Granzyme B levels and granzyme B polymorphisms in peripheral blood of patients with endometriosis: a preliminary study.

The chronic course of endometriosis suggests that the immune system may play a role in its aetiology. There may be resistance to cell lysis, as well as an immune defect underlying endometriosis. Granzyme B is a serine protease that is secreted by Natural Killer (NK) cells and cytotoxic T lymphocytes during a cellular immune response and can induce apoptosis. The aim of this study was to evaluate the relationship between both Granzyme B levels and Granzyme B gene polymorphisms in endometriosis patients. Women between the ages of 20 - 45 were included in the study. The patients were divided into two groups: those diagnosed with endometriosis and those who had not been diagnosed with endometriosis. In the blood samples, Granzyme B gene polymorphisms and serum levels of Granzyme B were studied. There was no difference between the groups in terms of median Granzyme B levels and the presence of AA, AG, and GG genotypes. There was a difference in median granzyme levels for the control group; the GG genotype was found at a lower frequency. The immune defect within endometriosis-related immune cells may not be exclusively due to Granzyme B. Other mediators that are secreted from immune cells may have additive effects.IMPACT STATEMENTWhat is already known on this subject? NK cells are cytotoxic and inhibit the implantation of autologous endometrial cells that are spilled into the peritoneum by retrograde menstruation. Thus, a reduction in NK cell activity may facilitate the progression of endometriosis. The literature review reveals that there are studies suggesting that NK cell activity may be insufficient in endometriosis. Granzyme B is a serine protease that is secreted by NK cells and cytotoxic T lymphocytes during a cellular immune response.What do the results of this study add? Granzyme B is one of the cytotoxic granules in NK and cytotoxic T lymphocyte cells and its genetic polymorphisms were tested in endometriosis. We found that median Granzyme B levels were significantly different in patients with the GG genotype in the control group, compared to those with the AA and AG genotype. However, this difference was not detected between the control and endometriosis groups.What are the implications of these findings for clinical practice and/or further research? Our results contribute to uncovering the pathogenesis of endometriosis since there are no previous studies in the literature regarding this topic. Although we did not find a difference, our results will inform further studies made on this topic. Studies with different molecules and an increased number of patients are needed. The immune defect of endometriosis may not be due exclusively to Granzyme B. Other mediators that are secreted from immune cells may have mutual effects and interactions.

Antiinflammatory effects of adalimumab, tocilizumab, and steroid on lipopolysaccharide-induced lung injury.

BACKGROUND: Acute lung injury (ALI) is a major cause of death in the intensive care unit. Lipopolysaccharide (LPS) induced lung injury is the most widely used experimental ALI model and provides opportunities for new targeting therapy. In this study, we investigated the effects of tocilizumab, adalimumab, and methylprednisolone in LPS-induced acute lung injury. METHODS: Lung injury was established by intratracheal instillation of LPS. The rats were randomly divided into six groups: LPS, control, and treatment groups (adalimumab, tocilizumab, methylprednisolone, adalimumab + tocilizumab). Bronchoalveolar lavage (BAL) and lung tissues were collected at 48 h and 96 h following LPS administration from each group. For histological analysis, hematoxylin-eosin (H&E) staining was performed. The sections were obtained for immunohistochemical analysis. IL-6 and TNF-alpha immunoreactivity were measured. RESULTS: Intratracheal LPS application resulted in inflammatory cell infiltration of interstitial and alveolar spaces and thickening of the alveolar wall. All treatment groups showed significantly amelioration compared to LPS at 48 h. Interestingly, adalimumab and adalimumab + tocilizumab groups showed a significant amelioration of the lung histoarchitecture, compared to the prednisolone group at 96 h (p = 0.028, p = 0.025, respectively). Compared to the control group, LPS stimulation resulted in a significant increase in IL-6 and TNF-alpha immunoreactivity (p < 0.001). IL-6 and TNF-alpha expression were markedly reduced in all treatment groups at 48 h but the reduction was greater in the adalimumab and tocilizumab group than in the steroid. Administration with adalimumab and/or tocilizumab effectively decreased expression of TNF-alpha (p = 0.001) and IL-6 (p < 0.001) at 96 h, but prednisolone did not exert an effective decrease (p > 0.05). DISCUSSION: Adalimumab and/or tocilizumab significantly reduce the release of proinflammatory cytokines and improve the tissue inflammation in the experimental model of ALI. Our results suggest that adalimumab and/or tocilizumab have a more potent antiinflammatory effect on lung injury than the steroid.

Changes in pro-inflammatory cytokines and antimicrobial proteins in elderly women with iron deficiency anemia.

OBJECTIVE: Iron Deficiency Anemia (IDA) is common nutritional deficiency particularly in women and also common during the older age. Aging increases plasma levels of inflammatory mediators such as pro-inflammatory cytokines and acute phase proteins. However, there is little information about changes in antimicrobial proteins in elderly women with IDA. In this study, we aimed to determine the changes in pro-inflammatory cytokines and newly discovered antimicrobial proteins like hepcidin, chemerin and defensin in elderly women with IDA. METHODS: Blood samples taken from healthy 20 women (55±7 years old) and 20 women with iron deficiency anemia (58±6) were used as material of the study that came to the Cankiri State Hospital in 2016 and 2017 years. RESULTS: In the study, plasma C-Reactive Protein (CRP) (P <0.01), tumour necrosis factor-α (TNF-α) (P <0.05) and interleukin-6 (IL-6) levels (P <0.05) were significantly increased in group with IDA when compared with healthy group. Also plasma hepcidin (P <0.001), chemerin (P <0.05) and defensin levels (P <0.05) were determined significantly higher than the healthy group. CONCLUSION: We found that inflammatory changes occur in elderly women with IDA. Besides pro-inflammatory cytokine levels (CRP, IL-6, TNF-α), antimicrobial protein levels (hepcidin, chemerin, defensin) were found higher in elderly women with IDA because of inflammatory changes.

Protective Effects of Quercetin on Necrotizing Enterocolitis in a Neonatal Rat Model.

INTRODUCTION: Necrotizing enterocolitis (NEC) is one of the major health problems of newborn period. To date, a large amount of chemicals have been tested for NEC and some showed limited beneficial effects. The research for better results still continues. This study aims to investigate the effects of quercetin (QE) on NEC treatment in rats. METHODS: Newborn rats were divided into control, NEC, and NEC + QE groups. In NEC and NEC + QE groups, experimental NEC was induced. NEC + QE group animals were also given QE. Weight changes of the animals were recorded, and serum total antioxidant status (TAS), total oxidant status (TOS), malondialdehyde (MDA), and glutathione (GSH) levels were measured. Histologic evaluation of the distal ileum and the terminal deoxynucleotidyl transferase dUTP nick end labeling staining were performed. RESULTS: A significant increase in the TAS levels was observed in NEC + QE group. Only NEC group exhibited significantly higher TOS and MDA levels and lower GSH levels. Rats in the NEC + QE group had better histopathology and less apoptosis than NEC group. CONCLUSION: QE is effective in enhancing antioxidant defense mechanism, limiting oxidative stress, reducing intestinal damage, and preventing NEC development.

Investigating the relationship between plasma neuropeptide-S levels and clinical depression.

PURPOSE: Neuropeptide-S (NPS) is a novel 20-amino acid peptide, mainly expressed in the central nervous system and endocrine tissues. NPS has been linked to anxiety and fear-related behaviors. The association of NPS with depression in a human population has not been previously examined. The aim of the current study was to explore the potential association of NPS with clinical depression and comorbid anxiety. MATERIALS AND METHODS: Seventy-nine patients diagnosed with major depressive disorder and seventy-eight controls were included in the study. The Hamilton Depression Scale (HAM-D) and Hamilton Anxiety Scale (HAM-A) were used to measure depression and anxiety levels, respectively. Venous blood samples were obtained to measure plasma NPS levels. RESULTS: There were no statistically significant differences between the patients and controls in terms of sex, marital status, and smoking status. Plasma NPS levels were also not significantly different between the patients and controls. In patients with major depressive disorder, HAM-A and HAM-D scores were significantly higher than those of controls. No correlation was found between plasma NPS levels and age, body mass index (BMI), median HAM-A scores, and median HAM-D scores. CONCLUSIONS: Despite a significantly high level of comorbid anxiety among the patient group, we found no relationship between plasma NPS levels and depressive symptomatology.

The effects of IL-1A and IL-6 genes polymorphisms on gene expressions, hormonal and biochemical parameters in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a multifactorial disease characterised by chronic inflammation. We aimed to investigate an association between IL-1A and IL-6 gene polymorphisms and both hormonal/biochemical parameters and levels of IL-1A and IL-6. A total of 103 women diagnosed with PCOS according to ESHRE/ASRM criteria were investigated. The patients were divided into two groups as obese and non-obese. IL-1A and IL-6 genes polymorphisms as well as hormonal/biochemical parameters and levels of IL-1A and IL-6 were analysed in the same groups. Serum IL-1A and IL-6 levels were found to increase both in obese and non-obese groups. However, there was no association between IL-1A level and IL-1A polymorphism. A relationship was detected between H score, FSH, LH, total testosterone, HDL-C and TG levels and CG + GG genotypes of IL-6. Furthermore, an association was found between IL-6 levels and CC genotype of IL-6 in the obese PCOS patients. The abnormalities in hormonal/biochemical parameters detected in Turkish PCOS patients may be related with IL-6 gene polymorphism rather than IL-1A.

NUCB2 gene polymorphism and its relationship with nesfatin-1 levels in polycystic ovary syndrome.

Nesfatin-1, encoded by the nucleobindin-2 (NUCB2) gene, is an anorexigenic protein related to energy metabolism, obesity, and insulin resistance. The aim of this study was to evaluate NUCB2 gene polymorphism (rs757081) and its association with serum levels of nesfatin-1 in obese and non-obese women with polycystic ovary syndrome (PCOS). In the study population, we analyzed 60 patients with PCOS and 26 age-matched healthy women as controls. The patients with PCOS were divided into two groups based on body mass index (BMI): obese group (n = 28) or non-obese group (n = 32). NUCB2 was genotyped using the polymerase chain reaction-restriction (PCR) technique. Serum nesfatin-1 level was measured by enzyme-linked immunosorbent assay (ELISA). Nesfatin-1 levels in the obese PCOS group were significantly lower than those in the non-obese PCOS and control groups (p < 0.001). There was no statistically significant difference in the distribution of NUCB2 genotypes among the groups (p > 0.05), whereas nesfatin-1 levels in the CC and CG genotypes were lower than those in the GG genotype. Nesfatin-1 decreases in PCOS, especially in obese women, and is negatively correlated with cardiometabolic risk factors. Although genotype disturbances of NUCB2 were similar among the groups, CC and CG genotypes accompanied lower nesfatin-1 levels. C allele of NUCB2 gene polymorphism and nesfatin-1 may play a role in the pathophysiology of PCOS.

Prevention of ovarian hyperstimulation syndrome in a rat model: comparison of the efficacy of tocilizumab with that of ranibizumab, cabergoline, and a gonadotropin-releasing hormone antagonist.

The aim of the study is to investigate the effects of the interleukin-6 (IL-6) blocker tocilizumab in a hyperstimulated rat model and compare it with ranibizumab, a gonadotropin-releasing hormone antagonist (GnRHA), and cabergoline. Forty-seven rats were randomly divided into the following seven groups: Group 1: OHS; Group 2: OHS+ GnRHA; Group 3: OHS + ranibizumab; Group 4: OHS + cabergoline; Group 5: OHS + low-dose tocilizumab (TL); Group 6: OHS + high-dose tocilizumab (TH); Group 7: sham. Ovarian weight was significantly lower only in the ranibizumab group than in the OHS group. Estrogen levels were significantly lower in the GnRHA group than in the OHS and the treatment groups. Progesterone levels were significantly lower in the ranibizumab, cabergoline, and TL groups than in the OHS group. Among the treatment groups, corpus luteum counts were lower than in the OHS group. Corpus luteum counts were lowest in the tocilizumab groups. IL-6 intensity was lower in all treatment groups than in the OHS group. In the ranibizumab group IL-6 intensity was the lowest. The TL group did not significantly differ from the GnRHA and cabergoline groups regarding IL-6 expression. Ovarian VEGF expression was significantly lower in all treatment groups. For the TL, ranibizumab, and cabergoline groups VEGF intensity was similar. Tocilizumab may be a new strategy for preventing ovarian hyperstimulation syndrome by inhibition of IL-6.

Oncostatin M Is Related to Polycystic Ovary Syndrome-Case Control Study.

Background: Oncostatin M, a novel adipokine, plays a role in oogenesis, lipogenesis, and inflammation and may contribute to polycystic ovary syndrome pathogenesis and related metabolic problems. Adipokines are believed to contribute to developing polycystic ovary syndrome and its accompanying metabolic parameters, such as dyslipidemia, insulin resistance, and cardiovascular diseases. Methods: In this case-control study, the patients were grouped in a 1:1 ratio into either the polycystic ovary syndrome (n = 32) or the control group (n = 32). Serum levels of fasting glucose, insulin, C-reactive protein, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, white blood cell count, thyroid-stimulating hormone, luteinizing hormone, follicle-stimulating hormone, total testosterone, prolactin, estradiol, homeostasis model assessment of insulin resistance, and oncostatin M were analyzed. Results: Oncostatin M levels were significantly lower, but C-reactive protein levels were substantially higher in the polycystic ovary syndrome group than in the control group (p = 0.002, p = 0.001, respectively). Oncostatin M was inversely correlated with total cholesterol, non-high-density lipoprotein cholesterol, fasting glucose, and the luteinizing hormone/follicle-stimulating hormone ratio (ρ = -0.329, p =0.017; ρ = -0.386, p = 0.005; ρ = -0.440, p = 0.001; ρ = -0.316, p = 0.023, respectively). Conversely, there was no correlation between oncostatin M and total testosterone level (ρ = 0.220; p = 0.118). In the context of inflammation and metabolic parameters, oncostatin M was inversely correlated with C-reactive protein, homeostatic model assessment for insulin resistance score, and low-density lipoprotein cholesterol (ρ = -0.353, p = 0.019; ρ = -0.275, p = 0.048; ρ = -0.470, p < 0.001, respectively). Conclusions: Plasma oncostatin M levels were considerably lower in patients with polycystic ovary syndrome than in the control group, and this was inversely correlated with the hormonal and metabolic parameters of polycystic ovary syndrome. Thus, oncostatin M may be a novel therapeutic target for polycystic ovary syndrome and its metabolic parameters.

Effects of melatonin hormone on hippocampus in pinealectomized rats: an immunohistochemical and biochemical study.

OBJECTIVE: The effects of melatonin on antioxidant status were examined in pinealectomized rats using enzymatic, histological and immunohistochemical techniques. The aim of this study is to investigate the effects of melatonin on hippocampal apoptosis. MATERIALS AND METHODS: Male Wistar rats (n=21) were divided into 3 groups: Group I and group II were designated as control (sham-pinealectomy) and pinealectomized rats, respectively. Rats in group III were pinealectomized and injected daily with melatonin (1 mg/kg) for 3 months beginning at day 7 after surgery. At the end of experimental period, all rats were killed by decapitation. The brains of the rats were removed and the hippocampus tissue was obtained from all brain specimens. The right hippocampal specimens of all rats were used for determination of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels. The left hippocampus tissue specimens of all animals were used for immunohistochemical and histological evaluation. RESULTS: The levels of SOD and GSH-Px were significantly decreased, and MDA levels were significantly increased in pinealectomized rats compared to the controls. In the histological and immunohistochemical evaluation of this group, increase of pyknotic cells, vacuolar degeneration and apoptosis were observed. However, increased SOD and GSH-Px enzyme activities, and decreased MDA levels were detected in the rats administered melatonin after pinealectomy. Furthermore, histological and apoptotic changes in hippocampus caused by pinealectomy were lost in the rats treated with melatonin. CONCLUSIONS: The results of our study revealed that pinealectomy-induced oxidative damage and morphological changes in the hippocampal tissue were suppressed by melatonin.

Neutrophil gelatinase-associated lipocalin serum level: A potential noninvasive biomarker of endometriosis?

Neutrophil gelatinase-associated lipocalin (NGAL, also known as lipocalin-2) is an acute-phase protein expressed in many tissues and plays a role in cell proliferation, regulation, and epithelial-mesenchymal transformation. Therefore, this study aimed to investigate serum NGAL levels and endometrioma tissue expression in women with endometriosis. This cross-sectional study was conducted at a university hospital. The endometrioma group included 36 women who underwent ovarian cystectomy for endometrioma, which was compared with a control group (n = 36) of women who underwent ovarian cystectomy due to benign persistent cysts (follicle cyst, theca lutein cyst, and serous cystadenoma). NGAL levels were analyzed using both serum enzyme-linked immunosorbent assay analysis and immunohistochemical tissue staining. Serum C-reactive protein and CA-125 levels were also evaluated. NGAL serum levels were significantly higher in the endometrioma group than in the control group (P < .05). C-reactive protein and CA-125 levels were also significantly higher in the endometrioma group (P < .05) and were correlated with NGAL levels. Immunohistochemical staining for NGAL was also higher in the endometrioma group (P < .001). NGAL may be considered a potential noninvasive biomarker of endometriosis.

The novel relationship between polycystic ovary syndrome and temporomandibular joint disorders.

INTRODUCTION: Studies investigating the relationship between sex hormones, inflammatory mediators and joint disorders have reported that sex hormones affect the pathogenesis of joint disorders. We aimed to investigate temporomandibular joint disorder (TJD) in polycystic ovary syndrome (PCOS) and the possible role of systemic mediators and sex hormones in TJD pathogenesis. MATERIAL AND METHODS: PCOS patients (n = 45) and controls (n = 30) aged 20-40 years, were enrolled in this case-control study. TJD diagnosis was performed by the specialist and blood samples were tested in the early follicular phase and on the 21 st (midluteal) day to investigate the levels of estrogen, progesterone, matrix metalloproteinase (MMP) 1-8-9, interleukin (IL)-1ß and Tumor necrosis factor (TNF)-α. RESULTS: TJD incidence was significantly higher in PCOS than the control group (51.1% and 6.9% respectively, p < 0.01). Midluteal progesterone (p < 0.01) was lower in PCOS group than the controls (p < 0.01). TNF-α (p < 0.01), MMP 1 (p < 0.01) and MMP 8 (p = 0.02) levels were found significantly higher in PCOS than the control group. Further, Progesterone levels were found significantly lower in TJD (+) PCOS patients than TJD (-) PCOS patients. However, significant difference was not found between the PCOS TJD (+) and PCOS TJD (-) patients for estrogen, MMP 1, MMP 8, MMP 9, TNF-α and IL-1ß. CONCLUSIONS: TJD frequency was found significantly increased in PCOS patients. Related with this, TJD co-occurrence should be kept in mind in the diagnosing and treatment process of PCOS due to hormonal alteration.

Plasma Neuropeptide-S Levels in Populations Diagnosed with Generalized Anxiety Disorder: A Controlled Study.

INTRODUCTION: Neuropeptide S (NPS) is a novel neuropeptide reported to be involved in fear-and stress-related conditions and their corresponding neuroendocrine processes. The aim of this study was to compare the plasma NPS levels in patients suffering from generalized anxiety disorder (GAD) and those of healthy controls. METHODS: A total of 40 subjects diagnosed with GAD and 40 healthy controls were recruited in the study. The Hamilton Anxiety Scale (HAM-A), Generalized Anxiety Disorder-7 (GAD-7), and Hamilton Depression Scale (HAM-D) were administered to all participants to determine the severity of participants' anxiety and concomitant depressive symptoms. The plasma NPS levels were measured from the fasting venous blood samples obtained from each participant. RESULTS: The median plasma NPS level was found to be significantly higher in the GAD group in comparison to the control group (28.8 pg/mL as against 19.1 pg/mL, p=0.01). A significant positive correlation was observed between the plasma NPS levels and HAM-A scores (rs=0.23, p=0.04) as well as the GAD-7 scores (rs=0.28, p=0.01). The p-value obtained from the correlation analysis between the plasma NPS levels and HAM-D scores was 0.052. A receiver operating characteristic (ROC) analysis revealed that the plasma NPS levels could enable the identification of GAD with 67.5% sensitivity and 62.5% specificity, when the cut-off value was determined as 25.06 pg/mL. CONCLUSIONS: Our results support the view that plasma NPS levels, which has demonstrated anxiolytic effects on the central nervous system, is related to the severity of anxiety in GAD and could be considered as a candidate marker for the identification of GAD.

Does progesterone have protective effects on ovarian ischemia-reperfusion injury?

OBJECTIVE: The aim of the present study was to evaluate the effects of progesterone (PG) against ovarian ischemia-reperfusion (I/R) injury through the evaluation of biochemical and histopathologic parameters. MATERIAL AND METHODS: Twenty-one female Wistar albino rats were divided into three groups. Group 1: Sham; group 2: I/R; group 3: I/R+PG (8 mg/kg). PG was administered intraperitoneally to the rats in group 3, 30 minutes before a detorsion operation. Ovarian I/R injury was evaluated in serum and tissue by using biochemical parameters including malondialdehyde (MDA), total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index, neutrophil gelatinase-associated lipocalin (NGAL) and immunofluorescence staining by using a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. RESULTS: Serum and tissue TOS levels were significantly lower in group 3 than in group 2. Tissue TAS levels were higher in group 3 than in group 2 (p<0.001). NGAL and MDA levels were similar between the groups. Histologic score, including vascular congestion, hemorrhage, polymorphonuclear neutrophils, and interstitial edema, was higher in group 2. Pre-treatment with PG decreased the score, but this difference was not statistically significant. The number of apoptotic cells was higher in group 2 than in groups 1 and 3. The TUNEL-positive cell number decreased with PG in group 3. CONCLUSION: Preoperative PG treatment might exert protective effects on ovarian I/R injury through its anti-apoptotic and antioxidative properties.

Oxidative stress, hepcidin and nesfatin-I status in childhood iron and vitamin B12 deficiency anemias.

BACKGROUND: Anemia is a disease that is long and often repetitive and can result in a great burden to the national economy. The most frequent nutritional deficiency anemias in children are related with iron and vitamin B12 deficiencies. OBJECTIVES: The aim of this study was to determine the oxidative stress, hepcidin, and nesfatin-I levels in childhood iron and vitamin B12 deficiency anemias. MATERIAL AND METHODS: The study had 3 groups of 15 children, iron anemia deficiency group, vitamin B12 deficiency group and a control group. RESULTS: The TBARS and nesfatin-I levels were significantly higher in the iron and vitamin B12 deficiency groups and the total antioxidant levels were significantly lower when compared to the control group. In contrast, the plasma hepcidin levels were significantly lower in the iron deficiency group (p < 0.01) when compared to the control group; however, no significant differences were observed in the vitamin B12 deficiency group. Plasma homocysteine levels were significantly higher in the vitamin B12 deficiency group when compared to the control group (p < 0.001), but no differences were determined between the iron deficiency and control groups. CONCLUSIONS: Our results showed that there are high levels of oxidative stress in childhood iron and vitamin B12 deficiency anemias, and we propose that plasma hepcidin and homocycteine levels may be useful in the differential diagnosis of childhood nutritional deficiency anemias. Nesfatin-1 hormone levels were identified for the first time in childhood iron deficiency and vitamin B12 deficiency anemias within this study and this hormone may also be useful in the differential diagnosis of anemias.

Paraoxonase 1 phenotype and paraoxonase activity in asthmatic patients.

Oxidative stress is involved in the pathogenesis of asthma. Paraoxonase 1 (PON1) and arylesterase are esterase enzymes displaying antioxidant characteristics. PON1 activity varies widely among individuals and ethnic groups, partly related to polymorphisms. The aim of this study was to determine the activities of PON1 and arylesterase including the phenotype distribution of PON1 in asthmatic patients and healthy subjects. Forty-nine asthmatic patients and 41 healthy people were included in this study. Serum PON1 and arylesterase activities were determined by spectrophotometric assays, as well as the lipid profiles. The PON1 ratio (salt stimulated paraoxonase/arylesterase) was trimodally distributed and this ratio was used to determine the individual phenotypes of all subjects. The PON1 activity in the asthmatic patients was significantly lower (p=0.024) when compared to the healthy control group, however no significant difference in the activity of arylesterase was observed between the two groups. The prevalence of the PON1 phenotypes in the asthmatic population were 26.5%, 16.3% and 57.2 % for QQ, QR and RR, respectively. PON1 activity was significantly lower in asthmatic patients; in addition, the results of this investigation indicated that PON1 RR phenotype may be an important risk factor in asthma disease.

Circulating levels of obestatin and copeptin in obese and nonobese women with polycystic ovary syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies, affecting 5-8% of reproductive-age women. It is associated with insulin resistance, central obesity, type 2 diabetes mellitus, dyslipidemia, and cardiovascular diseases. The current study was undertaken to evaluate serum copeptin and obestatin levels, carotid artery intima-media thickness, and brachial artery flow mediated dilatation in obese and nonobese women with PCOS and age-matched healthy controls and to investigate their relationship with each other and with clinical, metabolic, and hormonal parameters and cardiovascular risk factors. METHOD: In the study population, we analyzed 60 patients with PCOS and 30 age-matched healthy women as controls. The patients with PCOS were divided into two groups based on body mass index (BMI): obese group (BMI>30kg/m(2), n=30) or nonobese group (BMI<30kg/m(2), n=30). History was obtained and a physical examination, peripheral venous blood sampling, and carotid and brachial artery ultrasonography were performed. Serum copeptin and obestatin levels, total testosterone, C-reactive protein (CRP), glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, homeostasis model assessment for insulin resistance (HOMA-IR), carotid artery intima-media thickness (CIMT), and brachial artery flow-mediated vasodilation (FMD) were determined and compared among the groups. RESULTS: Women with PCOS, especially obese ones, had higher triglycerides, HOMA-IR, total testosterone, CRP, systolic and diastolic blood pressure, and waist-to-hip ratio (WHR), and lower HDL. Serum obestatin levels were significantly lower in the obese PCOS group than they were in the nonobese and control groups (p<0.001). Serum copeptin levels were significantly higher in the obese PCOS group than they were in the nonobese PCOS and control groups (p<0.001). CIMT values were similar among the groups (p>0.05). Brachial artery FMD was lower in the PCOS groups than it was in the control group (p<0.001). Obestatin and FMD values were negatively correlated with cardiovascular risk factors, whereas copeptin was positively correlated. A significant positive correlation was found between copeptin, BMI, WHR, hirsutism score, total testosterone, and HOMA-IR. There was no correlation between CIMT, copeptin, obestatin, and FMD. A positive correlation was seen between CIMT, BMI, triglycerides, and HOMA-IR. CONCLUSION: Copeptin and obestatin may provide useful information regarding future cardiovascular risk in PCOS patients as copeptin was positively correlated and obestatin was negatively correlated with cardiovascular risk factors.

Effect of 2-aminoethoxydiphenyl borate on ischemia-reperfusion injury in a rat ovary model.

OBJECTIVE: The aim of this study is to evaluate the effects of 2-aminoethoxydiphenyl borate (2-APB) as an antioxidant and analyze biochemical and histopathologic changes in experimental ischemia-reperfusion (I/R) injury in rat ovaries. STUDY DESIGN: Thirty female rats were utilized to create four groups. Group 1: I/R and 2-APB (2mg/kg); Group 2: I/R and 2-APB (4mg/kg); Group 3: I/R; Group 4: sham operation. Ovarian tissue and serum malondialdehyde, nitric oxide (NO) levels; ovarian tissue and serum total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI) were determined. In ovarian tissue samples histopathologic examination, immunoflourescence staining by TUNEL method was studied. RESULTS: Tissue TOS, serum TOS, and OSI levels were elevated in I/R group. After treatment with 2-APB, tissue and serum TOS levels and OSI levels were markedly decreased. There was a significant difference in terms of tissue and serum NO levels between the sham group and I/R group. Elevation in tissue NO and serum NO levels were decreased after treatment with 2-APB. TUNEL-positive cell number gradually decreased with dose of 2-APB in groups 1 and 2. CONCLUSION: Conservative treatment with 2-APB is beneficial for mitigation of I/R injury, and the ovarian protective effect of 2-APB appears to be mediated through its antiapopitotic and antioxidative effects.

Isolation and biochemical analysis of vesicles from taurohyodeoxycholic acid-infused isolated perfused rat livers.

AIM: To isolate biliary lipid-carrying vesicles from isolated perfused rat livers after taurohyodeoxycholic acid (THDC) infusion. Biliary lipid vesicles have been implicated in hepatic disease and THDC was used since it increases biliary phospholipid secretion. METHODS: Rat livers were isolated and perfused via the hepatic portal vein with THDC dissolved in Krebs Ringer Bicarbonate solution, pH 7.4, containing 1 mmol/L CaCl2, 5 mmol/L glucose, a physiological amino acid mixture, 1% bovine serum albumin and 20% (v/v) washed human erythrocytes at a rate of 2000 nmol/min for 2 h. The livers were then removed, homogenized and subjected to centrifugation, and the microsomal fraction was obtained and further centrifuged at 350000 g for 90 min to obtain subcellular fractions. These were analyzed for total phospholipid, cholesterol, protein and alkaline phosphodiesterase I (PDE). RESULTS: No significant changes were observed in the total phospholipid, cholesterol and protein contents of the gradient fractions obtained from the microsomal preparation. However, the majority of the gradient fractions (ρ= 1.05-1.07 g/mL and ρ = 1.95-1.23 g/mL) obtained from THDC-infused livers had significantly higher PDE activity compared to the control livers. The low density gradient fraction (ρ = 1.05-1.07 g/mL) which was envisaged to contain the putative vesicle population isolated from THDC-perfused livers had relatively small amounts of phospholipids and protein when compared to the relevant control fractions; however, they displayed an increase in cholesterol and PDE activity. The phospholipids were also isolated by thin layer chromatography and subjected to fractionation by high performance liquid chromatography; however, no differences were observed in the pattern of the fatty acid composition of the phospholipids isolated from THDC and control perfused livers. The density gradient fractions (ρ = 1.10-1.23 g/mL) displayed an increase in all the parameters measured from both control and THDC-infused livers. CONCLUSION: No significant changes in biliary lipids were observed in the fractions from THDC-infused livers; however, PDE activity was significantly increased compared to the control livers.

Biliary lipid secretion.

The liver has many biochemical functions, of which one of the most important is bile formation. Bile is both a secretory and an excretory fluid and two of its most important functions are the delivery to the intestinal tract of: (i) bile acids to assist in fat digestion and absorption; and (ii) liver-derived metabolites of potentially toxic materials prior to their elimination from the body in the feces. Bile contains numerous solutes, including bile acids, phospholipids and cholesterol. Biliary lipids mainly consist of cholesterol and phospholipids and their secretion into bile is affected by the secretion of bile acids. Phospholipids and cholesterol are synthesized in the hepatocytes and are thought to be transferred via vesicle- and non-vesicle-mediated mechanisms into the bile canaliculus. Hepatocytes acquire biliary lipid by three pathways, which are biosynthesis, lipoproteins and existing molecules drawn from intracellular membranes, with the newly synthesized biliary lipid accounting for less than 20% of the total lipids. The hepatic determinants of biliary cholesterol elimination are not limited to total cholesterol homeostasis, but also concern biliary disease conditions, since excess biliary cholesterol secretion is involved in cholesterol gallstone formation, as well as being a major risk factor for gallbladder cancer. The purpose of this review was to highlight some of the major mechanisms involved in biliary lipid secretion.