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Hipofiz bezinin ön bölümü (adenohipofiz) vücudumuzdaki diğer iç salgı bezlerinin çalışmasını kontrol eden, 5-7 mm büyüklüğünde bir salgı bezidir. Adenohipofiz, çeşitli trofik hormonları salgılamak üzere farklılaşmış hücreler içerir. Bu hücrelerin çeşitli genetik, epigenetik ve çevresel faktörlerle etkileşimi sonucunda çoğunluğu iyi huylu olan hipofiz tümörleri (hipofiz adenomları) ortaya çıkabilir. Hipofiz adenomları arasında tanı ve tedavisi en zor olarak bilinen ACTH-salgılayan adenomlar böbreküstü bezini aşırı uyararak kontrolsüz miktarda kortizol salgılanmasına neden olur. Vücutta yol açtığı değişikliklere Cushing hastalığı adı verilir. Cushing hastalığının USP8, USP48, EGFR, p16, p21 gibi birçok farklı genin işlevinin kaybolmasına bağlı olarak ortaya çıktığı bilinmektedir. Bunun dışında ilgili genlerin metillenmesi ve asetillenmesi gibi çeşitli epigenetik modifikasyonlar ve miRNA’lar gibi çeşitli düzenleyicilere maruz kalması sonucunda da Cushing hastalığı görülmektedir. Bu genlerin ve proteinlerin işlevlerinin belirlenmesi sayesinde yeni tedavi stratejilerinin geliştirilmesi mümkün olacaktır.

The aim of this study is to examine the effect of replacing waste aluminum sawdust (AS) with fine aggregate on the strength and durability properties of concrete. For this, concrete mixtures with a cement dosage of 400 kg/m3 and water/cement (W/C) ratio of 0.40-0.50-0.60 were prepared. AS obtained from Elazig industrial site was added to the concrete mixtures by replacing 0%, 0.5% and 1% fine aggregate by volume. After curing in the curing pool for 28 days, the produced concrete samples were subjected to accelerated carbonation test in the carbonation tank at three different time periods the 1st, 3rd and 7th days. Compressive strength test and carbonation depth measurement test were performed on the samples before and after carbonation. In addition, the microstructure of AS concrete was investigated using scanning electron microscopic images (SEM). In the microscopic images, larger cracks, openings and interfacial voids were observed in the concrete matrix with the addition of AS. In addition, it has been observed that the carbonation effect contributes to the compressive strength.

Introduction Acromegaly is a chronic disease of increased growth hormone (GH) secretion and elevated insulin-like growth factor-I (IGF-I) levels induced by a pituitary adenoma. HMGA2 (high mobility group A2) and AIP (aryl hydrocarbon receptor-interacting protein) expression levels are related to GH-secreting adenomas, and also a response to Somatostatin Analogs (SSAs). We studied SNPs in miR-107 and miR-23b that related with AIP and HMGA2 genes respectively and control their expression, and also SNP in the 3'UTR of HMGA2 gene. Our aim was to investigate genotype distributions of the studied SNPs, as well as the possible relationship between disease and/or response to SSAs treatment in patients with acromegaly. Material and Methods Genotypes were determined by qRT-PCR method from DNA materials obtained blood samples of acromegaly patients (141) and healthy individuals (99). The genotype distributions of patients and healthy groups, as well as the relationship between the clinical data of the disease and genotypes were statistically compared. Results In acromegaly patients with T-allele, p53 expression (p=0.049) was significantly higher. In patients with CT+TT genotype and T-allele who were responder to SSA-treatment Ki-67 index (respectively p=0.019, p=0.020 respectively) was higher. We did not observe the genotypes for miR-23b and miR-107 polymorphisms in the patients and control group of Turkish population. Conclusion The genetic variations of the miRNAs genes related with HMGA2 and AIP genes were not seen in our study. Although there is no relationship between HMGA2-rs1351394 polymorphism and acromegaly disease, T allele was associated with some clinical features related to adenoma in patients with acromegaly.

Background: Acromegaly is a disease that occurs as a result of excessive growth hormone caused by pituitary adenomas. Some acromegaly patients show resistance to somatostatin analog (SSA) treatment. Filamin-A (FLNA) and β-arrestins are thought to play a role in the response to SSAs. We aimed to investigate the relationship between FLNA-rs782079491 and β-arrestin-2-rs34230287 single-nucleotide polymorphisms and disease risk, as well as treatment response in patients with acromegaly in the Turkish population. Methods: The genotypes of 110 acromegaly patients and 99 controls were determined by realtime PCR. The genotype distributions were compared with clinical data on the disease. Results: There was no association between the β-arrestin-2 gene polymorphism and the response to SSA treatment in acromegaly patients. For responder patients to SSAs, the β-arrestin-2-rs34230287 CT+TT genotype was associated with higher microadenoma as compared with the CC genotype (p = 0.017). The FLNA polymorphism was not observed in the study group. Conclusions: We showed that there was no association between the polymorphic genotypes of FLNA and β-arrestin-2 genes with acromegaly disease and SSAs response in the Turkish population. However, there was a relationship between β-arrestin-2 and some of the clinical characteristics. Furthermore, the CC genotype and the C allele are risk factors associated with tumor growth rate in acromegaly patients. 34669321

Background/aim We aimed to investigate the synergistic effects of apigenin and curcumin on the cross-talk between apoptosis and autophagic cell death, as well as on paraptosis in HeLa cells. Materials and methods Cell viability was measured using the MTT assay. Synergistic effects were measured using the Bliss independence model. qRT-PCR was used to study the expression of genes related to apoptosis, autophagic cell death, and cross-talk. GRP78/BiP immunostaining was used to identify endoplasmic reticulum (ER) stress. Results Treatment with a combination of apigenin and curcumin increased the expression levels of genes related to cell death in HeLa cells 1.29- to 27.6-fold. The combination of curcumin and apigenin showed a synergistic anti-tumor effect via cross-talk between processes leading to apoptosis and autophagic cell death, as well as ER stress-associated paraptosis. GRP78 expression was down-regulated, and massive cytoplasmic vacuolization was observed in HeLa cells. Conclusion The combination of curcumin and apigenin is an effective potential therapeutic for cervical cancers.

Intracellular aggregation of hyperphosphorylated tau in neurofibrillary tangles (NFTs) is a major neuropathological hallmark of taupathies such as Alzheimer's disease. Okadaic acid (OKA) is a potent inhibitor of PP2A, leading to abnormal tau phosphorylation. Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is selectively downregulated in AD. In this study, we investigated the effects of OKA induced tau hyperphosphorylation on secreted and cellular levels of BDNF in primary cortical neurons that were treated with 25nM OKA. Tau phosphorylation at threonine 231 (Thr231) sites was assessed by Western blot using antibodies against phospho-Thr231. Non-phosphorylated tau protein was detected with the Tau-1 antibody. Levels of BDNF secreted to the culture medium were determined by ELISA at the 8th and 24th hours of treatment. Cellular localization and protein expression of BDNF and tau were assessed by immunofluorescent labeling and fluorescent intensity measurements at 24h of treatment. Tau hyperphosphorylation was confirmed with increase in Thr231 and the decrease in Tau-1 signals after 8h of OKA treatment, compared with the control groups, secreted BDNF levels in the OKA-treated group were significantly lower after 24h of treatment but were not significantly different at 8h of treatment. BDNF immunoreactivity was seen in cytoplasm and neurites of the neurons in control group. BDNF immunoreactivity significantly decreased in the OKA treated group and this attenuation was significant especially at neurites. Our results suggest that the decrease in BDNF secretion and the BDNF expression might depend on the disruption of microtubule structure caused by tau hyperphosphorylation.

The molecular mechanisms underlying the formation of nonfunctioning pituitary adenomas (NFAs) are largely unknown. In this study, we aimed to understand the relationship between NFAs and functional pituitary adenomas and the possible role of proteins involved in cell cycle, senescence, and DNA damage control mechanisms in the etiology of NFA. We analyzed pATM-S1981, pRb-S608, Rb, pE2F1-S364, p16, E2F1, p73, cyclin D1, and CHEK2 protein expression (in a group of 20 patients with acromegaly, 18 patients with Cushing's disease (CD), and 29 NFA patients) by immunohistochemistry and their relevant mRNA expression by qRT-PCR (in a group of 7 patients with acromegaly, 7 patients with CD, and 7 NFA patients). The clinical and histopathological results on the patients were statistically evaluated. pE2F1-S364 protein expression in the CD group was significantly lower than that in the NFA and acromegaly groups (p = 0.025, p = 0.034, respectively). However, the expression of the p16 protein was lower than in the NFA group than in the CD and acromegaly groups (p = 0.030, p = 0.033, respectively), and E2F1 protein expression was significantly higher in the NFA group than in the CD group (p = 0.025). p73 protein expression in patients with acromegaly was significantly higher (p = 0.031) than that in the CD group. CHEK2 mRNA expression in the CD group was significantly higher than that in the acromegaly group (p = 0.012). The selective and tumor-specific associations between E2F1, pE2F1-S364, CHEK2, and p73 mRNA and protein levels indicate their involvement in pituitary adenoma formation in NFA, CD, and acromegaly patients.

Background Apoptosis contributes nephropathy pathogenesis in diabetes. However, its mechanisms still remain unclear. We examined the extent to which the angiotensin-II type 1 receptor blocker (AT1RB) irbesartan and the angiotensin converting enzyme inhibitor (ACEI) perindopril affected the apoptosis-related proteins Bcl-2, Bax, caspase-3, cytochrome-c and Ku70 in streptozotocin (STZ)-diabetic rats. Materials and methods Animals were divided into five groups of eight each, four of which received STZ (60 mg/kg in a single dose, i.p.) to induce diabetes. The groups were performed as untreated diabetic; non-diabetic control; daily irbesartan (15 mg/kg/day) or perindopril (6 mg/kg/day) and also combined irbesartan and perindopril (respectively, 5 mg/kg/day, 3 mg/kg/day) were applied by gavage for 30 days to STZ-diabetic rats. The kidney tissue analysis was performed by using immunohistochemical staining with Bcl-2, Bax, caspase-3, cytochrome-c and Ku70 antibodies and by using Western blot analysis with caspase-3 and cytochrome-c antibodies. Results Immunoreactivity of Bax, caspase-3, cytochrome-c and Ku70 was increased in the tubuli and glomeruli of the untreated diabetic group, but decreased in all treated diabetic groups. In the irbesartan and perindopril treated diabetic groups Bcl-2 immunoreactivity was higher than that of the untreated diabetic group. Caspase-3 and cytoplasmic cytochrome-c protein levels increased in the untreated diabetic group. Conclusions We conclude that the increased expression of Bax and caspase-3, and the increased level of cytoplasmic cytochrome-c relate to renal tissue injury. This case is also seen in the early stages of diabetes as a result of the damage caused by local increased expression of renin angiotensin system (RAS) in the renal tissue, which is induced by hyperglycemia. The increase of the cytosolic cytochrome-c, caspase-3 and Ku70 expression in the tubuli is suggestive of apoptosis. Overall, our results show that treatments of irbesartan and perindopril are effective and efficient in preventing renal tissue injury and apoptosis by blocking the RAS in experimental diabetic nephropathy and reducing the expression of proteins associated with apoptosis.

Objective: To evaluate the effect of preoperative somatostatin analog (SRL) treatment on proteins associated with apoptosis and autophagy in patients with acromegaly and to determine factors correlating with these parameters. Methods: Ex-vivo tumor samples of 11 SRL-treated and 9 SRL-untreated patients were retrospectively included in the study. Apoptotic and autophagic proteins were determined via immunohistochemical staining and apoptosis was evaluated via in situ DNA end labeling (TUNEL). Results: TUNEL, caspase-3, and ATG-5 immunopositivity was significantly increased (p0.05 for all). Preoperative SRL treatment was the only factor that had a significant effect on TUNEL positivity (adjusted R2=0.39, p=0.02). Preoperative treatment duration was positively correlated with TUNEL and caspase-3 immunopositivity (r=0.526, p=0.02; r=0.475, p=0.04, respectively) and negatively correlated with survivin immunopositivity (r=−0.533, p=0.01). Conclusions: Somatostatin analog treatment might induce apoptosis, increase autophagy, and decrease cell proliferation in GH-secreting adenomas. Also, proteins related to cross-talk between autophagy and apoptosis are upregulated after SRL treatment.

We aimed to study the effect of nicotinamide (NA) on beta (β)-cell regeneration and apoptosis in streptozotocin induced neonatal rats (n-STZ). Three groups were performed: Control group, n2-STZ group (100 mg/kg STZ on the second day-after birth), n2-STZ + NA group (STZ;100 mg/kg + NA;500 mg/kg/day for 5 days). The pancreatic tissue sections were immunostained with insulin, glucagon, somatostatin, Pdx1, Notch1 and active caspase-3 antibodies, and double immunostained with insulin/PCNA, insulin/glucagon and insulin/somatostatin antibodies. In situ hybridization carried out with insulin probe. Apoptotic β-cell were shown by TUNEL assay, followed by immunostaining. The number of insulin/PCNA, insulin/glucagon and insulin/somatostatin double-positive cells significantly increased in n2-STZ + NA group compared with the other groups (p < 0.001). n2- STZ group had lower number of insulin and Pdx1 positive cells in islets, compared to NA treated diabetics. The insulin and Pdx1 immun positive cells were located in the small clusters or scattered through the exocrine tissue and around to ducts in n2-STZ + NA group. Notch1 positive cell numbers were increased, whereas caspase-3 and TUNEL positive β-cell numbers were decreased in n2-STZ + NA group. NA treatment induces the neogenic insulin positive islets orginated from the differentiation of ductal progenitor cells, transdifferentiation of acinar cells into β cells, and transformation of potent precursor cells and centroacinar cells via the activated Notch expression into β-cells in n-STZ rats.

Cervical cancer is one of the frequent types of cancer seen in females. It has been suggested that natural compounds can be used effectively for cancer treatment. Apoptosis and autophagy related cell death play important roles in suppression of tumorigenesis. Apigenin and curcumin are natural products isolated from plant extracts known to have antitumoral, antibacterial and antiviral effects. Varying doses of curcumin and apigenin were applied to HeLa cancer cell lines. The expression of the genes related to apoptosis and/or autophagy related cell death were measured using qRT-PCR and cell viability was measured using MTT assay. Our results showed that curcumin and apigenin are effective on apoptosis and autophagy related cell death in HeLa cells. We suggested that these natural products seem to be a new promising therapeutic approach in cancer.

We investigated the cytotoxic and apoptotic effects of a methanol extract of Centaurea nerimaniae, a plant endemic in Turkey, on HeLa and MDA-MB-231 cells. Eight concentrations of C. nerimaniae extract were applied to cells, and cytotoxic effects were measured using the xCELLigence system. The TUNEL assay was used to assess apoptotic cell death and immunohistochemistry was used to determine active caspase-3 using the effective cytotoxic doses of the extract. Doses of 1.42 mg/ml C. nerimaniae inhibited the growth of HeLa cells and 3.67 mg/ml C. nerimaniae inhibited the growth of MDA-MB-231 cells in a dose- and time-dependent manner. The apoptotic indexes for HeLa and MDA-MB-231 cells were increased significantly compared to control groups. Immunohistochemistry showed that the number of caspase-3 immunostained cells increased in the extract treatment groups for both HeLa and MDA-MB-231 cells. In the MDA-MB-231 cell line, caspase-3 immunostaining was observed in nuclei and/or cytoplasm in the extract treated group. Caspase-3 activation was greater in HeLa cells than in MDA-MB-231 cells. We found that the extract of C. nerimaniae had a strong antiproliferative effect and induced apoptosis via caspase-3; MDA-MB-231 cancer cells were more resistant than HeLa cells.

Karabay, Arzu/0000-0001-5150-5349; Gezen-Ak, Duygu/0000-0001-7611-2111; Dursun, Erdinc/0000-0003-3701-6674; WOS:000443662800005 PubMed: 29860071 Hyperphosphorylation of tau leading to neurofibrillary tangles (NFT) is one of the key pathological hallmarks in neurodegenerative disorders such as Alzheimer disease (AD). Peptidyl-prolyl cis-trans isomerase (Pin1) regulates the phosphorylation of Ser/Thr sites of tau protein, and promotes microtubule assembly. In this study, we aimed to determine the effect of tau hyperphosphorylation on Pin1 expression in primary cortical neurons in order to investigate the results of the pathological process on Pin1, an important enzyme involved in various cellular mechanisms. Primary cortical neurons were prepared from embryonic day 16 -Sprague Dawley rat embryos. The cultures were treated with 25 nM okadaic acid (OKA) on day 7 in order to promote tau hyperphosphorylation. The cytotoxicity was determined with LDH release and measured by ELISA. Tau phosphorylation was confirmed by western blot using anti-tau antibodies Thr231 and Tau-1. Pin1 mRNA expression level was determined by qRT-PCR at 8 and 24 h. Pin1 protein expression was analyzed with immunofluorescent labeling at 8 and 24 h. Tau phosphorylation on Thr231 was increased and non-phosphorylated Tau-1 was decreased in OKA treated group compared with the untreated control at 8 h of treatment. While Pin1 mRNA expression levels at 8 h post-OKA treatment were lower than that of control groups, there were no differences between OKA-treated group and control groups in Pin1 protein expression. Whereas no significant differences for Pin1 mRNA expression, protein expression levels were decreased OKA-treated group compared to control groups at 24 h of treatment. The LDH release of OKA-treated group was significantly increased at 24 h. Our study indicates that although OKA treatment suppressed Pin1 mRNA expression and induced tau phosphorylation at 8 h of treatment, its influence on Pin1 protein expression has 16 h phase delay. Given the important role of Pin1 in many cellular mechanisms these results might indicate that tau hyperphosphorylation involved in many neurodegenerative disorders may cause some alterations in brain microenvironment via Pin1.This is the first demonstration of the alteration of the Pin1 mRNA and protein expression in OKA induced model in primary cortical neurons. Research Fund of Istanbul UniversityIstanbul University [21342, 22455] The present study was supported by the Research Fund of Istanbul University (Project No: 21342 and 22455).

Amac: Bu calismada koroner arter baypas greftleme yapilan hastalarda statin on tedavisinin sag atriyal miyositlerin apoptozisine karsi olasi koruyucu etkileri arastirildi. Ca­lis­ma­ pla­ni:­Calismaya 29 ardisik hasta dahil edildi. Grup 1’deki hastalara (n=12; erkek: 83.3%) hastaneye yatis gununden itibaren atorvastatin 40 mg/gun tedavisi uygulandi, grup 2’deki hastalara (n=17; erkek: 82.3%) ise statin tedavisi uygulanmadi. Sag atriyal ornekler kardiyopulmoner baypasa girilmeden once alindi ve %10’luk notral formalin ile fikse edildi. Apoptotik hucrelerin tespiti icin immunoperoksidaz boyama ve TUNEL yontemi kullanildi. Immun boyamali aktif kaspas-3 ve proliferatif hucre nukleer antijen (PCNA) hucrelerinin sayimi isik mikroskopu kullanilarak yapildi. Bul gu lar: Grup 1’deki hastalarin endokardiyal (p=0.04) ve epikardiyal (p=0.01) katmanlarindaki ortalama apoptotik indeks degerleri grup 2’dekilere kiyasla, anlamli duzeyde dusuk bulundu. Miyokardiyal katmanlardaki degerler arasinda fark olmadigi goruldu (p=0.35). Katmanlar arasinda ortalama PCNA indeksi acisindan anlamli fark yoktu. So­nuc:­ Koroner arter baypas greftleme oncesi statin on tedavisinin kardiyak miyosit kaybini azaltabilecegi gorunmekte olup, acik kalp cerrahisi sonrasi yararli etkilere isaret edebilir.

ABS TRACT Ob jec ti ve: It is known that high fat di ets can ca u se en dot he li al dysfunc ti on, me di a ted by oxi da ti ve stress. In the pre sent study, we ai med to eva lu a te the vas cu lar res pon se of pol yun sa tu ra ted fatty acids (PU FA) and alp ha li po ic acid (ALA) on rat tho ra cic ar te ri es. Ma te ri al and Met hods: The pre sent study was con duc ted on ma le Wis tar al bi no rats. The n-6 and n-3 gro ups we re cre a ted from the rats that we re fed with pol yun sa tu ra ted fatty acid-rich di et, and 60% of the to tal ca lo ri e con tent com pri sed of fat. Furt her mo re, n-6/ALA and n-3/ALA gro ups we re cre a ted by the ad di ti on of strong an ti o xi dant alp ha li po ic acid in to the di et of n-6 and n-3 gro ups. The ef fects of di e tary n-6 and n-3 fatty acids and ALA on vas cu lar res pon se of the rat tho ra cic ar te ri es we re eva lu a ted in the iso la ted or gan bath. In ad di ti on, the ef fects of n-6 and n-3 fatty acids and ALA on the vas cu lar morp ho logy we re eva l u a ted using his toc he mi cal met hods. On the ot her hand, the glu tat hi o ne le vels in the red blo od cells we re com pa red bet we en n-6, n-3, n-6/ALA, and n-3/ALA gro ups. Re sults: We fo und dec re a sed en dot he li um de pen dent re la xa ti on and in cre a sed oxi da ti ve stress in n-6 and n-3 gro ups. Tre at ment with ALA im pro ved en dot he li um-de pen dent re la xa ti on and oxi da ti ve stres, and pre ven ted the wor se ning of vas cu lar his to pat ho logy. Conc lu si on: The re sults in di ca te that a high PU FA di et ca u sed en dot he li al dysfunc ti on by in cre a sing oxi da ti ve stress. Be si des, di e tary to tal amo unt of PU FA se ems to be mo re im por tant than n-6/n-3 ra ti o for car di o vas cu lar pro tec ti on.

We studied the effect of alpha-lipoic acid (ALA) on the liver cell damages and apoptosis by n-6 polyunsaturated fatty acids (PUFA) rich diet in young rats. 24 Wistar rats were divided into four groups. During the study, 12 of them (control) were fed with standard chow and other 12 (n-6) were fed with the food containing high-fat n-6 for 8 weeks. At the end of the fourth week, control and n-6 groups were randomly divided into two groups and then, 4 weeks, 35 mg/kg ALA are injected. Groups; control, control + ALA, n-6, n-6 + ALA. The liver tissue glutathione (GSH) activity was determined. Immunohistochemistry for caspase-3 and TUNEL method for apoptosis were performed. The GSH levels have significantly decreased (p < 0,001), and vacuolization in the hepatocytes, infiltration and the collagen accumulation around the central vein, hepatic stellate cells in the sinusoids have increased in n-6 group compared with the other groups. TUNEL (p < 0,001) and caspase-3 (p < 0,001) positive cells increased in n-6 group whereas all degenerative observations decreased in n-6 + ALA group. Our results demonstrate that the feeding with n-6 PUFA causes fatty liver, fibrosis development, inflammations and apoptosis in the liver of young rats. ALA has a beneficial effects on these degenerative effects.

Autophagy is important in cellular homeostasis for the cell survival mechanism. Deficiency or excess of autophagy is generally related to some of diseases such as cancer and neurodegeneration. Although autophagy is a cell survival mechanism, it can mediate programmed cell death in several conditions. Autophagy-related genes (ATGs) regulate the autophagy and also control the crosstalk with autophagy-associated cell death and apoptosis in some condition. Various methods have been used to detect the marker genes and the proteins involved in these processes. Quantitative real-time PCR (qRT-PCR) method for monitoring the expression of genes involved in autophagy or autophagic cell death is often preferred because of its sensitivity, high efficiency potential, accurate quantification, and high-grade potential automation. The detection of the markers for autophagy-related process by immunohistochemistry in paraffin sections of various patient tissues has become a reliable method for monitoring autophagy. Here, we introduce protocols for detecting autophagy and autophagy-associated cell death in HeLa cells by using gene expression assays qRT-PCR, and also in paraffin-embedded tissue section from human biopsy material by using immunohistochemistry.

Background: The natural products have increasing important for the development of anticancer agents. Colchicum baytopiorum C.D. Brickell (C. baytopiorum), an endemic species for Turkey, contains colchicine and its derivatives. Stimulation of apoptotic and autophagy-mediated cell deaths are effective strategy for anticancer therapies. Aim: The aim of the study is to determine the role of the extract on both apoptotic and autophagic cell death in HeLa cell line. Methods: The cell viability of C. baytopiorum (0.1 mg/ml) was determined by MTT assay. Active caspase-3 and t-Bid expressions were evaluated by immunohistochemical method. The mRNA expression of apoptotic regulatory genes (Bcl-xL, Bid, Bad, PUMA, NOXA, Caspase-3, -8, -9, Fas, FADD, TRADD, TRAF2, TNF, TNFR1), autophagic cell death related genes (Atg5-12, Beclin-1, DAPK), and also both autophagic and apoptotic cell death regulatory genes (Bif-1 and BNIP-3) were investigated by qRT-PCR. Results: We determined that the expressions of both apoptotic and autophagic regulatory genes were significantly increased in the treatment group compared to control group. Also, we showed that C. baytopiorum crude extract induces the cross-connection between apoptotic and autophagic cell deaths in HeLa cells. Conclusion: We suggested that this endemic plant extract seems to be a new promising therapeutic approach in cancer.

Fat mass and obesity-associated protein (FTO) gene expression is known to correlate with obesity. Our aim was to investigate the FTO gene expression in paired omental and subcutaneous human adipose tissues from morbid and obese patients. To understand the role of CD68-positive macrophages in adipose tissues, the correlation with adiposity parameters such as adipocyte diameter and adipocyte radius was also measured. Drug and adiposity correlations were also analyzed.Paired omental and subcutaneous adipose tissue were excised during elective surgery from morbidly obese (n = 9) and obese (n = 5) patients. FTO expressions were determined by quantitative PCR. Tissue sections were analyzed for their CD68 protein expressions by immunuhistochemistry.Omental and subcutaneous adipose tissue FTO gene expression levels were not found to differ significantly among morbidly obese and obese study groups. Serum aspartate aminotransferase e and alanine transaminase levels were found to be in negative correlation with subcutaneous fat tissue FTO expression rate. Antidiabetic drug use was found to be in correlation with adiposity. Both subcutaneous and omental fat cell diameters were found to have correlation with antidiabetic drug use. Omental fat cell diameter was found to enlarge together with omental CD68 protein expression. Subcutaneous macrophage number decreased while omental fat cell radius increased. Omental macrophage number was found in correlation with subcutaneous macrophage number.Antidiabetic therapy was found to increase adiposity in omental and subcutaneous fat. Further research is needed with larger samples to explore the exact role of FTO in obesity.

Streptozotocin (STZ) is known to induce insulin-dependent diabetes in experimental animals. In STZ-induced diabetes atrophy of the thymus is caused by elevated intracellular calcium levels leading to apoptosis. Hyperglycemia is known to result in a decrease in numbers of T cells in the thymus and circulation. Intracellular calcium levels increase in diabetic animals after induction by STZ. Hyperglycemia inhibits Ca2+-ATPase and increases intracellular calcium levels. We have investigated apoptosis in thymus tissue of neonatal STZ (n-STZ)-diabetic rats and the effects of isradipine as a calcium channel blocker (CCB) on apoptosis. Five groups of newborn Wistar rats were used. On the second day after birth 100mg/kg STZ was given i.p. to the first two groups. The first group was n-STZ diabetic. To the second group starting from the 12th week 5 mg/kg/day isradipine (i.p) was given for 6 weeks. To the third group the same dose of isradipine was given on the second day followed by STZ treatment. The fourth group was non-diabetic and treated with 5 mg/kg/day isradipine for six weeks. The fifth group consisted of non-diabetic rats. To the sixth group dexamethasone (5 mg/kg i.p.) was given to adult rats. For detection of apoptotic cells in paraffin-embedded thymus sections the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end Labelling (TUNEL) assay was used. The DNA ladder method was performed for anaLysis of DNA fragmentation. In the isradipine-treated non-diabetic group typical apoptotic banding patterns were found whereas thick bands between 123 and 246 bp length were found in the n-STZ- and n-STZ+isradipine-treated groups. More apoptotic cells were observed in the thymus of isradipine-treated n-STZ-treated and n-STZ+isradipine-treated groups when compared with the non-diabetic control and isradipine+n-STZ-treated groups. In conclusion we observed that long-term STZ diabetes results in apoptosis in the thymus. We also found that isradipine administered before STZ has protective effects against apoptosis whereas isradipine alone induces apoptosis. (c) 2005 Elsevier GmbH. All rights reserved.

Apoptosis is one of the most important forms of cell death seen in a variety of physiological and pathological conditions, including traumatic injuries. This type of cell death occurs via mediators known as caspases. Previous studies have investigated the roles that apoptosis and different caspases play in the pathogenesis of secondary damage after spinal cord injury (SCI). The aim of this research was to assess the neuroprotective effect of z-DEVD.fmk, a caspase-3 inhibitor, in a rat model of SCI.Forty-five Wistar albino rats were studied in 3 groups of 15 animals: sham-operated control animals (group 1); trauma-only control animals (group 2); and rats subjected to trauma + z-DEVD.fmk treatment (group 3). Spinal cord injury was produced at the thoracic level using the weight-drop technique. Responses to injury and the efficacy of z-DEVD.fmk were assessed by light microscopy and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining in cord tissues collected at 4 and 24 hours posttrauma. Five rats from each group were used to assess functional recovery at 7 days after SCI. The functional evaluations were done using the inclined-plane technique and a modified Tarlov motor grading scale.At 4 hours postinjury, the mean apoptotic index in groups 1, 2, and 3 was 0, 33.01+/-6.62, and 16.40+/-4.91, respectively. The group 3 count was significantly lower than the group 2 count (P.01). At 24 hours postinjury, light microscopic examination of group 2 tissues showed widespread hemorrhage, necrosis, polymorphonuclear leukocyte infiltration, and vascular thrombi. The group 3 tissues showed similar features. The prominent findings in group 2 were hemorrhage and necrosis, whereas the prominent findings in group 3 were focal hemorrhage and leukocyte infiltration. The mean inclined-plane angles in groups 1, 2, and 3 were 64.5 degrees+/-1.0 degrees, 41.5 degrees+/-1.3 degrees, and 47 degrees+/-2.0 degrees, respectively. Motor scale results in all groups showed a similar trend.Local application of z-DEVD.fmk after SCI in rats reduces secondary tissue injury and helps preserve motor function. These effects can be explained by inhibition of apoptotic death in all cell types in the spinal cord.

Effects of the angiotensin II type 1 (AT1) receptor antagonist valsartan and the angiotensin-converting enzyme (ACE) inhibitor enalapril were studied in streptozotocine (STZ)-induced diabetes in rats on the basis of microalbuminuria (Ma) and renal morphology. Five groups of Wistar rats were used, one group was the non-diabetic control, one group consisted of untreated STZ-diabetics and 3 groups of STZ-diabetics were treated with either enalapril and/or valsartan for 30 days. Blood glucose (BG) and Ma levels, body and kidney weight and glomerular size were measured. Immunohistochemical staining with an anti-transforming growth factor-beta1 (TGF-beta1) antibody was performed as well. In STZ-diabetics, BG and Ma levels were significantly increased when compared with the non-diabetic group. Although Ma levels in the valsartan-treated group was found to be higher than those in the non-diabetics group after 15 days of treatment, in all treated diabetic groups Ma levels were significantly decreased as compared with STZ-diabetics at the end of the experiment. Thickening of the glomerular and tubular basement membranes, increased mesangial matrix and glomerular size were found in the untreated diabetic group. All these changes were less in the treated groups. A significant increase in TGF-beta1 immunoreactivity was found in glomeruli of untreated STZ-diabetics as compared with non-diabetics. Again, TGF-beta1 expression was decreased in the treated groups as compared with untreated STZ-diabetics. We conclude that valsartan and enalapril have renoprotective effects in diabetic nephropathy. A combined therapy has an advantage because lower dosages of these drugs can be used. Their beneficial effects are related to a blockade of the renin-angiotensin system (RAS) and a decrease in TGF-beta1 expression in glomeruli.

Non-radioactive in situ hybridization (ISH) and immunocytochemistry (ICC) have been used to detect somatostatin (SS) messenger RNA (mRNA) and peptide in antropyloric mucosa of the stomach in the rats. We have applied a method of non-radioactive in situ hybridization histochemistry using digoxigenin labelled oligonucleotide probes to detect somatostatin gene expression in the stomach. In prehybridization stage we used proteinase K (PK) in various concentrations (from 1 to 10 micrograms/ml) and periods (from 10 min to 1 h) but we maintained high background. However it was possible to detect the somatostatin mRNAs in the stomach mucosa making use of either background preventing solutions during the prehybridization, or of levamisole (20 microliters/mg) added into the hybridization buffer or of pepsin. Somatostatin mRNA and peptide signals were scattered all through the mucosa especially localized particularly at the base of the pyloric glands. SS peptide shown by ICC and SS mRNA shown by ISH were observed in different cells.

We investigated the effects of exendin-4 (Ex4) treatment on expression of clusterin and β cell regeneration in the endocrine pancreas in neonatal streptozotocin (nSTZ) diabetic rats. Three groups were used: (1) n2-STZ group; on the second day after birth 100 mg/kg STZ was given i.p. to two groups of newborn rats, (2) n2-STZ + Ex4 group; 3 μg/kg/day Ex4 was given for 5 days starting on the third day, and (3) control group. In situ hybridization for mRNAs of insulin and clusterin, double immunostaining for insulin/clusterin and insulin/BrdU were carried out. Immunostaining for insulin, glucagon, somatostatin, clusterin, synaptophysin and pdx-1 was performed. In the n2-STZ + Ex4 group, BrdU/insulin and insulin/clusterin immunopositive cells were significantly increased in the islets of Langerhans in comparison to the other groups. The areas occupied by the insulin mRNA and peptide positive cells and also pdx-1 immunopositive cells were decreased in the n2-STZ diabetic group compared with the other groups. The clusterin mRNA and protein positive cells, and also the glucagon and somatostatin cells, were significantly increased in the islets of the n2-STZ and the n2-STZ + Ex4 groups compared with the control group. The results show that Ex4 treatment induces new beta cell clusters via up-regulation of clusterin, which might be effective on beta-cell proliferation and neogenesis.

Zinc is an element that under physiological conditions preferentially binds to and is a potent inducer of metallothionein under physiological conditions. The present study was conducted to explore whether zinc supplementation morphologically and biochemically protects against diabetic nephropathy through modulation of kidney metallothionein induction and oxidative stress in streptozotocin-induced diabetic rats. Thirty-two Wistar albino male rats were equally divided into four groups. The first group was used as untreated controls and the second group was supplemented with 30 mg/kg/day zinc as zinc sulfate. The third group was treated with streptozotocin to induce diabetes and the fourth group was treated with streptozotocin and supplemented with zinc as described for group 2. The blood glucose and micro-albuminuria levels, body and kidney weights were measured during the 42-day experimental period. At the end of the experiment, the kidneys were removed from all animals from the four groups. Diabetes resulted in degenerative kidney morphological changes. The metallothionein immunoreactivity level was lower and the kidney lipid peroxidation levels were higher in the diabetes group than in the controls. The metallothionein immunoreactivity levels were higher in the tubules of the zinc-supplemented diabetic rats as compared to the non-supplemented diabetic group. The zinc and metallothionein concentrations in kidney tissue were higher in the supplemented diabetic group compared to the non-supplemented diabetes group. The activity of glutathione peroxidase did not change in any of the four groups. In conclusion, the present study shows that zinc has a protective effect against diabetic damage of kidney tissue through stimulation of metallothionein synthesis and regulation of the oxidative stress.

In this study, we aimed to investigate the relationship among trace elements (Cu, Fe, Zn and Mg) on oxidative and anti-oxidative substances in liver and kidneys tissues in streptozotocin (STZ) diabetic rat model. The mean levels of Fe and Cu were found significantly higher in the liver and kidneys of the diabetic rats, in comparison to the control rats. On the other hand, the mean levels of Zn and Mg in the liver and kidneys of the diabetic rats were significantly lower than in the control rats. The liver and kidneys malonaldehyde (MDA) levels of the experimental group were found to be higher than in the control group (p < 0.001; p < 0.01, respectively) after 4 weeks of the experimental period. Superoxide dismutase (SOD) activities and glutathione (GSH) levels in the liver tissue of STZ-induced diabetic rats were found to be lower in the experimental group than in the control group (p < 0.01). SOD activity and GSH concentration in kidneys of the diabetic rats were significantly diminished with respect to the control group (p < 0.01). In conclusion, the present results indicate that the increase of Fe and Cu together with decreas of Zn and Mg concentration in liver and kidney of STZ-induced diabetic rats may be involved in disturbances of oxidative balance in both the tissues. Therefore, these findings may contribute to explain the role of impaired ion metabolism of some elements in the progression of diabetic oxidative complications.

WOS: 000315752400004, PubMed ID: 23116585, Objectives: We aimed to investigate the effects of AR-A014418, a strong inhibitor specific to GSK-3beta, on neuronal apoptosis and neuroprotection in the traumatic SCI model. Materials and methods: In this study, three groups were generated from 36 Wistar rats; (1) control, (2) spinal cord trauma group created by clip compression technique after laminectomy, and (3) AR-A014418 (4mg/kg, i.p., DMSO) treatment group after laminectomy and spinal cord trauma. The TUNEL assay for apoptosis detection, immunohistochemical staining for bax and TGF-beta were applied in spinal cord tissues. For light microscopic examination, necrotic, and apoptotic cells were counted, and PMNL counting was applied to detect inflammation. Functional recovery was tested by field locomotor test in the 3rd and 7th days following surgery. Results: In the trauma group, diffuse hemorrhage, cavitation, necrosis and edematous regions, degeneration in motor neurons and leukocyte infiltration were observed in gray matter. In the AR-A014418-treated groups, healthy cells were observed in more places compared to the trauma groups, however, cavitation, hemorrhagic, and edematous areas were seen in gray matter. In the AR-A014418-treatment groups, the number of apoptotic cells in the 3rd and 7th days (respectively; p, Scientific Research Projects Coordination Unit of Istanbul University [UDP-17368], This work was supported by Scientific Research Projects Coordination Unit of Istanbul University, project number UDP-17368.

In this study, we investigated the protective effect of losartan as an AT1 receptor antagonist by evaluating the expression of apoptosis-regulatory genes that contribute to the progressive damage in the renal tubules of hyperoxaluric rats. Rats were divided into 4 groups of 10 each; control (C), ethylene glycol (EG), ethylene glycol + losartan (EG + L) and Losartan (L). For 4 weeks 0.8% EG, as a precursor for oxalate, was administered to EG and EG + L and losartan (300 mg/l) was administered to groups EG + L and L. Urine and blood samples were collected for biochemical determination. Bcl-2, bax, caspase-3 and TGF-beta 1 antibodies were used for immunohisto-chemistry. Apoptosis was determined by TUNEL method. A marked increase in urinary oxalate levels of the rats in EG and EG + L groups was found. In the EG group a diffuse amount of oxalate crystals into the tubular lumina and interstitium in the cortex was observed. In the EG group GBM thickening, interstitial fibrosis and tubular atrophy with infiltration of mononuclear cell findings reduced in the EG + L group were presented as well. In the EG group, immunoreactivity of TGF-beta 1 was increased in glomeruli and tubuli. In the EG + L group, immunoreactivity of TGF-beta 1 was decreased compared to the EG group. Bax expression increased in the renal tubules of EG group and reduced in the EG + L group comparing to the control. In the EG + L group, the immunoreactivity of bcl-2 was increased in glomeruli. In EG + L treated group, number of caspase-3 immunopositive cells were decreased compared to all groups (P < 0.01). Apoptotic cells were increased in the EG-treated group compared to the other groups. Decreased apoptotic cell number was observed in the EG + L compared to the EG group (P < 0.01). Our findings suggest that losartan may provide a beneficial effect against tubulointerstitial damage and decrease renal tubular apoptosis caused by hyperoxaluria. © Springer-Verlag 2010.

Vitamin D(3) is known to be involved in neuroprotection and exert its neuroprotective effects by modulating neuronal calcium homeostasis and production of neurotrophins. The single nucleotide polymorphisms (SNP) in vitamin D receptor (VDR) gene which can influence the affinity of vitamin D(3) to its receptor may be related to neurodegenerative diseases and neuronal damage by altering the vitamin D-mediated pathways. In this study, our aim was to determine whether there is an association between VDR gene and late-onset Alzheimer's disease (AD) in order to see if vitamin D contributes to AD or not. One hundred and four cases of dementia of Alzheimer type and 109 age-matched controls were genotyped according to ApaI (a: + restriction site and A: no restriction site) and TaqI (t: + restriction site and T: no restriction site) sites in intron 8 and exon 9 of the ligand-binding site of VDR gene. When the controls and patients were compared for their ApaI genotypes, the frequency of the patients with Aa genotype was significantly higher than the frequency of the healthy individuals with the same genotype (p = 0.008, chi(2) = 9.577, OR = 2.30). Thus, the "Aa" genotype may increase the risk of developing AD 2.3 times when compared with the "AA" genotype. On the other hand, the "AT" haplotype was significantly higher in controls (p = 0.006) indicating a protective role of the "AT" haplotype in AD. Consequently, this study provides evidence for a possible link between AD and vitamin D.

The aim of this study was to evaluate the effect of long-term use of progesterone treatment on proliferation and apoptosis in simple endometrial hyperplasia without atypia. In this prospective control study, endometrial tissue samples of 19 patients with simple endometrial hyperplasia without atypia (group 1), posttreatment biopsy materials of the patients after 3 months of cyclic progesterone treatment with noretisterone for 10 days (group 2), and 18 endometrial biopsy materials of the control group (group 3) were examined for proliferative and apoptotic activities. There was a statistically significant difference between the median values of the proliferative index of the three groups (P = 0.000). The proliferative index was significantly higher in the endometrial hyperplasia group than in posttreatment group (P = 0.000). But there was no significant difference between posttreatment group and control group. The median value of apoptotic activity was significantly different between three groups (P = 0.000). Apoptotic index was highest in hyperplasia group. A significant decrease in apoptosis was observed after the progesterone treatment (P = 0.002). The lowest apoptotic activity was detected in the control group. In conclusion, 3 months of cyclic progesterone treatment reduces both proliferative and apoptotic activities in endometrial tissue with simple hyperplasia.

We have examined the frequency of the EcoRI, XbaI and MspI RFLPs of the apolipoprotein B (apo B) gene in 110 type 2 diabetic patients and 91 healthy control subjects in order to ascertain whether variation in this gene may influence the development of non-insulin dependent diabetes mellitus (type 2 diabetes). Serum lipids including total-cholesterol (T-Chol), triacylglycerol (TAG), apolipoprotein E (apo E), apolipoprotein AI (apo AI), apolipoprotein B and lipoprotein (a) (Lp(a)) were analysed. Genomic DNA was extracted and the apo B polymorphic regions amplified by the polymerase chain reaction. Regions carrying EcoRI, XbaI, and MspI restriction sites present in the apo B gene were amplified and digested separately by the respective enzymes. No significant difference for genotypic frequencies was observed for the EcoRI, XbaI and MspI restriction sites in type 2 diabetic patients as compared to controls. Type 2 diabetic patients and controls with EcoRI +/+ and XbaI +/+ genotypes had higher apo E levels. The MspI +/+ genotype is more frequent in the patient and control groups with elevated T-Chol. Furthermore, the EcoRI −/−, XbaI −/−, and MspI +/+ genotypes were found to be significantly more frequent in type 2 diabetic patients with higher blood glucose levels. This study identifies the apo B gene polymorphisms in modulating plasma lipid/lipoprotein and glucose levels in patients with type 2 diabetes. Copyright © 2005 John Wiley & Sons, Ltd.

In this study, we aimed to determine the alterations of beta-cell ultrastructure, insulin mRNA and protein products of the same gene on the pancreas of rats following long-term treatment of 5-aminoimidazole-4-carboxamide riboside (AICAR). A single dose of streptozotocin (STZ) 100 mg/kg was injected intraperitoneally (i.p.) to 2-day-old newborn (n2) rats. The rats were divided into three groups. The first group was the n2 STZ-diabetic rats. The second group consisted of n2 STZ-diabetic rats treated with AICAR 10 mg/kg/day for one month. The third group was non-diabetic control rats. Our findings demonstrate that AICAR treatment decreases the blood glucose level but increases the body weight in n2 STZ-diabetic rats. In the AICAR-treated group, numerous beta cells showed increased insulin gene expression. We also observed increased exocytosis in this group, in an ultrastructural manner. As a result, it is suggested that AICAR may induce insulin synthesis and betacell regeneration in n2 STZ-diabetic rats.

We studied the effect of variation at the lipoprotein lipase (LPL) gene locus on the susceptibility of individuals with non-insulin dependent diabetes mellitus (NIDDM) in a population of 110 NIDDM patients and 91 controls. Our objective was to study the relationship between the LPL-Pvu II polymorphism and NIDDM and lipid metabolism. PCR-RFLP was used to determine the DNA polymorphism of the sixth intron of the LPL gene. The frequencies of the genotypes in case and control groups were 29.1 and 30.8% for P+/P+ 45.5 and 36.3% for P+/P- 25.5 and 33% for P-/P- respectively. There was no significant difference in frequencies of genotypes between the two groups. Logistic regression analysis revealed that triacylglycerol (TAG) and apolipoprotein E levels were associated with NIDDM whereas Pvu II genotypes were not found as independent risk factors for the disease. Overall this study demonstrates the role of the Pvu II polymorphism in the LPL gene in modulating plasma lipid/lipoprotein levels in patients with NIDDM. Copyright (c) 2004 John Wiley & Sons Ltd.

Non-insulin dependent (Type 2) diabetes mellitus (NIDDM) is a risk factor for cardiovascular diseases (CVD). Oxidative stress mechanisms are often reported to be implied in type 2 diabetes mellitus. In order to determine their clinical relevance, we investigated several plasma indicators in the Turkish patients with NIDDM: (i) homocysteine (Hcy) and cysteine (Cys) which contribute to increase the risk of atherosclerosis during NIDDM, (ii) glutathione (GSH) and cysteinylglycine (CysGly) resulting from GSH degradation catalyzed by gamma-glutamylcysteine transferase (GGT), (iii) malonaldehyde (MDA) as a marker for lipid peroxidation, and (iv) total antioxidant status (TAS). Our main results were evaluated based on sex and diabetic status. In female patients, plasma concentrations of MDA and Hcy were significantly higher than in controls, while GSH levels were significantly lower. In males, a difference between control and diabetic groups was noticed only for Hcy, levels being also higher in patients. In the diabetic group, increase in serum glucose concentration was significantly correlated with increased GGT activity. In both controls and diabetic patients, GGT activity was correlated with a raised Cys concentration and a decreased GSH level. In both controls and diabetic patients, there were significant positive correlations between Cys and Hcy and between GSH and Hcy. We concluded that GSH and MDA levels are clinical indicators for an oxidative process linked to type 2 diabetes mellitus, especially in women.

In the present study, we examined electron microscopically and immunohistochemically the effects of perindopril, an angiotensin-converting enzyme inhibitor, on renal microangiopathy in streptozotocin-induced diabetes in rats. To investigate changes in glomerular basement membrane (GBM) and tubular basement membrane components, we immunohistochemically localized type IV collagen and laminin. Animals have been divided into three groups of eight adult male rats each. The first group was the non-diabetic control group. The second group consisted of untreated diabetic rats. The third group consisted of diabetic rats that were treated with perindopril for 6 weeks. Blood glucose levels and body weight were measured. Morphometric analysis of kidney tissue was performed using light and electron microscopy to quantify glomerular size and thickness of the GBM. Blood glucose levels in diabetic rats were significantly increased when compared with non-diabetic controls. Blood glucose levels were not affected by perindopril treatment. Untreated diabetic rats showed increased glomerular size, thickening of the GBM and an increase in mesangial matrix as compared with controls. Treatment with perindopril prevented effectively glomerular hypertrophy and thickening of the GBM. Significant increase in type IV collagen and laminin was found in thickened GBM and mesangial matrix in kidneys of untreated diabetic rats. In perindopril-treated diabetic rats, staining of type IV collagen and laminin was less strong when compared with untreated diabetic rats. In conclusion, our data suggest that perindopril treatment is effective in preventing renal lesions possibly by ameliorating the diabetes-induced increase in expression of type IV collagen and laminin.

Objective: Vitamin D receptor (VDR) gene polymorphisms and bone metabolic markers were investigated as potential genetic markers for osteoporosis in postmenopausal Turkish women. The relationship between their VDR gene polymorphisms and bone states was determined. Materials and Methods: Restriction fragment length polymorphisms at the VDR gene locus (i.e., for BsmI, ApaI, and TaqI) was investigated in 75 postmenopausal osteoporotic (53.16 ± 1.31 years) and 66 healthy (52.62 ± 1.69 years) Turkish women and the genotypes were related to bone mineral density (BMD) at femoral neck (FN), lumbar spine (L1–4), trochanter, Ward’s triangle (Ward’s) and metabolic parameters of bone turnover. Results: In osteoporotic women, TaqI genotype-related differences of the VDR gene were found to be significant at all BMD sites; TT genotype had higher L1–4 BMD values than Tt and tt (p < 0.05); tt genotype had significantly lower BMD at FN (p < 0.05), trochanter (p < 0.01), and Ward’s (p < 0.05) compared to TT genotype. The tt genotype was found to be associated with higher (p < 0.05) serum osteocalcin levels compared to Tt and TT genotypes in the osteoporotic women, whereas no such association was found for the healthy women. Conclusion: Our data showed an association between VDR TaqI genotype and BMD at the FN, L1–4, trochanter and Ward’s triangle in nonobese postmenopausal osteoporotic women. Thus the VDR gene Taql polymorphism modulates differences in BMD in the postmenopausal osteoporotic women.

Summary Somatostatin plays a role in the regulation of gastric acid secretion. Omeprazole, a potent inhibitor of gastric acid secretion, has been reported to cause either a significant decrease or increase in the formation of gastric somatostatin-producing cells. Therefore, we determined in the present study distribution patterns of somatostatin mRNA and protein in fundus mucosa of rats after long-term inhibition of gastric acid secretion. Female Sprague-Dawley rats were given 0, 20 and 100 mg/kg/day omeprazole, respectively, as gastric instillations during 2 months. Serum gastrin levels were significantly higher in the third group than in the other groups. The omeprazole-treated groups also showed an increase in the number of somatostatin-containing cells in fundus mucosa. Moreover, the intensity of somatostatin-positivity was higher in the treated groups than in the control group. We also observed an increase in the number of cells containing somatostatin mRNA in fundus mucosa of omeprazole-treated rats. These results suggest that long-term inhibition of acid secretion does not inhibit but stimulate somatostatin production in mucosa of rat gastric fundus.

Resistin, an adipocyte-secreted hormone, has been associated with obesity, insulin resistance and type 2 diabetes mellitus (T2DM) in some, but not all, rodent models. In humans, the exact function of resistin is unkown. Because 3'-untranslated region (3'-UTR) single nucleotide substitutions (SNPs) have been shown to affect gene expression, we examined the EX4-44G-->A SNP in the 3'-UTR of exon 3 within the resistin gene. The objective of this study was to investigate, for the first time in a Turkish study group, whether the 3'-UTR EX4-44G-->A variation in the resistin gene influences the development of T2DM, obesity and insulin-related phenotypes. We analyzed the genotype frequencies of the EX4-44G-->A polymorphism of the resistin gene in 116 type 2 diabetic and 102 normal subjects. Serum lipids, obesity-related and insulin-related phenotypes were analyzed. No significant difference for genotypic frequencies were observed for the BseRI restriction site in type 2 diabetic patients as compared to controls. Waist-to-hip ratio, BMI, body fat and apoAI levels were found to be affected by resistin genotype. In the control group, BMI (p < 0.01), HIS (p < 0.05) and BF (p < 0.05) levels were found to be elevated, whereas HOMA β-cell index (p < 0.01) and apo AI (p < 0.05) levels were found to be decreased in GG genotype carriers. In the diabetic group, the GG genotype carriers were found to have higher BMI levels (p < 0.001), waist-to-hip ratio (p < 0.05), body fat (p < 0.01), HOMA (p < 0.001) and fasting insulin (p < 0.05), but lower HbA1c levels in comparison to GC + AA carriers. These data suggest that, in the Turkish study group, the EX4-44G-->A polymorphism of the resistin gene is associated with insulin and obesity-related phenotypes.