Clinical and Experimental Medicine (CLIN EXP MED)

Publications in this journal

• Article: Osteoclastogenesis and arthritis

  Nicola Maruotti, Maria Grano, Silvia Colucci, Francesca d’Onofrio, Francesco Paolo Cantatore
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  ABSTRACT: There is emerging interest for osteoclasts as key players in the erosive and inflammatory events leading to joint destruction in chronic arthritis. In fact, chronic inflammatory joint diseases such as psoriatic arthritis and rheumatoid arthritis are often characterized by destruction of juxta-articular bone and erosions due to the elevated activity of osteoclasts, which are involved in bone resorption. The main step in inflammatory bone erosion is an imbalance between bone resorption and bone formation: osteoclast formation is enhanced by proinflammatory cytokines such as TNF-α, IL-1β, and IL-17 and is not balanced by increased activity of bone-forming osteoblasts. T-cells, stromal cells, and synoviocytes enhance osteoclast formation via expression of RANKL and, under pathologic conditions, of proinflammatory cytokines. In rheumatoid arthritis, accumulation of osteoclasts in synovial tissues and their activation associated with osteoclastogenic cytokines and chemokines at cartilage erosion sites suggest that they could be usefully selected as therapeutic target. In particular, in consideration of the primary role of RANKL and TNF-α in osteoclastogenesis, the control of the production of RANKL and the inhibition of TNF-α represent important strategies for reducing bone damage in this disease. KeywordsArthritis–Cytokines–Chemokines–Osteoclast–RANKL–TNF-α
  Clinical and Experimental Medicine 04/2012; 11(3):137-145.
• Article: Stress-related Epstein–Barr virus reactivation

  Omer Coskun, Kenan Sener, Selim Kilic, Hakan Erdem, Halil Yaman, Ahmet Bulent Besirbellioglu, Hanefi Cem Gul, Can Polat Eyigun
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  ABSTRACT: Epstein–Barr virus (EBV) remains latent in 90% of the patients following primary infection. The infection might be reactivated due to various stress factors. We, therefore, examined the levels of stress hormones (epinephrine, norepinephrine and cortisol), viral capsid antigen (VCA) immunoglobulin Ig G, VCA IgM, EBV early antigen IgG, Epstein–Barr nuclear antigen (EBNA) IgG, EBNA IgM antibody screening tests and performed EBV polymerized chain reaction (PCR) test and EBV DNA PCR in 100 draftees on their first day of recruitment and at the end of 1month. Examination of the initial samples revealed that 94 (94%) subjects previously had EBV infection and 6 (6%) were seronegative. Second samples obtained at the end of first month showed that 7 (7.4%) reactivations occurred in 94 subjects who previously had EBV infection (P<0.001). Two out of six (33.3%) who were initially seronegative had acute infection (P=0.289). There was no significant difference between the median values of the levels of stress hormones in the initial and second serum and plasma samples. There was a significant difference between the rates of acute infection and reactivation among subjects with elevated cortisol and epinephrine levels in the second samples compared to subjects with normal levels (P<0.001). No significant difference was determined between the first and second sample hormone levels of all nine subjects whose EBV-DNA turned positive. Routine examinations might not reveal any specific findings since EBV infection often has an asymptomatic course. EBV reactivations should always be kept in mind in patients subject to such stressful conditions.
  Clinical and Experimental Medicine 04/2012; 10(1):15-20.
• Article: The effects of staphylococcal bacteriophage lysates on cancer cells in vitro

  Krystyna Dąbrowska, Grzegorz Skaradziński, Aneta Kurzępa, Barbara Owczarek, Maciej Żaczek, Beata Weber-Dąbrowska, Joanna Wietrzyk, Magdalena Maciejewska, Paulina Budynek, Andrzej Górski
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  ABSTRACT: Bacteriophages constitute a serious alternative to antibiotic therapy of bacterial infections. They are also extremely numerous entities: phages can be found in almost all places on Earth and are constantly present in human and animal bodies. Observations of the effect of therapeutic staphylococcal phages and their bacterial hosts on melanoma migration in vitro are reported in this article. Together with bacteriophage preparations, disrupted Staphylococci (host strains) were investigated to compare the effects of bacteria with those of bacteriophages. Migration was decreased by all the investigated preparations in various ways and this was rather due to the activity of the bacterial components. Importantly, none of the investigated bacteriophage or bacterial preparations induced an increase in the migration activity of melanoma cells, which is important from the perspective of the therapeutic use of phage lysates. The possible presence of staphylococcal enterotoxins in the therapeutic bacteriophage preparations was also verified. All the studied therapeutic bacteriophage preparations were negative for the Staphylococcal enterotoxins A, B, C, D, and E (i.e., the enterotoxin content was less than 0.2–0.5ng/ml).
  Clinical and Experimental Medicine 04/2012; 10(1):81-85.
• Article: CD164 and other recently discovered activation markers as promising tools for allergy diagnosis: what’s new?

  Salvatore Chirumbolo
  Clinical and Experimental Medicine 04/2012; 11(4):255-257.
• Article: Advances in the understanding of the Fc gamma receptors-mediated autoantibodies uptake

  Sabrina Lisi, Margherita Sisto, Dario Domenico Lofrumento, Simona D’Amore, Massimo D’Amore
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  ABSTRACT: Receptors for the Fc fragment of immunoglobulin G (FcγRs) are important molecules not only to mediate and control the effectors’ functions of IgG antibodies, but they also control the autoimmunity-tolerance balance in the periphery. In humans, three different types of FcγRs, belonging to the Ig gene superfamily, have been identified; FcγRI (cluster of differentiation (CD64), FcγRII (CD32) and FcγRIII (CD16). A wide range of inflammatory and autoimmune diseases, such as vasculitis, glomerulonephritis, and autoimmune hemolytic anemia, seems to be mediated, in part, by FcγRs. Recent findings supposed that, under certain conditions, FcγRs are involved in the penetration of antibodies into cells and FcγRs constitute one of the main effector mechanisms through which autoantibodies exert their action. In this review, we concentrate on the role of human FcγRs in autoantibodies penetration and summarize the current knowledge on the structure, ligand binding capacity and their role in autoimmunity and pathogenic effect of autoantibodies. KeywordsAutoantibodies–Fcγ Receptors–IgG–Adalimumab–Salivary gland
  Clinical and Experimental Medicine 04/2012; 11(1):1-10.
• Article: Macrophage chemotactic protein-1 mRNA levels in non-Hodgkin lymphoma

  Toni Valković, Antica Duletić-Načinović, Sanja Štifter, Milena Hasan, Ita Hadžisejdić, David Zombori, Blaženka Grahovac, Nives Jonjić
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  ABSTRACT: Non-Hodgkin lymphoma (NHL) is one of the most common malignancies whose incidence increases, and the treatment results are not satisfactory. The aim of this study was to determine the capacity of NHL to produce MCP-1, chemokine that induces chemotaxis of macrophages and lymphoid cells. The mRNA expression and protein MCP-1 expression were determined in the samples of 20 patients with NHL and 8 reactive tonsils. MCP-1 mRNA was detected in 8/8 tonsils and in 19/20 patients with NHL by real-time PCR analysis. In addition, the amount of detected MCP-1 cDNA was significantly higher in patients with limited stage, good IPI, normal level of fibrinogen and LDH. Finally, in patients with aggressive NHL, the level of MCP-1 cDNA was higher than in indolent tumours. Immunohistochemical analysis revealed that majority of stromal elements such as macrophages, endothelial and smooth muscle cells in reactive as well as in neoplastic lymphoid tissue showed strong cytoplasmic MCP-1 expression. Moderate cytoplasmic MCP-1 expression was also observed in reactive lymphocytes, while tumour cells of indolent NHL were mostly pale in comparison with aggressive lymphomas which predominantly demonstrated intense MCP-1 staining. These intriguing preliminary results emphasize the need for further investigations that must be conducted on the representative sample with concordant measurement of serum MCP-1 level. KeywordsNon-Hodgkin lymphoma-Monocyte chemotactic protein-1
  Clinical and Experimental Medicine 04/2012; 10(4):229-235.
• Article: Regulation of mRNA caspase-8 levels by anti-nuclear autoantibodies

  Sabrina Lisi, Margherita Sisto, Dario Lofrumento, Maria Antonia Frassanito, Simone Caprio, Maria Luisa Romano, Vincenzo Mitolo, Massimo D’Amore
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  ABSTRACT: Apoptosis of the acinar and ductal epithelial cells of the salivary glands has been proposed as a mechanism possibly responsible for the impairment of the secretory function in Sjögren’s syndrome, an organ-specific autoimmune disorder characterized by destruction of these glandular structures. The presence of serum autoantibodies (Abs) directed against the ribonucleoproteic antigens Ro and La is one of the classification criteria used to identify Sjögren patients, and there is increasing evidence of the direct involvement of Abs in tissue pathogenesis. Our recent report demonstrated that anti-Ro and anti-La Abs are able to trigger the extrinsic pathway of apoptosis in the human salivary gland cells. To better understand how the anti-Ro and anti-La Abs exert their apoptotic effect, human caspase-8 gene expression was examined in primary human salivary gland epithelial cell (SGEC) cultures established from biopsies of labial minor salivary glands. To measure mRNA expression changes of initiating caspase-8, the real-time polymerase chain reaction was employed. This was combined with western blot to study the activation of caspase-8 detecting the cleaved form of caspase-8 and the cleaved poly (ADP-ribose) polymerase, downstream consequences of caspases activation. Data obtained suggest that the anti-Ro and anti-La Abs determine a transcriptional up-regulation and activation of caspase-8. Study of the mRNA in SGEC experimental model may provide insight into the signal transduction pathway stimulated by anti-nuclear autoantibodies. KeywordsCaspase-8-Anti-nuclear autoantibodies-Up-regulation
  Clinical and Experimental Medicine 04/2012; 10(3):199-203.
• Article: Plasminogen activator inhibitor-1 C/G polymorphism in relation to plasma levels in rheumatoid arthritis

  Norma Torres-Carrillo, Nora Magdalena Torres-Carrillo, Gloria Esther Martínez-Bonilla, Mónica Vázquez-Del Mercado, Claudia Azucena Palafox-Sánchez, Edith Oregón-Romero, Ana Guilaisne Bernard-Medina, Héctor Rangel-Villalobos, José Francisco Muñoz-Valle
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  ABSTRACT: Plasminogen activator inhibitor type 1 (PAI-1) is an inhibitor of plasmin production. Plasmin can directly or indirectly to degrade cartilage and bone matrix. The PAI-1 HindIII polymorphism has been associated with high PAI-1 plasma levels in myocardial infarction patients and control populations. Furthermore, it has been associated with the angiographic extent of coronary artery disease, but their involvement in other diseases is still uncertain. Here, we assessed the relationship between PAI-1 HindIII polymorphism and PAI-1 plasma levels in rheumatoid arthritis (RA). One hundred and twenty-five RA patients and 132 control subjects (CS) were included. Genotypes were identified by the polymerase chain reaction-restriction fragment length polymorphism technique and PAI-1 plasma levels were quantified using an ELISA kit. Not significant differences in genotype and allele frequencies between both studied groups were observed (P>0.05). RA patients showed lower PAI-1 plasma levels (18.92±12.94ng/ml) than CS (23.68±23.38ng/ml), without significant difference (P=0.299). However, in RA patients the C/G genotype carriers showed higher PAI-1 plasma levels (23.00±13.81ng/ml) with respect to C/C (16.77±11.97ng/ml) and G/G (10.47±7.07ng/ml) genotype carriers (P=0.036). The PAI-1 HindIII polymorphism was not associated with RA susceptibility. However, the C/G genotype is associated with high PAI-1 plasma levels in RA patients.
  Clinical and Experimental Medicine 04/2012; 9(3):223-228.
• Article: Mannose-binding lectin polymorphisms in common variable immunodeficiency

  Asghar Aghamohammadi, Farshad Foroughi, Nima Rezaei, Saeid Dianat, Ghasem Solgi, Ali Akbar Amirzargar
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  ABSTRACT: Common variable immunodeficiency (CVID) is a heterogeneous group of disorders, characterized by hypogammaglobulinemia and increased susceptibility to infections, autoimmunity and malignancies. This study was performed to analyze the Mannose-binding lectin (MBL) polymorphisms in Iranian patients with CVID. Thirty-five CVID patients who were treated at Children’s Medical Center and 100 matched controls were enrolled in this study. Sixth single-nucleotide polymorphisms of the MBL gene were analyzed using PCR–SSP method. Comparison of MBL exon 1 coding alleles between patients and controls revealed that A allele (wild-type) was significantly decreased in CVID group, whereas B allele was overrepresented in the patient group. High frequency of heterozygous (A/O) in the patient group and high frequency of homozygous for wild-type coding regions in the control group were detected. Comparison of MBL haplotype promoters between CVID patients and controls showed that LYPB haplotype was significantly overrepresented in the CVID group. Mutant and low-producing MBL alleles and haplotypes might reflect as an associated genetic factor in CVID patients, which could play as a susceptibility factor in CVID.
  Clinical and Experimental Medicine 04/2012; 9(4):285-290.
• Article: The effect of methylprednisolone on treatment in rats with induced sepsis

  Rıza Aytaç Çetinkaya, Levent Görenek, Ömer Coşkun, Can Polat Eyigün, Zeynep Şenses, Tayfun Ide, Selim Kiliç
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  ABSTRACT: In this study, an appropriate sepsis model was created in rats. Additionally, the effects of steroid treatments on survival, in connection with antibiotic treatment, were investigated. The sepsis model performed via intraperitoneal injection of 3ml/kg fecal suspension was determined as the most appropriate model for our study. Fifteen rats were used to investigate the effect of piperacillin–tazobactam on sepsis treatment. Forty-five randomly selected rats were used to investigate the efficacy of the antibiotic-plus-steroid combination. The rats were divided into three groups of 15 rats each. Twelve hours after the administration of fecal suspension, methylprednisolone (MP) at the dose of 0.25, 0.5, and 2mg/kg/day was given to each group, respectively, in addition to an antibiotic administered intravenously. In order to investigate the effect of steroids alone in the treatment of sepsis, 0.5mg/kg/day MP was given intravenously to 15 rats, 12h after the fecal suspension was administered. It was concluded that administration of MP alone shortens survival time in rats with sepsis, whereas antibiotic therapy alone increases survival time significantly in rats with sepsis. It was seen that the antibiotic-plus-steroid treatment increases survival significantly compared to rats with no treatment (p<0.05). In addition, steroids, when added to an antibiotic treatment in sepsis, affect survival positively when compared to the group with antibiotic therapy alone, depending on the dose given. Although, not statistically significant, high doses decrease survival (p>0.05), and very low doses increase survival and mean survival time (p>0.05) on the basis of clinical observation and average life time. However, low doses were found to increase survival significantly (p<0.05). We concluded that low-dose MP, in addition to the appropriate antibiotic therapy, is the optimal in the treatment of rats with intraabdominal sepsis.
  Clinical and Experimental Medicine 04/2012; 9(1):45-50.
• Article: Serovar-specific immune responses to peptides of variable regions of Chlamydia trachomatis major outer membrane protein in serovar D-infected women

  Pragya Srivastava, Rishein Gupta, Hem Chandra Jha, Rajneesh Jha, Apurb Rashmi Bhengraj, Sudha Salhan, Aruna Mittal
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  ABSTRACT: The role of major outer membrane protein (MOMP) variable regions in the interaction of chlamydiae and host cells has been evaluated and their role in neutralization of antibodies has been clearly demonstrated. There are also studies that delineate the contribution of these regions to the cell-mediated immune response of the host and suggest that serovar E elicits serovar-specific immune responses in infected humans. However, further studies with other serovars are required to confirm these findings and to elucidate the role and importance of serovar-specific responses of variable regions of MOMP in other serovars. We, therefore, performed a detailed analysis of the humoral and cellular immune responses against the serovar D-specific variable segments (VS) of MOMP in women infected with Chlamydia trachomatis. We found that VS4 elicits significantly higher responses (both humoral and cellular) than other VS peptides (VS1, VS2 and VS3). VS4 elicited significantly higher (P<0.0001) proliferative responses, interferon-gamma levels (P<0.0001) as well as higher prevalence (P<0.0001) of IgG antibodies against VS4 in serovar D-infected patients as compared to patients infected with other serovars, suggesting its role in serovar-specific immune responses.
  Clinical and Experimental Medicine 04/2012; 8(4):207-215.
• Article: Apolipoprotein A1 gene polymorphisms as risk factors for hypertension and obesity

  Elizabeth Suchi Chen, Diego Robles Mazzotti, Tatiane Katsue Furuya, Maysa Seabra Cendoroglo, Luiz Roberto Ramos, Lara Quirino Araujo, Rommel Rodriguez Burbano, Marília de Arruda Cardoso Smith
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  ABSTRACT: Several polymorphisms in apolipoprotein A1 (APOA1) gene have been associated with metabolic diseases. Increased transcription efficiency was observed in −75A allele carriers compared to −75G allele homozygotes. +83C allele was associated with higher body mass index and waist-to-hip ratio in type II diabetes subjects. −75G/A and +83C/T polymorphisms were analyzed by RFLP-PCR in 334 individuals from a Brazilian elderly cohort. APOA1 polymorphisms were associated with age-related morbidities, as well as with triglycerides, total cholesterol, HDL, VLDL, LDL, creatinine, urea, albumin, glycated hemoglobin and fasting glucose serum levels. Allele frequencies were 0.102 and 0.21, respectively, for −75A and +83T. −75G allele showed significant association with hypertension (P=0.001). An association between +83C allele and obesity was observed (P=0.040) and this allele also showed an association with hypertension in the presence of cardiovascular disease (P=0.047). Moreover, +83T allele was associated with lower glycated hemoglobin values (P=0.026). To our knowledge, there is no data associating this polymorphism with glycated hemoglobin. Furthermore, individuals carrying AT haplotype have lower risk for developing hypertension (P=0.0002), while GT haplotype carriers present decreased risk to develop obesity comparing to GC haplotype (P=0.025). APOA1 polymorphisms analysis may be a useful tool to identify risk factors for subjects and families and clarify the physiopathological role of these polymorphisms in age-related diseases, such as hypertension and obesity.
  Clinical and Experimental Medicine 04/2012; 9(4):319-325.
• Article: Association between polymorphisms in the biometabolism genes CYP1A1, GSTM1, GSTT1 and GSTP1 in bladder cancer

  João Paulo Souto Grando, Hellen Kuasne, Roberta Losi-Guembarovski, Iara Sant’Ana Rodrigues, Henrique Mitsu Matsuda, Paulo Emílio Fuganti, Émerson Pereira Gregório, Farid Libos Júnior, Rodrigo Paes de Menezes, Marco Aurélio de Freitas Rodrigues, Ilce Mara de Syllos Cólus
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  ABSTRACT: Numerous enzymes, including Cytochrome P450s (phase I) and Glutathione-S-transferases (phase II), are involved in the metabolic activation and detoxification of carcinogens. Epidemiological studies have consistently demonstrated that bladder cancer is strongly associated with cigarette smoking, and the risk for the development of this neoplasia may be modified by individual differences in carcinogen-metabolizing genes. We investigated the relationship between polymorphisms in the CYP1A1, GSTM1, GSTT1, and GSTP1 genes in a case–control study with 100 bladder cancer patients and 100 controls matched for age, gender, race, and smoking status. The GSTM1, GSTT1, CYP1A1 (A2455→G), and GSTP1 (A313→G) genotypes were determined using a multiplex PCR, an allele specific PCR, and a restriction fragment length polymorphism-PCR method. The present case–controlled association study did not detect any positive or negative association for the GSTM1 and GSTP1 genes [odds ratios (OR)=1.35; 95% confidence interval (CI)=0.76–2.41 and OR=0.75; 95% CI=0.41–1.38, respectively]. Notably, the genes GSTT1 and CYP1A1 exhibited a statistically significant association with bladder cancer (OR=1.77; 95% CI=1.01–3.12 and OR=1.99; 95% CI=1.07–3.73). No differences for GSTM1 and GSTP1 genotype prevalence between the bladder cancer cases and the controls were observed, however, the null genotype for the GSTT1 gene and the A/G and G/G variants of the CYP1A1 gene may contribute to the development of bladder cancer.
  Clinical and Experimental Medicine 04/2012; 9(1):21-28.
• Article: Acute pericarditis in the era of the invasive strategy in acute coronary syndromes – a case report

  Z. Szafraniec, Malgorzata Lelonek FESC
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  ABSTRACT: The invasive strategy in acute coronary syndrome (ACS) caused a necessity of differential diagnosis in other clinical situations with ST segment elevation. This article deals with the most important aspects of diagnosis and treatment of acute pericarditis. Case Report: We describe the case of a 43-year-old gym teacher, admitted to our hospital during emergency service with suspected ACS. Given the typical ECG pattern and characteristic signs and symptoms, acute pericarditis was the primary diagnosis, which was confirmed later. Early and adequate diagnosis gave the opportunity to start guided treatment and saved this patient from a totally unnecessary angiography and possible complications from the invasive procedure. Conclusions: This case report is a good example of differential diagnosis of acute pericarditis and ACS, which should especially interest general practitioners and emergency physicians.
  Clinical and Experimental Medicine 12/2011;
• Article: APOE genotyping: comparison of three methods.

  B Rihn, S Berrahmoune, M Jouma, S Chamaa, L Marcocci, A Le Faou
  Clinical and Experimental Medicine 05/2009;