Mustafa Ulas

Regulation of renal organic anion and cation transporters by thymoquinone in cisplatin induced kidney injury.

In previous studies, we have demonstrated the biological activity of thymoquinone (TQ), an active compound extracted from the Nigella sativa plant, against cisplatin-induced neurotoxicity. Recenty, it was observed that there is an inherent lack in regulation of renal organic anion and cation transporters in cisplatin-induced nephrotoxicity. Here, we report, for the first time, the effect of TQ on alterations in the renal expression of organic anion transporters (OATs) and organic cation transporters (OCTs), as well as multidrug resistance-associated proteins (MRPs) in rats treated with cisplatin. Twenty-eight 8-week-old male Wistar rats were divided into four groups of control, TQ treated (10 mg/kg b.w. in drinking water for 5 days), cisplatin (7 mg/kg b.w., i.p.) and TQ and cisplatin combination treatment. Cisplatin-induced malondialdehyde (MDA) and 8-isoprostane increase was found to be markedly reduced in rats treated with TQ. In cisplatin only treated rats, the induced renal injury increased protein levels of the efflux transporters MRP2 and MRP4 while expression of OAT1, OAT3, OCT1 and OCT2 was reduced. In combination TQ- and cisplatin-treated rats, expression of MRP2 and MRP4 proteins was decreased in the kidneys. Conversely, TQ treatment increased levels of OCT1, OCT2, OAT1 and OAT3 and decreased levels of 8-isoprostane and MDA levels in cisplatin-treated rats. In conclusion, the present study shows that the TQ synergizes with its nephroprotective effect against cisplatin-induced acute kidney injury in rats.

Maternal and fetal adropin levels in gestational diabetes mellitus

Abstract Aim: To evaluate maternal and cord blood serum adropin concentrations in pregnant women with gestational diabetes mellitus (GDM). Study design: Twenty pregnant women with GDM and 20 gestational age-matched healthy pregnant women participated in the study. Maternal serum and cord blood adropin levels were assessed using an enzyme immunosorbent assay, at the time of birth. The relation of maternal serum and cord blood adropin levels with metabolic parameters were also assessed. Results: The mean maternal and cord serum adropin in the GDM group were significantly lower than those of the control women (P=0.01 and P<0.001, respectively). Maternal serum adropin levels did not correlate with either fetal serum adropin levels or maternal metabolic values. Conclusion: The data suggest that low adropin levels may contribute to the underlying pathogenesis of GDM.

Assessment of imidacloprid toxicity on reproductive organ system of adult male rats.

In the current study it was aimed to investigate the toxicity of low doses of imidacloprid (IMI) on the reproductive organ systems of adult male rats. The treatment groups received 0.5 (IMI-0.5), 2 (IMI-2) or 8 mg IMI/kg body weight by oral gavage (IMI-8) for three months. The deterioration in sperm motility in IMI-8 group and epidydimal sperm concentration in IMI-2 and IMI-8 groups and abnormality in sperm morphology in IMI-8 were significant. The levels of testosterone (T) and GSH decreased significantly in group IMI-8 compared to the control group. Upon treatment with IMI, apoptotic index increased significantly only in germ cells of the seminiferous tubules of IMI-8 group when compared to control. Fragmentation was striking in the seminal DNA from the IMI-8 group, but it was much less obvious in the IMI-2 one. IMI exposure resulted in elevation of all fatty acids analyzed, but the increases were significant only in stearic, oleic, linoleic and arachidonic acids. The ratios of 20:4/20:3 and 20:4/18:2 were decreased and 16:1n-9/16:0 ratio was increased. In conclusion, the present animal experiments revealed that the treatment with IMI at NOAEL dose-levels caused deterioration in sperm parameters, decreased T level, increased apoptosis of germ cells, seminal DNA fragmentation, the depletion of antioxidants and change in disturbance of fatty acid composition. All these changes indicate the suppression of testicular function.

Concentrations of preptin, salusins and hepcidins in plasma and milk of lactating women with or without gestational diabetes mellitus

This study was undertaken to ascertain whether human milk contains preptin, salusin-alpha (salusin-α) and -beta (salusin-β) and pro-hepcidin and hepcidin-25, and whether there are relationships between plasma and milk preptin, salusin-α and -β and pro-hepcidin and hepcidin-25 concentrations in lactating mothers with and without gestational diabetes mellitus (GDM). Blood was obtained from non-lactating women (n = 12), non-diabetic lactating women (n = 12), and GDM lactating women (n = 12). Colostrum, transitional milk, and mature milk samples were collected just before suckling from healthy and GDM lactating women. Peptides concentrations were determined by ELISA and EIA. Mammary gland tissues were screened immunohistochemically for these peptides. Women with GDM had significantly higher plasma and colostum preptin concentrations than healthy lactating women during the colostral and transitional milk period. Salusin-alpha and -beta levels in milk and plasma were lower in women with GDM. Salusin-α and -β were significantly lower in both plasma and colostrums of GDM than of healthy lactating women. Women with GDM had significantly higher colostum prohepcidin and hepcidin-25 concentrations than healthy lactating women during the colostral period. Plasma prohepcidin was also higher in women with GDM than in healthy lactating women during the colostral period, but plasma prohepcidin and hepcidin-25 levels decreased during mature milk period. Transitional milk pro-hepcidin and hepcidin-25 levels in women with GDM were higher than in healthy lactating women. All these results revealed that the mammary gland produces those peptides, which were present in milk at levels correlating with plasma concentrations.

Surgical Removal of Endometrioma Decreases the NF-kB1 (p50/105) and NF-kB p65 (Rel A) Expression in the Eutopic Endometrium During the Implantation Window

We aimed to investigate whether the surgical removal of endometrioma alters the nuclear factor-kappa B1 (NF-kB1; p50/105) and NF-kB p65 (Rel A) expression in the eutopic endometrium of infertile women with endometrioma before and after laparoscopic removal of the ovarian endometrioma during the mid-secretory phase. Infertile women with endometrioma (n = 15) were enrolled. Infertile patients with nonendometriotic ovarian cyst (n = 10) and healthy fertile women (n = 10) were recruited as controls. Endometrial samples were obtained before and 3 months after the laparoscopic cystectomy. The NF-kB1 (p50/105) levels were analyzed by enzyme-linked immunosorbent assay (ELISA) in the endometrium of all groups before and after laparoscopic ovarian cystectomy during implantation window. Expression of NF-kB1 (p50/105) in eutopic endometrium was significantly higher in infertile women with endometrioma compared to nonendometriotic cyst and fertile controls (P < .05). Laparoscopic cystectomy resulted in a significant decrease in NF-kB1 expression in women with endometrioma. The NF-kB p65 (Rel A) immunoreactivity of eutopic endometrium decreased significantly subsequent to the surgical removal of the endometrioma. In conclusion, increased endometrial NF-kB expression may contribute to endometriosis-associated infertility.

A novel nutritional supplement containing chromium picolinate, phosphatidylserine, docosahexaenoic acid, and boron activates the antioxidant pathway Nrf2/HO-1 and protects the brain against oxidative stress in high-fat-fed rats

Abstract Aims A novel nutritional supplement complex (N21 #125) composed of four well-known compounds (chromium picolinate, phosphatidylserine, docosahexaenoic acid, and boron) was designed to improve memory function and maintain brain health. The present study evaluated the complexs potential mechanism of action and its role in reducing oxidative stress in the brain of obese rats fed a high-fat diet (HFD). Methods Male Wistar rats (n = 40, 8-week-old) were divided into four groups. Group I was fed a standard diet; Group II was fed a standard diet and supplemented with N21 #125; Group III was fed an HFD; and Group IV was fed an HFD and supplemented with N21 #125 for 12 weeks. Results Rats fed HFD had greater serum C-reactive protein (CRP) and tumor necrosis factor alpha (TNF-α) and brain malondialdehyde (MDA) concentrations than rats fed the control diet. Supplementation of N21 #125 decreased CRP, TNF-α, and MDA concentration in rats fed HFD. The levels of brain nuclear factor-E2-related factor-2 (Nrf2), heme oxygenase, extracellular signal-regulated kinases and protein kinase B were lower in rats fed the control diet than for rats fed the HFD. These parameters were increased by supplementation of N21 #125. Discussion The data indicate that N21 #125 protected the brain from oxidative damage and inflammation induced by the HFD. This effect may be through up-regulation of the transcription factor Nrf2 expression.

Hysteroscopic polypectomy decreases NF-κB1 expression in the mid-secretory endometrium of women with endometrial polyp

OBJECTIVES Endometrial polyps have been identified as a possible factor for sub-fertility, their implication on endometrial NF-κB1 activity; the central regulator of the immune system gene expression involved in implantation has yet been little studied. We evaluated the NF-κB1 level and NF-κB p65 expression in the endometrium before and after hysteroscopic removal of the endometrial polyp during the mid-secretory phase. STUDY DESIGN Infertile women with polyp (n=15) were enrolled. Unexplained infertile patients with normal endometrium (n=5) and healthy fertile women (n=5) were recruited as controls. Endometrial samples were obtained before and 4 months after the hysteroscopic polypectomy. NF-κB1 levels were analyzed by ELISA in the endometrium of all groups before and after polypectomy. The H-Score method was used to evaluate immunohistochemical NF-κB p65 expression in the endometrium. RESULTS NF-κB1 expression and NF-κB p65 immunoreactivity in the endometrium were significantly higher in women with polyp compared to unexplained infertile and fertile controls. Hysteroscopic polypectomy resulted in a significant decrease in endometrium NF-κB1 and NF-κB p65 activity. CONCLUSIONS Endometrium of women with endometrial polyp has abnormalities in expression of NF-κB1 and NF-κB p65 which may contribute to endometrial receptivity and so polyp related sub-fertility. Hysteroscopic polypectomy may help to the normalization of endometrial NF-κB concentrations.

Ghrelin action on GnRH neurons and pituitary gonadotropes might be mediated by GnIH-GPR147 system.

Abstract Acylated ghrelin (AG) effect on GnRH secretion is mediated, at least in part, by GH secreta-gogue receptor (GHS-R) which is present in the GnRH neurons. As the acylation is mandatory for binding to GHS-R, unacylated isoform of ghrelin (UAG) action on gonadotropin secretion is likely to be mediated by other receptors or mediators that have not been identified yet. UAG, therefore, may act partially via a GHS-R-independent mechanism and inhibitory impact of UAG on GnRH neurons may be executed via modulation of other neuronal networks. Ghrelin and gonadotropin inhibitory hormone (GnIH), two agonistic peptides, have been known as important regulators of reproductive events. Potential impact of ghrelin on the activity of GnIH neurons is not exactly known. Both GnIH and ghrelin are potent stimulators of food intake and inhibitors of gonadotropin release. By binding G-protein coupled GnIH receptor (GnIH-R), GPR147, which is located in the human gonadotropes and GnRh neurons, GnIH exerts an inhibitory effect on both GnRH neurons and the gonadotropes. The GnIH-GPR147 system receives information regarding the status of energy reservoir of body from circulating peptides and then transfers them to the kisspeptin-GnIH-GnRH network. Due to wide distribution of this network in brain GnIH neurons may project on ghrelin neurons in the arcuate nucleus and contribute to the regulation of UAG’s central effects or vice versa. Together, the unidentified ghrelin receptor in the hypothalamus and hypophysis may be GnIH-R. Therefore, it is reasonable that ghrelin may act on both hypothalamus and hypophysis via GnIH-GPR147 system to block gonadotropin synthesis and secretion.

PISTACIA TEREBINTHUS COFFEE PROTECTS AGAINST THIOACETAMIDE-INDUCED LIVER INJURY IN RATS

AIM/BACKGROUND Pistacia terebinthus is used as a coffee substitute in the East and Southern Anatolia regions of Turkey. It contains unsaturated fatty acids, tocopherols, polyphenols and carotenoids. P. terebinthus has anti-inflammatory and potential antioxidant activity. In this study we evaluated the protective effects of P. terebinthus coffee (PTC) on thioacetamide (TAA)-induced liver injury in rats. MATERIALS AND METHODS Twenty-eight male Sprague-Dawley rats were equally randomized into four groups. Chronic liver injury was induced with TAA (100 mg/kg i.p. three times weekly). The first group of rats served as control and received only tap water (G1), and the remaining groups of rats received PTC, p.o (G2); TAA (G3); TAA plus PTC, p.o (G4), respectively. RESULTS After 8 weeks, PTC intake significantly reduced fibrosis/inflammation scores (p PTC intake reduced transforming growth factor beta (TGF-β) concentrations in the liver (p PTC intake. DISCUSSION AND CONCLUSION PTC intake provided beneficial effects against TAA-induced liver injury in rats. PTC probably suppresses the proinflammatory cytokines through NF-κB signaling pathway.

The Use of Kernel-Based Extreme Learning Machine and Well-Known Classification Algorithms for Fall Detection

Fall is a common occurrence in older people and causes dangerous consequences. Therefore, the fall detection needs to be done quickly and efficiently. In our developed expert system, three different algorithms have been tried to find fall detection by classification method. Two of these algorithms are the widely used naive Bayesian and k-nearest neighbor algorithms for fall detection. The other used algorithm is kernel-based extreme learning machine algorithm. The main purpose of this study is to compare these three algorithms in detecting falls. As a result of the work, the kernel-based extreme learning machine algorithm has been shown to find the fall detection with better results than the k-nearest neighbor and naive Bayesian algorithms. The kernel-based extreme learning machine algorithm achieves a better F-measure value of 3.5% according to the k-nearest neighbor algorithm (k = 1), 1.8% according to the k-nearest neighbor algorithm (k = 5) and 6.6% according to the naive Bayesian algorithm.