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Background: Hyperprolactinemia is associated with changes in body composition and metabolic abnormalities. Normalization of prolactin (PRL) has been suggested to reverse these abnormalities. The present study was designed to determine the effect of treatment duration on metabolism as well as metabolic alterations after treatment in comparison with baseline in patients with prolactinoma in Iranian individuals. Methods: In a prospective and longitudinal study, 27 consecutive patients with prolactinoma were assessed during 6 months. Anthropometric data and metabolic variables were studied at baseline and at 3 and 6 months after normalization of PRL. Results: In the present study, there was a statistically significant decrease of metabolic syndrome (Met.S) after 3 months (P = 0.01), with a further decline after 6 months (P < 0.001) of cabergoline therapy. Moreover, a statistically significant decline was seen in total cholesterol (P = 0.007 and P = 0.01 after 3 and 6 months, respectively) and uric acid (P = 0.05 and P = 0.03 after 3 and 6 months, respectively) after normalization of the serum PRL. Conclusions: We found a significant reduction in Met.S after normalization of PRL level in patients with prolactinoma. We suggest that it is important to consider the metabolic profile of patients with prolactinoma. Then, patients may benefit even at 3 months after treatment.

Background Pituitary adenomas are benign brain tumors that cause considerable morbidity and neurological symptoms. SOX9 as a regulatory transcriptional mediator affects normal and tumor cell growth with an undefined role in pituitary adenomas pathogenesis. Thus, in the present study, the expression pattern of SOX9 in GH-secreting pituitary tumors and normal pituitary tissues is investigated. Methods The SOX9 gene expression level was evaluated in 60 pituitary tissues including different types of GH-secreting adenomas and normal pituitary tissues through Real-Time PCR. The protein level of SOX9 was assessed using immunohistochemistry. The correlations of SOX9 gene and protein expression level with the patient’s clinical and pathological features were considered. Results The SOX9 over-expression was detected in GH-secreting adenomas tumor tissues compared to normal pituitary tissues which were accompanied by overexpression of SOX9 protein in tumor tissues. The over-expression of SOX9 had a significant impact on GH-secreting adenomas tumor incidence with the odds ratio of 8.4 and the diagnostic value of SOX9 was considerable. The higher level of SOX9 expression was associated with invasive and macro tumors in GH-secreting pituitary adenoma patients. The positive correlation of SOX9 gene and protein level was observed and the tumor size and tumor invasive features were valuable in predicting SOX9 expression level in GH-producing pituitary tumors. Conclusion The study provided the first shreds of evidence regarding the expression pattern of SOX9 in the GH- secreting pituitary adenomas at both gene and protein levels which may emphasize the possible involvement of SOX9 as a mediator in pituitary adenoma tumor formation also open up new intrinsic molecular mechanism regarding pituitary adenoma pathogenesis.

The present study aimed to evaluate the efficacy of add-on therapy of cabergoline versus raloxifene to long-acting somatostatin analogues (SAs) in patients with inadequately controlled acromegaly.This was a prospective, randomized open label clinical trial. Forty-four patients (22 per group) completed the study; where participants received either cabergoline (3 mg/week) or raloxifene (60 mg twice daily) add-on therapy for 12 weeks in a parallel manner. The primary outcome was the rate of reduction in serum insulin-like growth factor 1 (IGF-1) from baseline. Secondary outcomes comprised normalization of serum IGF-1 for age and sex.Serum IGF-1 was significantly decreased in both the cabergoline (40.3 ± 25.6%, P.001) and raloxifene (31.5 ± 24.6%, P.001) groups, with no significant difference between arms ( P.05). Normalization in serum IGF-1 values occurred in 40.9% of patients who were on cabergoline compared to 45.5% of those receiving raloxifene ( P = .76). The subsequent logistic regression analysis highlighted baseline IGF-1 as a significant predictor of IGF-1 normalization (odds ratio, 0.995; 95% confidence interval, 0.990-0.999; P = .02). Using the receiver operating characteristic (ROC) curve analysis for the entire group, the baseline IGF-1 value of 1.47 the upper limit of normal (ULN) was the best cut-off point to identify patients with normal IGF-1 at the end of the study (sensitivity: 52.6%, specificity: 84.0%, Yoden's index: 0.366). Full biochemical control of acromegaly was achieved in 22.7% of patients in the cabergoline group compared to 13.6% of those in the raloxifene group ( P = .43).Cabergoline and raloxifene add-on therapy could effectively decrease serum IGF-1 level in patients with inadequately controlled acromegaly. The efficacy profiles of both drugs are comparable.DA = dopamine agonist; FBG = fasting blood glucose; GH = growth hormone; IGF1 = insulin-like growth factor-1; IQR = interquartile range; OR = odds ratio; ROC = receiver operating characteristic; SA = somatostatin analogue; SERM = selective estrogen modulator receptor; ULN = upper limit of normal.

Background Pituitary adenoma accounts as a complex and multifactorial intracranial neoplasm with wide range of clinical symptoms which its underlying molecular mechanism has yet to be determined. The bioactive lipid mediators received attentions toward their contribution in cancer cell proliferation, progression and death. Amongst, 15-Lipoxygense (15-Lox) enzymes and products display appealing role in cancer pathogenesis which their possible effect in pituitary adenoma tumor genesis is perused in the current study. Methods The 15-Lipoxygenses isoforms expression level was evaluated in tumor tissues of prevalent functional and non-functional pituitary adenomas and normal pituitary tissues via Real-Time PCR. The circulating levels of 15(S) HETE and 13(S) HODE as 15-Lox main products were assessed in serum of patients and healthy subjects using enzyme immunoassay kits. Results Our results revealed that 15-Lox-1 and 15-Lox-2 expression levels were elevated in tumor tissues of pituitary adenomas comparing to normal pituitary tissues. The elevated levels of both isoforms were accompanied with 15(S) HETE and 13(S) HODE elevation in the serum of patients. The 15-Lox-1 expression and activity was higher in invasive tumors as well as tumors with bigger size indicating the possible pro-tumorigenic role of 15-Lox-1, more than 15-Lox-2 in pituitary adenomas. The diagnostic value of 15-Lipoxygense isoforms and products were considerable between patients and healthy groups. Conclusion The possible involvement of 15-Lipoxygense pathway especially 15-Lox-1 in the regulation of pituitary tumor growth and progression may open up new molecular mechanism regarding pituitary adenoma pathogenesis and might shed light on its new therapeutic strategies.

Background: Women with type 2 diabetes are more susceptible to coagulopathy disorders and endothelial dysfunction. One possible explanation is the effects of different sex hormones in inflammatory conditions. Increased plasminogen activator inhibitor-1 (PAI-1) activity has been observed as a possible predisposing factor for coagulopathy disorders and endothelial dysfunction. However, the effect of gender on PAI-1 in patients with type 2 diabetes (T2D) and albuminuria has not been studied sufficiently. Objectives: In this study, we examined whether changes of PAI-1 activity according to the albuminuria state in patients with type 2 diabetes are different in males and females. Materials and Methods: A matched case-control study was performed among participants with T2D, as 38 microalbuminuric patients were matched with 38 normoalbuminuric patients who were similar in age and body mass index (BMI). PAI-1 activity was compared between the two groups with and without gender stratification. Results: PAI-1 activity in microalbuminuric women was higher in comparison to that of the normoalbuminuric controls (P-value < 0.05). There was no significant difference in PAI-1 activity between macroalbuminuric and normoalbuminuric men. In women with type 2 diabetes and albuminuria, PAI-1 activity was independently and significantly associated with urinary albumin excretion. Conclusions: Gender differences in PAI-1 activity, seen in the early stages of diabetic nephropathy, are a possible explanation for the higher incidence of vasculopathy in women with type 2 diabetes Keywords : plasminogen activator inhibitor-1; coagulopathy; microalbuminuria; type 2 diabetes; gender

Context Melanoma is an invasive type of skin cancer, with a rapidly increasing incidence. Therefore, new approaches are required to treat this aggressive cancer. MicroRNAs (miRNAs) are introduced as novel components in melanoma. This review study aimed to determine the relationship between melanoma and miRNAs. Evidence Acquisition Prognostic, diagnostic, and therapeutic applications of miRNAs in skin cancer have been recently investigated from different aspects. Some of these studies on miRNAs were reviewed, and the mechanisms of some genetic modifications were determined in this study. Results Since recommendations for miRNAs have increased in the past decades, and scientists have confirmed their great efficacy in multiple aspects of cancer treatment, different strategies have been developed considering their therapeutic effects. Therefore, further studies are required to confirm miRNA application in melanoma treatment. Conclusions This review study included various investigations concerning miRNA traces as molecular rearrangements in melanoma. It was revealed that multiple miRNAs are efficient in molecular signaling and can be used as prognostic, diagnostic, and therapeutic biomarkers. Although the exact relationship between aberrant expression of miRNAs and cancers has been confirmed, further studies are required to introduce more thorough and accurate applications of miRNAs in melanoma.

We aimed to study the relation between plasma levels of stress-induced heat shock protein 70 (HSPA1A) with plasminogen activator inhibitor-1 (PAI-1) and high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (Apo-A1), and HDL-C/Apo-A1 ratio. In a matched case-control study on patients with diabetes (40 patients with albuminuria and 40 without albuminuria matched for age, sex, and body mass index), we observed that plasma levels of HSPA1A and PAI-1 are increased in patients with albuminuria (0.55 ± 0.02 vs. 0.77 ± 0.04 ng/ml, p value

BACKGROUND 8-iso-PGF2α is a family of PGF2α that could be offered as a non-invasive tool to represent in vivo oxidation status, as a link between oxidative milieus and vascular dysfunction. METHODS A total of 45 patients with type 2 diabetes and 45 healthy adults were studied in this cross-sectional analysis. Blood samples were collected to measure the level of lipid profile, oxidative stress, and glycemic control indices. The sensitivity and specificity of 8-iso-PGF2α as a screening test were analyzed in the cut-off range 252 - 377.5 pg/mL and the corresponding receiver operating characteristics (ROC) were plotted to assess performance of the test. RESULTS 8-iso-PGF2α level was significantly higher in the diabetic group (439.11 pg/mL ± 181.13 vs. 380.93 pg/mL ± 146.52). After adjustments for age, gender, and body mass index (BMI), linear regression analysis revealed that homeostasis model assessment of insulin resistance (HOMA-IR), blood pressure, fasting blood sugar (FBS), serum creatinine, insulin, oxLDL, and CRP levels are directly correlated with 8-iso-PGF2α in the 25% - 75% quartiles. Moreover, their mean levels were higher in quartiles with greater 8-iso-PGF2α levels. The cut-offs showing the best equilibrium between sensitivity and specificity approached 269.5 pg/mL with 83% and 62.5% sensitivity and specificity, respectively. CONCLUSIONS Our study provides evidence for the application of serum 8-isoPGF2α in the 25 - 75% quartile ranges to screen for the severity of oxidative reactions and glycemic control in vivo without need for any further in vitro enzymatic reactions, with higher levels, reflecting more severe oxidation and poor glycemic control.

Background Diabetes is probably responsible for worsening of metabolic syndrome (MetS)components. The aim of the present study was to compare the components of MetS between premenopausal and postmenopausal women with type 2 diabetes (T2DM). Method In this cross sectional study, we studied 639 women with T2DM that were divided in pre-menopausal (n = 221) and post-menopausal (n = 418) group. They were selected from participants of a diabetes clinic and assessed for MetS and its components. All MetS components were evaluated to follow age and duration of diabetes adjusted according to the ATP III criteria. Results The mean ages of pre-menopausal and post-menopausal were 43.33 ± 0.47 and 60.35 ± 0.38 years, respectively. MetS was defined for 88.3% of total subjects (87.5% and 87.7% in pre-menopausal and post-menopausal women with T2DM respectively). Systolic blood pressure (SBP) and waist circumference (WC) were significantly higher in post-menopausal women with T2DM in comparison with pre-menopausal ones. There were no significant differences in triglyceride (T.G) level, diastolic blood pressure (DBP) and high density lipoprotein cholesterol (HDL-C) between the two groups. Myocardial infarction (MI) occurred in 1% total subjects (1.3% and 1.8%) in pre-menopausal and post-menopausal women with T2DM, respectively (p = 0.21). Conclusion Worsening of MetS and its components except for SBP and waist circumference has been shown in pre-menopausal women with T2DM similar to post-menopausal ones. The observed differences may be explained by increasing age. With respect to increasing of myocardial infarction in premenopausal subjects, we suggest that diabetes can abolish the protective effects of premenopausal status for MetS and MI.