Melatonin: is it an effective antioxidant for pulmonary contusion?

BACKGROUND: The goal of the present study was to evaluate the antioxidant effects of melatonin on pulmonary contusion (PC) caused by isolated blunt thoracic trauma (BTT) in an experimental rat model. MATERIALS AND METHODS: A total of 49 rats were divided into three groups: control group (CG), trauma group (TG), and melatonin group (MG). PC was induced by isolated BTT for all the groups except the control group. Intraperitoneal melatonin was administered to the MG after trauma. Blood and tissue samples were collected from the groups. Malondialdehyde (MDA), total oxidant capacity and total antioxidant capacity (TAOC), arterial blood gas, and other biochemical parameters such as urea, creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase were measured. Lung tissue samples were collected for histopathology. RESULTS: On day 2, blood MDA and total oxidant capacity levels were lower, and TAOC levels were higher in the MG compared with the TG (P < 0.001). Blood pH, PO2, and PCO2 of the MG significantly improved on day 2 compared with the TG (P ≤ 0.001). Compared with the TG, histologic damage scores of the MG decreased on day 2 (P = 0.013). Urea, creatinine, ALT, and aspartate aminotransferase levels of the MG on day 2 were lower than TG parameters (P = 0.01, P = 0.02, P = 0.05, and P < 0.001, respectively). CONCLUSIONS: Our findings demonstrate that melatonin can improve the histopathology of PC and distant organs such as liver and kidney by diminishing oxidative stress. All these findings suggest that melatonin may be an effective new therapeutic agent for PC caused by BTT.

[Effect of IL-28B polymorphisms on the natural course of HBV infection]. / HBV enfeksiyonun dogal seyrine IL-28B gen polimorfi zminin etkisi.

The prediction of the consequences of disease is important to determine the therapy approaches and prevention of the chronical state in patients infected with hepatitis B virus (HBV). In recent years various studies are carried on to investigate the effect of IL-28B gene polymorphisms on the clinical course or therapy response in patients with chronic hepatitis B infection. The aim of the study was to evaluate the influence of IL-28B rs12979860 polymorphisms on the natural course of HBV infection. The study was designed prospectively, and the subjects were randomly selected among patients admitted to infectious disease outpatient clinics of Kocatepe University Medical School Hospital and Yunus Emre State Hospital located at provinces in Central Anatolia, Turkey. A total of 99 cases were included in the study and evaluated into three groups, namely, chronic hepatitis B patients (group 1, n= 43); inactive HBV carriers (group 2, n= 34) and subjects with acquired immunity after native infection (group 3, n= 22). There were no significant differences regarding the age and gender distribution between the groups (p> 0.05). All subjects were investigated for the IL-28B promoter single nucleotide polymorphism rs12979860 at position 3176 C/T, by real-time polymerase chain reaction (RT-PCR). Evaluation of the range of IL-28B rs12979860 C/T polymorphisms observed in the study groups showed that, the frequency of CC, CT and TT allels were as follows; 34.9%, 48.8% and 16.3 % in group 1; 47.1%, 35.3% and 17.6% in group 2; 63.6%, 27.7% and 13.6% in group 3, respectively. No significant differences were observed between the groups in terms of C/T allel distriubution (p> 0.05). However, in spite of statistical insignificance, the rate of CC allel in IL-28B rs12979860 gene was the highest in immune subjects (63.6%), while it was the lowest in chronic hepatitis B patients (34.9%). According to our data, IL-28B rs12979860 gene polymorphisms were not effective on the clinical course of HBV infection. In conclusion, further studies with large numbers of patients are needed to support these data.

L-Carnitine: a new insight into the pathogenesis of endometrial cancer.

OBJECTIVES: The present study aims to specify the role of L-carnitine in the pathogenesis of endometrial cancer by comparing the serum total L-carnitine levels of endometrial cancer patients with those of healthy women. METHODS: Serum total L-carnitine concentrations were measured in patients with endometrioid-type endometrial cancer (n = 20) and healthy controls (n = 20) who were matched with respect to age and body mass index (BMI). RESULTS: Stage I endometrial cancer was diagnosed in 12 women (60.0%) whereas three women (15.0%) had stage II disease, three women (15.0%) had stage III disease and two women (10.0%) had stage IV disease. The healthy controls and endometrial cancer patients were statistically similar in aspect of age, gravidity, parity, BMI, waist-to-thigh ratio, waist-to-hip ratio, menopause, complete blood count parameters, and serum biochemistry. Serum total L-carnitine levels of women with endometrial cancer were significantly lower than those of healthy women (respectively, 5,519.4 ± 2,712.5 vs 7,940.8 ± 3,566.6 ng/dl, p = 0.021). Moreover, serum total L-carnitine levels decreased significantly and progressively with advancing stage (stage I vs II vs III vs IV; 6,294.0 ± 2,885.1 vs 5,800.0 ± 441.2 vs 4,016.0 ± 2,833.3 vs 2,560.0 ± 67.9 ng/dl; p = 0.021). CONCLUSIONS: This is the first study to hypothesize that L-carnitine deficiency participates in the pathogenesis of endometrial cancer by means of a mechanism which is unrelated with obesity and increased amount of fat in human body.

The effect of phototherapy on fecal calprotectin levels.

OBJECTIVE: Fetal calprotectin levels increase in the early stages of necrotizing enterocolitis. Although the effects of several factors on fetal calprotectin have been studied, the effect of phototherapy is not known. In this study, we analyzed the effect of phototherapy on fetal calprotectin levels. METHODS: Ninety breast-fed newborns (46 male, 44 female) who were hospitalized for indirect hyperbilirubinemia and treated with phototherapy were included to the study. Forty-two of them were term and 44 of them were preterm. Newborns treated with phototherapy (n = 53) constituted the phototherapy group (29 preterm, 24 term) and 37 newborns who did not receive phototherapy (19 preterm, 18 term) constituted the control group. Fecal samples were collected 24 hours after phototherapy had been started. Fecal samples (100 mg) were weighed with sensitive scales and preserved at -80°C after buffering with a special solution. All samples were studied at the same time with a fecal calprotectin kit by using enzyme-linked immunosorbent assay. RESULTS: There were no statistically significant difference between fecal calprotectin levels of term and preterm babies who received phototherapy and babies who did not receive phototherapy. CONCLUSION: There was no effect of 24-hour phototherapy on fecal calprotectin levels in preterm and term newborns.

The protective effect of quercetin on long-term alcohol consumption-induced oxidative stress.

Long-term alcohol consumption can cause oxidative stress and cytokines induction, which are associated with free radicals. Quercetin, one of the most widely distributed flavonoids in plants, is a natural antioxidant. We investigated the hypothesis that quercetin could prevent the ethanol-induced oxidative stress and decreases tumor necrosis factor-α (TNF-α) and interferon-γ (INF-γ) as pro-inflammatory cytokines. Twenty-eight rats were randomly divided into control group (C), ethanol treatment group (EtOH) (~1 ml/day, 80%; 2 g/kg body wt), intragastrically (i.g.), quercetin treatment group (Q), (100 mg/kg-body wt per 3 days) i.g. and ethanol plus quercetin treatment group (EtOH + Q) (1 ml/day, 80% of ethanol and 100 mg/kg-body wt of quercetin per 3 days) i.g. for 30 days Plasma thiobarbituric acid reactive substance (TBARS) levels and protein carbonyl content were significantly higher in the EtOH group than the C group (P < 0.01). On the other hand, TBARS level and protein carbonyl content in the EtOH + Q group was decreased significantly by quercetin (P < 0.05, P < 0.01; respectively). While GSH levels in whole blood decreased in EtOH group compared to C group, they increased significantly by quercetin (P < 0.05). Plasma ALT, TNF-α and IFN-γ levels increased significantly in the EtOH group compared to control group (P < 0.05, P < 0.01, P < 0.01, respectively), but they decreased significantly in the EtOH + Q group in comparison with EtOH group (P < 0.05, P < 0.01, P < 0.01, respectively). Our results demonstrate that quercetin treatment may provide a protection as reflected by decreased plasma TBARS, protein carbonyls, TNF-α, INF-γ and ALT levels against ethanol-induced oxidative damage.

Anti-apoptotic and antioxidant effect of leptin on CCl4-induced acute liver injury in rats.

The aim of this study is to investigate the effect of leptin in rats on carbon tetrachloride (CCl(4)) induced acute liver damage using immunohistochemical methods for apoptosis and biochemical parameters. In this experimental study, 18 Spraque-Dawley rats were divided into three groups viz; control, CCl(4) and CCl(4)+leptin treatment. 0.8 ml/kg olive oil was administered intraperitoneally (i.p.) to the control group and 0.8 ml/kg CCl(4) (1:1 dissolved in olive oil) was administered i.p. to the CCl(4) and CCl(4)+leptin treatment groups, respectively. After 6 h of administrating CCl(4), CCl(4)+leptin treatment group was given i.p. leptin (10 µg/kg). Twenty-four hours after administrating CCl(4) all of the groups were euthanized. Biochemical assessments were performed using serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), plasma tumor necrosis factor alpha (TNF-α) levels and tissue malondialdehyde (MDA), and TNF-α levels. Histological assessments were then performed using Hematoxylin&Eosin (H&E) staining in light microscope and apoptosis assessment using Terminal Transferase dUTP Nick End Labeling (TUNEL)-staining. Serum AST, ALT, ALP and plasma TNF-α levels, tissue MDA and TNF-α levels had all increased in CCl(4) group, but were found to be significantly decreased in CCl(4)+leptin treatment group. Moreover, TUNEL-positive cell counts in liver had significantly increased in CCl(4) group, but decreased in CCl(4)+leptin treatment group (P < 0.05). The results of our study the biochemical, histological and TUNEL-staining showed that leptin has treatment effects on liver CCl(4) induced injury. It plays a role as a potent free radical scavenger, a powerful antioxidant and it also has anti-apoptotic effects.

The comparison of effects of balneotherapy, water-based and land-based exercises on disease activity, symptoms, sleep quality, quality of life and serum sclerostin level in patients with ankylosing spondylitis: A prospective, randomized study.

Objectives: This study aims to compare the effects of balneotherapy, water-based exercise (WBE), and land-based exercise (LBE) on disease activity, symptoms, sleep quality, quality of life, and serum sclerostin level (SSL) in patients with ankylosing spondylitis (AS). Patients and methods: Between January 2019 and January 2020, a total of 60 patients (35 males, 25 females; mean age: 40.9±11.2 years; range, 18 to 55 years) who were diagnosed with AS were randomly divided into the balneotherapy (n=20), WBE (n=20), and LBE (n=20) groups (20 sessions of treatment in groups of five to six patients). The patients were evaluated before treatment and at 4 and 12 weeks using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP), Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), Ankylosing Spondylitis Quality of Life (ASQoL) Scale, Fatigue Severity Scale (FSS), and Pittsburg Sleep Quality Index (PSQI), and SSL were measured. Results: Statistically significant improvements in the BASDAI, BASFI, MASES, BASMI, ASQoL, FSS, and ASDAS-CRP scores were observed in all groups at 4 and 12 weeks of follow-up (p<0.05). A significant improvement in sleep latency was seen in the balneotherapy and WBE groups. Changes in SSL were not statistically significant in any group (p>0.05). Conclusion: Balneotherapy, WBE, and LBE are effective in the treatment of AS, and the beneficial effects may last for at least 12 weeks.

Effects of doxycycline on renal ischemia reperfusion injury induced by abdominal compartment syndrome.

BACKGROUND: The aim of this study was to determine the effects of doxycycline on renal ischemia reperfusion (I/R) injury in a rat model of abdominal compartment syndrome (ACS). MATERIALS AND METHODS: Forty-two Sprague-Dawley rats were divided into six groups. In the control group (group 1), kidney samples were collected with no manipulation; in the sham group (group 2) induction of ACS was followed by decompression. In groups 3 and 4, 1 cc of saline was administered intraperitoneally (i.p.) during the induction of ACS, and the kidneys were removed 1 and 24h after decompression, respectively. In groups 5 and 6, doxycycline (10mg/kg i.p.) was injected during the induction of ACS, and similarly all tissue samples were removed 1 and 24h after decompression, respectively. MDA, IL-1ß, IL-6, TNF-α, MMP-2, and TIMP-1 were studied, and the apoptotic cells were enumerated histopathologically, and apoptosis and bcl-2 expression were assessed immunohistochemically. RESULTS: Creatinine, MDA, IL-1ß, and IL-6 levels were significantly higher in group 3, 1h after the reperfusion period compared with the control group, and the same parameters were significantly lower in the groups in which doxycycline was administered, 1 hour after decompression. However, there remained no difference between groups at 24h, except IL-1ß, which was decreased to even lower values. TNF-α and TIMP-1 levels were not statistically different in all groups. The MMP-2 level was significantly higher in group 4 by 24h, and there remained no difference between groups 1, 2, and 6. In group 6, there were not any apoptotic cells as were observed in the other groups. The number of apoptotic cells and the expression of bcl-2 was significantly less in the groups in which doxycycline was administered. CONCLUSION: Doxycycline had protective effects on I/R injury by decreasing apoptosis via reducing the level of pro-inflammatory cytokines, increasing the level of TIMP-1, and inhibiting the activity of MMP-2.

Comparison of three different immunoassay methods for the evaluation of intact parathyroid hormone levels in hemodialysis patients.

BACKGROUND: Intact parathyroid hormone (iPTH) assays react with the non-(1-84) molecular form of PTH. This form behaves as a carboxy-terminal fragment and accumulates during renal failure. We wanted to examine the variation of iPTH levels between the more commonly used different immunoassay methods in hemodialysis patients. METHODS: Our study was designed to compare three commercial second-generation immunoassays based on electrochemiluminescent immunoassay (ECLIA), enzyme immunoassay (EIA) and immunoradiometric assay (IRMA) for intact PTH. The serum samples from 88 patients were collected and the iPTH concentrations measured. RESULTS: The median iPTH (IRMA) concentration (99 pg/mL) was lower than both median iPTH (ECLIA) concentration (290.5 pg/ml; p < 0.001) and iPTH (EIA) concentration (369 pg/mL; p < 0.001). The Bland-Altman graphs, which are plots of the percentage differences between the two methods against their mean, suggested that the IRMA methods are not in agreement with the other methods. CONCLUSION: It would be useful to reduce the variability among the methods with the use of a more standardized calibrator and of the same specific antibodies that only recognize the active PTH molecule.

Maternal and fetal leptin and ghrelin levels: relationship with fetal growth.

PURPOSE: In our study, we investigated the influence of plasma levels ghrelin, leptin and other metabolic hormones (ILGF-1 and ILGF-2) in pregnants in regulating fetal body weight and mode of delivery. METHODS: A total of 36 appropriately healthy pregnants 19-36-year-old were involved in the study. Demographic characteristics, serum ghrelin, leptin, IGF-1 and IGF-2 levels of the pregnants were studied. RESULTS: Plasma ghrelin and leptin levels did not differ significantly among trimesters and delivery, in contrast to IGF-I and IGF-II concentrations were significantly higher in the first half of the pregnancy (P < 0.05). Serum leptin was significantly associated with mode of delivery (r = 0.231; P = 0.008), BMI (r = 0.462; P = 0.004). CONCLUSION: Metabolic factors are associated with fetal growth, but in AGA babies, there were no differences between any parameter and clinical factor.

Prevention of ovarian hyperstimulation syndrome in a rat model: efficacy comparison between cabergoline and meloxicam.

OBJECTIVE: To compare the efficacy of cabergoline (Cb2) and meloxicam in curbing vascular endothelial growth factor (VEGF) expression and preventing ovarian hyperstimulation syndrome (OHSS). DESIGN: Randomized controlled, animal study. SETTING: Academic facility. SAMPLE: We used a total of 50 immature Wistar female rats randomly to create an experimental OHSS model. METHODS: Ten rats each formed the control group and mild OHSS group. The remaining 30 were separated into three equal groups of severe OHSS. Mild and severe OHSS were induced through ovarian stimulation with gonadotropins. One group with severe OHSS was administered a low-dose 100 microg/kg Cb2 therapy; another group with severe OHSS received 600 microg/kg meloxicam. Body weight, vascular permeability (VP), VEGF expression, ovary weight, and diameter were then compared. MAIN OUTCOME MEASURES: The efficacy of Cb2 and meloxicam for preventing OHSS. RESULTS: Comparison of the severe OHSS groups with the controls and mild OHSS group revealed significant increases in VEGF expression, VP, ovary weight, and diameter. The increase in VEGF expression was demonstrated to be dependent on human chorionic gonadotropin doses. However, low-dose Cb2 and meloxicam therapies were shown to be ineffective in decreasing VEGF expression and VP, ovary weight, and ovary diameter in severe OHSS. CONCLUSIONS: VEGF elevation played a critical part in OHSS pathogenesis, but the therapies administered failed to curb VEGF expression.

Effects of hemodialysis period on levels of blood trace elements and oxidative stress.

INTRODUCTION: As a treatment method for chronic renal failure (CRF), hemodialysis (HD) alters inorganic components containing trace elements. It was shown that decreased renal function is accompanied by insufficient antioxidant systems and/or increased free oxygen radicals. In this study, we aimed to investigate the effects of HD on trace element levels and oxidative stress markers. METHODS: We included 111 CRF patients on HD treatment three times a week and 24 healthy controls. Patients were divided into four groups according to HD duration. Plasma malondialdehyde (MDA), protein carbonyls and total sulfhydryl (-SH) levels, zinc (Zn), copper (Cu), and magnesium (Mg) levels, and erythrocyte superoxide dismutase (SOD) activity were measured from blood taken from patients before HD. RESULTS: SH levels and SOD activity in all groups were significantly lower than those in the control group (p < 0.001). All groups had significantly higher plasma MDA levels than did controls (p < 0.001). Whereas there was no significant difference in -SH levels and SOD activity between groups, increased periods of HD were associated with increases in MDA. MDA levels of the third and fourth groups were significantly higher than in the first and second groups (p < 0.05, p < 0.001, respectively). There was no significant difference of Zn, Cu, Mg, and protein carbonyl levels in and between all groups. However, plasma Cu levels and MDA concentrations were correlated (r = 0.26, p < 0.01). CONCLUSION: Prolonged exposure to HD can cause increased oxidative damage but has no effect on trace element concentration.

Protective effects of leptin on ischemia/reperfusion injury in rat bladder.

The aim of the study was to evaluate protective effects of exogenous leptin on ischemia/reperfusion (I/R)-induced injuries to the urinary bladder tissue and to investigate the effect on tumor necrosis factor alpha (TNF-alpha) levels and apoptotic cells during I/R injury. Bladder I/R injury was induced by abdominal aorta occlusion by ischemia for 45 min, followed by 60 min of reperfusion in rats. The rats were divided into three groups: control (n = 8 + 8), I/R (n = 8 + 8) and I/R+leptin group (n = 8 + 8). The rats in the I/R+leptin group were treated intraperitoneally with leptin (10 microg/kg) 60 min prior to ischemia induction. At the end of the reperfusion period, urinary bladders of the first eight rats from each group were removed for TUNEL staining processing while the others were removed for biochemical analyses for MDA and TNF-alpha levels. In the I/R group, the ratios of TUNEL-positive nuclei were higher than the control and the I/R+leptin groups. The MDA and TNF-alpha levels of the bladder tissue in the I/R group were higher than the control and leptin-treated groups. TUNEL-staining and biochemical studies revealed that leptin has a protective effect on urinary bladder I/R injury.

Effects of doxycycline on intestinal ischemia reperfusion injury induced by abdominal compartment syndrome in a rat model.

BACKGROUND: Abdominal compartment syndrome (ACS) refers to organ dysfunction and ischemia resulting from intra-abdominal hypertension (IAH). Ischemia of the gut results in the triggering of a systemic inflammatory response by releasing cytokines which, in turn, causes capillary leakage leading to bowel edema, further increasing intra-abdominal pressure and resulting in a morbid cycle of ischemia and edema. OBJECTIVE: The aim of this study was to determine the effects of doxycycline on intestinal ischemia reperfusion (I/R) injury in a rat model of ACS. METHODS: Sprague-Dawley rats were divided into 5 equal groups. In groups 1 and 2, saline (1 cc IP) was administered during induction of ACS and intestinal samples were removed at 1 and 24 hours, respectively, after decompression. In groups 3 and 4, doxycycline (10 mg/kg IP) was injected during induction of ACS and, similarly, intestinal samples were removed at 1 and 24 hours after decompression. In the control group (group 5), intestinal samples were collected without induction of ACS. Malon-dialdehyde (MDA), interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinase-1 were studied and the apoptotic cells were enumerated histopathologically. Apoptosis and ß-cell lymphoma 2 (ßcl-2) expression were assessed immunohistochemically. RESULTS: Thirty-five rats were evenly divided into 5 groups of 7 rats each. MDA, IL-1ß, IL-6, TNF-α, and MMP-2 levels were significantly higher in group 1 one hour after the reperfusion period compared with the control group (P < 0.001, P < 0.001, P < 0.05, P < 0.001, and P < 0.01, respectively). The same parameters were significantly lower in group 3, in which doxycycline was administered, than in group 1 (P < 0.001, P < 0.05, P < 0.05, P < 0.001, and P < 0.01, respectively). However, there was no significant difference between groups 2 and 4 in the 24th hour (all, P > 0.05). The mean (SD) number of apoptotic cells and the expression of ßcl-2 was highest in group 2 at 24 hours after the reperfusion period (92.5 [11.4] and 35.9 [5.0], respectively) and significantly greater than that in group 4 (P < 0.001 and P < 0.05, respectively). CONCLUSION: Doxycycline was associated with protective effects against I/R injury through decreasing apoptosis via attenuating the response of proinflammatory cytokines and inhibiting the activity of MMP-2 in this rat model.

Increased serum osteoprotegerin levels associated with decreased bone mineral density in familial Mediterranean fever.

Familial Mediterranean fever (FMF) has episodic or subclinical inflammation that may lead to a decrease in bone mineral density (BMD). The aim of this study was to evaluate the effect of FMF on bone metabolism and to investigate the factors that can influence bone metabolism, such as body mass index (BMI), mutations in Mediterranean fever (MEFV) gene, osteoprotegerin (OPG), leptin and inflammatory cytokines, including interleukin (IL)-1beta, IL-6 and tumor necrosis factor-alpha (TNF-alpha). OPG, a soluble protein produced by osteoblasts, favors increased bone mass. Leptin may influence bone metabolism by acting on differentiated osteoblasts, having anabolic effects on bone. Thirty-one FMF patients in attack-free period (12 females and 19 males; mean age 31.4 +/- 9.3 years) and 18 healthy controls (11 females and 7 males; mean age 34.6 +/- 9.5 years) were compared according to the above parameters. BMD (g/cm(2)) and standard deviation scores (Z-score) were measured at the lumbar spine L(1)-L(4) (BMD-L(1-4)) and proximal femur by dual X-ray absorptiometry. Osteopenia is defined as a Z-score between -1 and -2.5 and osteoporosis is equal or below -2.5. FMF patients showed statistically significant reduction in BMD-L(1-4) and Z-score-L(1-4). Moreover, serum OPG concentration was significantly elevated in FMF patients. In contrast, MEFV gene mutations, leptin and the inflammatory cytokines did not differ between the patient and control groups. In conclusion, BMD was decreased and OPG was increased in our FMF patients. The high OPG levels may reflect a preventive mechanism against bone loss; namely, OPG might protect the FMF patients from excessive osteoporosis.

Evaluation of adiponectin and leptin levels and oxidative stress in bipolar disorder patients with metabolic syndrome treated by valproic acid.

INTRODUCTION: An increased risk for metabolic syndrome (MS) has been described for people with psychotic and mood disorders. The aim of this study was to determine the influence of valproic acid (VPA) treatment on adiponectin, leptin levels and oxidative stress in bipolar disorder (BD). METHODS: Forty patients with BD receiving VPA monotherapy and 20 healthy control subjects were included in this study. BD patients were divided into two groups with and without MS as group 1 and group 2, respectively. Twenty BD patients diagnosed according to the Diagnostic and Statistical Manual for Mental Disorders (DSM IV) were assessed for MS according to the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP III) criteria. Adiponectin, leptin, protein carbonyls, sulfhydryl (-SH) and malondialdehyde (MDA) levels were measured in 40 BD patients and 20 control subjects. RESULTS: Serum adiponectin levels were significantly lower in group 1 patients than in group 2 and control subjects ( p<.001). Serum leptin levels were significantly higher in group 1 patients than in group 2 and control subjects ( p<.001). Serum -SH levels were significantly lower in group 2 patients than in group 1 ( p<.001) and control subjects ( p<.05). Serum carbonyl levels were significantly higher in group 1 and group 2 patients than in control subjects ( p<.001). Serum MDA levels were significantly higher in group 1 patients than in group 2 and control subjects ( p<.001). CONCLUSION: These results provide further evidence that VPA treatment for patients with BD contributed to the metabolic disturbances, such as the decreased serum adiponectin and -SH levels, as well as the increased serum leptin, MDA and carbonyl levels.

Role of Uremic Toxins on Apoptosis With Varying Periods of Hemodialysis.

Increased apoptotic cell death in uremic patients has been confirmed by a variety of studies. The present study aimed to investigate the effect of uremic toxins and duration of hemodialysis (HD) therapy on apoptosis by means of measuring serum caspase cleaved CK18 (CCCK-18) levels. Seventy chronic HD patients were recruited and divided into three groups with differing periods of HD, from 6 months to 10 years. Twelve healthy subjects served as controls. Serum CCCK-18 level was found significantly higher in HD patient groups (Group 2; 189 ± 71 IU/L, Group 3; 182 ± 65 IU/L, Group 4; 204 ± 111 IU/L) as compared to the control group (122 ± 20 U/L) (P < 0.05). When all hemodialysis patients considered together serum CCCK-18 showed positive correlation with serum uric acid and phosphorus (P < 0.05). In conclusion, our results suggest that apoptosis is enhanced in HD patients, phosphorus and uric acid might play a role in this increment, but duration of HD therapy has no effect on apoptosis.

Effect of lung ischemia--reperfusion on oxidative stress parameters of remote tissues.

OBJECTIVE: Ischemia-reperfusion injury induces a systemic inflammatory response and production of reactive oxygen species, which potentially can be more detrimental than its local effects. Although the lung injury that is formed by the effects of ischemia-reperfusion injury on remote organs has been previously studied, no previous study that investigated the effects of pulmonary ischemia-reperfusion injury on remote organs has been considered. We hypothesized that the lung ischemia-reperfusion injury may cause the spread of inflammation to remote organs such as liver and heart. METHODS: Thirty New Zealand white rabbits were subjected to either sham operation or lung ischemia-reperfusion injury in various periods of time (60 min ischemia-60 min reperfusion and 120 min ischemia-60 min reperfusion, respectively). Pulmonary, myocardial and hepatic myeloperoxidase, protein sulfhydryl, thiobarbituric acid-reactive substances, and protein carbonyl levels were evaluated to show pulmonary, hepatic, and myocardial responses to lung ischemia-reperfusion injury. RESULTS: Reperfusion after 60 min of lung ischemia led to increased myeloperoxidase and protein carbonyl levels and decreased protein sulfhydryl groups in pulmonary tissue, increased myeloperoxidase and decreased protein sulfhydryl groups in hepatic tissue, and increased myeloperoxidase, thiobarbituric acid-reactive substances and protein carbonyl levels in myocardial tissue. Reperfusion after 120 min of lung ischemia led to increased thiobarbituric acid-reactive substance levels in pulmonary tissue, increased protein carbonyl and thiobarbituric acid-reactive substance levels in hepatic tissue, and decreased protein sulfhydryl groups in myocardial tissue. CONCLUSIONS: The data of the present study suggests that pulmonary ischemia-reperfusion induces liver and heart injury characterized by activated neutrophil sequestration and release of significant amounts of reactive oxygen species. The remote organ injury has to be kept in mind when performing a lung intervention or surgery and care should be taken to protect other organs remote from ischemia-reperfusion site.

Expression of cathepsin D in bladder carcinoma: correlation with pathological features and serum cystatin C levels.

AIMS AND BACKGROUND: The aim of this study is to evaluate the expression of cathepsin D in primary bladder cancer and to determine its relationship with conventional pathological features and serum cystatin C levels. METHODS: The immunohistochemical cathepsin D expression and staining patterns of epithelial and stromal cells were investigated in 21 patients with primary bladder carcinoma. Serum cystatin C levels were determined by immunoturbidimetry and compared with matched controls. RESULTS: There were 7 papillary neoplasms of low malignant potential, 7 low-grade and 7 high-grade carcinomas. Six tumors were invasive. Statistical analysis showed a significant inverse relationship between cathepsin D expression of the tumor cells and tumor grade and stage (P = 0.018 and P = 0.046, respectively). Serum cystatin C levels of the controls and patients varied between 0.39 mg/L and 1.99 mg/L (P > 0.05). There was no significant relation between cathepsin D expression in tumor tissue and serum cystatin C levels. CONCLUSIONS: Loss of cathepsin D expression in bladder carcinomas may be associated with high-grade and invasive tumors. Thus, increased cathepsin D expression by tumor cells may be related to local tumor invasion at an early stage, but it seems that extracellular cystatin C is not affected by cathepsin D expression of tumor or stromal cells, and cystatin C concentrations are not directly correlated with the progression of primary bladder carcinomas.

Effects of N-acetylcysteine on the lung histopathology and oxidant-antioxidant status in rabbits exposed to cigarette smoke.

We aimed to evaluate the effects of smoking on the histopathology and the oxidant-antioxidant status of lungs and to test the effects of N-acetylcysteine (NAC) on the induced changes. Rabbits were exposed to cigarette smoke (CS) in a glass chamber for one hour daily for one month. An NAC control group was given intraperitoneal NAC only. CS + NAC rats were exposed to smoke and given intraperitoneal NAC. A control group was exposed to clean air only. At the end of one month, animals were sacrificed and lung tissues were examined histopathologically. Blood levels of protein sulfhydryls, carbonyls, prostaglandin F(2alpha) (PGF(2alpha)) and malondialdehyde (MDA) were measured. Intraparenchymal vascular congestion and thrombosis, intraparenchymal hemorrhage, respiratory epithelial proliferation, number of macrophages in the alveolar and bronchial lumen, alveolar destruction, emphysematous changes and bronchoalveolar hemorrhage scores were significantly increased in rabbits exposed to CS compared with the control group. Protein sulfhydryls were significantly decreased; carbonyls, PGF(2alpha) and MDA levels were significantly increased in the smoke exposed rabbits. Administration of NAC to rabbits exposed to CS caused a reduction in the bronchoalveolar hemorrhage score and blood PGF(2alpha) levels. Other parameters were unaffected by NAC. Exposure to CS causes severe histopathological changes and negatively effects the oxidant-antioxidant status in the lungs of rabbits. A low daily dose of NAC has some ameliorative effects on histopathological changes and oxidant-antioxidant status of the lungs in smoke exposed rabbits.