Serum prolidase and oxidative stress levels in patients with recurrent aphthous stomatitis: a prospective, controlled study.

BACKGROUND: Recurrent aphthous stomatitis is a common disease characterized by single or multiple, self-healing, well-circumscribed, periodic ulcers occurring in the oral cavity. Although the relationship between recurrent aphthous stomatitis and oxidative stress has been extensively reviewed in the past, its relationship with prolidase enzyme levels has not been previously investigated. AIM: The aim of this study is to investigate plasma antioxidant status and prolidase enzyme levels in patients with recurrent aphthous stomatitis. METHODS: The serum total oxidant status, total antioxidant status, oxidative stress index, prolidase and paraoxonase levels of 34 recurrent aphthous stomatitis patients (mean age 35.1) and 34 healthy controls (mean age 37.7) were compared in this study. RESULTS: Total oxidant status was significantly higher in the recurrent aphthous stomatitis group (P < 0.005). The mean total oxidant status value was 5.19 mmol/L in the recurrent aphthous stomatitis group, while it was 2.90 mmol/L in the control group. Oxidative stress index was significantly higher in the recurrent aphthous stomatitis group (P = 0.016*). The mean oxidative stress index level was 0.28 AU in the recurrent aphthous stomatitis group, while it was 0.18 AU in the control group. When control and patient groups were compared, there was no significant difference between groups with regard to the total antioxidant status (P = 0.343). The total antioxidant status levels were 1.09 and 1.14 mmol/L in control and patient groups, respectively. There was no statistically significant difference between PON1 levels of recurrent aphthous stomatitis and control groups (P = 0.218). Mean PON1 levels were 326 U/L in the recurrent aphthous stomatitis group and 381 U/L in the control group. Prolidase levels were not significantly different between recurrent aphthous stomatitis and control groups (P = 0.955). The mean prolidase level was 219.79 U/L in the recurrent aphthous stomatitis group and 219.26 U/L in the control group. LIMITATIONS: The limitation of this study is the small size of both patient and control groups and exclusion of pediatric patients., Similar studies performed in pediatric patient populations with a comparison to adults may be useful in providing meaningful results. CONCLUSIONS: We detected that the total oxidant status and oxidative stress index was higher in patients with recurrent aphthous stomatitis as compared to healthy controls. We could not demonstrate a significant difference in total antioxidant status, PON1 and prolidase values.

Overlapping responses between salt and oxidative stress in Debaryomyces hansenii.

Debaryomyces hansenii is a halotolerant yeast of importance in basic and applied research. Previous reports hinted about possible links between saline and oxidative stress responses in this yeast. The aim of this work was to study that hypothesis at different molecular levels, investigating after oxidative and saline stress: (i) transcription of seven genes related to oxidative and/or saline responses, (ii) activity of two main anti-oxidative enzymes, (iii) existence of common metabolic intermediates, and (iv) generation of damages to biomolecules as lipids and proteins. Our results showed how expression of genes related to oxidative stress was induced by exposure to NaCl and KCl, and, vice versa, transcription of some genes related to osmotic/salt stress responses was regulated by H2O2. Moreover, and contrary to S. cerevisiae, in D. hansenii HOG1 and MSN2 genes were modulated by stress at their transcriptional level. At the enzymatic level, saline stress also induced antioxidative enzymatic defenses as catalase and glutathione reductase. Furthermore, we demonstrated that both stresses are connected by the generation of intracellular ROS, and that hydrogen peroxide can affect the accumulation of in-cell sodium. On the other hand, no significant alterations in lipid oxidation or total glutathione content were observed upon exposure to both stresses tested. The results described in this work could help to understand the responses to both stressors, and to improve the biotechnological potential of D. hansenni.

Protective effects of glutamine on human melanocyte oxidative stress model.

BACKGROUND: Vitiligo is a disorder caused by the loss of the melanocyte activity on melanin pigment generation. Studies show that oxidative-stress induced apoptosis in melanocytes is closely related to the pathogenesis of vitiligo. Glutamine is a well known antioxidant with anti-apoptotic effects, and is used in a variety of diseases. However, it is unclear whether glutamine has an antioxidant or anti-apoptotic effect on melanocytes. AIMS: The aim of this study was to investigate the protective effects of glutamine on a human melanocyte oxidative stress model. METHODS: The oxidative stress model was established on human melanocytes using hydrogen peroxide. The morphology and viability of melanocytes, levels of oxidants [reactive oxygen species and malondialdehyde], levels of antioxidants [superoxide dismutase and glutathione-S-transferase], and apoptosis-related indicators (caspase-3, bax and bcl-2) were examined after glutamine exposure at various concentrations. Expressions of nuclear factor-E2-related factor 2, heme oxygenase-1, and heat shock protein 70 were detected using western blot technique after glutamine exposure at various concentrations. RESULTS: Our results demonstrate that pre-treatment and post-treatment with glutamine promoted melanocyte viability, increased levels of superoxide dismutase, glutathione-S-transferase and bcl-2, decreased levels of reactive oxygen species, malondialdehyde, bax and caspase-3, and enhanced nuclear factor-E2-related factor 2, heme oxygenase-1, and heat shock protein 70 expression in a dose dependent manner. The effect of pre-treatment was more significant than post-treatment, at the same concentration. LIMITATIONS: The mechanisms of glutamine activated nuclear factor-E2-related factor 2 antioxidant responsive element signaling pathway need further investigation. CONCLUSIONS: Glutamine enhances the antioxidant and anti-apoptotic capabilities of melanocytes and protects them against oxidative stress.

Phototherapeutic modalities pose no significantly increased risk of oxidative damage to DNA in dark skinned individuals.

BACKGROUND: 8-oxoguanine, a major product of DNA oxidation, is considered a key parameter in measuring the carcinogenic effects of ultraviolet radiation. OBJECTIVE: To assess and compare the carcinogenic potential of different photo (chemo) therapeutic modalities in photoresponsive skin diseases by measuring the levels of 8-oxoguanine in dark-skinned individuals before and after photo (chemo) therapy. METHODS: A prospective, randomized controlled pilot study was conducted in 63 patients of skin types III-V with photo-responsive dermatoses including vitiligo, psoriasis and mycosis fungoides. Patients were divided into three groups; Group 1 (received narrowband ultraviolet-B), Group 2 (received psoralen plus ultraviolet-A) and Group 3 (received broadband ultraviolet-A). Biopsies were taken before and after phototherapy to measure 8-oxoguanine levels using enzyme-linked immunosorbent assay. Biopsies were also taken from the sun-protected skin in 21 controls subjects who had no dermatological disease. RESULTS: Regardless of the disease, a significantly higher level of 8-oxoguanine was found after treatment when compared to the pre-treatment baseline levels; however, these levels were comparable to those in control subjects. A weakly significant positive correlation was found between cumulative dose and 8-oxoguanine levels following psoralen plus ultraviolet-A therapy. In controls, comparing the 8-oxoguanine levels between skin types III and IV showed significantly lower 8-oxoguanine in skin type IV. CONCLUSION: Therapeutic doses of ultraviolet radiation are relatively safe in dark skinned patients; however, minimizing the cumulative dose of phototherapeutic modalities (particularly psoralen plus ultraviolet-A) is recommended.

Comprehensive lipid tetrad index, atherogenic index and lipid peroxidation: Surrogate markers for increased cardiovascular risk in psoriasis.

BACKGROUND AND OBJECTIVES: Recently, the concept of "psoriatic march" has come to the fore, in which chronic cutaneous inflammation in psoriasis leads to systemic inflammation which, in conjunction with increased oxidative stress, triggers a cascade of events resulting in increased cardiovascular risk in patients with severe psoriasis. We, therefore, decided to study the levels of some biochemical cardiovascular risk markers: lipid peroxidation (malondialdehyde), lipoprotein (a), lipid indices and atherogenic index, in patients with psoriasis and their association with disease severity. METHODS: Forty five patients with psoriasis and 45 age and gender-matched healthy controls were included in this cross-sectional study. Disease severity was assessed by the Psoriasis Area Severity Index (PASI). Serum malondialdehyde, lipoprotein (a) and fasting lipid profile were estimated in all study subjects. Lipoprotein ratios were computed using standard formulae. Atherogenic index was calculated as ratio of lipoprotein (a)/high-density lipoprotein. RESULTS: In psoriasis, we observed significantly higher levels of malondialdehyde, total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, lipoprotein (a), lipid ratios, atherogenic index and comprehensive lipid tetrad index, compared to controls. These levels were directly proportional to disease severity. Serum levels of malondialdehyde correlated positively with serum lipoprotein (a), comprehensive lipid tetrad index and atherogenic index. LIMITATIONS: Different morphological types of psoriasis were not included and follow-up post-therapy was not done. A larger sample size would have validated the results further. CONCLUSION: Our results indicate that psoriasis, especially the severe variants, are associated with increased oxidative stress and dyslipidemia, which correlate positively with atherogenic index and hence, an increased cardiovascular risk.

Inhibition of Janus kinase signaling during controlled mechanical ventilation prevents ventilation-induced diaphragm dysfunction.

Controlled mechanical ventilation (CMV) is associated with the development of diaphragm atrophy and contractile dysfunction, and respiratory muscle weakness is thought to contribute significantly to delayed weaning of patients. Therefore, therapeutic strategies for preventing these processes may have clinical benefit. The aim of the current study was to investigate the role of the Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in CMV-mediated diaphragm wasting and weakness in rats. CMV-induced diaphragm atrophy and contractile dysfunction coincided with marked increases in STAT3 phosphorylation on both tyrosine 705 (Tyr705) and serine 727 (Ser727). STAT3 activation was accompanied by its translocation into mitochondria within diaphragm muscle and mitochondrial dysfunction. Inhibition of JAK signaling during CMV prevented phosphorylation of both target sites on STAT3, eliminated the accumulation of phosphorylated STAT3 within the mitochondria, and reversed the pathologic alterations in mitochondrial function, reduced oxidative stress in the diaphragm, and maintained normal diaphragm contractility. In addition, JAK inhibition during CMV blunted the activation of key proteolytic pathways in the diaphragm, as well as diaphragm atrophy. These findings implicate JAK/STAT3 signaling in the development of diaphragm muscle atrophy and dysfunction during CMV and suggest that the delayed extubation times associated with CMV can be prevented by inhibition of Janus kinase signaling.-Smith, I. J., Godinez, G. L., Singh, B. K., McCaughey, K. M., Alcantara, R. R., Gururaja, T., Ho, M. S., Nguyen, H. N., Friera, A. M., White, K. A., McLaughlin, J. R., Hansen, D., Romero, J. M., Baltgalvis, K. A., Claypool, M. D., Li, W., Lang, W., Yam, G. C., Gelman, M. S., Ding, R., Yung, S. L., Creger, D. P., Chen, Y., Singh, R., Smuder, A. J., Wiggs, M. P., Kwon, O.-S., Sollanek, K. J., Powers, S. K., Masuda, E. S., Taylor, V. C., Payan, D. G., Kinoshita, T., Kinsella, T. M. Inhibition of Janus kinase signaling during controlled mechanical ventilation prevents ventilation-induced diaphragm dysfunction.

Micronutrients influencing the immune response in leprosy / Micronutrientes que influyen en la respuesta immune en la lepra

La lepra es una enfermedad infecciosa crónica causada por el Mycobacterium leprae, un bacilo intracelular de transmisión aérea. La enfermedad afecta la piel y los nervios periféricos y causa secuelas neurológicas. El bacilo se multiplica lentamente en el hospedador y posiblemente la enfermedad ocurre por el mal funcionamiento de la respuesta inmunitaria del hospedador. Esta revisión aborda el papel de algunos micronutrientes específicos en la respuesta inmunitaria, tales como las vitaminas A, D, E, C, el cinc y el selenio, detallando sus mecanismos de acción en las enfermedades infecciosas y en la lepra. La respuesta inmunitaria a los patógenos libera sustancias nocivas que producen lesión tisular. Esta revisión también aborda cómo una menor cantidad de antioxidantes puede contribuir a un aumento del estrés oxidativo y a complicaciones de las enfermedades infecciosas y la lepra. Puesto que los micronutrientes poseen un efecto regulador de la respuesta inmunitaria innata y adaptativa, es importante un equilibrio perfecto de sus concentraciones para mejorar la respuesta inmunitaria frente a los patógenos (AU)

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, an intracellular bacillus of airborne transmission. The disease affects the skin and peripheral nerves and can cause neurological sequelae. The bacillusmultiplies slowly in the host and the disease probably occurs due to malfunctioning in host immune response. This review addresses the role of some specific micronutrients in the immune response, such as Vitamins A, D, E, C, Zinc and Selenium, detailing their mechanisms of actions in infectious diseases, and in leprosy. The immune response to pathogens releases harmful substances, which lead to tissue damage. This review discusses how a decreased level of antioxidants may contribute to an increased oxidative stress and complications of infectious diseases and leprosy. As the nutrients have a regulatory effect in the innate and adaptative immune responses, a perfect balance in their concentrations is important to improve the immune response against the pathogens (AU)

Antioxidant factors, nitric oxide levels, and cellular damage in leprosy patients.

INTRODUCTION: The immune response caused by Mycobacterium leprae is a risk factor for the development of oxidative stress (OS) in leprosy patients. This study aimed to assess OS in leprosy patients before the use of a multidrug therapy. METHODS: We evaluated the nitric oxide (NO) concentration; antioxidant capacity; levels of malondialdehyde, methemoglobin and reduced glutathione; and the activity of catalase and superoxide dismutase (SOD) in leprosy patients. RESULTS: We observed lower SOD activity in these leprosy patients; however, the NO levels and antioxidant capacity were increased. CONCLUSIONS: The infectious process in response to M. leprae could primarily be responsible for the OS observed in these patients.

Status of free radicals and antioxidants in leprosy patients.

Oxidative stress is a condition associated with an increased rate of cellular damage induced by the oxygen derived oxidants commonly known as reactive oxygen species (ROS). ROS are capable of damaging cellular constituents generated in excess during the chronic, inflammatory, neurodegenerative disease process of leprosy. Severe oxidative stress has been reported in leprosy patients because of malnutrition and poor immunity. The decreased levels of SOD, glutathione and total antioxidant status in leprosy patients may indicate a degradation of these antioxidant enzymes by free radicals during detoxification processes. The subjects for this study comprises of Normal human volunteers (NHV, n = 20) and treated MB patients (MB, n = 20). The levels of lipid peroxidation products are increased in MB Patients (*P < 0.001). SOD (**P < 0.0001) and glutathione levels (***P < 0.0001) decreased in MB Patients in comparision with normal human volunteers. The present study of estimation of antioxidants conclude that the free radical activity was increased and the total antioxidant status was decreased in all MB patients, indicating that there was an oxidative stress even after the treatment with MDT. The decreased levels of SOD, glutathione indicate a link between oxidative stress and leprosy. Since the MB patients are unable to produce sufficient amount of antioxidant to cope up with the increased oxidative stress in them. Providing nutritional supplementation may present a novel approach for fast recovery. Administration of exogenous antioxidants like vitamin C, tocopherols would prevent tissue damage and make the patient therapeutically benefited.

Antioxidant factors, nitric oxide levels, and cellular damage in leprosy patients

Introduction The immune response caused by Mycobacterium leprae is a risk factor for the development of oxidative stress (OS) in leprosy patients. This study aimed to assess OS in leprosy patients before the use of a multidrug therapy. Methods We evaluated the nitric oxide (NO) concentration; antioxidant capacity; levels of malondialdehyde, methemoglobin and reduced glutathione; and the activity of catalase and superoxide dismutase (SOD) in leprosy patients. Results We observed lower SOD activity in these leprosy patients; however, the NO levels and antioxidant capacity were increased. Conclusions The infectious process in response to M. leprae could primarily be responsible for the OS observed in these patients. .

Tissue and blood superoxide dismutase activity and malondialdehyde level in leprosy.

BACKGROUND: Oxidative stress (OS) results from an imbalance between free radical generating and scavenging systems. The end product of lipid peroxidation, malondialdehyde (MDA) serves as a marker of cellular damage. Superoxide dismutase (SOD) traps free radicals and acts as a free radical scavenging system. OBJECTIVE: To study OS indices in paucibacillary (PB) and multibacillary (MB) leprosy in tissues and blood. MATERIALS AND METHODS: The study group comprised untreated PB patients (n = 14), untreated MB patients (n = 18) and normal human volunteers (n = 20). SOD activity, MDA level and MDA/SOD ratio were estimated in both blood and tissue. RESULTS: Compared with controls, SOD activity in tissues decreased significantly in both PB and MB patients, while SOD activity in erythrocytes decreased significantly only in MB. In addition, MDA levels increased significantly in tissues of both PB and MB patients. Moreover, the mean level of MDA in plasma of MB patients was significantly higher, whereas there was no significant difference in that of PB patients. This study showed significant increase in OS index (MDA/SOD ratio) in tissue of PB and MB patients and in blood of MB patients only, whereas there was no significant difference in OS index in blood of PB patients compared with that in the controls. CONCLUSION: Oxidative stress was observed in both tissues and blood of MB patients and in tissues of PB patients, denoting its crucial involvement in the pathogenesis of leprosy. This can constitute an important tool in prognosis, treatment and control of leprosy.

Determination of oxidative stress in vitiligo by measuring superoxide dismutase and catalase levels in vitiliginous and non-vitiliginous skin.

BACKGROUND: Vitiligo is an acquired disorder characterized by circumscribed depigmented macules devoid of identifiable melanocytes. Complex genetic, immunological, neural and self destructive mechanisms interplay in its pathogenesis. According to autocytotoxic hypothesis, oxidative stress has been suggested to be the initial pathogenic event in melanocyte degeneration. AIMS: The aim of our investigation was to evaluate the role of oxidative stress by measuring levels of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) in lesional and normal skin of patients with vitiligo and in the skin of normal controls. METHODS: We determined the activity of SOD in lesional and non-lesional skin and CAT in lesional skin only of 25 vitiligo patients and 25 controls by using the spectrophotometric assay and Aebi's method, respectively. RESULTS: There was statistically significant increase in the levels of SOD in vitiliginous and non vitiliginous skin of patient group compared to the control group (P < 0.001). No significant difference was found between the levels of SOD in lesional skin and non-lesional skin of vitiligo patients. The levels of CAT in the skin of patients were found to be significantly lower than those of controls (P < 0.001). CONCLUSIONS: There is increased oxidative stress in vitiligo as is indicated by high levels of SOD and low levels of CAT in the skin of vitiligo patients.

Protective role of vitamin E on the oxidative stress in Hansen's disease (Leprosy) patients.

BACKGROUND: A constellation of reactive oxygen species (ROS) capable of damaging cellular constituents generated in excess during the chronic, inflammatory, neurodegenerative disease process of leprosy. The consequences of this leads to enhanced oxidative stress and lower antioxidant status. Enzymatic antioxidants provide first line defense against ROS. We have measured the levels of oxidative stress indices like lipid peroxidation (LPO), protein carbonyls together with enzymatic antioxidants in the blood samples of control and leprosy patients. Nutritional rehabilitation by way of exogenous supplementation of functionally efficient antioxidants like vitamin E reactivates the enzymatic antioxidant system and guards against the insult caused by ROS during the pathogenesis of the disease and antileprosy chemotherapy. DESIGN: Untreated leprosy patients were selected on the basis of clinical examination and skin smear. All diagnosed untreated leprosy patients received multi drug therapy (MDT) consisting of rifampicin, dapsone and clofazimine as recommended by World Health Organization. A small number of untreated cases were selected for co-supplementation of vitamin E along with MDT. Oxidative stress indices, enzymatic and nonenzymatic antioxidant status were assayed in untreated, MDT treated and those supplemented vitamin E along with MDT. STATISTICAL METHODS: We have compared the significance in the mean+/-s.d. values of the oxidative stress indices and the levels of antioxidants using one way analysis of variance (ANOVA) between control, untreated, MDT treated and those supplemented vitamin E with MDT and the results were significant at P < 0.05. Statistical analysis of the results suggests that oral administration of vitamin E lowers oxidative stress and augments antioxidant status in affected individuals. RESULTS: Enhanced oxidative stress as evidenced by increased LPO and protein carbonyl in leprosy cases lowers the antioxidant status. Treatment with MDT has a limited impact on increased oxidative stress and decreased antioxidant status. Coadministration of vitamin E along with MDT decreases oxidative stress and activate the antioxidant status. DISCUSSION: The excess production of ROS as seen in leprosy cases could lead to degeneration of tissues and derangement of internal organs. The possible reason for the decreased antioxidant status in leprosy cases may be increased production of ROS, deranged liver function, and the free radical producing ability of drugs used in MDT of leprosy. Intervention with antioxidant supplementation like vitamin E prevents oxidative stress mediated through ROS and activates the net antioxidant status during the chronic course of the disease and antileprosy chemotherapy.

Estresse oxidativo e atuacao do sistema antioxidante como removedor de radicais livres no sangue periferico de pacientes hansenianos / Oxidativo Estresse and performance of the antirust system as remover of free radicals in the peripheral blood of hansenianos patients

A hanseniase e uma doença infecciosa cronica causada pelo mycobacterium leprae com um amplo espectro clinico e imunopatologico. Entre os mecanismos de defesa devenvolvidos pelo hospedeiro esta a geração de radicais livres, os quais promovem a destruição do bacilo. Os radicais livres são produzidos dentro das celulas por reaçoes endogeneas, geralmente oxidativas, que ocorrem em processos metabolicos normais, e temabem em condições anormais, como na inflamação causada por doença infecciosas. Este trabalho visa estudar a atividade de substâncias antioxidantes e sua relação com o estresse oxidativo gerado na resposta à hanseniase. Foram realizados experimentos com as enzimas superoxido dismutase(SOD) e catalase(CAT), além do antioxidantes glutationa(GSH) e a participação de óxido nitrico(NO) como indicador da presença de radicais livres. Os resultados foram comparados com um grupo controle e aqueles de pacientes sem tratamento e em tratamento com PQT. Os resultados obtidos indicam um aumento de até 280 por cento dos niveis dos antioxidantes, bem como dos metabolitos do oxido nitrico (596 por cento) em relação ao controle, sugerindo estresse oxidativo severo nos pacientes hansenianos. Os pacientes em tratamento mostram um aumento de até 87 por cento nos niveis de antioxidantes comparados ao controle, reduzindo a geração de radicais livres em relação aos individuos sem tratamento. Portanto, a medida do balanço entre defesas antioxidantes e a presença de radicais livres pode ser uma excelente ferramenta de estudo dos niveis de estresse oxidativo e sua contribuição na evolução da hanseniase.

Oxidative stress and anti-oxidant status in leprosy patients.

Severe oxidative stress has been reported in leprosy patients because of malnutrition and poor immunity. The purpose of this study was to investigate the serum lipid peroxidation products, serum LDH and important free radical scavenging enzymes, i.e. superoxide dismutase (SOD), and catalase and anti-oxidant glutathione levels and total anti-oxidant status, in different types of leprosy patients. The subjects for this study were normal human volunteers (NHVs, n=14), paucibacillary leprosy patients (PB, n=18), untreated MB patients (MB1, n=18), MB patients under treatment (MB2, n=19), and MB patients released from treatment (RFT) (MB3, n=28). The levels of lipid peroxidation product, malondialdehyde (MDA), and LDH increased significantly (p<0.001) in MB (MB1, MB2, MB3) patients, and both gradually decreased with clinical improvement following MDT. The levels of SOD, catalase and glutathione, and the total anti-oxidant status decreased significantly in MB (MB1, MB2, MB3) patients (p<0.001), in comparison with NHVs. They gradually increased with clinical improvement with MDT. There was no significant variation of these parameters in PB leprosy patients in comparison with healthy volunteers. High free radical activity and low anti-oxidant levels observed in MB (MB1, MB2, MB3) leprosy patients indicate that there is an oxidative stress in MB cases, irrespective of the treatment status and suggest a suitable anti-oxidant therapy to prevent possible tissue injury.