath benefits of the triclosan dentifrice were first-person noticeable.
Article
The objective of this study was to determine the effect of various toothbrushing regimens with a standard fluoride dentifrice on the plaque inhibitory properties of an alcohol-free, high bioavailable 0.07% cetylpyridinium chloride (CPC) mouthrinse. The study was a randomized, single-centre, examiner blind, four-period cross-over study involving 29 healthy subjects. Four treatment regimens were evaluated: (1) Toothbrushing with dentifrice followed by a water rinse (B-W, negative control); (2) Toothbrushing with dentifrice followed by a CPC mouthrinse use (B-CPC); (3) Toothbrushing with dentifrice followed by a water rinse and then a CPC mouthrinse use (B-W-CPC); and (4) Toothbrushing with dentifrice and waiting 60 min. prior to a CPC mouthrinse use (B-60 min.-CPC). Three days before the baseline exam of treatment periods, subjects were instructed to brush only the lingual surfaces of their teeth for up to 60 s twice daily. At baseline, subjects received a plaque exam using the Turesky modification of the Quigley-Hein index (MQH) followed by a polishing on the lingual and buccal surfaces of their teeth. During treatment periods, subjects were asked to brush only the lingual surfaces of their teeth with a standard fluoride dentifrice. Rinsing with 20 ml of the experimental CPC solution was done for 30 s twice daily. The evening before the last day of treatment periods (Day 4), subjects were asked to refrain from any oral hygiene, eating, and drinking after brushing. On Day 4, plaque was scored using the MQH Index. A 10-day wash-out of normal oral hygiene was allowed between each of the four treatment periods. The data were analysed using analysis of covariance for cross-over designs. Twenty-five to 29 subjects were evaluable at any given visit. With respect to unbrushed buccal and brushed lingual surfaces, all three CPC regimens had highly significantly (p < or = 0.0006) lower mean plaque scores than the B-W regimen, reductions ranging from 20% to 38% in magnitude. With respect to unbrushed surfaces, there was a significant difference between the B-CPC regimen and the B-60 min.-CPC regimen (p < 0.01) in favour of the latter regimen. No other pairwise treatment comparisons were statistically significant for unbrushed sites. Results for brushed surfaces and all sites combined showed that both the B-W-CPC and the B-60 min.-CPC groups reduced mean plaque levels significantly (p < or = 0.013) more than B-CPC. There were no statistically significant differences between B-W-CPC and B-60 min.-CPC for measurements of brushed, unbrushed, or all sites combined. Results show that the alcohol-free, 0.07% high bioavailable CPC rinse provides an additive anti-plaque benefit beyond toothbrushing with a standard fluoride dentifrice regardless of the regimen. Of the regimens, a water rinse between toothbrushing and CPC rinsing enhances therapeutic efficacy while fitting into the patient's typical oral hygiene routine.
Article
To determine the effects of herbal mouthwash containing the pericarp extract of Carcinia mangostana L on volatile sulfur compound (VSC) levels, plaque index (PI) and papillary bleeding index (PBI) in gingivitis subjects and the recurrence of these parameters after periodontal treatment. Sixty subjects who were diagnosed as having mild or moderate chronic gingivitis were randomly distributed into herbal or placebo mouthwash groups. On day 1, all parameters were recorded. Subjects rinsed with the assigned mouthwash and VSC was measured at 30 min and 3 h post-rinsing. For the following 2 weeks, subjects practiced their usual oral hygiene and rinsed with the assigned mouthwash twice daily after tooth brushing. On day 15, parameters were recorded. In the 4-week washout period that followed, subjects received scaling and polishing. After another baseline examination, they were re-randomized into the herbal or placebo group and rinsed with mouthwash for 2 weeks. All parameters were re-evaluated on day 15. All parameters were significantly different compared to baseline in both groups at 30 min, 3 h and day 15 (p < 0.05). When compared between groups, VSC was significantly different at day 15 (p < 0.05). After scaling, poloshing and rinsing with mouthwash for 2 weeks, PI and PBI were significantly different compared to baseline (p < 0.05) while VSC was not (p > 0.05). When compared between groups, VSC was significantly different (p < 0.05). Herbal mouthwash containing the pericarp extract of G. mangostana may be used as an adjunct in treating oral malodor.
Article
Volatile sulfur compounds (VSC), mainly derived from bacteria located in deep crypts at the back of the tongue and from periodontal pockets, are responsible for approximately 90% of halitosis (bad breath, malodor). The objective of this double blind clinical study was to assess the clinical efficacy of a new formulation for halitosis containing a combination of zinc (0.3% Zn) and chlorhexidine (0.025% CHX) in low concentrations. The new formulation was compared to some widely used and commercially available formulations containing various enzymes and antibacterial agents in a clinical setting under controlled conditions. Ten healthy volunteers participated in this study (5 female, 5 male, mean age: 46.6, range: 26-79). Each participant served as their own control, and neither the investigator nor the ten test subjects knew which formulation they were testing at any given time (double-blind design). Baseline H2S data were obtained by cysteine rinsing for 30 seconds, 90 seconds mouth closure, and gas chromatographic (GC) analysis of mouth air. On separate days, each participant then rinsed for 60 seconds with 10 ml of each of the eight various formulations. Cysteine rinses were repeated at 1 hour, 2 hours, and 3 hours, and GC measurements of oral H2S levels were again recorded. The test rinse (0.3% Zn + 0.025% CHX) reduced the intraoral H2S levels to 0.16% of control (range: 0.01-0.54%) after 1 hour, 0.4% after 2 hours, and 0.75% after 3 hours, providing superior efficacy in reducing H2S compared to the other formulations tested (p < 0.05). A combination of Zn and CHX in low concentrations seems to be the most efficient way to remove the VSC that causes bad breath at present. Studies are underway to further explore the extraordinary efficacy of this combination (close to 100%), suggesting a specific mode of action and a synergistic effect of these two components.
Article
Many food products are claimed to be effective in controlling halitosis. Halitosis is caused mainly by volatile sulfur compounds (VSCs) such as H(2)S and CH(3)SH produced in the oral cavity. Oral microorganisms degrade proteinaceous substrates to cysteine and methionine, which are then converted to VSCs. Most treatments for halitosis focus on controlling the number of microorganisms in the oral cavity. Since tea polyphenols have been shown to have antimicrobial and deodorant effects, we have investigated whether green tea powder reduces VSCs in mouth air, and compared its effectiveness with that of other foods which are claimed to control halitosis. Immediately after administering the products, green tea showed the largest reduction in concentration of both H(2)S and CH(3)SH gases, especially CH(3)SH which also demonstrated a better correlation with odor strength than H(2)S; however, no reduction was observed at 1, 2 and 3 h after administration. Chewing gum, mints and parsley-seed oil product did not reduce the concentration of VSCs in mouth air at any time. Toothpaste, mints and green tea strongly inhibited VSCs production in a saliva-putrefaction system, but chewing gum and parsley-seed oil product could not inhibit saliva putrefaction. Toothpaste and green tea also demonstrated strong deodorant activities in vitro, but no significant deodorant activity of mints, chewing gum or parsley-seed oil product were observed. We concluded that green tea was very effective in reducing oral malodor temporarily because of its disinfectant and deodorant activities, whereas other foods were not effective.
Article
To examine the psychosomatic aspects of patients complaining of halitosis. Breath malodor in 165 patients was measured using an organoleptic test (OLT), sulfide monitoring, and gas chromatography. Clinical evaluation included oral examination, OLT, and volatile sulfur compound measurement. The psychologic condition of patients was assessed using the Cornell Medical Index (CMI). Every item in the CMI questionnaire was negatively correlated with the OLT scores. Nine of 21 subjects (42.9%) diagnosed with pseudohalitosis and approximately 20% of subjects diagnosed with genuine halitosis were considered to be provisionally neurotic. Subjects with pseudohalitosis reported significantly higher physical scores, but not mental scores, than those with genuine halitosis. Subjects with physiologic halitosis showed significantly higher symptoms of depression than those with oral pathologic halitosis. The psychologic condition of patients complaining of halitosis was associated with the actual degree of malodor and the clinical characteristics.
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  • The
The R project homepage. 2010. Available at: http://www.r-project. org. (accessed October 30, 2012).
Oral malodor reduction by a combination of chemotherapeutical and mechanical treatments.
  • Farrell S.
  • Baker R.A.
  • Somogyi-Mann M.
  • Eitt J.J.
  • Gerlach R.W.