New emerging roles of the novel hepatokine SERPINB1 in type 2 diabetes mellitus: Crosstalk with ß-cell dysfunction and dyslipidemia.

Diabetes mellitus (DM) is a devastating metabolic disease. Recently, the cross-talk between insulin-secreting-ß-cells and various organs has sparked much interest. SerpinB1 emerged as a novel hepatokine inducing ß-cell proliferation. However, its role in type-2-DM (T2DM) patients has not been adequately studied. This study was designed to investigate its circulating levels in subjects with/without T2DM, and to study its association with ß-cell function, as well as various glycemic-control and lipid-profile parameters. Anthropometric data and biochemical markers including fasting plasma glucose (FPG), HbA1C % and lipid profile parameters were measured in 55 T2DM patients, as well as 30 healthy nondiabetic subjects. Serum serpinB1, insulin and C-peptide levels were measured by ELISA. The homeostasis model assessment of both ß-cell function (HOMA2-ß%) and insulin resistance (HOMA-IR) were calculated. SerpinB1 levels were found to be significantly lower in T2DM patients 0.7 (0.2-12.4) ng/mL, compared to nondiabetic subjects 1.2 (0.94-24) ng/mL, P < 0.001, regardless of glycemic control, obesity, or insulin resistance. Additionally, serpinB1 levels were found to be positively associated with C-peptide, HOMA2-ß% in all subjects; and BMI only in non-DM subjects; while negatively associated with FPG, HbA1C% and lipid-profile parameters. Higher serum serpinB1 levels were found to be associated with lower susceptibility for T2DM. Conclusively, serpinB1 is associated with various aspects of ß-cell dysfunction, glycemic-control, and dyslipidemia with a possible role in ß-cell compensation in obese nondiabetic subjects. The results of the current study shed lights on potential novel roles of serpinB1 in T2DM besides its action as an inducer for ß-cell proliferation.

Potential Role of New Anthropometric Parameters in Childhood Obesity with or Without Metabolic Syndrome.

BACKGROUND: Obese children and adolescents are more prone to have metabolic syndrome (MS).MS is a cluster of cardiovascular risk factors associated with insulin resistance. Body round index [BRI], visceral adiposity index [VAI] and a body shape index [ABSI] are among the new obesity anthropometric parameters. AIM: To evaluate the new markers for obesity in children and their possible association with other laboratory and clinical variables of MS. METHODS: Eighty nine obese children and 40 controls aged 10-18 years were recruited. Full history taking, thorough clinical examination, anthropometric and biochemical features were performed in the studied groups. Subcutaneous fat thickness (SFT) and visceral fat thickness (VFT) were estimated by ultrasonography. RESULTS: Obese children, exhibited significantly higher values in all anthropometric measurements (P < 0.001). Diastolic and systolic blood pressure were significantly higher (P < 0.001) in the obese group. ABSI, BRI and VAI have been found to be significantly higher in obese subjects (P < 0.001), with no significant gender difference. BMI, WHtR, WC/HR, SBP, DBP, subcutaneous fat thickness and visceral fat thickness, Liver Span, ABSI, BRI, VAI and HOMA_IR were significantly higher among children with MS than those without MS. Positive significant correlations of VAI with BMI, WC/Ht, WC/Hip, SBP, DBP, SFT, VFT, Liver size and HOMA-IR (r = 0.384, 0.239, 0.268, 0.329, 0.516, 0.320, 0.254, 0.251, and 0.278 respectively) are shown. The area under the ROC curve (AUC) of BMI, VAI, ABSI, BRI for predicting MS was 0.802 (0.701-0.902), 0.737 (0.33-0.841), 0.737 (0.620-0.855), 0.816 (0.698-0.934). CONCLUSION: We suggest using the VAI and WHtR indexes, as they are better predictor of MS.

Monocyte chemoattractant protein 1 and macrophage migration inhibitory factor in children with type 1 diabetes.

BACKGROUND: Serum monocyte chemoattractant protein 1 (MCP-1) and macrophage migration inhibitory factor (MIF) could be involved in the pathophysiological process of diabetes. The aim of the study was to evaluate MCP-1 and MIF in patients with diabetes mellitus type 1 (T1DM) and to assess its relation to diabetic control. METHODS: The study included 39 patients with type 1 diabetes and 38 healthy volunteers. Blood sample was taken for assessment of glycosylated hemoglobin, serum MIF and MCP-1. RESULTS: Serum MIF and MCP-1 were significantly higher in diabetic cases than in healthy controls. HbA1c levels, were significantly higher in cases than in controls. Serum MIF had a significant positive correlation with serum MCP-1 (r=0.361, p=0.03). No other significant correlation with glycosylated hemoglobin or duration of diabetes was detected. CONCLUSIONS: A significant increase of serum level of MIF and serum MCP-1 was found in patients with T1DM. These results support that MCP-1 and MIF could be a therapeutic target to treat diabetes and to prevent its complications.

Fetuin-A and Ghrelin Levels in Children with End Stage Renal Disease and the Effect of a Single Hemodialysis Session on Them.

BACKGROUND: Fetuin-A and ghrelin have been implicated in cardiovascular diseases and mortality among end stage renal disease patients. The exact mechanisms have not been fully elucidated. There is robust data supporting an association between ghrelin and various cardiovascular conditions, and some common processes such as inflammation, oxidative stress, and endoplasmic reticulum stress have been implicated. AIM: This study was conducted to assay serum fetuin-A and ghrelin in chronic renal failure pediatric patients and to study changes in their level that may occur after a single hemodialysis. MATERIAL AND METHODS: Forty nine pediatric patients suffering from ESRD on maintenance hemodialysis (HD), 20 patients with chronic renal failure (CRF) not on dialysis and 35 healthy subjects as control group were included. The mean age of the study population was 10.58 ± 3.94, 10.62 ± 3.24 and 10.61 ± 3.97 years respectively. Serum fetuin-A and plasma acyl ghrelin levels were measured by using ELISA method. RESULTS: The present study revealed that predialysis serum fetuin-A level was significantly increased in pediatric HD patients compared with the normal population, while ghrelin levels were significantly reduced. Furthermore, serum levels of fetuin-A decreased significantly after a single HD session. CONCLUSION: Our study concluded that fetuin-A and acyl ghrelin may play a role in inflammatory process among HD pediatric patients which may account for cardiovascular insults and mortality but their use as biochemical markers among ESRD pediatric patients have limitations due to wide fluctuations.

MDM2 SNP309 and p53 codon 72 genetic polymorphisms and risk of AML: an Egyptian study.

BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous disease with numerous genetic abnormalities corresponding to a variety of subtypes. p53 is involved in multiple cellular pathways including apoptosis, transcriptional control, and cell cycle regulation. A single nucleotide polymorphism (SNP) at codon 72 of the p53 gene is associated with the risk for development of various neoplasms. MDM2 SNP309 is a single nucleotide T to G polymorphism located in the MDM2 gene promoter, which enhances the expression of MDM2 protein and thereby leads to attenuation of the p53 stress response. OBJECTIVE: The current study aimed to define the roles of MDM2 and p53 genetic polymorphisms with the risk of AML. METHODOLOGY: Genotyping for MDM2 was done by AS-PCR technique while p53 codon 72 genotyping was done by PCR- RFLP for 50 patients and 50 controls. RESULTS: The study did not detect any significant differences regarding MDM2 or p53 polymorphisms in AML cases, as compared to controls. A borderline significance was found between cases and controls regarding combined MDM2 T/G and p53 genotyping. MDM2 variant genotype was significantly associated with a younger age group and lower Hb level, while the P53 variant was significantly associated with less frequent CD117 expression.

Bone mass and biochemical markers of bone turnover in children and adolescents with chronic immune thrombocytopenia: relation to corticosteroid therapy and vitamin D receptor gene polymorphisms.

Optional drug therapy in refractory chronic immune thrombocytopenia (ITP) includes standard oral, pulsed high-dose steroid therapy, intravenous gamma globulin, anti-D, and immunosuppressive therapy or thrombopoietin receptor agonists. This work aimed to study the bone mass in children and adolescents with chronic ITP in relation to biochemical markers of bone turnover, cumulative steroid therapy, and the possible modulating effect of vitamin D receptor (VDR) gene polymorphisms. Thirty-six children and adolescents with chronic ITP were recruited from the Hematology Clinic, Children's Hospital, Ain Shams University and the Hematology Clinic of the National Research Centre in Egypt and compared with 43 healthy age- and sex-matched controls. The total cumulative dose of steroids was calculated. Bone markers (serum osteocalcin (OC) and propeptide I precollagen (PICP) and urinary deoxypyridinoline (DPD) excretion), analysis of VDR gene distribution, and dual energy X-ray absorptiometry at lumbar and hip regions were performed for patients and controls. Compared to controls, chronic ITP patients had higher body mass index (BMI) and lower height for age standard deviation score (SDS). Chronic ITP patients had lower levels of OC and C-terminal propeptide of type I procollagen (PICP) and higher urinary DPD excretion, and bone mineral density (BMD) was significantly lower for both spine and hip z-score (<0.001). BMD was inversely correlated with urinary DPD excretion, age, BMI, and cumulative steroid dose. There was significant negative correlation between cumulative oral steroid dose and BMD (r = -0.4, P = 0.01 and r = -0.45, p = 0.001 for spine and hip z-scores, respectively), but the correlation was non-significant in relation to cumulative pulsed steroid therapy. FokI polymorphism was significantly related to BMD for both spine and hip z-score (p = 0.015 and p = 0.008, respectively), but there was no relation between BMD and Bsm1 polymorphism. FokI gene polymorphism may be one of the contributing factors in bone loss in patients on chronic steroid therapy. High cumulative doses of corticosteroids increased bone resorption in young chronic ITP patients. Longitudinal studies are needed to confirm the effect of different steroid protocols on bone turnover. Protocols of therapy of chronic ITP should restrict corticosteroid use in growing children and favor alternative less harmful therapies.

Fetuin-A levels in obesity: differences in relation to metabolic syndrome and correlation with clinical and laboratory variables.

INTRODUCTION: Fetuin-A is an important player in the enhancement of insulin resistance. There are very limited data available concerning the relationships between fetuin-A, weight status and features of the metabolic syndrome (Met S) in obese Egyptian subjects, and especially in children. The aim of the study was to evaluate fetuin-A serum level in subjects with obesity and its possible association with other laboratory and clinical variables. MATERIAL AND METHODS: A total of 140 obese subjects and 50 controls aged 10-40 years were recruited. Demographic, anthropometric and biochemical features were collected according to a standard protocol. Serum fetuin-A levels were measured using ELISA and the modified Third Report of the National Cholesterol Education Program (NCEP-ATP III) criteria were adopted to diagnose Met S. RESULTS: A higher level of serum fetuin-A was detected in obese subjects. Met S cases were also significantly associated with higher serum fetuin-A. Fetuin-A correlated significantly with BMI (r = 0.437), systolic (r = 0.228) and diastolic blood pressure (r = 0.295), waist circumference (r = 0.332), insulin resistance calculated by the homeostasis model (HOMA-IR) (r = 0.295) and high-density lipoprotein (HDL) (r = 0.362). CONCLUSIONS: Fetuin-A levels were higher in adults and children with obesity and Met S. They were related to insulin resistance and to features of the Met S in cross-sectional analyses. Our study demonstrates a novel association between human fetuin-A and the Met S among obese subject. Therefore, fetuin-A might be a new promising link between obesity and its comorbidities.

Cytotoxic potency and induced biochemical parameters in mice serum of new furan derivatives against liver cancer cell line.

On the basis of monitoring the inhibition of the growth of human cancer cells, a series of novel furan derivatives of possessing a broader spectrum of antitumor activity and fewer toxic side effects than traditional anticancer drugs have been studied. Ten selected furan derivatives were subjected to a screening system for investigation of their antitumor potency against liver (HEPG2) cell line. Moreover, the biochemical effects of the selected furan derivatives on some enzymes such as aspartate and a lanine aminotransferases (ASTand ALT) and alkaline phosphatase (ALP), in addition to albumin, globulins, creatinine, total lipids, cholesterol, triglycerides and bilirubin in serum of mice were studied in comparison to 5-fluorouracil and doxorubicin. The antitumor activity results indicated that the selected furan derivatives showed growth of inhibition activity against the tested cell line but with varying intensities extents. Results of the biochemical investigations indicated that 5-fluorouracil and doxorubicin caused significant changes in the level of all parameters tested while treatment with the selected compounds showed slight, moderate or no significant changes.

Frequency of Firmicutes and Bacteroidetes in gut microbiota in obese and normal weight Egyptian children and adults.

INTRODUCTION: Obesity and associated metabolic disorders are a worldwide epidemic. Recent evidence suggests that the microbial community in the human intestine may play an important role in the pathogenesis of obesity. The aim of this study was to assess the differences in the composition of the intestinal microbiota between obese and normal weight Egyptian children and adults. MATERIAL AND METHODS: The study included 79 subjects among whom 51 were obese (23 children and 28 adults), and 28 were subjects of normal weight (17 children and 11 adults). Faecal samples were collected from all subjects. Total DNA was extracted from collected stool samples and submitted to conventional PCR for detection of Firmicutes and Bacteroidetes. All the studied group was subjected to clinical and anthropometric evaluation. Laboratory assessment of fasting glucose, high-sensitivity C-reactive protein (hsCRP) and lipid profile was performed. RESULTS: The proportions of the phyla Firmicutes and Bacteroidetes were statistically significantly increased in the obese group compared to the normal weight group (p < 0.001, p = 0.003 respectively). The study also found a statistically significant positive trend for higher hsCRP in subjects with positive Firmicutes (p = 0.004). However, no associations were found between positive Bacteroidetes and hsCRP. CONCLUSIONS: The results of this study indicate that obesity in Egyptian children and adults is associated with compositional changes in faecal microbiota with increase in the phyla Firmicutes and Bacteroidetes. This could be considered when developing strategies to control obesity and its associated diseases by modifying the gut microbiota.

Predictors of bone disease in Egyptian prepubertal children with ß-thalassaemia major.

INTRODUCTION: Thalassaemic osteopathy is a multifactorial disorder and limited information exists about bone accrual and bone mineral density (BMD) in prepubertal thalassaemic children. The study aimed to investigate some potential genetic and biochemical bone markers as possible early predictors of BMD variations in children with ß-thalassaemia major (TM) before puberty. MATERIAL AND METHODS: Thirt-one prepubertal children with ß-TM, and 43 matched controls were subjected to BMD assessment by dual energy X-ray absorptiometry (DEXA). Vitamin D receptor (VDR) gene polymorphisms (Bsm1, Fok1) and the biochemical bone markers serum osteocalcin and propeptide I procollagen (CPIP) and urinary deoxypyridinoline (DPD) excretion were assessed. RESULTS: Bone mineral density was reduced in 25% of thalassaemics at the spine and 15.4% at the hip region. Significantly higher levels of urinary DPD and lower serum osteocalcin and CPIP levels were found in the studied thalassaemic children compared to controls (p < 0.001). A significant negative correlation was present between BMD in spine and hip and the patients' age (r = -0.6367, p = 0.0002 and r = -0.616, p = 0.00079, respectively). There was a significant reduction in BMD in males compared to females. Reduced BMD was more frequent in male patients with genotypes bb and Ff but not in females. Bone mineral density was not related to the studied biochemical bone markers, mean pre-transfusion haemoglobin or serum ferritin. CONCLUSIONS: Routine BMD screening with DEXA is proposed to be a sensitive predictor for early bone changes, particularly at the lumbar spine. DR gene polymorphisms of Bsm1 and Fok1 polymorphisms may be determinants of BMD in Egyptian prepubertal male thalassemics.

Red cell alloimmunization and autoantibodies in Egyptian transfusion-dependent thalassaemia patients.

INTRODUCTION: The objective of this study was to explore the frequency of red cell alloantibodies and autoantibodies among ß-thalassaemia patients who received regular transfusions. MATERIAL AND METHODS: This study included 501 patients with ß-thalassaemia. This work planned to study the presence of alloantibodies and autoantibodies to different red cell antigens in multitransfused thalassaemia patients using the ID. Card micro typing system. RESULTS: Of a total of 501 ß-thalassaemia patients included in the study, 11.3% of patients developed alloantibodies; 9.7% of these alloantibodies were clinically significant. The most common alloantibodies were anti-K, anti-E and anti-C. The rate of incidence of these alloantibodies was 3.9%, 3.3% and 1.7% respectively. Autoantibodies occurred in 28.8% of the patients and 22.1% of these antibodies were typed IgG. There was a significant association between splenectomy with alloimmunization and autoantibody formation (p = 0.03, p = 0.001 respectively). There was no significant association between alloantibody, autoantibody formation and number of transfused packed red cells. CONCLUSIONS: Alloimmunization to minor erythrocyte antigens and erythrocyte autoantibodies of variable clinical significance are frequent findings in transfused ß-thalassaemia patients. There is an association between absence of the spleen and the presence of alloimmunization and autoantibody formation.

Study of factor VII, tissue factor pathway inhibitor and monocyte tissue factor in noninsulin-dependent diabetes mellitus.

Changes in plasma tissue factor (TF)-activated factor VII (FVIIa) and plasma tissue factor pathway inhibitor (TFPI) in type II diabetes mellitus are assessed, vascular complicated and noncomplicated patients compared, and whether these novel hemostatic activity markers predict vascular complications in diabetic patients, improving risk assessment, is determined. Fifty type II diabetic patients and 20 healthy controls (age, sex and body mass matched) underwent medical history and examination, fasting plasma glucose level, glycosylated hemoglobin (HbA1c), lipid profile, hemostatic parameters, plasma TF activity, and TFPI and TF expression on blood monocytes. Mean TF, TF activity, TFPI, and FVIIa significantly increased among hyperlipidemic compared with normolipidemic diabetic patients, and normolipidemic diabetic patients compared with controls. Mean percentage TF-positive monocytes with and without lipopolysaccharide, plasma TF activity, TFPI and FVIIa were significantly higher among complicated than noncomplicated diabetic patients. Mean percentage TF-positive monocytes without and with lipopolysaccharide, plasma TF activity, plasma TFPI and FVIIa were higher among diabetic patients with macrovascular compared with microvascular complications. High significant correlation occurred between HbA1c, triglycerides and percentage TF-positive monocytes with and without lipopolysaccharide stimulation, plasma TF activity and both FVIIa and TFPI. High activity levels of plasma TF and FVIIa with increased circulating TF-positive monocytes occurred in type II diabetic patients, especially with vascular complications. Results reflect high procoagulant activity possibly involved in diabetic vascular complications. Elevated TFPI levels were observed, but were not sufficient to balance high procoagulant activity. Correlation of procoagulant activity markers with HbA1c reinforces the importance of optimal glycemic control in type II diabetes.