Ucler Kisa

Increased tumor necrosis factor alpha (TNF‐α) and interleukin 1 alpha (IL1‐α) levels in the lesional skin of patients with nonsegmental vitiligo

Increased tumor necrosis factor alpha (TNF-α) and interleukin 1 alpha (IL1-α) levels in the lesional skin of patients with nonsegmental vitiligo Dear Sir, Depigmentation in vitiligo is caused by melanocyte destruction. There are different hypotheses including neural, selfdestruction, and immune hypotheses to explain the pathogenesis of vitiligo There is growing evidence that cytokines are important in the depigmentation process of vitiligo. Granulocytemacrophage colony-stimulating factor (GM-CSF), endothelins, b-FGF are the mitogens for melanocytes whereas TNFα, IL1α, IL-6, TGFβ are the potent inhibitors of melanocyte growth. IL1α is remembered as one of the cytokines of inflammation, and is also known as a B-cell activating factor. It produces similar biological effects with TNF α and is produced in most inflammatory and immunological diseases. b-FGF, produced by fibroblasts and epidermal keratinocytes, is a polypeptide and is capable of promoting angiogenesis and mitogenesis through autocrine and paracrine mechanisms. The role of peripheral blood and lesional cytokine expression in patients with vitiligo has not been clarified yet. Herein we wanted to investigate the levels of cytokines in the skin and serum of vitiligo patients and to compare them with the levels in healthy controls. Six female and 18 male vitiligo patients aged (32 years ± 17 SD) were enrolled in the study after giving informed consent. Thirteen (54.2%) had symmetrical generalized, seven (29.2%) had acrofacial, and four (16.7%) had focal vitiligo. Six (25%) had progressive and 18 (75%) had stabile vitiligo (no new depigmentation had been observed for more than 3 months). Fourteen ageand sex-matched healthy volunteers consisted the control group. Samples of peripheral blood from patients and healthy volunteers were collected by venipuncture. Serum was separated and stored at −70 °C before use. Four-millimeter punch biopsies were taken in all patients from lesional skin and nonlesional skin (at least 3 cm far from lesional biopsy) and from healthy volunteers. The biopsies were frozen in liquid nitrogen (−196 °C) and preserved at −70 °C. Levels of IL1α, TNFα, and b-FGF were measured with specific ELISA kits (Biosource International, Camarillo, California, USA) according to the manufacturer’s instructions. Skin cytokines were measured as described by Lowry et al. Level of the cytokines were expressed as μmol/mg protein. Statistical analysis was carried out using spss 10.0. Differences in values of cytokine amount between lesional vs. healthy volunteers, nonlesional vs. healthy controls, serum of patients vs. serum of healthy volunteers were carried out using Mann– Whitney U-test. The parameters of lesional vs. nonlesional skin were analyzed by the Wilcoxon-signed rank test. P-value of less than 0.05 was considered to be statistically significant. The mean (± SD) values of IL1α, TNFα, b-FGF in lesional, nonlesional, healthy skin, and the serum from healthy controls and the study group are given in Table 1. The expression of IL1α and TNFα was significantly higher in lesional skin than in nonlesional skin in patients with vitiligo (P = 0.007 and P = 0.002), respectively. The exact mechanism how cytokines effect pigmentation is not fully understood. The different hypotheses are: (a) TNFα induces IL1α promoting B-cell differentiation and immunoglobulin production. (b) Cytokines such as IFNγ, TNFα, TNFβ, IL1α, and IL-6 can induce cell surface ICAM-1 on melanocytes which is necessary for leukocyte–melanocyte attachment. ICAM-1 may also induce B-cell activation, increasing autoantibody production and may cause melanocyte damage in vitiligo. (c) TNFα and IL1α also have the capacity to induce apoptosis in many cell types. (d) Melanogenesis is also inhibited by TNFα through an inhibitory effect on tyrosinase and tyrosinase related protein. Moretti et al. found increased levels of IL-6 and TNFα in the epidermis of lesional skin compared with the healthy controls. Swope et al. investigated the role of epidermal cytokines in pigmentation and found that IL1α, TNFα, and IL-6 elicited a dose-dependent decrease in the activity of the enzyme tyrosinase of cultured normal human melanocytes and also inhibited melanocyte proliferation. Ozdemir et al. demonstrated increased skin blister fluid b-FGF levels and serum levels in vitiligo patients compared with healthy controls and proposed that b-FGF plays a role in the pathogenesis of vitiligo. However,

The Effect of Hyperbaric Oxygen Treatment on the Renal Functions in Septic Rats: Relation to Oxidative Damage

PurposeTo investigate the effects of hyperbaric oxygen (HBO) treatment on renal functions and damage in septic rats.MethodsThe animals were divided into four groups, each containing ten animals: control, hyperbaric oxygen, sepsis, and sepsis/hyperbaric oxygen. One milliliter of saline containing live Escherichia coli cells (2.1 × 109) was injected intraperitoneally to induce sepsis. The groups treated with HBO were given five sessions of 2 atmospheres absolute of 100% oxygen at intervals of 6 h. Blood, urine, and tissue samples were then collected, and the functional renal parameters, malondialdehyde (MDA) levels, and superoxide dismutase (SOD) and catalase activities were examined.ResultsThe reduced glomerular filtration rate and urine flow returned to normal levels after HBO treatment; however, the increase in fractionated sodium excretion continued. The increased MDA levels in the renal cortex and medulla also decreased to the level of the control group. In the sepsis group, both the SOD and catalase activities decreased in the renal cortex, while a reduction was observed only in the catalase activity in the medulla. The reduced enzyme activities significantly increased in the sepsis/hyperbaric oxygen group.ConclusionHBO treatment has a beneficial effect on renal dysfunction in sepsis. The probable reason for this effect is the reduction in oxidative damage because of the increase in antioxidative capacity.

Neuroprotective effects of thymoquinone against spinal cord ischemia-reperfusion injury by attenuation of inflammation, oxidative stress, and apoptosis

OBJECTIVE Ischemia-reperfusion (I/R) injury of the spinal cord following thoracoabdominal aortic surgery remains the most devastating complication, with a life-changing impact on the patient. Thymoquinone (TQ), the main constituent of the volatile oil from Nigella sativa seeds, is reported to possess strong antioxidant, antiinflammatory, and antiapoptotic properties. This study investigated the effects of TQ administration following I/R injury to the spinal cord. METHODS Thirty-two rats were randomly allocated into 4 groups. Group 1 underwent only laparotomy. For Group 2, aortic clip occlusion was introduced to produce I/R injury. Group 3 was given 30 mg/kg of methylprednisolone intraperitoneally immediately after the I/R injury. Group 4 was given 10 mg/kg of TQ intraperitoneally for 7 days before induction of spinal cord I/R injury, and administration was continued until the animal was euthanized. Locomotor function (Basso, Beattie, and Bresnahan scale and inclined plane test) was assessed at 24 hours postischemia. Spinal cord tissue samples were harvested to analyze tissue concentrations of malondialdehyde, nitric oxide, tumor necrosis factor-α, interleukin-1, superoxide dismutase, glutathione-peroxidase, catalase, and caspase-3. In addition, histological and ultrastructural evaluations were performed. RESULTS Thymoquinone treatment improved neurological outcome, which was supported by decreased levels of oxidative products (malondialdehyde and nitric oxide) and proinflammatory cytokines (tumor necrosis factor-α and interleukin-1), increased activities of antioxidant enzymes (superoxide dismutase, glutathione-peroxidase, and catalase), as well as reduction of motor neuron apoptosis. Light microscopy and electron microscopy results also showed preservation of tissue structure in the treatment group. CONCLUSIONS As shown by functional, biochemical, histological, and ultrastructural analysis, TQ exhibits an important protective effect against I/R injury of the spinal cord.

Effect of Initial Periodontal Therapy on Oxidative Stress Markers in Gingival Crevicular Fluid, Saliva, and Serum in Smokers and Non-Smokers With Chronic Periodontitis

BACKGROUND The aim of this case-control study with an intervention arm is to determine the effect of initial periodontal treatment on oxidative stress biomarkers in smokers and non-smokers with chronic periodontitis (CP). METHODS The study included 47 patients with CP (24 smokers [S+P+] and 23 non-smokers [S-P+]) and 46 periodontally healthy individuals (23 smokers [S+P-] and 23 non-smokers [S-P-]) for a total of 93 participants. Gingival crevicular fluid (GCF), serum, and saliva samples were obtained and clinical periodontal measurements were recorded at baseline and at the first and third months after periodontal therapy. 8-hydroxydeoxyguanosine (OHdG) and 4-hydroxynonenal (HNE) and enzyme activity of glutathione peroxidase (GSH-Px) were analyzed with enzyme-linked immunosorbent assay. RESULTS The level of 8-OHdD in GCF was found to be significantly higher in both periodontitis groups compared with both periodontally healthy groups. 8-OHdG and GSH-Px in saliva in both periodontitis groups were significantly increased compared with the S-P- group. In the S+P+ group, 4-HNE in GCF was found to be significantly higher than in periodontally healthy participants. After initial periodontal treatment, the levels of 8-OHdG in GCF and saliva were significantly decreased in both periodontitis groups. CONCLUSION Initial periodontal therapy may be helpful for diminishing oxidative stress in periodontitis.

Effects of losartan treatment on T-cell activities and plasma leptin concentrations in primary hypertension

Recent evidence shows that leptin may contribute to elevated blood pressure (BP) and interact with the renin-angiotensin-aldosterone and cellular immune systems. Altered T-cell activities and changes in T-cell subset ratios have also been reported in hypertension. However, little is known about the effects of AT1-receptor antagonism on T-cell activities and plasma leptin concentrations in primary hypertension. We have, therefore, investigated the relationship between leptin and T-cell activities and the effect of an AT1-receptor antagonist, losartan, in primary hypertension. Twenty recently-diagnosed and untreated young adults (11 males and 9 females, age; 39.9±7.6 years, range 23—49 years, BMI; 27.6±3.7 kg/m2) and 20 normotensive healthy, age-, sex- and BMI-matched controls were studied. The [3H]-thymidine uptakes of cultured lymphocytes were determined, both spontaneously and after stimulation with phytohaemagglutinin. The tests were performed before and after three months of treatment with losartan. The results indicate that the blastogenic responses of T-cells to phytohaemagglutinin are significantly higher in the patient group compared with controls (p=0.02). After normalisation of BP, T-cell responses were significantly reduced and were lower than in the controls (p=0.01). Pretreatment plasma leptin levels were significantly higher in hypertensives than in controls (p=0.01). However, losartan treatment had no significant effect on leptin concentrations; moreover, no correlation between leptin levels and T-cell activity was found. Our data show that plasma leptin levels and T-cell activity are markedly enhanced in untreated essential hypertension and that the alteration of T-cell activity is not related to plasma leptin levels. Antihypertensive treatment with losartan decreases T-cell activities but does not influence plasma leptin levels. We conclude that leptin levels are not affected by AT1-receptor blockade and are not related to T-cell activity.

PLASMA LEPTIN CONCENTRATIONS IN POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS

Osteoporosis is less common in obese individuals with increased bone mineral density (BMD) and plasma leptin concentrations. The aim of this study was to determine the correlation between leptin levels and BMD in postmenopausal women. The study consisted of 90 postmenopausal women with a mean age of 53.45 ± 0.87 years who visited our outpatient clinic for the evaluation of BMD. Thirty-six postmenopausal women with osteoporosis (mean age: 54.52 ± 1.41 years and mean body mass index (BMI, kg/m2) 29.33 ± 0.66), 30 age- and BMI-matched postmenopausal women with normal BMD, and 24 postmenopausal women (mean age: 52.79 ± 1.48 years and mean BMI: 29.45 ± 0.89) with osteopenic BMD were included in the study. Plasma concentrations of leptin after an overnight fast were measured by radioimmunoassay. BMD values were measured by dual-energy X-ray absorptiometry (DEXA) at the L2-L4 lumbar spine and femoral neck. The median spine BMD value in the patient group (0.67 ± 0.08 g/cm2, mean ± SEM) was significantly lower than that in the control group (1.02 ± 0.25 g/cm2, mean ± SEM ) and osteopenic group (0.87 ± 0.05 g/cm2, mean ± SEM) (p < 0.005). The mean spine BMD value (T score −3.63 ± 0.25, mean ± SEM) and the mean femur neck BMD value (T score −2.55 ± 0.18, mean ± SEM) of the osteoporosis group were significantly lower than that in the normal BMD group (+ 0.33 ± 0.14 and + 0.27 ± 0.18, p < 0.001) and in the osteopenia group (−1.74 ± 0,1 and –1.18 ± 0.05, p < 0.005). The mean plasma leptin concentration in the osteoporotic group (17.03 ± 1.40 ng/ml) was not significantly different from that in the normal BMD group and the osteopenia group (16.55 ± 1.50 ng/ml; 16.16 ± 1.60, respectively, p < 0.150). Plasma leptin concentrations were correlated with BMI in three groups (r(s) = 0.450, p = 0.025 in normal BMD group and r(s) = 0.4254, p = 0.009 in the osteoporotic group, and r(s) = 395, p = 0.015 in the osteopenia group. There was no correlation between plasma leptin concentrations and BMD values in three groups (r(s) = −0.89 in normal BMD group, r(s) = −0.124 in osteopenia group, and r(s) = −0.195 in osteoporosis group). From this study we conclude that circulating plasma leptin does not have a significant direct influence on bone mass in postmenopausal women.

Use of autologous platelet rich fibrin in urethracutaneous fistula repair: preliminary report.

Urethrocutaneous fistula (UCF) is one of the most common complications occurring after hypospadias repair. Despite the surgical advancement in hypospadias, multiple failed fistula closures are commonly referred to paediatric urologists. Although several techniques have been described to interpose a waterproof layer between urethral and skin closures, occurrence of urethrocutaneous fistula cannot be eliminated completely. In addition to several local tissue grafts, autologous and homologous fibrin sealants are used to prevent UCF. Platelet rich fibrin (PRF) is known as an autologous source of growth factors obtained from the sera of the patient. PRF supports collagen synthesis and tissue repair and accelerates wound healing. We aimed to present our initial experience about the use of autologous PRF in a 3‐year‐old boy with a UCF after hypospadias repair.

Microalbuminuria in Chronic Obstructive Pulmonary Disease

Abstract Background: Microalbuminuria is an important risk factor for cardiovascular diseases. Microalbuminuria may be seen due to hypoxemia in patients with chronic obstructive pulmonary disease (COPD). Objectives: In this study, we investigated prevalence and relationship of microalbuminuria with clinical and physiological parameters in patients with COPD. Method: During the research, 66 consecutive patients with COPD and 40 cases smokers with normal spirometry were included. The urinary albumin creatinin ratio (UACR) was calculated according to previously described formula. The presence of microalbuminuria was defined as UACR being ≥20 in men and ≥30 in women. The severity index of chronic diseases was evaluated by using MCIRS. Results: The rate of presence of microalbuminuria and UACR were higher in patients with COPD than smokers with normal spirometry. Pearson correlation analysis showed a significant inverse relationship between UACR and PaO2, FEV1%, FVC%. On the other hand, there was a positive relationship between UACR and BODE index. There was a significant relationship between the presence of microalbuminuria with PaO2 and BODE index. In the linear regression model, there was a negative relationship between UARC and PaO2 yet there was a significantly positive relationship between UARC and MCIRS score, BODE index. In the logistic regression model, the presence of microalbuminuria showed significant associations with PaO2, BODE index. Conclusion: Microalbuminuria may be seen in patients with COPD, depending on the severity of disease and hypoxemia. Microalbuminuria in patients with severe COPD should be examined in regular periods for risk of cardiovascular morbidity or mortality.

Curcumin Attenuates Inflammation, Oxidative Stress, and Ultrastructural Damage Induced by Spinal Cord Ischemia–Reperfusion Injury in Rats

OBJECTIVES Curcumin is a molecule found in turmeric root that possesses anti-inflammatory and antioxidant properties and has been widely used to treat neurodegenerative diseases. We investigated whether curcumin stimulates the neurorepair process and improves locomotor function in a rat model of spinal cord ischemia-reperfusion injury. METHODS Thirty-two Wistar albino rats (190-220 g) were randomly allocated into 4 groups of 8 rats each: 1 sham-operated group and 3 ischemia-reperfusion injury groups that received intraperitoneal injections of saline vehicle, methylprednisolone (MP, 30 mg/kg following induction of ischemia-reperfusion [IR] injury), or curcumin (200 mg/kg for 7 days before induction of IR injury). Spinal cord IR injury was induced by occlusion of the abdominal aorta for 30 minutes. After 24 hours of reperfusion, locomotor function was assessed using the Basso, Beattie, and Bresnahan scale. All animals were sacrificed. Spinal cord tissues were harvested to evaluate histopathological and ultrastructural alterations and to analyze levels of malondialdehyde, tumor necrosis factor-alpha, interleukin-1 beta, nitric oxide, and caspase-3, as well as enzyme activities of superoxide dismutase and glutathione peroxidase. RESULTS Intraperitoneal administration of curcumin significantly reduced inflammatory cytokine expression, attenuated oxidative stress and lipid peroxidation, prevented apoptosis, and increased antioxidant defense mechanism activity in comparison to treatment with MP or saline. Histopathological and ultrastructural abnormalities were significantly reduced in curcumin-treated rats compared to the MP- and saline-treated groups. Furthermore, curcumin significantly improved locomotor function. CONCLUSIONS Curcumin treatment preserves neuronal viability against inflammation, oxidative stress, and apoptosis associated with ischemia-reperfusion injury.

Evaluation of serum resistin levels in patients with ocular and non-ocular Behçet’s disease

BACKGROUND Resistin, a recently identified adipocytokine, has been found to play an important role in inflammation and the processes of inflammation-related diseases. Serum resistin levels in patients with Behçets disease (BD) have not yet been investigated. We aimed to evaluate the relation between resistin and interleukin-6 (IL-6) in Behçet patients with or without ocular involvement and in normal controls. METHODS Twenty-two patients with BD and 19 healthy control subjects were included in this study. While 14 patients had posterior segment involvement of the eye, the other 8 did not have ocular disease. Serum resistin and interleukin-6 (IL-6), levels were measured in all samples. Data from all groups were tested for statistical significance. RESULTS The mean resistin and IL-6 concentrations were significantly higher in patients with BD than the control subjects (p = 0.011 and p = 0.0001, respectively). There was a significant difference in resistin and IL-6 levels between the patients with non-ocular BD and controls (p = 0.013 and p = 0.0001, respectively), as well as resistin and IL-6 levels between the ocular BD group and the control group (p = 0.05 and p = 0.0001, respectively). However, there was no significant difference between patients with ocular versus non-ocular BD. INTERPRETATION Resistin levels were found to be raised in Behçet patients with or without ocular involvement compared with the control subjects.