Article

Chlorine Dioxide (CLO2) As a Non-Toxic Antimicrobial Agent for Virus, Bacteria and Yeast (Candida Albicans)

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Abstract

The use of a family of chemical agents, releasing active species of oxygen, effective against infectious microorganisms and viruses is described with emphasis on Chlorine Dioxide (CLO2), one of the oxides of chlorine. Also discussed are ozone, hypochlorite, periodate and the known mechanisms of action by which certain white blood cells attach and eradicate infectious microorganisms and primitive bacteria also known as viruses. Explanation of the biochemical mechanisms of acid of CLO 2 as an antimicrobial agent, is presented. Particular attention is given to Candida albicans, cytomegalovirus, polio virus, Herpes I and II, HTLV-III and Pseudomonas responding to the clinical application of CLO2. It is implied that these biochemical mechanisms are so fundamental that the development of resistant strains of bacteria and/or yeast would not occur with other anti-infectious agents. Limited lists of health abnormalities that respond to CLO2 are discussed.

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... As a solution to these shortcomings, chlorine dioxide (ClO 2 ) gas is a type of disinfectant that has recently attracted attention [7][8][9][10]. ClO 2 gas is already known for its excellent effects on deodorization [11], sterilization, or inhibition of viral amplification [8,[12][13][14]. It is safe and has eco-friendly properties, such as easy decomposition by light and cost-effectiveness. ...
... The use of ClO 2 gas is still controversial in terms of safety [8,9,[20][21][22]. Safety issues are constantly being raised, but many recent reports have stated that the effective use of ClO 2 gas is beneficial in quarantine living environments and medical fields [7,10,12,16,18,[23][24][25]. Most studies pointing out the dangers of ClO 2 gas also warn of the risks of unintentional workplace accidents and unspecified hyperreactivity [20][21][22]. ...
... According to Young's review, as a safe disinfectant, ClO 2 has an inhibitory effect on bacteria, viruses, and fungi. It has been recognized as an effective substance with very little toxicity [12]. In our study, a single-dose inhalation toxicity test was conducted according to the guidelines of the 'Single dose inhalation toxicity study (Appendix 10)' in the 'Standard for Toxicity Study of Pharmaceuticals' provided by the MFDS [31] by applying a high ClO 2 gas concentration to mice that could not be realistically reached in daily life. ...
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Since the onset of the COVID-19 pandemic, there has been a growing demand for effective and safe disinfectants. A novel use of chlorine dioxide (ClO2) gas, which can satisfy such demand, has been reported. However, its efficacy and safety remain unclear. For the safe use of this gas, the stable release of specific concentrations is a must. A new type of ClO2 generator called Dr.CLOTM has recently been introduced. This study aimed to investigate: (1) the effects of Dr.CLOTM on inhibiting adenoviral amplification on human bronchial epithelial (HBE) cells; and (2) the acute inhalation safety of using Dr.CLOTM in animal models. After infecting HBE cells with a recombinant adenovirus, the inhibitory power of Dr.CLOTM on the virus was expressed as IFU/mL in comparison with the control group. The safety of ClO2 gas was indirectly predicted using mice by measuring single-dose inhalation toxicity in specially designed chambers. Dr.CLOTM was found to evaporate in a very constant concentration range at 0–0.011 ppm/m3 for 42 days. In addition, 36–100% of adenoviral amplification was suppressed by Dr.CLOTM, depending on the conditions. The LC50 of ClO2 gas to mice was approximately 68 ppm for males and 141 ppm for females. Histopathological evaluation showed that the lungs of female mice were more resistant to the toxicity from higher ClO2 gas concentrations than those of male mice. Taken together, these results indicate that Dr.CLOTM can be used to provide a safe indoor environment due to its technology that maintains the stable concentration and release of ClO2 gas, which could suppress viral amplification and may prevent viral infections.
... Chlorine dioxide gas in solution is known to exhibit antiviral activity against SARS-CoV, influenza A, adenovirus type 40 and feline calicivirus, cytomegalovirus, polio virus, herpes I and II, human Tlymphotropic virus type III (HTLV-III), measles virus, canine distemper virus, human adenovirus-2, canine adenovirus-2, and canine parvovirus Sanekata et al., 2010;Thurston-Enriquez et al., 2005;Wang et al., 2005;Young, 2016). ...
... The antiviral activity of chlorine dioxide against influenza A is attributed to the oxidation of amino acids particularly tryptophan and tyrosine at the receptor-binding site Ogata, 2012;Ogata & Shibata, 2008). Young (2016) While there were some differences in the methods used to assess the viral load reductions, it is important to note that these assays are internally controlled and the reduction values are informative. ...
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Objective: To determine the antiviral activity in-vitro of oral care products containing stabilized chlorine dioxide towards infectious viruses that harbor in the oral cavity. Methods: Validated in-vitro suspension virucidal assays were used. Test product was mixed with the test virus for 30-, 60- or 120- seconds, neutralized with sodium thiosulfate, serially diluted in dilution medium in a 96 well plate and incubated in a carbon dioxide incubator for 7 days. The 50% Tissue Culture Infectious Dose per mL was determined. Results: Two rinses, one oral spray and one fluoride toothpaste showed log reduction of severe acute respiratory syndrome coronavirus-2 ranging from 1.81 to 2.98 and of influenza A from 2.58 to 4.13, respectively, within 30 seconds of contact time; similar results were obtained at 60 seconds. Further, the Ultra Sensitive rinse showed 0.19, 0.75, 1.58, 1.75, 2.66 and 3.24 log reduction of severe acute respiratory syndrome coronavirus, human coronavirus 229E, rhinovirus type 14, adenovirus type 5, and herpes simplex virus type 1 and type 2, respectively, within 30 seconds of contact time. Conclusion: Stabilized chlorine dioxide containing ClōSYS® oral care products reduced the viral load of multiple viruses within 30 seconds. The results warrant further investigation for potential in-vivo applications.
... The Korean Ministry for Food, Agriculture, Forestry and Fisheries (MIFAFF) has permitted the use of ClO 2 for organic handling of materials and sanitization (groceries selection section 22, schedule 2, August 2010). Toxicity studies in humans have revealed that daily ingestion of 500 mL of ClO 2 at a concentration of 5 ppm can be safely tolerated (Robert, 2016). In a postharvest test of Gerbera 'Jenny' and Rosa 'Beast', the antibacterial effect of ClO 2 was maintained six days after treatment, while the ClO 2 in the solution disappeared in two days . ...
... Similar results were reported previously (Spotts and Peters, 1980), showing that treatment of B. cinerea conidia with 10 μg·mL −1 ClO 2 for 0.5, 5, or 10 mins inhibited B. cinerea spore germination. It has been reported that mycelial fungi are sensitive to the destructive action of ClO 2 due to their low tolerance for nascent oxygen and to changes in the acidic medium in which they thrive following the liberation of organic acids (Robert, 2016). ...
Article
This study investigated the antifungal effect of chlorine dioxide (ClO2) dipping on Botrytis cinerea, the causal agent of gray mold, on cut rose flowers (Rosa hybrida L.). In vitro, the spore germination of gray mold was inhibited 100% by instant dipping with ClO2 solution (5 to 10 μL·L⁻¹). In particular, ClO2 at 5 μL·L⁻¹ was found to be ideal for hindering spore activity without causing any damage to the petals. This ClO2 antifungal effect on cut flowers was investigated in a white cultivar ‘Beast’ with different treatments: dipping (one second), spraying (4.8 mL), or gassing (two hours) with 5 μL·L⁻¹ ClO2. Six days after ClO2 treatment, the incidence of gray mold in the artificially-inoculated flowers was 2.5% (dipping), 9.4% (spraying), or 8.4% (gassing), respectively, which were all significantly lower than the control incidence of 17.6%. Especially, ClO2 dipping reduced the incidence of gray mold by up to 26.1% compared to the control in five other rose cultivars (‘Antique Curl’, ‘Green Beauty’, ‘Feel Lip’, ‘Pink Heart’, and ‘Venus Berry’). No petal discoloration was detected, and petal color values (chroma or hue) were maintained regardless of ClO2 dipping. This result suggests that immediate ClO2 dipping is applicable to inhibit gray mold on cut rose flowers at a level of 5 μL·L⁻¹ just before postharvest storage.
... ClO 2 -based disinfectants have been shown to be effective in eliminating B. anthracis spores in solutions and less toxic than sodium hypochlorite in an in vitro study with human skin keratinocytes [11] . Besides, another study has shown that virus inactivation by ClO 2 is achieved through denaturation of viral envelope proteins, thereby able to prevent aerosol-induced influenza virus infection at low concentrations [12] . ...
Article
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Chlorine dioxide plays a significant role in the industrial settings as disinfectants due to its broad antimicrobial property. Despite commonly use as germicide, chlorine dioxide demonstrates a good safety profile, rendering its suitability for use at water treatment and food preparation zones. Protein denaturation including envelope proteins is the major mechanism of chlorine dioxide to inactivate microorganisms even at low concentrations. Adverse reactions are not widely reported due to the typical use at a low concentration. The effectiveness of chlorine dioxide against various microorganisms, in both liquid and gaseous forms, over a wide range of pH and at an extremely low concentration has confirmed chlorine dioxide as a vital and versatile disinfectant.
... Like a "mirror trading strategy" that allows us to copy the function of experienced and successful virus (as a natural system) and implement the same trades, in almost real time. Despite this tactic, the work of nanodrug is still remained; i.e. in-situ chemical oxidation/engineering issue by releasing electrons [11]. Herein, oxidant NPs (such as ZnO & Fe3O4) play an effective role in oxidizing/repairing major damaged bonds in body that causes by reductant virus, repairing thiols to disulfide bonds. ...
Article
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Keywords: Research on the chemical mechanism and reciprocal behavior of the coronavirus relate to living organisms, engaging in the give and take of electrochemical mediators, is a very important, controversial and vital issue. What we should accept is the chemical identity of this scenario, and not preferably a characteristic of a biological system. This chemical reaction should be familiar, referring to the theory of chemical pathways involved in DNA/proteins in the body against aggressive guests (such as viruses). From the point of view of a chemist, this simple reaction is nothing more than an oxidation-reduction reaction (redox-stress signaling) which conducted and carried out by coronavirus in a biointerface medium. Thereby, oxidizing as well as reducing reagents should be very constructive, promoting development in such chemical process. We understand redox reactions as switchable thiol/disulfide exchanges (formation and cleavage of inherent disulfide bonds), then, we can hugely profit from redox-responsive nano-surfaces equipped with multiple new ionic and covalent interactions. This game-changing idea can substantiate by surface modified-nanoparticles to play powerful roles in synthesis of nano oxidizers as well as reducing agents in nanomedicine. Chemists and pharmacists must then explore new thoughts and present modern experiences/approaches of preparation nanoparticles and nanocomposites to create novel vaccines as well as coronavirus drugs. In this regard, this experience can also be so helpful for HIV/AIDS, which is caused by viruses.
... Because of it' s fungicidal and sporicidal activity in solutions, ClO2 is considered the most effective on hard surfaces compared to other disinfectants. (Young, 2016.Sun X1, et al.2014. ...
Article
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Infection control in hospitals is the key strategy for prevention of nosocomial infections by breaking down the transmission rout of infection from the source to susceptible patient by using of suitable disinfectants.
... Because of it' s fungicidal and sporicidal activity in solutions, ClO2 is considered the most effective on hard surfaces compared to other disinfectants. (Young, 2016.Sun X1, et al.2014. ...
Article
Infection control in hospitals is the key strategy for prevention of nosocomial infections by breaking down the transmission rout of infection from the source to susceptible patient by using of suitable disinfectants.
... The concerning organisms in drinking water are disease causing viruses and pathogens. Bacterial spores (e.g., Bacillus) in drinking water treatment processes have been investigated using ClO2 for disinfection (Young, 2016). The generated ClO2 gas is dissolved into the drinking water for further treatment with the desired dose of chemical agent by adjusting the gas flow rate. ...
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During the sever pandemic of coronavirus, the development and deployment of efficient disinfection technology have attracted hospitals’ attention. Chlorine dioxide (ClO2) gas has been validated as an efficient disinfector and air pollution control due its high oxidation ability. This article reviewed the principles and application of ClO2 gas on disinfection, sterilization and air pollutants abatement. The principles of ClO2 gas production, chemistry and related generator issues were discussed. We also review some case studies of the application of ClO2 gas in the medical field and food industry as a sterilizer. Oxidation of nitrogen oxide (NOx), sulfur oxide (SOx), mercury (Hg), and volatile organic compounds (VOCs) using ClO2 gas has been investigated. The process chemistry and demonstration of applying ClO2 gas for air pollutants oxidation and absorption have also been provided. In conclusion, we suggest the future priority research direction of ClO2 gas application are included the development of smart and robust ClO2 gas release system, the integration of an innovative robotic technology in ClO2 sterilization for epidemic prevention, and the evaluation of ClO2 emissions impact on indoor air quality in hospitals.
... Like a "mirror trading strategy" that allows us to copy the function of experienced and successful virus (as a natural system) and implement the same trades, in almost real time. Despite this tactic, the work of nanodrug is still remained; i.e. in-situ chemical oxidation/ engineering issue by releasing electrons [11]. Herein, oxidant NPs (such as ZnO & Fe3O4) play an effective role in oxidizing/repairing major damaged bonds in body that causes by reductant virus, repairing thiols to disulfide bonds. ...
Preprint
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Research on the chemical mechanism and reciprocal behavior of the coronavirus relate to living organisms, engaging in the give and take of electrochemical mediators, is a very important, controversial and vital issue. What we should accept is the chemical identity of this scenario, and not preferably a characteristic of a biological system. This chemical reaction should be familiar, going back to the theory of chemical pathways involved in DNA/proteins in the body against aggressive guests (such as viruses). From the point of view of a chemist, this simple reaction is nothing more than an oxidation-reduction reaction (redox-stress signaling) which conducted and carried out by coronavirus in a biointerface medium. Thereby, oxidizing as well as reducing reagents should be very constructive, promoting development in such chemical process. We understand redox reactions as switchable thiol/disulfide exchanges (formation and cleavage of inherent disulfide bonds), thereby, we can hugely profit from redox-responsive nano-surfaces equipped with multiple new ionic and covalent interactions. This game-changing idea can substantiate by surface modified-nanoparticles to play powerful roles in synthesis of nano oxidizers as well as reducing agents in nanomedicine. Chemists and pharmacists must then explore new thoughts and present modern experiences/approaches of preparation nanoparticles and nanocomposites to create novel vaccines as well as coronavirus drugs. In this regard, this experience can also be so helpful for HIV/AIDS, which is caused by viruses.
... Chlorine kills pathogens such as bacteria and viruses by breaking their chemical bond. Chlorine compounds also serve as decontaminants via interchanging their atoms with other compounds, such as enzymes in microbes and other cells [185][186][187]. ...
Chapter
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This chapter contains sections titled:Physical Methods for the Wastewater Treatment ProcessesChemical Methods for Wastewater TreatmentConclusion Acknowledgments
... Chlorine kills pathogens such as bacteria and viruses by breaking their chemical bond. Chlorine compounds also serve as decontaminants via interchanging their atoms with other compounds, such as enzymes in microbes and other cells [185][186][187]. ...
Chapter
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Water is one of the dynamic requirements for existence of human beings. Only 3% is accessible as fresh water. Out of this 3%, only 0.06% can be simply retrieved. The water requirement doubles universally after every 21 years due to speedy rise in population and industrial needs. Several countries are facing the lack of fresh drinking water and 5-10 million people suffer from numerous diseases due to polluted water. Thus, exploitation of benign water sources to overwhelm the shortage of water has been a worldwide task. Textile industries are fronting a task in the arena of quality and yield due to globalization of world market. The major concern of textile processors is to be conscious of about the quality of their products and the eco-friendly nature of their industrial procedures. There is a substantial vital need to develop treatment methods that must be operative in removing contaminants from textile wastes. Different methods are in use, though each has its positive and negative points. Their choice is based on the wastewater features, accessible technology , and economic aspects. This chapter illustrates the applications of physical and chemical methods in the treatment of textile effluents for a safe environment.
... Chlorine dioxide is composed of three electronegative atoms (2 oxygens and 1 chloride) held together by covalent and coordinated covalent bonds. When chlorine dioxide meets microbes, one reactive oxygen from a molecule is released to oxidize and kill microbes such as virus, bacteria, and fungi [23]. The generation of reactive oxygens has been regarded as an insecticidal mechanism of ClO 2 with respect to oxidative stress [11]. ...
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Polyunsaturated fatty acids usually undergo lipid peroxidation induced by reactive oxygen species (ROS). Calcium-independent cellular phospholipase A2 (iPLA2) can maintain fatty acid compositions in phospholipids depending on physiological conditions. An insect iPLA2 (Pi-iPLA2) was predicted from the transciptome of the Indianmeal moth, Plodia interpunctella. It encodes 835 amino acids. It possesses five ankyrin repeats in the N terminal and patatin lipase domain in the C terminal. Pi-iPLA 2 was expressed in all developmental stages of the Indianmeal moth. In the larval stage, it was expressed in all tissues tested. RNA interference (RNAi) specific to Pi-iPLA 2 was performed using specific double-stranded RNA (dsRNA). It resulted in almost 70% of reduction in gene expression. Under such RNAi condition, P. interpunctella exhibited significant accumulation of lipid peroxidation based on the amount of malondialdehyde. RNAi of Pi-PLA 2 expression also impaired cellular immune response of P. interpunctella. Chlorine dioxide (ClO2), an insecticidal agent by generating ROS, increased lipid peroxidation in a dose-dependent manner. However, the addition of vitamin E (an antioxidant) reduced the formation of lipid peroxidation. ClO2 treatment significantly reduced expression of Pi-iPLA 2 but increased lipid peroxidation in larval fat body of P. interpunctella. Furthermore, larvae treated with dsRNA specific to Pi-iPLA 2 were significantly susceptible to ClO2 treatment. These results suggest that Pi-iPLA2 plays a crucial role in repairing damaged fatty acids from phospholipids. Our results also suggest that ClO2 can elevate lipid peroxidation through inhibiting Pi-iPLA 2 expression in addition to direct ROS production.
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Scanning electron microscopy may be used successfully to demonstrate the changes in the morphology and surface characteristics of Candida albicans after treatment with nystatin, and to elucidate the mechanism of action of the antibiotic. Nystatin at concentrations above 2.0 ^g/ml effected the function of the cell membrane leading to its distortion, and as a result many deformed cells with depressions in the cell surface were produced. After 24 hours contact with 5 and 10 μg/ml, many cells were ruptured. The effect of nystatin was observed on growing and non-growing cells. Therefore, nystatin exerted a general fungicidal effect against yeast cells. Mittels Rasterelektronenmikroskopie können Morphologie und Oberflächenmerkmale von Candida albicans nach Behandlung mit Nystatin mit Erfolg dargestellt werden, was fur die Aufklärung des Wirkungsmechanismus des Antibiotikum bedeutungsvoll ist. In Konzentrationen über 2,0 μg/ml beeinflußt Nystatin die Funktion der Zellmembran und verursacht Membranschäden, die sich bei vielen defekten Zellen in Form von einge-sunkenen Zelloberflächen äußern. Nach 24stündiger Einwirkung von 5 und 10,μg/ml werden viele Zellen zerstört. Die Nystatin-Wirkung erstreckte sich auf wachsende und ruhende Zellen. Demzufolge besitzt Nystatin eine generelle fungizide Wirkung auf Hefezellen.
Since chlorination of drinking water produces organochlorinated substances (some possibly carcinogenic), the use of chlorine dioxide disinfectant would avoid halogenation. There is scarcely any data published on the effects of ClO2 in drinking water on human or animal health. The kinetics of 36ClO2 was studied in rats. Radioactivity was rapidly absorbed from the gastrointestinal tract following the administration of (0.07 microCi) 36ClO2 orally. 36Cl in plasma reached at peak at 1 hr. The half life for the elimination of 36Cl from the rat was 44 hr, corresponding to a rate constant of 0.016 hr-1. After 72 hr radioactivity was highest in plasma, followed by kidney, lung, stomach, duodenum, ileum, liver, spleen, thymus, and bone marrow. 36Cl excretion was greatest at 24 and 48 hrs after the administration of 36 ClO2. Forty-three percent of the total initial dose was excreted at 72 hr in the urine and feces. No 36 Cl was detected in expired air throughout the 72 hr studied. ClO2, ClO2-, and ClO3- (1, 10, 100, 1000 ppm) given daily in drinking water decreased blood glutathione, decreased osmotic fragility, and changed the morphology of erythrocytes in both chicken and rat after two months. Methemoglobin was not detected throughout these studies.
Chlorine dioxide (ClO2) is under consideration as an alternative to chlorination as a disinfectant for public water supplies. A new assay was developed to qualitatively and quantitatively measure the metabolites of 36ClO2 in water and biological fluids. Studies in the rat indicated that the metabolites of ClO2 were Cl-, ClO-2, and ClO-b. At maximum absorption the percentage of ClO; formed in plasma from an initial oral dose of 10 mg/l 36ClO, was higher than from a 100 mg/l dose. The 36Cl concentration in washed packed cells indicated that 36Cl readily exchanges with chloride of saline.
Article
This review will survey environmental controls on the morphology of Candida albicans, describe the cellular and ultrastructural events associated with morphological transitions in this fungus, and attempt to relate biochemical phenomena that have been reported to be associated with dimorphic change to C. albicans cell biology. The synthesis of the cell wall of C. albicans and its control remain largely undiscovered, but it is clear that the cell wall is the principal component involved in shape determination. Possible models for C. albicans dimorphism will be critically reviewed.
Article
SUMMARY Treatment of purified Semliki Forest virus with neuraminidase released sialic acid, raised the isoelectric point of the virus by o'35 pH units but had no effect on the infectivity, haemagglutinating (HA) activity or surface antigenic properties and did not alter the electrophoretic mobility of the envelope glycoproteins on poly- acrylamide gels. Treatment of virus with a mixture of sugar hydrolases lowered infectivity and HA activity and slightly increased the electrophoretic mobility of the envelope glycoproteins, but had no measurable effect on surface antigenic pro- perties. Treatment with bromelain digested the envelope glycoproteins, destroyed infectivity, HA activity and surface antigenicity and yielded a sub-viral particle containing lipid. Treatment of this particle with phospholipase C produced a core particle indistinguishable by sedimentation analysis from the nucleocapsids found in infected cells.
Article
The mechanism of enteroviral inactivation by ozone was investigated with poliovirus 1 (Mahoney) as the model virus. Ozone was observed to alter two of the four polypeptide chains present in the viral protein coat of poliovirus 1. However, the alteration of the protein coat did not significantly impair virus adsorption or alter the integrity of the virus particle. Damage to the viral RNA after exposure to ozone was demonstrated by velocity sedimentation analysis. It was concluded that the damage to the viral nucleic acid is the major cause of poliovirus 1 inactivation by ozone.
Article
Chlorine dioxide and iodine inactivated poliovirus more efficiently at pH 10.0 than at pH 6.0. Sedimentation analyses of viruses inactivated by chlorine dioxide and iodine at pH 10.9 showed that viral RNA separated from the capsids, resulting in the conversion of virions from 156S structures to 80S particles. The RNAs release from both chlorine dioxide- and iodine-inactivated viruses cosedimented with intact 35S viral RNA. Both chlorine dioxide and iodine reacted with the capsid proteins of poliovirus and changed the pI from pH 7.0 to pH 5.8. However, the mechanisms of inactivation of poliovirus by chlorine dioxide and iodine were found to differ. Iodine inactivated viruses by impairing their ability to adsorb to HeLa cells, whereas chlorine dioxide-inactivated viruses showed a reduced incorporation of [14C]uridine into new viral RNA. We concluded, then, that chlorine dioxide inactivated poliovirus by reacting with the viral RNA and impairing the ability of the viral genome to act as a template for RNA synthesis.
Article
The antimicrobial properties of aqueous solutions of peracetic acid and hydrogen peroxide have been compared. Peracetic acid exhibited excellent antimicrobial properties, especially under acidic conditions. Reductions by a factor of 10(6) in the numbers of vegetative bacteria are obtained within 1 min at 25 degrees C using a solution containing 1.3 mmol/l of peracetic acid. Rapid activity against bacterial spores and yeasts also occurs. Hydrogen peroxide is more effective as a sporicide than as a bactericide, with sporicidal action being obtained using a solution containing 0.88 mol/l. Bactericidal action is poor but hydrogen peroxide was bacteriostatic at concentrations above 0.15 mmol/l.
Article
Human polymorphonuclear leukocytes (PMNLs), when added to arthroconidial suspensions of Coccidioides immitis, markedly inhibit fungal incorporation of the cell-wall precursor N-acetylglucosamine. This effect does not require serum but is facilitated by a heat-labile serum component(s), probably by promoting PMNL attachment to the arthroconidia. Inhibition is entirely reversible within 24 hr. In parallel with this finding, PMNLs exhibited virtually no killing of arthroconidia and (as determined by electron microscopy) did not produce damage to the fungal ultrastructure. PMNLs from a patient with chronic granulomatous disease suppressed fungal incorporation of N-acetylglucosamine by only 0%–22% under various conditions, as compared with 54%–85% suppression by PMNLs from normal donors. Our studies demonstrate that PMNLs can influence the metabolism of C immitis and raise the possibility that their presence in coccidioidal histopathology may be an important immediate host defense in limiting progression early after infection.
Article
Candida albicans and Saccharomyces cerevisiae cells were examined by scanning scanning electron microscopy before and after extraction of the mannans of the cell wall. The surfaces of control cells were smooth; after mannan extraction they were rough and showed erosions which were particularly striking within the area of the scars. Helicase digested irregular holes through the cell wall within 20 min; these increased in size during an additional 40 min of digestion. These holes were not localized in or on the bud scars, which remained intact even after the long digestion period. The results were used to construct a model for yeast cell wall structure.
Article
The degradation of a mixture of four 5'-ribonucleotides (AMP, GMP, CMP and UMP), yeast RNA, yeast phenylalanine tRNA, and tobacco mosaic virus RNA (TMV-RNA) with ozone (concentration in inlet gas, 0.1-0.5 mg/l) was examined in a phosphate buffer (pH 6.9). In the case of the mixture, GMP alone was degraded in the initial stage. In the ozonization of yeast RNA, the guanine moiety was less vulnerable to attack by ozone than in the case of free GMP, but it again degraded most rapidly among the four nucleotides. In the treatment of tRNA with ozone, the guanine moiety degraded first. When the numbers of degraded nucleotides reached 4.8 (remaining amino acid acceptor activity was 3.6%), the polyacrylamide gel electrophoresis of the ozonized tRNA gave a single band with the same mobility as that of the intact tRNA. It is evident that ozonolysis of tRNA proceeded without cleavage of the polynucleotide chain. In the case of TMV-RNA, the loss of the infectivity by ozone proceeded rapidly within 30 min and was followed by preferential degradation of the guanine moiety. The outstanding lability of the guanine moiety observed in each case is discussed in connection with the inactivation of tRNA and TMV-RNA.
Article
The growth of human cancer cells from lung, breast, and uterine tumors was selectively inhibited in a dose-dependent manner by ozone at 0.3 to 0.8 part per million of ozone in ambient air during 8 days of culture. Human lung diploid fibroblasts served as noncancerous control cells. The presence of ozone at 0.3 to 0.5 part per million inhibited cancer cell growth 40 and 60 percent, respectively. The noncancerous lung cells were unaffected at these levels. Exposure to ozone at 0.8 part per million inhibited cancer cell growth more than 90 percent and control cell growth less than 50 percent. Evidently, the mechanisms for defense against ozone damage are impaired in human cancer cells.
Article
Two superoxide dismutases (SOD I and SOD II) were purified from Acanthamoeba castellanii and characterized for several biochemical properties. Analysis of the primary structure and inhibition studies revealed that SOD I is iron SOD (Fe-SOD), with a molecular mass of 50 kDa, and SOD II is copper-zinc SOD (Cu,Zn-SOD), with a molecular mass of 38 kDa. Both enzymes have a homodimeric structure consisting of 2 identical subunits, each with a molecular mass of 26 and 19 kDa for SOD I and SOD II, respectively. The isoelectric points of SOD I and SOD II were 6.4 and 3.5, respectively, and there were no isoenzyme forms detected. Both enzymes show a broad optimal pH of 7.0-11.0. Because no differences were observed in the apparent molecular weight of SOD I after addition of the reducing agent 2-mercaptoethanol, the subunits do not appear to be linked covalently by disulfide bonds. However, the subunits of SOD II were covalently linked by intra- and interdisulfide bonds. Western blot analyses showed that the 2 enzymes have different antigenicity. Both enzymes occur as cytoplasmic and detergent-extractable fractions. These enzymes may be potential virulence factors of A. castellanii by acting both as antioxidants and antiinflammatory agents. These enzymes may be attractive targets for chemotherapy and immunodiagnosis of acanthamoebiasis.
Article
Mitochondria are not only the major site for generation of reactive oxygen species, but also one of the main targets of oxidative damage. One of the major products of DNA oxidation, 8-oxodeoxyguanosine (8-oxodG), accumulates in mitochondrial DNA (mtDNA) at levels three times higher than in nuclear DNA. The main pathway for the repair of 8-oxodG is the base excision repair pathway initiated by oxoguanine DNA glycosylase (OGG1). We previously demonstrated that mammalian mitochondria from mice efficiently remove 8-oxodG from their genomes and isolated a protein from rat liver mitochondria with 8-oxoguanine (8-oxodG) DNA glycosylase/apurinic DNA lyase activity. In the present study, we demonstrated that the mitochondrial 8-oxodG DNA glycosylase/apurinic DNA lyase activity is the mitochondrial isoform of OGG1. Using mouse liver mitochondria isolated from ogg1(-/-) mice, we showed that the OGG1 gene encodes for the mitochondrial 8-oxodG glycosylase because these extracts have no incision activity toward an oligonucleotide containing a single 8-oxodG DNA base lesion. Consistent with an important role for the OGG1 protein in the removal of 8-oxodG from the mitochondrial genome, we found that mtDNA isolated from liver from OGG1-null mutant animals contained 20-fold more 8-oxodG than mtDNA from wild-type animals.
Article
Respiration of a normal strain of Candida albicans was compared with that of a divisionless mutant which has a biochemical lesion such that metabolically generated hydrogen "spills over," during growth, for non-specific dye reduction. This waste is not at expense of growth, since both strains grow at essentially similar rates, nor at expense of respiration, since the mutant reduces oxygen more rapidly than the normal strain. Respiration in both strains is qualitatively similar, and seemingly unique among highly aerobic organisms in that it is not mediated by cytochrome oxidase. In resting cells of both strains, respiration is not only resistant to, but markedly stimulated by, high concentrations of cyanide, carbon monoxide, and azide. In contrast, growth of these yeasts is inhibited by low concentrations of cyanide and azide. Cytochrome oxidase could not be detected in cell-free preparations; reduced cytochrome c was not oxidized by such preparations. Cytochrome bands could not be observed in thick cell suspensions treated with reducing agents. However, incorporation of superoptimal levels of zinc and iron into the culture medium resulted in growth of cells possessing distinct cytochrome bands; respiration of these cells remained insensitive to cyanide, monoxide, and azide, and the bands were maintained in a reduced form on oxygenation. In the divisionless yeast, tetrazolium dyes compete with oxygen for reduction; this is not the case in the normal strain. The firmness with which hydrogen transfer is channeled in the latter for reduction of disulfide bonds (of importance in the division mechanism) and of oxygen, is contrasted with the lack of such control in the mutant.
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