Altered islet Beta-cell function before the onset of Type 1 (insulin-dependent) diabetes mellitus

Summary To define the glucose to insulin dose-response relationship before the onset of diabetes, we studied 22 nondiabetic co-twins of patients with Type 1 (insulin-dependent) diabetes mellitus and nine control subjects. All had intravenous glucose tests at 0.02, 0.1 and 0.5 g/kg and were followedup prospectively for at least 6 years. Seven twins developed diabetes a mean of 7 months later; the remaining 15 are now unlikely to develop diabetes. The seven pre-diabetic twins had higher fasting insulin levels than control subjects (4.2±2.0 vs 1.8±1.8 nmol/l; p<0.05); but lower glucose clearance (1.0±0.5 vs 1.9±0.7 %/min; p<0.05), first phase insulin response at 0.5 g/kg (21.1±23.2 vs 143±50 nmol/l; p<0.0001), and total insulin responses at 0.1 g/kg (p<0.05) and 0.5 g/kg (p<0.00005). Using a curve-fitting programme, the normal glucose to insulin relationship was lost in prediabetic twins who had lower coefficient of determination (R²) than control subjects (p<0.01). In contrast, 15 low-risk twins and their nine control subjects had similar fasting glucose and insulin levels, glucose clearance, R² and insulin secretory responses to different glucose loads. The positive predictive values of subnormal R² and subnormal first phase insulin response were 67 % and 58 % respectively. These observations demonstrate an altered glucose to insulin dose-response relationship and loss of maximum insulin secretory response to glucose before the onset of Type 1 diabetes.     

Treg-Cell Control of a CXCL5-IL-17 Inflammatory Axis Promotes Hair-Follicle-Stem-Cell Differentiation During Skin-Barrier Repair

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Stability of Th1 and Th2 populations

Using an in vitro model for the development of IFN-y-producIng(Th1) and IL-4-produclng (Th1) cells from CD4 T lymphocytesexpressing a transgenlc TCR, we show that IL-12 and IL-4 arethe most potent stimuli for the differentiation of naive T cellsto effector populations. When combinations of cytokines arepresent during T cell priming, the effect of IL-4 Is dominant.Furthermore, differentiated Th1 cells can be converted intoIL-4 producers by exposure to IL-4, but the Th2 phenotype Isnot reversible. The stability of Th2 populations may limit theability to regulate Th2-domlnant responses In pathologic situations.     

Baclofen,a gamma-aminobutyric acid-b receptor agonist,delays diabetes onset in the non-obese diabetic mouse

Glutamic acid decarboxylase (GAD) is the enzyme responsible for the synthesis of gamma-aminobutyric acid (GABA). GAD has been identified as a 64-kDa antigen expressed in pancreatic beta-cells, to which autoantibodies are generated prior to the onset of type 1 (insulin-dependent) diabetes mellitus. GAD may therefore be an initiating factor in beta-cell destruction. We administered baclofen, a GABA-B receptor agonist, to non-obese diabetic (NOD) mice in an attempt to down-regulate GAD expression and thereby reduce the incidence of diabetes. Twenty-four female NOD mice were given baclofen in their drinking water at a final dose of 50 mg/kg body weight daily from weaning to 30 weeks of age. Twentyfour sex-and litter-matched mice were used as controls. At 30 weeks there was no difference in the incidence of diabetes in the treated group compared with the controls. However, there was a significant delay in the onset of diabetes in the treated group (P<0.001, parallelism test). The degree of insulitis and the GAD activity in the pancreas per mg of protein were unchanged by baclofen treatment with respect to controls. These results suggest that baclofen may be effective in delaying diabetes onset in NOD mice by stimulating GABA activity, as this neurotransmitter, localised in the islets, may modulate insulin secretion and the antigen expression associated with it.     

Management of thyroid carcinoma-an experience in Bangladesh

All patients (n=154) of thyroid malignancy admitted in the Otoluryngology Department of Bangabandhu Sheikh Mujib Medical University (former IPGMR) between 1986 and 2000 were retrospectively analyzed to find out the extent and result of surgery used for thyroid carcinoma. The other objectives were to find out the incidence of differentiated thyroid carcinoma among the thyroid malignancy and also to find out the age, sex and clinical presentation of papillary and follicular carcinoma. Among all the thyroid malignancy (n-154), Differentiated Thyroid Carcinoma (DTC) was seen in 130 (84.41%) cases, where as papillary carcinoma occurred in 98(63.64%), and follicular carcinoma in 32(20.77%)cases. On the basis of risk factors, the DTC were designated as low and high risk. The year-wise incidence of DTC revealed increasing trend from 1986 (3 cases) to 2000 (23 cases). Among the 98 papillary thyroid carcinoma highest number of cases (35.71%) were seen in 31-40 year age group. The male to female ratio was 1: 1.64. In follicular carcinoma, highest number (35.25%) of cases were also seen in 31-40 year age group. The male to female ratio was 1:1.66. The commonest presentation in papillary carcinoma was thyroid swelling (96.93%). The other presentations were occult thyroid (3.06%), Cervical lymph node metastasis (38.77%) and distant metastasis (2.04%). In Follicular carcinoma, the presentations were thyroid swelling (100%), Cervical lymph node metastasis (6.25%) and Distant metastasis (21.87%). In this series, low risk DTC were treated by Lobectomy & Isthmusectomy plus Thyroxin. In low risk group the rate of recurrence was 6.89% and the mortality was nil in five years follow-up. Except two inoperable cases, all high risk patients were managed by Total thyroidectomy (with or without neck dissection, plus removal of metastatic lesion when required) with Radioiodine ablation plus Thyroxin. . The rate of recurrence was 7.81% and mortality was 1.56% in high risk group in similar period of time. Vocal cord palsy were noted in 5 (3.84%) unilateral, and inane (0.76%) bilateral cases. Hypoparathyroidism was found in 4.61%.     

Transarterial Infusion of Cisplatin and Doxorubicin in Bladder Cancer: Original Article

Forty-five patients (median age 63 years) with muscle invasive bladder cancer were treated with transcatheter intraarterial infusion (TAI) of cisplatin (CDDP) and doxorubicin. They received a total of 114 courses (median 3 courses per patient) of TAI. Complete response was obtained in 20 patients (44%), partial response in 17 (38%), stable disease in 6(13%), and progression of disease in 2 patients (5%). The overall response rate was 82% at a median follow-up of 36 months. The actuarial survival of the patient population was 72% at 5 years; 36 patients were alive and 9 had died of cancer progression. The treatment was generally extremely well tolerated without major complications. The current study also revealed the fact that papillary carcinomas were more sensitive to this therapy than were non-papillary tumors. Overall, response rate and local control were significantly higher in low-grade than in high-grade tumors. The observed high complete response and good survival rate suggest that intraarterial CDDP and doxorubicin might be highly effective for localized invasive bladder cancer.     

Do self‐efficacy and depression predict oral impacts on daily performances across time? A 2‐yr follow‐up of students in Tanzania

This study aimed to assess the longitudinal validity of the oral impacts on daily performance (OIDP) and to identify psychosocial determinants, in terms of self‐efficacy and depressive symptoms, of the OIDP across time. Following conceptual frameworks of oral health, it was hypothesized that sociodemographic, clinical, and psychosocial factors predict oral impacts across time at both population‐ averaged and person‐specific levels. Whether the effects of sociodemographic and clinical factors were accounted for, totally or in part, by psychosocial factors were also investigated. Self administered questionnaires and oral clinical examinations at baseline (2009) and follow‐up (2011) were completed by 1,714 and 727 secondary school students, respectively. Generalized equalized equations and a random intercept model were used to account for the dependency in repeated observations. Mean OIDP change scores were negative (worsened) among those who reported worsened self‐reported oral health. Psychosocial, clinical, and sociodemographic factors were independently associated with oral impacts at the population‐averaged and person‐specific levels. Mediation of sociodemographic and clinical variables according to psychosocial variables was not observed. Satisfactory longitudinal evaluative properties of the OIDP, and independent effects of psychosocial factors on oral impacts across time, were confirmed among secondary school students in Tanzania.     

Development and validation of stability-indicating high performance liquid chromatography method to analyze gatifloxacin in bulk drug and pharmaceutical preparations

Quantitative determination of gatifloxacin in tablets, solid lipid nanoparticles (SLNs) and eye-drops using a very simple and rapid chromatographic technique was validated and developed. Formulations were analyzed using a reverse phase SUPELCO® 516 C-18-DB, 50306-U, HPLC column (250 mm × 4.6 mm, 5 μm) and a mobile phase consisting of disodium hydrogen phosphate buffer:acetonitrile (75:25, v/v) and with orthophosphoric acid pH was adjusted to 3.3 The flow rate was 1.0 mL/min and analyte concentrations were measured using a UV-detector at 293 nm. The analyses were performed at room temperature (25 ± 2 °C). Gatifloxacin was separated in all the formulations within 2.767 min. There were linear calibration curves over a concentration range of 4.0–40 μg.mL⁻¹ and correlation coefficients of 0.9998 with an average recovery above 99.91%. Detection of analyte from different dosage forms at the same R_t indicates the specificity and stability of the developed method.