Tumour necrosis factor-alpha polymorphism as one of the complex inherited factors in pemphigus

The aim of our study was to analyse a significance of tumour necrosis factor (TNF)-alpha promoter gene polymorphisms in relation to the HLA-DR locus in genetic predisposition to pemphigus. TNF-alpha gene polymorphisms in position -238 and -308 were identified using a modified polymerase chain reaction-restriction fragment length polymorphism method in 53 patients with pemphigus (38 with pemphigus vulgaris, 15 with pemphigus foliaceus) and 87 healthy controls. The HLA-DRB1 locus was typed using the polymerase chain reaction SSO method in all the patients and 152 population controls. Carriers of the TNF-alpha polymorphic -308 A allele were found to be more frequent in the pemphigus foliaceus group in comparison with the control group (odds ratio (OR) = 8.12; p = 0.0005). A significant association between HLA-DRB1*04 (OR = 3.86; pcor = 0.0001) and DRB1*14 (OR = 8.4; pcor = 0.0001) and pemphigus vulgaris was found. In this group of patients a decreased frequency of HLA-DRB1*07 (OR = 0.08; pcor = 0.006) was also identified. We have shown for the first time a positive association of TNF-alpha polymorphism in position -308 with pemphigus foliaceus.     

Serum malondialdehyde levels,myeloperoxidase and catalase activities in patients with nephrotic syndrome

Abstract

Objectives

Some studies have indicated the pathophysiological importance of reactive oxygen species (ROS) in patients with nephrotic syndrome. Myeloperoxidase (MPO) is a leukocyte-derived enzyme-generating ROS that has been proposed to exert a wide array of pro-atherogenic effects throughout all stages of the atherosclerotic process. The aim of this study was to investigate the serum malondialdehyde (MDA) levels, MPO and catalase activities in patients with adult nephrotic syndrome.

Patients and Methods

Twenty-four patients with nephrotic syndrome and 24 healthy controls were enrolled. Serum MPO activity, catalase activity, and MDA levels were assessed.

Results

Serum MPO activity and MDA levels were signi?cantly higher in patients with nephrotic syndrome than controls (both, P < 0.001), while catalase activity was signi?cantly lower (P < 0.001). Serum catalase activity was found to be significantly correlated with MPO activity (r = ?0.417, P = 0.003) and MDA levels (r = ?0.532, P = 0.007). The serum MDA levels were also found to be significantly correlated with MPO activity (r = 0.419, P = 0.003).

Conclusions

We concluded that serum MPO activity and oxidative stress were increased and that serum catalase activity was decreased in patients with adult nephrotic syndrome. In addition, these results indicate that increased MPO activity is associated with an oxidant–antioxidant imbalance that may contribute to atherosclerosis in patients with adult nephrotic syndrome.     

Determining oxidant and antioxidant status in patients with genital warts

Abstract

Objectives

Warts are abnormal skin growths caused by human papilloma virus (HPV) infections within the skin of patients. Genital warts usually appear in the perianal and perigenital regions. Asymptomatic warts may be activated after years and may damage natural immunity. The inflammation that occurs during this process may lead to an imbalance between the prooxidant and the antioxidant systems. The aim of this study was to investigate erythrocyte glutathione peroxidase (GSH-Px) activity, serum paraoxonase enzyme levels, and oxidative stress levels in patients with genital warts.

Patients and Methods

In total, 32 patients with genital warts and 35 healthy subjects were included in this study. Erythrocyte GSH-Px activity, serum catalase activity, and paraoxonase enzyme, and malondialdehyde (MDA) levels were determined.

Results

Erythrocyte GSH-Px activity, serum MDA levels, and catalase activity were significantly higher in patients with genital warts than in controls (P < 0.01, P < 0.05, and P < 0.05, respectively). However, serum paraoxonase enzyme levels were not significantly different between groups (P > 0.05). Serum triglyceride levels were significantly lower in patients with genital warts than in controls (P < 0.01). However, there were no statistically signi?cant differences between groups with respect to total cholesterol, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol levels (all P > 0.05).

Conclusions

Our data suggest that oxidative stress is increased in genital warts. Increased oxidative stress levels may contribute to the pathogenesis of genital warts, and prolonged HPV infection due to chronic inflammation could also affect oxidative stress.     

Lipid Peroxidation and Antioxidant System in the Tumor and in the Blood of Patients with Nasopharyngeal Carcinoma

Reactive oxygen species play a key role in cancer development by inducing and maintaining the oncogenic phenotypes of cancer cells. In this study, we examined lipid peroxidation and antioxidant enzymes activities in the blood and in the tumor of nasopharyngeal carcinoma patients. Plasma malondialdehyde, conjugated dienes, erythrocytes catalase, and superoxide dismutase activities have been measured in 30 untreated nasopharyngeal carcinoma patients and 30 controls on one hand. On the other hand, tumor malondialdehyde level, catalase, and superoxide dismutase activities have been measured in five nasopharyngeal carcinoma patients and compared with four controls. The lipid peroxidation was confirmed in the plasma by the high levels of malondialdehyde and conjugated dienes (p?<?0.001, respectively). Additionally, significantly higher concentrations of malondialdehyde were found in biopsies compared to the control group (p?<?0.001). In erythrocytes, superoxide dismutase activity was higher in patients than in controls (p?<?0.05), while it was unchanged in the tumor (p?>?0.05). Both erythrocytes and tumor catalase activities were significantly lower in patients than in controls (p?<?0.001, respectively). Statistical studies have shown a positive correlation between malondialdehyde level and IgA antibodies level against Epstein–Barr virus capsid antigen (p?<?0.05). In conclusion, we reported the presence of an oxidative stress in the blood and in the biopsies of nasopharyngeal carcinoma patients where Epstein–Barr virus seems to play a role.     

Evaluation of Selenium,Redox Status and Their Association with Plasma Amyloid/Tau in Alzheimer’s Disease

The aim of the study was to evaluate blood selenium and antioxidants as possible oxidative stress markers in Alzheimer’s disease (AD) along with amyloid β42 (Aβ42) and tau by comparing them with vascular dementia (VD) and age-matched healthy controls. Selenium, total tau, Aβ42, glutathione (GSH) and malondialdehyde (MDA) levels and the activities of antioxidant enzymes were analysed in the blood of AD patients (n?=?30), VD patients (n?=?35) and controls (n?=?40) from South India. Plasma Aβ42 level was significantly higher (P?<?0.001) in both AD and VD compared to controls. Total tau and tau-to-amyloid ratio were significantly lower in both AD and VD (P?<?0.001), compared to controls, and a significant difference (P?<?0.01 and P?<?0.05, respectively) was also observed between AD and VD. The receiver operating characteristic (ROC) curve-derived cutoff values of <3.5 for tau-to-Aβ42 ratio and <520 pg/ml for total tau showed sensitivity and specificity of around 67–72 % for differentiating AD from VD and around 90 % for AD from controls, indicating that they could serve as reliable AD-specific markers. The MDA levels were significantly higher (P?<?0.001) in both dementia groups along with a significant decrease (P?<?0.001) in reduced GSH levels, indicating elevated oxidative stress and altered redox status in both forms of dementia. Selenium levels did not vary significantly between the three groups. The activity of glutathione peroxidase increased in both AD and VD compared to controls, with a concomitant decrease in glutathione reductase and glucose-6-phospate dehydrogenase (P?<?0.001) activity. The activity of thioredoxin reductase was significantly lower in both patient groups (P?<?0.001) compared to healthy controls. No correlation was observed between selenium and activities of selenoenzymes, tau, Aβ42 or tau-to-Aβ42 ratio, when analysing independently, indicating that blood selenium may not be directly involved in Aβ production and in regulating tau/Aβ42-mediated mechanism in AD. The present study emphasizes the enhanced oxidative stress in AD pathology and plasma tau and tau-to-amyloid ratio as possible markers to differentiate AD from VD. The study also points that blood selenium may not be involved in regulating oxidative stress in AD, and a longitudinal study correlating plasma and cerebrospinal fluid (CSF) selenium and selenoprotein levels is warranted.     

A Comparative Study of the Oxidative Profile in Graves’ Disease, Hashimoto’s Thyroiditis, and Papillary Thyroid Cancer

The aim of this study was to evaluate and compare the oxidative profiles of three thyroid disorders: Graves’ disease (GD), Hashimoto thyroiditis (HT), and papillary thyroid cancer (PTC). Malondialdehyde levels (MDA), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) activities were examined in the plasma of 52 patients (29 untreated HT, 16 untreated GD, and 7 PTC who underwent surgical therapy). Results were compared with those of 30 healthy controls and among the three groups of patients. The GD, HT, and PTC patients exhibited increased plasma MDA levels and SOD activities compared with the controls (p?<?0.05, p?<?0.05, and p?<?0.001, respectively). CAT activities significantly increased only for the PTC and HT patients (p?<?0.001 and p?<?0.05, respectively), whereas GPx activities significantly decreased only in the GD and PTC (p?<?0.05 and p?<?0.01, respectively). The comparison among the three groups of patients has shown increased MDA level and SOD activity for the PTC patients as compared to the GD patients (p?<?0.01 and p?<?0.001, respectively). Compared with HT, PTC patients exhibited significant higher MDA level, SOD, and CAT activities and a significant lower GPx activity (p?<?0.01, p?<?0.001, p?<?0.05, and p?<?0.05, respectively). No significant discrepancies were noted between the GD and HT patients. Our results have clearly shown an oxidative profile that is highly disturbed for the PTC patients as compared to those of autoimmune disorders. Future studies are needed to determine whether or not the oxidative stress has a prognostic value in this pathology.     

Serum Paraoxonase and Arylesterase Activities and Oxidative Stress Levels in Patients with SSRI Intoxication

Oxidative stress is a critical route of damage in various psychological stress-induced disorders, such as depression. Paraoxonase-1 (PON1) plays an important role as an endogenous free-radical scavenging molecule. The aim of this study was to evaluate the influence of serum PON1 activity and oxidative stress in patients with selective serotonin reuptake inhibitor (SSRI) intoxication. A total of 11 patients with SSRI intoxication and 20 healthy controls were enrolled. The serum total antioxidant capacity (TAC) and malondialdehyde (MDA) levels, as well as the paraoxonase and arylesterase activities, were measured spectrophotometrically. The serum TAC levels and the paraoxonase and arylesterase activities were significantly lower (for all, p < 0.001), whereas the serum MDA levels were significantly higher in the patients with SSRI intoxication than in the controls (p < 0.001). These results indicated that decreased PON1 activity and increased oxidative stress represent alternative mechanisms in SSRI toxicity. More studies are needed to elucidate the role of PON1 activity in the etiology of SSRI intoxication.     

The Effect of Iron–Vitamin C Co-supplementation on Biomarkers of Oxidative Stress in Iron-Deficient Female Youth

There is no study that assessed the effect of co-supplementation of iron and vitamin C on biomarkers of oxidative stress in non-anemic iron-deficient females. We investigated the effects of iron vs. iron?+?vitamin C co-supplementation on biomarkers of oxidative stress in iron-deficient girls. In a double-blind randomized controlled clinical trial, performed among 60 non-anemic iron-deficient girls, participants were randomly assigned to receive either 50 mg/day elemental iron supplements or 50 mg/day elemental iron?+?500 mg/day ascorbic acid for 12 weeks. Fasting blood samples were taken at baseline, weeks 6 and 12 for assessment of biomarkers of oxidative stress. Compared with the baseline levels, both iron and iron?+?vitamin C supplementation resulted in a significant reduction in serum malondialdehyde (MDA) levels (P _time?<?0.001) and remarkable elevation in serum total antioxidant capacity (TAC; P _time?<?0.001) and vitamin C levels (P _time?=?0.001); however, comparing the two groups we failed to find an additional effect of iron?+?vitamin C supplementation to that of iron alone on serum TAC and MDA levels (P _group was not statistically significant). Iron?+?vitamin C supplementation influenced serum vitamin C levels much more than that by iron alone (P _group?<?0.01). We also found a significant interaction term between time and group about serum vitamin C levels while this interaction was not significant about serum TAC and MDA levels. In conclusion, we found that iron supplementation with/without vitamin C improve biomarkers of oxidative stress among non-anemic iron-deficient females and may strengthen the antioxidant defense system by decreasing reactive oxygen species. Co-supplementation of iron?+?vitamin C has no further effect on oxidative stress compared with iron alone.     

The evaluation of protective and mitigating effects of vitamin C against side effects induced by radioiodine therapy

The goal of this study was to evaluate the protective and mitigative effect of vitamin C on oxidative stress in differentiated thyroid cancer (DTC) patients ablated with radioiodine. 58 DTC patients selected for radioactive iodine therapy (RAIT) with 5550 MBq ¹³¹Iodine were divided into four groups. Group 1 (control group) consisted of patients who underwent RAIT routinely. Other patients received 1500 mg vitamin C daily 2 days after (group 2), 2 days before to 2 days after (group 3) and 2 days before RAIT (group 4). Serum oxidative stress markers including malondialdehyde (MDA), glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) were measured immediately before and 2 days after RAIT. A significant increase in MDA after RAIT was observed in all groups (p?<?0.05). The concentrations of MDA were significantly higher in the control group compared to the intervention groups (p?<?0.05). A significant decrease in the control group (p?<?0.05) and increase in group 4 (p?<?0.05) were observed in GSH level after RAIT (p?<?0.05). Mean variation of GSH was significant between control group with groups 3 (p?<?0.01) and 4 (p?<?0.01). The results indicate that activity of SOD remained unchanged in all groups (p?>?0.05). A significant increase was observed in CAT activity after RAIT in all groups (p?<?0.05), which was higher in control group than intervention groups. In groups 3 (p?<?0.05) and 4 (p?<?0.05), this increase in CAT activity was significantly lower than the control group. RAIT causes serum oxidative stress, which can be ameliorated using vitamin C as an antioxidant. These results indicate that radioprotective effect of vitamin C is preferable to its mitigative effect.     

Thiamine deficiency induces oxidative stress in brain mitochondria of Mus musculus

The present investigation evaluates the changes in the levels of antioxidant enzymes, lipid peroxidation (LPO), and protein carbonyl content (PCC) in brain mitochondria following thiamine deficiency (TD). The study was carried out on Mus musculus allocated into three groups, namely control and thiamine-deficient group for 8 (TD 8) and 10 (TD 10) days. The LPO was measured in terms of reduced glutathione (GSH) and thiobarbituric acid reactive substance (TBARS). Antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were measured biochemically. A significant increase in the TBARS (p?<?0.0001) and PCC (p?<?0.001) levels in group II (TD 8) and group III (TD 10) animals was observed in comparison to controls. The GSH levels were found to be reduced in both the treated groups compared to the control. A significant reduction in the activities of SOD was also observed in group II (p?<?0.01) and group III (p?<?0.0001) animals in comparison to the control. Enzymatic activities of CAT (p?<?0.001) and GPx (p?<?0.05) were found to be significantly reduced in group III (TD 10) in comparison to the control. In conclusion, reduction in the activities of antioxidant enzymes as well as an increase in LPO and PCC following TD implies oxidative stress in brain mitochondria that may further leads to neurodegeneration.     

Evidence for a role of autoantibodies to heat shock protein 60, 70, and 90 in patients with dermatitis herpetiformis

Heat shock proteins (Hsp) are highly conserved immunomodulatory molecules upregulated when cells are exposed to stressful stimuli, such as inflammation. Their involvement in various autoimmune diseases, including autoimmune bullous diseases and celiac disease, has been increasingly recognized. To further study the role of Hsp in autoimmune bullous diseases, we have investigated for the first time the humoral autoimmune response to Hsp40, Hsp60, Hsp70, and Hsp90 in patients with dermatitis herpetiformis (DH; n = 26), bullous pemphigoid (BP; n = 23), and pemphigus vulgaris (PV; n = 16), the first representing a cutaneous manifestation of celiac disease. While in patients with active BP and PV, serum levels of autoantibodies against these Hsp did not differ from the corresponding age- and gender-matched healthy controls (n = 9–14); circulating autoantibodies against Hsp60, Hsp70, and Hsp90 were found to be increased at the active disease stage of DH. Further analysis of this latter patient subgroup showed that these anti-Hsp autoantibodies decreased in parallel with serum autoantibodies against epidermal and tissue transglutaminase during remission of skin lesions following a gluten-free diet, revealing significantly positive correlations. Although further studies on larger groups of patients will be needed to confirm the present data, our results support the notion that autoantibodies against Hsp60, Hsp70, and Hsp90 deserve attention in the study of the mechanisms that promote the development and maintenance of DH and possibly also the underlying celiac disease as well as potential novel disease biomarkers.     

Carvacrol improves pulmonary function tests,oxidant/antioxidant parameters and cytokine levels in asthmatic patients: A randomized,double-blind,clinical trial

BackgroundCarvacrol effects on inflammatory mediators, lung pathology and tracheal responsiveness were indicated in animal models of pulmonary diseases.PurposeTo evaluate carvacrol effects on respiratory symptoms, pulmonary function tests (PFT), oxidative stress markers and cytokine levels in asthmatic patients.Study DesignThis study was a randomized, placebo-controlled double-blind, clinical trial.MethodsThirty-three moderate asthmatic patients were divided to the two groups of: placebo group (n = 16) and carvacrol group (1.2 mg/kg/day, n = 17). Prepared capsules were taken for two months along, 3 times/day along with routine medications. Respiratory symptoms, PFT, and oxidative stress markers were evaluated before the treatment (step 0), and one (step I) and two months (step II) after the beginning of the treatment. However, cytokine levels in serum and supernatant of peripheral blood mononuclear cells (PBMC), and their gene expression were evaluated in step 0 and II.ResultsIn carvacrol-treated group, respiratory symptoms significantly decreased after one- and two-month treatment with carvacrol compared to pre-treatment values (p < 0.05 to p < 0.001). Compared to step 0, PFT values were significantly increased in step I and II, in treated group with carvacrol (p < 0.05 to p < 0.001). Most oxidative stress markers were improved following carvacrol treatment (p < 0.05 to p < 0.001). Treatment with carvacrol for two‐month also significantly improved cytokine levels in serum and supernatant of PBMC, compared to step 0 (p < 0.05 to p < 0.001). However, no significant changes were observed in the above-noted parameters in the placebo group.ConclusionDue to anti-inflammatory and antioxidant effect, carvacrol could be suggested as a therapeutic agent for asthma.     

Can we reduce oxidative stress with liver transplantation?

BackgroundThe aim of this study was to determine the levels of lipid peroxidation (MDA) and antioxidants such as reduced glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) in the blood serum of patients with cirrhosis and liver transplantation.MethodsIn this study, serum malondialdehyde acid (MDA) levels, superoxide dismutase (SOD), reduced glutathione (GSH), and catalase (CAT) activities were measured spectrophotometrically and compared to the results of the healthy control group.ResultsSOD, CAT and GSH activities were significantly decreased in the patient groups compared to the healthy control group (p<0.05). MDA levels were significantly higher in the patient group compared to the healthy control group (p <0.05).ConclusionsIn conclusion, this study demonstrated that oxidative stress may play an important role in the development of liver cirrhosis and in liver transplantation. This study is the first one to show how MDA, SOD, CAT and GSH levels change in liver cirrhosis and liver transplantation, while further studies are essential to investigate antioxidant enzymes and oxidative stress status in patients with cirrhosis and liver transplantation.     

Paraoxonase and arylesterase levels in autoimmune thyroid diseases

Objective: The aim of this study was to evaluate serum paraoxonase-1 (PON1) activity and its association with oxidative stress in autoimmune thyroid disease (AITD).

Methods: A total of 50 patients with AITD, including 25 with Hashimoto's thyroiditis and 25 with Graves’ disease were enrolled. The control group comprised 27 healthy subjects. Blood samples were obtained in the euthyroid period and 3 months after initiation of medical treatment. Serum samples from patients with AITD and the healthy control group were analyzed for basal PON1, salt-stimulated PON1, and arylesterase (ARE) activities, along with lipid hydroperoxide (LOOH) and total free sulfhydryl (–SH) levels.

Results: Serum PON1 activities and –SH levels were significantly lower (P?<?0.001, for each), whereas LOOH levels were significantly higher (P?<?0.001, for each) in patients with AITD, compared to the control group. We observed no significant differences in ARE levels between the patient and healthy control groups (P?>?0.05). PON1 activity was positively correlated with –SH (r?=?0.522, P?<?0.001) and negatively correlated with LOOH (r?=??0.487, P?<?0.001). PON1 phenotype distribution of the subjects was not significantly different among the three groups (P?=?0.961).

Conclusions: Serum PON1 activity is decreased in patients with AITD, and correlated positively with –SH, a well-known antioxidant, and negatively with LOOH, an index of lipid oxidation.     

Increased oxidative stress alters nucleosides metabolite levels in sickle cell anemia

Objectives: This study was conducted to assess the markers of oxidative stress, myeloperoxidase (MPO), acetylcholinesterase (AChE) and xanthine oxidase (XO) activities as well as the levels of nucleotide metabolites in sickle cell anemia (SCA) patients.

Methods: Fifteen SCA treated patients and 30 health subjects (control group) were selected. The markers of oxidative stress (levels of reactive oxygen species (ROS), plasma proteins, carbonyl content, lipid peroxidation (TBARS), total thiols (T-SH), glutathione and catalase activity), MPO, AChE and XO activities as well as the levels of nucleotide metabolites were measured in SCA patients.

Results: ROS, thiobarbituric acid-reactive substances (TBARS) and T-SH levels as well as the activities of catalase and MPO were significantly increased while glutathione level was reduced in SCA patients. Furthermore, a significant (P?P?P?P?Discussion: The altered parameters in SCA patients suggest that the generation and impairment of oxidative stress in this disease as well as antioxidant markers are contributory factors towards cellular redox homeostasis and alteration of purine metabolites.     

Serum Myeloperoxidase Activity, Total Antioxidant Capacity and Nitric Oxide Levels in Patients with Chronic Otitis Media

It has been suggested that oxidative stress may play an important role in the pathogenesis of chronic otitis media (COM), but the role of oxidative stress in the pathogenesis of COM has not yet been fully explored. Therefore, the aim of this study was to investigate serum myeloperoxidase (MPO) activity, 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), total antioxidant capacity (TAC) and nitric oxide (NO) in patients with COM. Sixty-one patients with COM and 30 controls were enrolled in the present study. Patients were divided into two groups according to the presence (n = 21) or absence (n = 40) of cholesteatoma. Serum MPO activity and 4-HNE, MDA and NO levels were significantly higher in patients with COM than controls (for all, p < 0.001), while TAC levels were significantly lower (for all, p < 0.001). Serum MPO activity and MDA, 4-HNE and NO levels were significantly higher in patients with cholesteatoma than in those without cholesteatoma, while TAC levels were significantly lower; but the difference between groups was not statistically significant (p > 0.05). Increased oxidative stress seems to be associated with decreased antioxidant levels in patients with COM. Thus, increased oxidative stress may play a role in the pathogenesis of COM. It is believed that the administration of antioxidant vitamins such as A, C and E may be useful in preventing and treating COM.     

Decreased Serum Selenium Levels are Correlated with Diminished Coronary Flow Reserve Among Hemodialysis Patients

Cardiovascular diseases are the main reason of high mortality among hemodialysis patients. Decreased serum selenium levels may have a role in accelerated atherosclerosis in this patient group. The hypothesis of this study was to show a correlation between decreased serum selenium levels and coronary flow reserve as an indicator of endothelial dysfunction and atherosclerosis in HD patients. Seventy-one chronic hemodialysis patients and age 65 and sex-matched healthy controls were included in the study. Plasma selenium levels were measured by spectrophotometry, and coronary flow reserve was assessed by transthoracic Doppler echocardiography. Serum selenium levels (34.16?±?6.15 ng/ml vs. 52.4?±?5.51 ng/ml, P?<?0.001) and coronary flow reserve values (1.73?±?0.11 vs. 2.32?±?0.28, P?<?0.001) were significantly lower in hemodialysis patients compared with controls, respectively. There was a significant positive correlation between coronary flow reserve and serum levels of selenium (r?=?0.676, P?<?0.001). A linear regression analysis showed that serum levels of selenium were independently and positively correlated with coronary flow reserve (regression coefficient?=?0.650, P?<?0.05). This study was the first to show a positive and independent correlation between decreased selenium levels and diminished coronary flow reserve as an indicator of endothelial dysfunction and atherosclerosis in hemodialysis patients. Our data suggest that decreased serum selenium levels may facilitate the development of endothelial dysfunction and disruption of coronary flow reserve which occur before the development of overt atherosclerosis.     

Further analysis of pemphigus autoantibodies and their use in studies on the heterogeneity, structure, and function of desmosomes

Pemphigus is an autoimmune disease that causes blistering of human epidermis. We have recently shown that autoantibodies in the serum of three pemphigus patients bind to desmosomes (Jones, J. C. R., J. Arnn, L. A. Staehelin, and R. D. Goldman, 1984, Proc. Natl. Acad. Sci. USA., 81:2781-2785), and we suggested that pemphigus blisters form, at least in part, from a specific antibody-induced disruption of desmosomes in the epidermis. In this paper, experiments are described that extend our initial observations. 13 pemphigus serum samples, which include four known pemphigus vulgaris (Pv) and four known pemphigus foliaceus (Pf) serum samples, have been analyzed by both immunofluorescence and by immunoblotting using cell-free desmosome preparations. Tissue sections of mouse skin processed for double indirect immunofluorescence using each of the pemphigus serum samples and a rabbit antiserum directed against a component of the desmosomal plaque (desmoplakin) show similar punctate cell surface staining patterns. This suggests that all 13 pemphigus serum samples contain autoantibodies that recognize desmosomes. These autoantibodies appear specific for stratified squamous epithelial cell desmosomes and do not recognize desmosomes of other tissues (e.g., mouse heart and mouse intestine). Cultured mouse keratinocytes, which possess well-defined desmosomes, were processed for indirect immunofluorescence using the pemphigus serum samples. Eight of the 13 sera (including the four known Pv samples but not the known Pf sera) stain desmosomes in these preparations. By double indirect immunofluorescence the desmoplakin antiserum stains a double fluorescent line along the contacting edges of cultured keratinocytes, whereas the positive pemphigus serum samples stain a single fluorescent line along this same border. We believe that these pemphigus autoantibodies recognize extracellular antigens located somewhere within the region between the two apposing membranes that comprise the desmosome. The pemphigus sera exhibit positive immunoblotting reactions with desmosome-enriched fractions obtained from bovine tongue epithelium. Three serum samples (including two of the four known Pf serum samples) react with 160- and 165-kD desmosome-associated polypeptides (Koulu, L., A. Kusimi, M. S. Steinberg, V. Klaus-Kovtun, and J. R. Stanley, 1984, J. Exp. Med., 160:1509-1518). Another eight serum samples (including the four known Pv sera) recognize a 140-kD desmosome-associated polypeptide. We propose that the antigens recognized by these human autoantibodies may play important roles in the adhesion of cells within the epidermis.(ABSTRACT TRUNCATED AT 400 WORDS)     

Protective role of erdosteine on vancomycin-induced oxidative stress in rat liver

Drug-induced liver toxicity is a common cause of liver injury. This study was designed to elucidate whether high dose vancomycin (VCM) induces oxidative stress in liver and to investigate the protective effects of erdosteine, an expectorant agent. Twenty-two young Wistar rats were divided into three groups as follows: control group, VCM, and VCM plus erdosteine. VCM was administered intraperitoneally in the dosage of 200 mg/kg twice daily for 7 days. Erdosteine was administered orally administered once a day at a dose of 10 mg/kg body weight. The activities of antioxidant enzymes such as superoxide dismutase and catalase as well as the concentration of malondialdehyde, as an indicator of lipid peroxidation, were measured to evaluate oxidative stress in homogenates of the liver. VCM administration increased malondialdehyde levels (p < 0.001), superoxide dismutase (p < 0.01) and catalase (p < 0.001) activities. Erdosteine co-administration with VCM injections caused significantly decreased malondialdehyde levels (p < 0.001), superoxide dismutase (p < 0.01) and catalase (p < 0.001) activities in liver tissue when compared with VCM alone. It can be concluded that erdosteine may prevent VCM-induced oxidative changes in liver by reducing reactive oxygen species.     

Oxidative Stress and S100B Protein in Cirrhotic Children

Cirrhosis represents the terminal stage of a number of chronic liver diseases. Consequences include accumulation of toxic metabolic wastes, reduced synthesis of key proteins, increased portal venous pressure, and portosystemic shunting. We conducted a case-control study to assess the serum levels of S100B protein and parameters of oxidative stress, superoxide dismutase (SOD), catalase (CAT) and oxidative stress measured by the thiobarbituric acid method (TBARS), in a group of 14 pediatric patients with cirrhosis. No differences were found between groups in S100B protein levels. SOD activity and TBARS levels were higher; and CAT activity was lower in the cirrhotic group. A negative correlation between S100B and TBARS in the case group was found (r = −0.815, p = 0.001). Conclusions: This study didn’t indicate a possible role of S100B serum levels as marker of brain damage in cirrhotic children but suggest a possible relation between astrocyte function and oxidative damage in cirrhotic children.