Role of pioglitazone, simvastatin and their combination in ameliorating complications of high fructose diet in rats

Recently, TNF-alpha was found to play an important role in development of insulin resistance, one of the hallmarks of metabolic syndrome. The current study aimed to investigate the effect of pioglitazone [PIO] and simvastatin [SIM] on serum level of tumor necrosis factor-alpha [TNF-alpha], as well as on the metabolic perturbations and disturbed homeostasis of glucose and lipids in a fructose-induced insulin resistance [HFD] rat model. To this end sixty male Wistar rats were divided into two dietary regimen-groups that lasted for a period of 8 weeks. Ten rats were fed normal chow and served as normal group [control]. Fifty rats were fed a fructose rich chow containing 60% fructose, 5% fat and 20% protein for a period of 8 weeks. Following confirmation of insulin resistance, rats obtained from the latter group were further subdivided into 4 groups [10 rats; each]. GpI: high fructose diet group [HFD]; Gp II: HFD + PIO [10 mg kg-1]; GpIII: HFD + SIM [20 mg kg-1]; Gp IV: HFD + a combination of PIO/SIM for two weeks. Fructose-fed rats developed insulin resistance [IR] as manifested by the significant increase in body weight, serum levels of glucose, glycosylated hemoglobin [HbA1c], insulin, homeostasis model of assessment insulin resistance index [HOMA-IR index], Triglycerides [TG], Total cholesterol [T-Chol], low density lipoprotein cholesterol [LDL-C] and significant decrease in high density lipoprotein cholesterol [HDL-C]. increase in serum TNF-alpha, as well as increased ratios of epidedymal fat/body weight, visceral fat/body weight and liver weight/ body weight were prominent findings in this study. The results revealed a positive correlation between TNF-alpha and HOMA IR-index. Treatment with PIO or SIM significantly reduced serum glucose, insulin HbA1c, TO, T-Chol, LDL-C and increase of HDL-C. A significant decrease in TNF-alpha, were observed, as well as normalization of increased percentage ratios of epidedymal fat/body weight, visceral fat/body weight and liver weight/body weight. Treatment with PIO or SIM significantly improved disturbed glucose metabolism and HOMA-IR index, co-administration of SIM and PIO synergistically enhanced the overall metabolic parameters

Longitudinal study of growth parameters in beta-thalassemia major on oral iron chelation

Children with thalassemia suffer from growth retardation. It had mainly been attributed to iron overload in the tissues and endocrine glands, chronic anemia, hypersplenism, folic acid deficiency, delayed or absent puberty. In addition a direct toxic effect on the bones has been observed in patients, before and during puberty, receiving continuous subcutaneous chelation therapy. The aim of this work is to monitor the growth of children with beta-thalassemia on oral iron chelation for early detection of growth and pubertal disorders. In this study, auxological, pubertal and laboratory data of 82 patients with beta-thalassemia major on hypertransfusion regimen and adjusted oral iron chelation following up at the hematology clinic at Cairo University Children's Hospital are studied. Height, weight, Body Mass Index, and US/LS ratio were followed up on a 3-monthly basis, over a period of 4 years. Height velocity and bone age were assessed yearly. Serum ferritin, thyroid including free T3, freeT4 and TSH and parathyroid functions including serum calcium, albumin, alkaline phosphatase and parathormone, folic acid, vitamin B12 levels, were measured in 38 of the cases at the end of the study and compared to 20 age and sex matched control. In this study 24/82 [29%] of the patients are short and remained so during the study. The US/LS ratio was abnormal in 17 cases [21%] and the ratio normalized in 7 by the end of the study. Bone age improved by the second year and returned slowed down thereafter. 52% of adolescents suffered pubertal delay and 35% needed HCG replacement to induce puberty. Serum ferritin, B12 and folic acid, Parathormone, calcium, phosphorus, alkaline phosphatase, free T3, T4, TSH were significantly different from controls. Patients in this series are hypocalcemic, hypoalbuminemic, with 65% B12 and 71% folic acid deficient, 8% had preclinical hypothyroidism while 34% had clinical hypothyroidism, one third are short and half of them have delayed puberty. The stature is not correlated to thyroid status. There was a significant correlation of height SDS and folic acid and albumin. Upper segment/Lower segment ratio was correlated to serum albumin, calcium and parathormone. Short stature is common among thalassemic patients. Puberty is delayed in half of them. Egyptian children with thalassemia are hypocalcemic, hypoalbuminemic, with an increased incidence of hypothyroidism, B12 and folic acid deficiency. Emphasis must be put on an adequate, balanced nutrition in these children with increased cell turn over