Trimetazidine has protective effects on spermatogenesis in a streptozotocin-induced diabetic rat model.

The aim of this study was to investigate the protective effects of trimetazidine (TMZ), as an antioxidant agent, on streptozotocin (STZ)-induced diabetic rats. A total of 50 male Sprague Dawley rats were randomly classified into five groups as follows: Group 1 (control), Group 2 (STZ-induced diabetic rats), Group 3 (STZ-induced diabetic rats treated orally with 1 cc/day isotonic saline), Group 4 (diabetic rats treated orally with 10 mg/kg/day TMZ) and Group 5 (diabetic rats treated orally with 20 mg/kg/day TMZ). After 8 weeks, orchiectomy was carried out. Histopathological and electron microscopic examinations were performed in all groups. In groups 1 and 5, the structural and ultra-structural findings of the testicular tissue and spermatogenesis were found normal. In groups 2, 3 and 4, similar results were obtained in terms of the impaired testicular architecture and degeneration of spermatogenesis. The administration of an optimal dose of TMZ protects against the harmful effects of diabetes mellitus on spermatogenesis in rats. TMZ therapy can be used to maintain normal spermatogenesis in diabetic rats.

Protective effect of curcumin on ovarian reserve in a rat ischemia model: an experimental study.

PURPOSE OF INVESTIGATION: To determine the protective effect of curcumin on ovarian reserve in a rat ischemia model. MATERIALS AND METHODS: Thirty female Albino rats were randomly divided into two groups by time of unilateral, left ovary ischemia/reperfusion (group 1: two-hour ischemia / two-hour reperfusion; group 2: four-hour ischemia / four-hour reperfusion). Each group was subdivided into three subgroups, sham, control, and curcumin (intraperitoneal curcumin (200 mg/kg) simultaneously with reperfusion). Histological grading of ischemic indices of paraffin-embedded ovarian tissue using hematoxylin and eosin (H&E), and anti-Mulerian hormone (AMH) levels by enzyme-linked immunosorbent assay (ELISA), were measured 40 days later. RESULTS: No difference was found between groups 1 and 2 or among subgroups within either group for right and left ovary grades. AMH levels were significantly higher in the curcumin subgroup compared to sham and control within group 2 and in group 2 versus group 1 curcumin subgroups. CONCLUSION: Curcumin maintains and protects ovarian functions in an ischemia-reperfusion rat model.

Ultrastructural view of a promising anti TNF-α agent on hepatic ischaemia reperfusion injury.

BACKGROUND: Ischemia reperfusion causes injury to the liver cells during transplantation, trauma and emergency surgery. We investigated whether the anti TNF-α agent, etanercept, can reduce injury in an animal model of ischemia reperfusion owing to the fact that TNF-α plays a critical role in the process of inflammation. MATERIALS AND METHODS: Thirty rats were divided into three groups: sham (Group 1), control (Group 2), etanercept (5 mg/kg) treatment (Group 3). Ischemia-reperfusion model was carried out by clamping the hepatic pedicle for 45 min and then reperfusing the liver for 60 min. Etanercept (5 mg/kg) was injected intraperitoneally 5 min prior to reperfusion. At the end of the procedures, blood and liver tissue samples were obtained for biochemical and histopathological assessment. RESULTS: Control and treatment groups showed significant differences in hepatic function tests, plasma and tissue oxidative stress parameters. Samples in the control group histopathologically showed morphologic abnormalities specific to ischemia reperfusion. Histomorphologic findings in the treatment groups showed similar features as the sham group. CONCLUSIONS: Our evidence suggests that TNF-α plays a key role in liver ischemia reperfusion injury and etanercept may provide a novel therapeutic approach for patients undergoing liver surgical procedure (Tab. 3, Fig. 4, Ref. 22).

Increased serum levels of GDF-15 associated with mortality and subclinical atherosclerosis in patients on maintenance hemodialysis.

BACKGROUND/AIMS: Increased carotid intima-media thickness (CIMT) was shown to be an independent predictor of cardiovascular (CV) mortality in dialysis patients and the general population. Growth differentiation factor 15 (GDF-15), a member of the transforming growth factor superfamily, is produced by cardiomyocytes and atherosclerotic lesions under stress conditions such as inflammation. We assessed associations between serum concentrations of GDF-15, mortality, and CIMT for subclinical atherosclerosis in hemodialysis (HD) patients. METHODS: A total of 87 patients on maintenance hemodialysis and 45 sex- and age-matched healthy controls were included in this prospective study. Serum GDF-15 levels were measured by ELISA. CIMT was assessed by Doppler ultrasonography. The association between serum GDF-15 levels and mortality was assessed using Cox regression analysis with serum levels categorized into two groups according to the median value (328.18 pg/ml). Patients were followed for 2 years and cause-specific and all-cause mortality were determined. RESULTS: The median level of serum GDF-15 was significantly higher in HD patients than controls [328 (198-522) vs. 176 (101-289) pg/ml, p < 0.01, respectively]. Serum GDF-15 levels were correlated to CIMT (r = 0.607, p < 0.001), C-reactive protein (CRP; r = 0.250, p = 0.010), HD duration (r = 0.376, p = 0.004), and serum albumin (r = - 0.156, p = 0.030). The multivariate analysis revealed that GDF-15 was found to be an independent variable of CIMT in HD patients. In the study, the serum GDF-15 level was an independent marker of all-cause of mortality when adjusted for age, CRP, and history of diabetes mellitus. CONCLUSION: The relationship between serum GDF-15, mortality, and carotid artery thickening suggests that GDF-15 may be a novel marker of atherosclerosis, inflammation, and malnutrition in HD patients.

The coexistence of renal cell carcinoma and diffuse large B-cell lymphoma with hypercalcemic crisis as the initial presentation.

INTRODUCTOIN: Severe hypercalcemia can be life threatening. The causes of hypercalcemia can be divided into seven categories: hyperparathyroidism, vitamin D-related causes, malignancy, medications, other endocrine disorders, genetic disorders, and miscellaneous causes. Evaluation of a patient with hypercalcemia should include a careful history and physical examination focusing on clinical manifestations of hypercalcemia, risk factors for malignancy, causative medications, and a family history of hypercalcemia-associated conditions (e.g. kidney stones). Hypercalcemia was clasified as serum levels of calcium: 1) mild hypercalcemia (calcium 14 mg/dl). We should keep in mind that severe hypercalcemia was originated from two or more causes. This is the first report in the literature; renal cell carcinoma (RCC) and diffuse large B-cell lymphoma (DLBCL) presented severe paraneoplastic hypercalcemia. CASE PRESENTATION: We report a case of a 63-year-old Turkish man with RCC and DLBCL who showed severe hypercalcemia (calcium=15.01 mg/dl) accompanied by elevation of serum parathyroid hormone-related protein (PTH-rP) as the initial presentation. While hypercalcemia is one of the complications of various types of cancerous diseases, it has not been reported still as the first presentation of the coexistence of RCC and DLBCL. After radical nephrectomy, the patient underwent six courses of chemotherapy consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone and achieved a complete remission that lasts 2 years. CONLUSION: This case report describes a patient with two different malignancies (RCC and DLBCL) with the unusual presentation of hypercalcemia. We review the differential diagnosis and treatment of malignant hypercalcemia. We suggest that coexistence of DLBCL with RCC, although rare, should be considered as a possible causative in hypercalcemia of unknown underlying disease.

Elevated level of serum osteopontin in school-age children with asthma

BACKGROUND: The role of osteopontin (OPN) has not been elucidated in childhood asthma. OBJECTIVE: Our purpose was to investigate whether OPN levels change due to allergic inflammation in pre-school and school-age children. METHODS: In this prospective, cross-sectional study, 42 healthy children and a total of 51 children with asthma were recruited. OPN levels and its association with clinical and laboratory parameters were investigated in the study population. The asthma group were divided into two groups with respect to age, ≤5-years (n = 23) and >5-years (n = 28), and labelled Asthma Group 1 and Asthma Group 2, respectively. OPN levels were compared between subgroups. RESULTS: Serum OPN levels were significantly higher in the asthma group when compared to the control group (p = 0.004). OPN levels were similar in Asthma Group 1 and control groups, whereas it was found to be higher in Asthma Group 2 (p > 0.025, p = 0.001, respectively). In the >5-years age asthmatic group, OPN levels of the patients with allergic rhinitis (n = 15) were higher than those of the patients (n = 13) without allergic rhinitis (p = 0.021). CONCLUSION: The study underscores the relationship between childhood asthma and OPN as the first study in the literature. In this study we found that OPN, which plays a role in Th2 mediated inflammation, may also play a role in childhood asthma. The fact that OPN levels do not increase in preschool-age children with asthma might be due to the transient wheezing in this group

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Effects of aqueous soybean, mistletoe and red clover extracts on activities of adenosine deaminase and xanthine oxidase enzyme.

Soybean (Glycine max), mistletoe (Viscum album) and red clover (Trifolium pratence) have been argued to have anti-cancer effects. In the present study it was aimed to investigate possible effects of these plant extracts on the activities of DNA turn-over enzymes, namely adenosine deaminase (ADA) and xanthine oxidase (XO) in cancerous and non-cancerous gastric and colon tissues. For this aim, 6 cancerous and 6 non-cancerous adjacent human gastric tissues, and 7 cancerous and 7 non-cancerous adjacent colon tissues were obtained by surgical operations. Our results suggest that aqueous soybean, mistletoe and red clover extracts may exhibit anti-tumoral activity by depleting hypoxanthine concentration in the cancer cells through XO activation, which may lead to lowered salvage pathway activity necessary for the cancer cells to proliferate in the cancerous colon tissue. Some foods like soybean, mistletoe and red clover may provide nutritional support to medical cancer therapy through inhibiting and/or activating key enzymes in cancer metabolism (Tab. 4, Ref. 33).

Neutrophil-lymphocyte ratio may be superior to C-reactive protein for predicting the occurrence of postmenopausal osteoporosis.

OBJECTIVE: Recent studies revealed that inflammation plays a critical role in bone remodeling and the pathogenesis of postmenopausal osteoporosis, a major health concern. Neutrophil-lymphocyte ratio (NLR) is a cost-effective marker of inflammation that has been linked with several diseases. This study aimed to compare NLR and C-reactive protein (CRP) levels in osteopenic, osteoporotic, and control subjects and to assess the correlation between NLR levels, CRP, and bone mineral density (BMD) in postmenopausal women. METHODS: In this cross-sectional study, the relationship between NLR, CRP, and BMD in 438 women was investigated using uni- and multivariate analyses. BMD (g/cm²) was measured by dual-energy X-ray absorptiometry (DEXA) at the lumbar spine and femur. Complete blood count (CBC), CRP, glucose/lipid metabolism, and established risk factors were determined. RESULTS: In the osteoporotic group, NLR and CRP levels were found to be elevated as compared to the osteopenic and control groups (NLR: 4.68 ± 0.72, 3.17 ± 0.43, 2.01 ± 0.54; CRP: 12.3 ± 4.1, 4.1 ± 2.7, 3.2 ± 2.1, respectively). A negative correlation was present between NLR and the lumbar spine (L2-L4) and femoral neck BMD after adjusting other risk factors. There was no correlation between CRP levels and BMD after adjusting other risk factors. NLR was significantly associated with L2-L4 BMD (ß = -0.653, p<0.001) and femoral neck BMD (ß = -0.178, p<0.001), but CRP level had no association with BMD in a multivariate model. CONCLUSIONS: Our data indicate that NLR may be a better predictor than CRP for occurrence of osteoporosis in postmenopausal women.

Serum galectin-3 levels in women with PCOS.

AIM: Galectin-3 (Gal-3) plays a role in modulation of adiposity, glucose hemostasis and inflammation. The association between Gal-3 and the polycystic ovary syndrome (PCOS), is not investigated. We aimed to evaluate galectin-3 levels in serum and their relation with hyperandrogenism and insulin resistance (IR) in women with polycystic ovary syndrome (PCOS) and in control subjects. MATERIALS AND METHODS: 56 women with PCOS were enrolled along with a control group of 41 healthy women, matched for age and body mass index. We measured hormonal and metabolic parameters, as well as the serum galectin-3 concentration of each participant. We estimated the IR according to the homeostasis model assessment-insulin resistance (HOMA-IR). RESULTS: Women with PCOS had higher levels of serum Gal-3 compared to healthy individuals (3,588.77 ± 1,566.94 vs 2,491.33 ± 812.04, P < 0.001). Serum Gal-3 levels were correlated with progesterone (r = 0.241, P = 0.025), hirsutism score (r = 0.296, P = 0.006), insulin (r = 0.479, P = 0.028), HOMA-IR (r = 0.514, P = 0.017), dehydroepiandrosterone sulfate (r = 0.246, P = 0.022), testosterone (r = 0.252, P = 0.019), and free testosterone (r = 0.306, P = 0.004). CONCLUSION: Galectin-3 levels are higher in patients with PCOS, and there is a positive correlation between galectin-3 level and IR, androgen levels and hirsutismus scores. Gal-3 may be a new mediator of PCOS via IR, hyperandrogenism.

Benefits of the neutrophil-to-lymphocyte ratio for the prediction of gestational diabetes mellitus in pregnant women.

AIMS: There is growing consensus in the literature that inflammation plays a central role in the pathophysiology of obesity, Type 2 Diabetes Mellitus (T2DM), Gestational Diabetes Mellitus (GDM) and cardiovascular complications. Measuring the neutrophil-to-lymphocyte ratio (NLR) provides a simple inexpensive method for the assessment of inflammatory status. We investigated the predictive value of pre-procedural (before the oral glucose tolerance test (OGTT)) NLR on the development of GDM in pregnancy. METHODS: 42 women with GDM and 68 women without GDM were included in the study. Complete Blood Count and biochemical tests were followed by a diagnostic 4-point 100-g-OGTT within 2 weeks. GDM was diagnosed by the Carpenter and Coustan criteria. The NLR was calculated from the data. RESULTS: The mean NLR level was significantly higher in GDM women (3.00±0.83 vs. 2.26±0.43 p<0.001, respectively). In ROC analysis, NLR>2.93 had 76.2% sensitivity and 94.1% specificity in predicting GDM. Logistic regression analysis showed that elevated NLR (OR: 5.512, 95% CI: 1.352-22.475, p=0.017) was an independent variable for predicting GDM in pregnancy. CONCLUSIONS: An elevated NLR level is a powerful and independent predictor of GDM. The results of this study suggested that inflammation plays a central role in the pathogenesis of GDM.

Elevated level of serum osteopontin in school-age children with asthma.

BACKGROUND: The role of osteopontin (OPN) has not been elucidated in childhood asthma. OBJECTIVE: Our purpose was to investigate whether OPN levels change due to allergic inflammation in pre-school and school-age children. METHODS: In this prospective, cross-sectional study, 42 healthy children and a total of 51 children with asthma were recruited. OPN levels and its association with clinical and laboratory parameters were investigated in the study population. The asthma group were divided into two groups with respect to age, ≤ 5-years (n = 23) and >5-years (n = 28), and labelled Asthma Group 1 and Asthma Group 2, respectively. OPN levels were compared between subgroups. RESULTS: Serum OPN levels were significantly higher in the asthma group when compared to the control group (p = 0.004). OPN levels were similar in Asthma Group 1 and control groups, whereas it was found to be higher in Asthma Group 2 (p>0.025, p = 0.001, respectively). In the >5-years age asthmatic group, OPN levels of the patients with allergic rhinitis (n = 15) were higher than those of the patients (n=13) without allergic rhinitis (p = 0.021). CONCLUSION: The study underscores the relationship between childhood asthma and OPN as the first study in the literature. In this study we found that OPN, which plays a role in Th2 mediated inflammation, may also play a role in childhood asthma. The fact that OPN levels do not increase in preschool-age children with asthma might be due to the transient wheezing in this group.

Nitric oxide metabolism in cancerous and non-cancerous oral gingivomucosal tissues: possible implications of nitric oxide in cancer process.

PURPOSE: Nitric oxide (NO) is a molecule that plays various roles in the body tissues. NO plays important roles in vasodilatation, platelet aggregation, cytokine stimulation, neurotransmission, immune function, etc. NO also exerts dual functions as an oxidant and antioxidant substance depending on its concentrations and environmental conditions. In this study, we aimed to examine possible correlation between NO levels and NO synthase (NOS) activity in the patients with oral cancer. MATERIALS AND METHODS: The study included 19 tissues from human subjects (11 malign and eight benign lesions). RESULTS: NO level and NOS activity were found decreased in the malign lesions compared with those of the benign ones. CONCLUSIONS: In conclusion, two suggestions can be made; first, decreased NO synthesis may be an attempt to suppress angiogenesis, which is known to provide more essential nutrients to malign lesions and/or second, malign lesions may suppress NO production to be capable of creating more rapid proliferation as it has been known that NO is also a powerful free radical inducing apoptosis.