Objective:To investigate the combined effect of both pioglitazone and methotrexate on disease activity of rheumatoid arthritis in a biphasic study; experimental and clinical.Methods:Experimentally: 50 rats were divided into 5 equal groups; controls, experimental arthritis, methorexate treated (0.1 mg/Kg daily), pioglitazone-treated (10 mg/kg daily), and methotrexate and pioglitazone treated. Clinically: forty-nine diabetic rheumatoid arthritis patients were included. Patients group consisted of 28 patients and they received pioglitazone 30 mg orally beside their usual treatment. Control group consisted of 21 patients and they continued their usual treatment plus placebo. Disease activity was assessed using DAS28 score. Patients were followed up for 3 months.Results:Pioglitazone produced a significant improvement of serum oxidative stress parameters (P < 0.05), and inflammatory cytokines in the treated arthritic group (P < 0.05). Clinically, the pioglitazone treated group showed significant improvement in DAS28 (P = 0.001) and C-reactive protein (P < 0.0001) compared to placebo group.Conclusion:The concomitant use of the PPAR γ agonist pioglitazone and methotrexate appears to be promising therapeutic strategy for rheumatoid arthritis patients.

Aim of the studyBreast cancer is the most common cause of death in women. Obesity has been associated with increased risk of breast cancer in post-menopausal women. It induces chronic inflammation, which increases local and systemic levels of cytokines and adipokines such as leptin. Leptin (LEP) and leptin receptor (LEPR) genes have several polymorphisms in humans. This study aims to assess the association between blood levels of leptin and LEPR Q223R gene polymorphism in patients of cancer breast.Material and methodsThe current study was carried on 48 female breast cancer patients and 48 heathy female subjects. Carcinoembryonic antigen (CEA), cancer antibody CA15-3, and leptin hormone were determined. Single nucleotide polymorphism of LEPR Q223R was assessed by PCR/RFLP. Statistical analysis used: The statistical analysis of data was done by using SPSS version 20.ResultsThere were significant increases in the concentrations of CEA (p = 0.004), CA15-3 (p < 0.001), and leptin hormone (p < 0.001) in BC patients in relation to the respective concentrations in control subjects. CEA and CA 15-3 showed significant differences between various BC stages. As regard to LEPR Q223R gene polymorphism, AA genotype showed significantly higher frequency in BC patients when compared to their respective controls, with higher risk to develop BC.ConclusionsLeptin hormone shows significantly higher concentrations in BC patients. As regard to LEPR Q223R gene polymorphism, AA genotype showed significantly higher frequency in BC patients.

Background and purposeTo investigate the effects of vitamin D supplementation on glucose homeostasis and lipid profile in type 2 diabetic patients who have vitamin D deficiency.Patients and methodsOne hundred twenty-five type 2 diabetic patients taking oral hypoglycemic agents as mono- or combination therapy were recruited from the diabetes and endocrinology clinic. Subject demographics, duration of diabetes, antidiabetic medication, body mass index (BMI), pulse, and blood pressure (BP) were assessed. Laboratory measurements of serum vitamin D3 level, hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and lipid profile were measured. Homeostatic model assessment-insulin resistance (HOMA-IR) was calculated whenever fasting insulin (FI) was available. Forty-one patients (27 males and 14 females) were started on cholecalciferol replacement–45,000 units once weekly for 8 weeks and then 22,500 units once weekly for 16 weeks. Calcium carbonate tablets 500 mg once daily were also prescribed for the initial 2 months of treatment. Measured variables were reassessed after 6 months of replacement therapy. During the trial, subjects were instructed not to change their diabetes drugs or lifestyle.ResultsNo significant association was found between vitamin D3 level and any of the measured variables apart from a significant positive correlation with blood urea nitrogen. Vitamin D3 replacement was associated with a significant increase in its level (14.0±4.0 vs 31.0 vs 7.9 ng/mL, P<0.001). This was associated with a significant reduction of HbA1c (7.9±1.7 vs 7.4%±1.2%, P=0.001) and FPG (9.1±4.3 vs 7.9±2.4 mmol/L, P=0.034). Mean reduction of HbA1c was 0.54% and that of FPG was 1.22 mmol/L. FI, c-peptide and insulin resistance (IR) were reduced but this was statistically insignificant (P=0.069, 0.376, 0.058, respectively). FI decreased by 22%, HOMA-IR by 27.6%, and c-peptide by 1.83%. Total cholesterol, low-density lipoprotein cholesterol, parathyroid hormone, alkaline phosphatase, serum creatinine, and pulse rate significantly decreased (4.3±0.9 vs 4.0±0.9 mmol/L, P=0.036; 2.5±0.8 vs 2.2±0.8 mmol/L, P=0.018; 4.6±2.1 vs 3.5±1.8 pmol/L, P=0.001; 82.1±26.2 vs 66.2±19.5 U/L, P<0.001; 74.6±15.6 vs 70.7±14.7 μmol/L, P=0.047; and 81.6±11.9 vs 77.5±12.0 bpm, P=0.045, respectively). Triglycerides and high-density lipoprotein cholesterol, both systolic and diastolic BP, and BMI did not show significant change.ConclusionCholecalciferol helps improve blood glucose control and cholesterol profile in vitamin D3-deficient type 2 diabetic patients.

The objective of this study was to investigate the modulation of metabolic dysfunctions, adiponectin levels, and cardiac dysfunctions of type 2 diabetes mellitus (T2DM) by a combination of the insulin sensitizer rosiglitazone and angiotensin receptor blocker telmisartan in an experimental rat model. Fifty male adult Sprague-Dawley rats were divided equally into 5 groups. Group I: fed normal chow; served as normal control group. Groups II-V: fed a high-fat diet (HFD) for 2 weeks, followed by injection of streptozotocin (STZ; 35 mg/kg) to create a model of T2DM. Group II: treated with vehicle. Group III: treated with rosiglitazone (4 mg/kg). Group IV: treated with telmisartan (5 mg/kg). Group V: treated with both agents. Untreated HFD-STZ rats showed elevated fasting blood glucose, insulin, homeostasis model assessment (HOMA) index, triglycerides (TGs), low-density lipoprotein cholesterol (LDL), and total serum cholesterol (TC), with a decrease in high-density lipoprotein cholesterol (HDL) and adiponectin levels (p < 0.001). Rosiglitazone exerted more improvement in all parameters than telmisartan did, and a combination of both did not augment the improvement further, except for TGs and adiponectin. For the isolated atrial study, a combination of rosiglitazone and telmisartan corrected the responses of the atria of HFD-STZ rats to the negative inotropic effect induced by adenosine better than either one did alone, whereas this combination, surprisingly, significantly attenuated the positive inotropic response to β-adrenoreceptor and α-adrenoreceptor agonists. In conclusion, rosiglitazone significantly improved the metabolic and cardiac dysfunctions in T2DM. Moreover, a combination of rosiglitazone and telmisartan offered more improvement in serum TGs and adiponectin, and restored the atrial inotropic response to adenosine. Surprisingly, this combination significantly attenuates the positive inotropic response to α1-adrenoreceptor and β-adrenoreceptor agonists.

W HEAT leaf rust, caused by the fungus Puccinia triticina Eriks., is a destructive disease found throughout common wheat production areas worldwide. Fifty wheat leaf rust monogenic lines were tested with five of Puccinia triticina pathotypes, i.e. BJPPQ, LQFDS, PHFPG, PTPDN, TRFDJ at four stable temperatures (30 0 C, 25 0 C, 20 0 C and 15 0 C). The wheat monogenic lines viz. Lr 16, Lr 17 and Lr 23 were more resistant at 25 0 C, while these genes were found susceptible at 15 0 C, 20 0 C and 30 0 C to all tested races. Eight monogenic lines, i.e. Lr11,