In silico study of missense variants of FANCA, FANCC and FANCG genes reveals high risk deleterious alleles predisposing to Fanconi anemia pathogenesis.

Among the 22 Fanconi anemia (FA) reported genes, 90% of mutational spectra were found in three genes, namely FANCA (64%), FANCC (12%) and FANCG (8%). Therefore, this study aimed to identify the high-risk deleterious variants in three selected genes (FANCA, FANCC, and FANCG) through various computational approaches. The missense variant datasets retrieved from the UCSC genome browser were analyzed for their pathogenicity, stability, and phylogenetic conservancy. A total of 23 alterations, of which 16 in FANCA, 6 in FANCC and one variant in FANCG, were found to be highly deleterious. The native and mutant structures were generated, which demonstrated a profound impact on the respective proteins. Besides, their pathway analysis predicted many other pathways in addition to the Fanconi anemia pathway, homologous recombination, and mismatch repair pathways. Hence, this is the first comprehensive study that can be useful for understanding the genetic signatures in the development of FA.

Anti-breast cancer synthetic peptides derived from the Anabas testudineus skin mucus fractions.

Previous study has shown the antimicrobial activities of mucus protein extracted from Anabas testudineus. In this study, we are interested in characterizing the anticancer activity of the A. testudineus antimicrobial peptides (AMPs). The mucus was extracted, fractioned, and subjected to antibacterial activity testing to confirm the fish's AMPs production. The cytotoxic activity of each fraction was also identified. Fraction 2 (F2), which shows toxicity against MCF7 and MDA-MB-231 were sent for peptide sequencing to identify the bioactive peptide. The two peptides were then synthetically produced and subjected to cytotoxic assay to prove their efficacy against cancer cell lines. The IC50 for AtMP1 against MCF7 and MDA-MB-231 were 8.25 ± 0.14 µg/ml and 9.35 ± 0.25 µg/ml respectively, while for AtMP2 it is 5.89 ± 0.14 µg/ml and 6.97 ± 0.24 µg/ml respectively. AtMP1 and AtMP2 treatment for 48 h induced breast cancer cell cycle arrest and apoptosis by upregulating the p53, which lead to upregulate pro-apoptotic BAX gene and downregulate the anti-apoptotic BCL-2 gene, consequently, trigger the activation of the caspase-3. This interaction was supported by docking analysis (QuickDBD, HPEPDOCK, and ZDOCK) and immunoprecipitation. This study provided new prospects in the development of highly effective and selective cancer therapeutics based on antimicrobial peptides.

Effect of Vitamin D Supplementation on the Regulation of Blood Pressure in Iranian Patients with Essential Hypertension: A Clinical Trial.

BACKGROUND: Low serum vitamin D level is associated with both high blood pressure and incidence of primary hypertension. Experimental studies suggest that vitamin D supplements may reduce blood pressure. OBJECTIVE: The aim of this study was to investigate whether vitamin D supplementation reduces systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) in Iranian patients with essential hypertension. METHOD: A total of 173 patients with essential hypertension participated in this open-label clinical trial. SBP, DBP, and serum vitamin D levels were measured at baseline and at the end of the study. Vitamin D was administered at a dose of 50,000 IU/week, and 1000 IU/day in patients with serum vitamin D levels <20 ng/mL and 20-30 ng/mL, respectively, for 8 weeks. RESULTS: Based on serum vitamin D levels, 45.1%, 17.3%, and 29.5% of patients were deficient, insufficient, and sufficient for vitamin D intake, respectively. Baseline serum levels of vitamin D were not correlated with SBP, DBP, and MAP at the beginning of the study (p = ns). Multiple logistic regression analysis revealed that the risk of vitamin D deficiency was 2.5-fold times higher in women than in men (p = 0.03). After 8 weeks of supplementation with vitamin D, mean SBP and MAP were significantly reduced by 5.5 ± 16.16 (p = 0.01) and 3.7 ± 9.24 (p = 0.004) mmHg, respectively. Neither sex nor age could significantly predict BP response to vitamin D supplementation. CONCLUSION: Vitamin D supplementation may significantly reduce SBP and MAP but not DBP in patients with essential hypertension.

The effects of a Melissa officinalis L. based product on metabolic parameters in patients with type 2 diabetes mellitus: A randomized double-blinded controlled clinical trial.

Background Diabetic patients are at increased risk for coronary artery disease. Since phytotherapy has been greatly common, finding safe and effective treatments is of importance. This study aimed to evaluate the effects of a Melissa officinalis L. based product (MO) in patients with type 2 diabetes. Methods A randomized double-blinded controlled study was conducted with 37 dyslipidemic diabetic patients, assigned to either MO or placebo (P) groups receiving two 500 mg capsules daily for 3 months. Finally, 32 cases completed the study and were included in the analysis; MO (n=16) and P (n=16). Results Safe and significant effects in terms of decreasing the serum level of triglyceride (TG) in all patients after 2 months (p-value=0.02) and in patients with higher baseline serum levels of TG (TG≥200 mg/dl) after 3 months (p-value=0.04) were shown in the MO group. However, no metabolic significant changes were seen compared to the control group. Significant decrease in both systolic and diastolic blood pressure from baseline values were also found in patients with higher systolic blood pressure (SBP≥130 mmHg) (p-value=0.02) and those with higher diastolic blood pressure (DBP≥85 mmHg) (p-value=0.02) in the MO group. Conclusion This study showed that MO might be safe and beneficial in decreasing the serum TG level in dyslipidemic diabetic patients. Although, larger long-term studies are required.

Efficacy of comprehensive ozone therapy in diabetic foot ulcer healing.

BACKGROUND: Diabetic foot ulcer is one of the common complications of diabetes disease that is costly and difficult to treat. This problem can lead to morbidity and even mortality. Ozone is a gas that can optimize cellular metabolism and, because of its antioxidant and antibacterial effects, can help the better healing of diabetic foot ulcer. METHOD: Two hundred patients, aged 18-85 with diabetic foot ulcers ranging from grade 1 to 4 according to Wagner classification in two groups were studied. Group 1 was treated by full ozone therapy besides the standard regular DFU treatment while group two just was received routine diabetic foot care. Wound size, wound grade, healing time, Fasting blood sugar and inflammatory biomarker before and after treatment were checked. RESULTS: All patients have had complete wound closure in the ozone group. The mean age of the patients included in the results was 59.03 ±â€¯12.593 and 53.5 ±â€¯10.212 for ozone group and control group. The baseline average surface area of ulcers was 13.41 ±â€¯14.092 cm2 (range 1-70 cm2) in ozone group and 12.72 ±â€¯0.911 (range 1_64 cm2) in the control group. Average healing time was 69.44 ±â€¯36.055 days (range 15-180 days), which is significantly lower than the median healing time measured in the control group and some previous studies. CONCLUSION: Our study results support the efficacy of ozone therapy especially in its comprehensive use in DFU healing and reduction in the chances of infection and amputation.

Health-related quality of life in patients with chronic wounds before and after treatment with medical ozone.

Ozone therapy has been used to treat numerous diseases. Indications of its therapeutic application are increasing, and evidence for its usefulness is growing. Evidence of its antibacterial and proliferative activity suggests its efficacy in treating chronic wounds. The current study evaluated the effect of ozone therapy on the health-related quality of life of patients with chronic wounds.In the present cross-sectional study, the health-related quality of life was evaluated in 86 patients with chronic wounds undergoing ozone therapy. To measure quality of life, 2 previously established questionnaires were used, the Cardiff wound impact questionnaire and the SF-36 questionnaire. Questionnaires were completed through interviews with the patients.A total of 86 patients with chronic wounds undergoing ozone therapy participated in this study. The mean age of participants was 58.91 years; 69.8% of them were male, 91.9% had diabetes mellitus, and 50% were receiving insulin therapy. Patients were under local (26.7%), systemic (9.3%), and local plus systemic (64%) protocols of ozone therapy. Mean overall quality of life reported by the patients was 6.2, and mean overall quality of life satisfaction was 6.02 (measured by the Cardiff Wound Impact Questionnaire). Mean physical quality of life measured by the SF-36 questionnaire was 39.12, and mean mental quality of life was 44.37 (measured by the same questionnaire). Among the included variables, the number of ozone therapy sessions was the strongest predictor of quality of life in both questionnaires and remained significant after different levels of adjustment.In addition to the significant improvement observed in the healing of chronic wounds, medical O3 therapy has also shown to effect a significant improvement in the health-related quality of life of patients and could be a valuable therapeutic option in chronic wound cases.

Effects of Curcuminoids Plus Piperine on Glycemic, Hepatic and Inflammatory Biomarkers in Patients with Type 2 Diabetes Mellitus: A Randomized Double-Blind Placebo-Controlled Trial.

INTRODUCTION: Curcuminoids have been shown to reduce glycemia and related complications in diabetes. In the present study, we evaluated the impact of curcuminoids plus piperine administration on glycemic, hepatic and inflammatory biomarkers in type 2 diabetes (T2D) patients. METHODS: T2D patients aged 18-65 years were enrolled in a randomized double-blind placebo-controlled trial and randomly allocated to standard-of-care treatment and dietary advises plus either curcuminoids (daily dose of 500 mg/day co-administered with piperine 5 mg/day) or placebo for a period of 3 months. Glycemic, hepatic and inflammatory parameters were measured at baseline and final conditions. RESULTS: A total of 100 subjects (50 in each group) completed the 3-month period of trial. A significant reduction was found in serum levels of glucose (-9±16 mg/dL vs. -3±11 mg/dL in curcuminoids and placebo groups, respectively; p=0.048), C-peptide (-0.6±0.8 ng/mL vs. 0.02±0.6 ng/mL; p<0.001) and HbA1c (-0.9±1.1% vs. -0.2±0.5%; p<0.001) after curcuminoids supplementation versus placebo group. Additionally, participants in the intervention group showed lower serum alanine aminotransferase (-2±6 vs. -1±5; p=0.032) and aspartate aminotransferase (-3±5 vs. -0.3±4; p=0.002) levels compared with the placebo group. Finally, no significant differences in high-sensitivity C-reactive protein (hs-CRP) concentrations were observed between curcuminoids and placebo groups (p>0.05). CONCLUSION: The results of the present trial revealed a beneficial effect of curcuminoids plus piperine supplementation on glycemic and hepatic parameters but not on hs-CRP levels in T2D patients.

Silymarin, Olibanum, and Nettle, A Mixed Herbal Formulation in the Treatment of Type II Diabetes: A Randomized, Double-Blind, Placebo-Controlled, Clinical Trial.

Silybum marianum (L) Gaertn (milk thistle) seeds, Urtica dioica L (nettle) leaves, and Boswellia serrata (olibanum gum) resin are used traditionally by Iranian diabetic patients. The aim of this study was to evaluate the antihyperglycemic effects of these herbs in an herbal formulation in patients with type II diabetes mellitus. Sixty patients diagnosed as type II diabetes mellitus with fasting blood glucose level from 150 to 180 mg/dL, glycosylated hemoglobin level from 7.5% to 8.5%, and on oral antihyperglycemic drugs, were allocated to receive the mix herbal formulation or placebo for 90 days in a double-blind randomized placebo-controlled clinical trial. The mean serum fasting blood glucose, glycosylated hemoglobin, and triglyceride in the herbal drug group were significantly less than placebo group's values after 3 months of the intervention. The study showed a potential antihyperglycemic and triglyceride lowering effect of the herbal formulation, while it did not have any significant cholesterol or blood pressure lowering effect.

A systematic review of the efficacy and safety of Rosa damascena Mill. with an overview on its phytopharmacological properties.

Rosa damascena Mill. is one of the most famous ornamental plants cultivated all over the world mostly for perfumery industries. Traditionally it has been used as an astringent, analgesic, cardiac and intestinal tonic.The paucity ofauthoritative monographs urged usto summarize its clinical effectiveness and safety with acomprehensive review of the literature. "PUBMED", "SCOPUS", "WEBOF SCIENCE" were searched up to April 30, 2017 with search terms:("Rosa damascena" OR "Damask Rose"). All human studies with any mono-preparation were included. In vitro and animal studies from "PUBMED"were also reviewed and outlined. Of "1000" identified publications, twelveeligibleclinical trials were retrieved. Antimicrobial, anti-inflammatory, antioxidant, anticancer, protective neuronal, cardiac, gastrointestinal and hepatic effectsin 30 in vitro and 21 animal studies were also shown. there are promising evidences for the effectiveness and safety of Rosa damascena Mill in pain relief, but confirmatory studies withstandardized products is suggested.

Curcuminoids modify lipid profile in type 2 diabetes mellitus: A randomized controlled trial.

BACKGROUND: Type 2 diabetes (T2D) is an established risk factor for cardiovascular disease (CVD) and is associated with disturbed metabolism of lipids and lipoproteins. Curcuminoids are natural products with anti-diabetic and lipid-modifying actions but their efficacy in improving dyslipidemia in diabetic individuals has not been sufficiently studied. OBJECTIVE: To investigate the efficacy of supplementation with curcuminoids, plus piperine as an absorption enhancer, in improving serum lipids in patients with T2D. METHODS: In this 12-week randomized double-blind placebo-controlled trial, subjects with T2D (n=118) were assigned to curcuminoids (1000mg/day plus piperine 10mg/day) or placebo plus standard of care for T2D. Serum concentrations of lipids including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), lipoprotein(a) [Lp(a)], and non-HDL-C were determined at baseline and at the end of trial. RESULTS: Between-group comparison of change in the study parameters revealed significant reductions in serum levels of TC (-21.86±25.78 versus -17.06±41.51, respectively; p=0.023), non-HDL-C (-23.42±25.13 versus -16.84±41.42, respectively; p=0.014) and Lp(a) (-1.50±1.61 versus -0.34±1.73, respectively; p=0.001) and elevations in serum HDL-C levels (1.56±4.25 versus -0.22±4.62, respectively; p=0.048) in the curcuminoids group as compared with the placebo group (p<0.05). Serum TG and LDL-C changes did not show any significant difference between the study groups (p>0.05). CONCLUSION: Curcuminoids supplementation can reduce serum levels of atherogenic lipid indices including non-HDL-C and Lp(a). Therefore, curcuminoids supplementation could contribute to a reduced risk of cardiovascular events in dyslipidemic patients with T2D.

Curcuminoids Plus Piperine Modulate Adipokines in Type 2 Diabetes Mellitus.

OBJECTIVE: Curcumin is a naturally occurring polyphenol derived from tumeric that has been reported to have anti-inflammatory properties with effects on adipokine and ghrelin levels. Adiponectin, leptin and ghrelin modulate energy homeostasis but each has modulatory effects on inflammatory cytokines and the immune system. Therefore, this analysis was performed to investigate the effect of curcumin on adiponectin, leptin and ghrelin. METHOD: A double blind randomised control trial comparing curcumin 1000mg with 10mg of piperine daily to placebo over a 12 week period. 118 patients with type 2 diabetes were recruited out of which 50 control and 50 active subjects completed the trial. Adiponectin, leptin, ghrelin and tumor necrosis factor-α (TNF-α) were measured at baseline and 12 weeks. RESULTS: Between group comparison of the magnitude of changes showed serum levels of leptin (p<0.001), TNF-α (p<0.001) and leptin:adiponectin ratio (p<0.001) to be significantly reduced while serum adiponectin levels were elevated in the curcuminoids versus placebo group (p=0.032). Changes in serum ghrelin levels did not differ between the study groups (p=0.135). CONCLUSION: Curcumin supplementation increased adiponectin, whilst the the leptin:adiponectin ratio (a measure of atherosclerosis) and leptin levels were decreased independent of weight change and reflected a decrease in the inflammatory TNF-α levels.

Antioxidant effects of curcuminoids in patients with type 2 diabetes mellitus: a randomized controlled trial.

BACKGROUND: Oxidative stress has a key role in the pathogenesis of type II diabetes mellitus (T2DM) and its vascular complications. Antioxidant therapy has been suggested as a potential approach to blunt T2DM development and progression. The aim of this study was to assess the effects of supplementation with curcuminoids, which are natural polyphenolics from turmeric, on oxidative indices in diabetic individuals. METHODS: In this randomized double-blind placebo-controlled trial, 118 subjects with T2DM were randomized to curcuminoids (1000 mg/day co-administered with piperine 10 mg/day) or matching placebo for a period of 8 weeks. Serum total antioxidant capacity, superoxide dismutase (SOD) activities and malondialdehyde (MDA) concentrations were measured at baseline and after the supplementation period. RESULTS: Curcuminoids supplementation caused a significant elevation in serum total antioxidant capacity (TAC) (p < 0.001) and SOD activities (p < 0.001), while serum MDA levels were significantly reduced compared with the placebo group (p < 0.001). These results remained statistically significant after adjustment for potential confounders (baseline differences in body mass index and fasting serum insulin). CONCLUSION: The present results support an antioxidant effect of curcuminoids supplementation in patients with T2DM, and call for future studies to assess the impact of these antioxidant effects on the occurrence of diabetic complications and cardiovascular endpoints.

Effects of curcumin on serum cytokine concentrations in subjects with metabolic syndrome: A post-hoc analysis of a randomized controlled trial.

BACKGROUND: Cytokines are involved in the development of metabolic abnormalities that may result in metabolic syndrome (MetS). Since curcumin has shown anti-inflammatory properties, the aim of this study was to evaluate the effect of curcumin supplementation on serum cytokines concentrations in subjects with MetS. METHODS: This study was a post-hoc analysis of a randomized controlled trial in which males and females with diagnosis of MetS, according to the criteria defined by the National Cholesterol Education Program Adult Treatment Panel III guidelines, were studied. Subjects who met the inclusion criteria were randomly assigned to either curcumin (daily dose of 1g/day) or a matched placebo for a period of 8 weeks. RESULTS: One hundred and seventeen subjects were assigned to either curcumin (n=59) or placebo (n=58) groups. Within-group analysis revealed significant reductions in serum concentrations of TNF-α, IL-6, TGF-ß and MCP-1 following curcumin supplementation (p<0.001). In the placebo group, serum levels of TGF-ß were decreased (p=0.003) but those of IL-6 (p=0.735), TNF-α (p=0.138) and MCP-1 (p=0.832) remained unaltered by the end of study. Between-group comparison suggested significantly greater reductions in serum concentrations of TNF-α, IL-6, TGF-ß and MCP-1 in the curcumin versus placebo group (p<0.001). Apart from IL-6, changes in other parameters remained statistically significant after adjustment for potential confounders including changes in serum lipids and glucose levels, and baseline serum concentration of the cytokines. CONCLUSION: Results of the present study suggest that curcumin supplementation significantly decreases serum concentrations of pro-inflammatory cytokines in subjects with MetS.

Effects of supplementation with curcumin on serum adipokine concentrations: A randomized controlled trial.

OBJECTIVE: Previous experimental studies have suggested curcumin as a safe phytochemical that can improve insulin resistance through effects on adiponectin and leptin. This study aimed to investigate the effect of curcumin on circulating adiponectin and leptin concentrations in patients with metabolic syndrome. METHODS: In this pilot, randomized, double-blind, placebo-controlled trial, subjects who met the criteria of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria were randomly assigned to curcumin (n = 59; 1000 mg/d) or a placebo (n = 58) for 8 wk. Serum adiponectin and leptin concentrations were determined before and after intervention. The pooled effect size for the impact of curcumin supplementation on serum adiponectin and leptin levels was also estimated using random-effects metaanalysis. RESULTS: Eight-week supplementation with curcumin was associated with a significant increase in serum adiponectin levels (P < 0.001) and a reduction in serum leptin concentrations (P < 0.001). Serum leptin:adiponectin ratio was also improved by curcumin (P < 0.001). These beneficial effects of curcumin remained significant after adjustment for changes in serum lipids and glucose concentrations and baseline differences in body mass index and serum levels of glucose and glycated hemoglobin as potential confounders of treatment response. Metaanalysis suggested that curcumin supplementation can increase adiponectin levels by 76.78% (95% CI: 6.14-147.42; P = 0.0330), and reduce leptin by 26.49% (95% CI: -70.44 to 17.46), however this latter effect size did not reach statistical significance (P = 0.238). CONCLUSIONS: Curcumin can improve serum levels of adiponectin and leptin in patients with metabolic syndrome. This trial was registered at the UMIN Clinical Trials Registry (http://www.umin.ac.jp/ctr/) under Trial No. UMIN000018339.

Antioxidant and anti-inflammatory effects of curcuminoid-piperine combination in subjects with metabolic syndrome: A randomized controlled trial and an updated meta-analysis.

BACKGROUND: Oxidative stress and inflammation have been proposed as emerging components of metabolic syndrome (MetS). Curcuminoids are natural polyphenols with strong antioxidant and anti-inflammatory properties. OBJECTIVE: To study the effectiveness of supplementation with a bioavailable curcuminoid preparation on measures of oxidative stress and inflammation in patients with MetS. Our secondary aim was to perform a meta-analysis of data from all randomized controlled trials in order to estimate the effect size of curcuminoids on plasma C-reactive protein (CRP) concentrations. METHODS: In this randomized double-blind placebo-controlled trial, 117 subjects with MetS (according to the NCEP-ATPIII diagnostic criteria) were randomly assigned to curcuminoids (n = 59; drop-outs = 9) or placebo (n = 58; drop-outs = 8) for eight weeks. Curcuminoids were administered at a daily dose of 1 g, and were co-supplemented with piperine (10 mg/day) in order to boost oral bioavailability. Serum activities of superoxide dismutase (SOD) and concentrations of malondialdehyde (MDA) and CRP were measured at baseline and at study end. Regarding the importance of CRP as a risk marker and risk factor of cardiovascular disease, a random-effects meta-analysis of clinical trials was performed to estimate the overall impact of curcuminoid therapy on circulating concentrations of CRP. The robustness of estimated effect size was evaluated using leave-one-out sensitivity analysis. RESULTS: Supplementation with curcuminoid-piperine combination significantly improved serum SOD activities (p < 0.001) and reduced MDA (p < 0.001) and CRP (p < 0.001) concentrations compared with placebo. Quantitative data synthesis revealed a significant effect of curcuminoids vs. placebo in reducing circulating CRP concentrations (weighed mean difference: -2.20 mg/L; 95% confidence interval [CI]: -3.96, -0.44; p = 0.01). This effect was robust in sensitivity analysis. CONCLUSIONS: Short-term supplementation with curcuminoid-piperine combination significantly improves oxidative and inflammatory status in patients with MetS. Curcuminoids could be regarded as natural, safe and effective CRP-lowering agents.

Lipid-modifying effects of adjunctive therapy with curcuminoids-piperine combination in patients with metabolic syndrome: results of a randomized controlled trial.

BACKGROUND: Dyslipidemia is an established feature of metabolic syndrome (MS) that is associated with an increased risk of atherosclerotic cardiovascular disease. Curcuminoids are natural products with anti-atherosclerotic and lipid-modifying effects but their efficacy in patients with MS has not yet been tested. OBJECTIVE: To investigate the effects of bioavailability-enhanced curcuminoids, as adjunctive to standard of care, on serum lipid concentrations in patients with MS. METHODS: Patients diagnosed with MS according to the NCEP-ATPIII criteria who were receiving standard of care were assigned to either curcuminoids (C3 complex(®); 1000 mg/day; n=50) or placebo (n=50; matched with drug capsules in shape and color) for 8 weeks. In order to improve the oral bioavailability, curcuminoids were co-administered with piperine (bioperine(®)) in a ratio of 100:1. Serum concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, small dense LDL (sdLDL), lipoprotein(a) [Lp(a)], and non-HDL-C were determined at baseline and at the end of 8-week treatment period. RESULTS: Curcuminoids were more effective than placebo in reducing serum LDL-C, non-HDL-C, total cholesterol, triglycerides and Lp(a), and elevating HDL-C concentrations. However, changes in serum sdLDL levels were found to be comparable between the study groups. The effects of curcuminoids on triglycerides, non-HDL-C, total cholesterol and Lp(a) remained significant after adjustment for baseline values of lipids and body mass index. CONCLUSION: Curcuminoids-piperine combination is an efficacious adjunctive therapy in patients with MS and can modify serum lipid concentrations beyond what is achieved with standard of care.

Hyperglycemia after renal transplantation: frequency and risk factors.

BACKGROUND: Chronic renal failure is an important and common complication of diabetes mellitus; hence, renal transplantation is a frequent and the acceptable treatment in patients with diabetic nephropathy requiring renal replacement therapy. On the other hand, renal transplantation and its conventional treatment can lead to increased diabetes outbreak in normoglycemic recipients. Also, uncontrolled hyperglycemia may be increased and allograft lost thus decreasing patient survival. OBJECTIVES: We aimed to assess the frequency of hyperglycemia in transplant patients and its risk factors. PATIENTS AND METHODS: A large retrospective study was performed on 3342 adult kidney transplant recipients between 2008 and 2010. Demographic and laboratory data were gathered for each patient. All tests were done in a single laboratory and hyperglycemia was defined as a fasting plasma glucose of > 125 mg/dL. Univariate and multivariate logistic regression analyses were used to determine the risk factors of hyperglycemia following kidney transplantation. RESULTS: There were 2120 (63.4%) males and 1212 (36.3%) females. Prevalence of hyperglycemia was 22.5%. By univariate linear regression, hyperglycemia was significantly higher in patients with CMV infection (P = 0.001), elevated serum creatinine (P = 0.000), low HDL (P = 0.01), and increased blood levels of cyclosporine (P = 0.000). After adjusting for covariates by multivariate logistic regression, the hyperglycemia rate was significantly higher for patients with Cyclosporine trough level > 250 (P = 0.000), serum creatinine > 1.5 (P = 0.000) and HDL < 45 (P = 0.03). CONCLUSIONS: This study indicated that hyperglycemia is a common metabolic disorder in Iranian kidney transplant patients. Risk factors for hyperglycemia were higher Cyclosporine level, impaired renal function, and reduced HDL value.

Hyperglycemia after kidney transplantation: frequency and risk factors.

INTRODUCTION: Kidney transplantation and its conventional treatment can lead to increased risk of diabetes mellitus outbreak in normoglycemic recipients. Also, uncontrolled hyperglycemia may increase allograft loss and decrease patient survival. We aimed to assess the frequency of hyperglycemia in transplant patients and its risk factors. MATERIALS AND METHODS: A retrospective study was performed on 3342 adult kidney transplant recipients between 2008 and 2010. Demographic and laboratory data were collected. All laboratory tests were done in a one laboratory, and hyperglycemia was defined as a fasting plasma glucose level greater than 125 mg/dL. Univariable and multivariable logistic regression analyses were used to determine the risk factors of hyperglycemia following kidney transplantation. RESULTS: There were 2120 men (63.4%) and 1212 women (36.3%) included in the study. The prevalence of hyperglycemia was 22.5%. Hyperglycemia was significantly higher in patients with cytomegalovirus infection (P = .001), elevated serum creatinine (P < .001), low high-density lipoprotein cholesterol (P = .01), and increased blood levels of cyclosporine (P < .001). After adjusting for covariates by multivariate logistic regression, the hyperglycemia rate was significantly higher for patients with a cyclosporine trough level greater than 250 ng/mL (P < .001), a serum creatinine level greater than 1.5 mg/dL (P < .001), and a high-density lipoprotein cholesterol less than 45 mg/dL (P = .03). CONCLUSIONS: This study indicated that hyperglycemia is a common metabolic disorder in Iranian kidney transplant patients. Risk factors for hyperglycemia were higher cyclosporine level, impaired kidney function, and reduced high-density lipoprotein cholesterol values.

A new frameshift MEN1 gene mutation associated with familial malignant insulinomas.

MEN-1 is an autosomal dominant familial cancer syndrome characterized by involvement of parathyroid, enteropancreatic endocrine tissues and the anterior pituitary gland. Malignant insulinomas are rare, and therefore, there are few data regarding their clinical presentation and long-term prognosis. In this report we present a large family with malignant insulinoma and hyperparathyroidism with MEN-1 gene mutation analysis. A large family (three generations) with several members affected were evaluated for clinical and biochemical characteristic of MEN-1 syndrome. Genetic analysis for MEN1 gene was carried out in all family members using PCR amplification of coding regions followed by direct sequencing. In three brothers that presented with hypoglycemia, insulinoma was confirmed and two were malignant according to pathology and surgery report. Two of them had hyperparathyroidism too. Mutation screening revealed the presence of a two nucleotide deletion in the exon 2 (c199_200del2). In the current study, the deletion happens early in the sequence, and obviously results in a non-functional gene product. However, it will be helpful to further examine somatic mutations and other genetic markers for a more precise study of genotype-phenotype correlation.