Experimental determination of the anisotropy function for the model 200 103Pd "light seed" and derivation of the anisotropy constant based upon the linear quadratic model

Since the publication of the AAPM Task Group 43 report in 1995, Model 200 103Pd seed, which has been widely used in prostate seed implants and other brachytherapy procedures, has undergone some changes in its internal geometry resulting from the manufacturer's transition from lower specific activity reactor-produced 103Pd ("heavy seeds") to higher specific activity accelerator-produced radioactive material ("light seeds"). Based on previously reported theoretical calculations and measurements, the dose rate constants and the radial dose functions of the two types of seeds are nearly the same and have already been reported. In this work, the anisotropy function of the "light seed" was experimentally measured and an averaging method for the determination of the anisotropy constant from distance-dependent values of anisotropy factors is presented based upon the continuous low dose rate irradiation linear quadratic model for cell killing. The anisotropy function of Model 200 103Pd "light seeds" was measured in a Solid Water phantom using 1 X 1 x 1 mm micro LiF TLD chips at radial distances of 1, 2, 3, 4, 5, and 6 cm and at angles from 0 to 90 degrees with respect to the longitudinal axis of the seeds. At a radial distance of 1 cm, the measured anisotropy function of the 103Pd "light seed" is considerably lower than that of the 103Pd "heavy seed" reported in the TG 43 report. Our measured values at all radial distances are in excellent agreement with the results of a Monte Carlo simulation reported by Weaver, except for points along and near the seed longitudinal axis. The anisotropy constant of the 103Pd "light seed" was calculated using the linear quadratic biological model for cell killing in 30 clinical implants. For the model 200 "light seed," it has a value of 0.865. However, our biological model calculations lead us to conclude that if the anisotropy factors of an interstitial brachytherapy seed vary significantly over radial distances anisotropy constant should not be used as an approximation for anisotropy characteristics of a brachytherapy seed.     

IL-5 promotes induction of antigen-specific CD4+CD25+ T regulatory cells that suppress autoimmunity

Immune responses to foreign and self-Ags can be controlled by regulatory T cells (Tregs) expressing CD4 and IL-2Rα chain (CD25). Defects in Tregs lead to autoimmunity, whereas induction of Ag-specific CD4+CD25+ Tregs restores tolerance. Ag-specific CD4+CD25+ FOXP3+Tregs activated by the T helper type 2 (Th2) cytokine, IL-4, and specific alloantigen promote allograft tolerance. These Tregs expressed the specific IL-5Rα and in the presence of IL-5 proliferate to specific but not third-party Ag. These findings suggest that recombinant IL-5 (rIL-5) therapy may promote Ag-specific Tregs to mediate tolerance. This study showed normal CD4+CD25+ Tregs cultured with IL-4 and an autoantigen expressed Il-5rα. Treatment of experimental autoimmune neuritis with rIL-5 markedly reduced clinical paralysis, weight loss, demyelination, and infiltration of CD4+ (Th1 and Th17) CD8+ T cells and macrophages in nerves. Clinical improvement was associated with expansion of CD4+CD25+FOXP3+ Tregs that expressed Il-5rα and proliferated only to specific autoantigen that was enhanced by rIL-5. Depletion of CD25+ Tregs or blocking of IL-4 abolished the benefits of rIL-5. Thus, rIL-5 promoted Ag-specific Tregs, activated by autoantigen and IL-4, to control autoimmunity. These findings may explain how Th2 responses, especially to parasitic infestation, induce immune tolerance. rIL-5 therapy may be able to induce Ag-specific tolerance in autoimmunity.     

Effect of long term low-fat dietary intervention on change in hemostatic factors: results from the Women's Health Initiative

Low-fat diet may play a role in prevention of cardiovascular disease (CVD) by altering the levels of hemostatic factors. There are yet limited data on the effects of low-fat diet on the circulating levels of these factors and existing studies are limited by small sample size and short duration of follow-up. We conducted an analysis in a subset of women (active arm = 723; control arm = 1036) within the Women's Health Initiative Dietary Modification Trial to investigate the long term effect of a low-fat diet on circulating levels of fibrinogen, factor VII concentration and factor VII activity among postmenopausal women aged 50-79 years. Using linear mixed effects model with random intercept and data from three follow-up visits (years 1, 3 and 6) we evaluated the change in each factor over time. Overall, the changes in these factors were small (less than 5%) in both the arms of the trials at the end of intervention and there was no significant difference in mean change between the two arms. Our results indicate that the low-fat dietary intervention was not associated with significant changes in hemostatic factors among postmenopausal women.     

Oxidative stress and antioxidant capacity in patients with chronic pancreatitis with and without diabetes mellitus

Aim

To determine oxidant stress and antioxidant capacity in chronic pancreatitis (CP) patients with and without diabetes mellitus.

Methods

This study is a secondary data analysis of our earlier study on 127 (male?=?86) patients with CP, grouped as those with diabetes (case; n?=?23) and those without diabetes (control). Markers of antioxidant status included vitamins A and E, total antioxidant capacity (TAC; measured as ferric-reducing ability of plasma [FRAP]), and total glutathione (T-GSH). Markers for oxidative stress included lipid peroxidation, measured as thiobarbituric acid reactive substances (TBARS) and serum superoxide dismutase (s-SOD).

Results

Patients with diabetes were older (mean [SD] age 36.4 [9.7] vs. 29.3 [10.0] years; p?=?0.032), had longer duration of CP [4 (0.3?C21) vs. 3 (0.3?C24) years; p?=?0.07), and had a lower TAC (269.8 [92.4] vs. 355.5 [128.6] ??moles Fe⁺² liberated; p?=?0.003) compared to those without diabetes. In multiple logistic regression analysis taking all exploratory variables, FRAP (<270 ??moles Fe⁺² liberated) was associated with diabetes independent of duration of CP, age of patients, and TBARS levels. However, oxidative stress levels were not different between diabetic and nondiabetic patients.

Conclusions

Diabetes was found to be associated with longer duration of CP and with low antioxidant capacity. Further studies will be needed to evaluate a causal association.     

Prevalence and natural history of subclinical hepatic encephalopathy in cirrhosis

BACKGROUND AND AIMS: The natural history of subclinical hepatic encephalopathy (SHE) is unknown. The present study was conducted to study the prevalence and the natural history of SHE in patients with cirrhosis of the liver. METHODS: One hundred and sixty-five patients with cirrhosis of the liver were studied. A total of nine psychometric tests (trail making and Wechsler adult intelligence scale-performance (WAIS-P) tests) were administered. Subclinical hepatic encephalopathy was present if two or more psychometric tests were abnormal. Seventy-two patients (SHE 40, without SHE 32) also underwent serial psychometric testing on follow-up visits at 6-8 week intervals. RESULTS: Subclinical hepatic encephalopathy was present in 103 (62.4%) patients. The number and figure connection, block design and picture completion tests were the most useful in the detection of SHE. Severity of SHE, as assessed by the number of abnormal tests, was greater in patients with more severe liver disease. During follow up, SHE tended to persist or worsen in patients with poorer liver function. Although other clinical complications were similar in different groups, overt hepatic encephalopathy developed more commonly in those patients who had SHE at entry compared to those who did not (22.6 vs 5.6%, P = 0.044). Among the patients with SHE, the development of overt hepatic encephalopathy was more common in patients with Child's score of > 6 than with Child's score of 相似文献   

Effects of rhythm regularization and rate control in improving left ventricular function in atrial fibrillation patients undergoing atrioventricular nodal ablation

OBJECTIVES: To assess the relative contributions of rate control and rhythm regularization to left ventricular function in atrial fibrillation (AF) patients undergoing atrioventricular nodal ablation. This was performed by assessing the effect of ventricular rhythm regularization on left ventricular function during AF, and the effect of varying heart rate on left ventricular function after ablation. PATIENTS AND METHODS: Eleven patients with continuous AF and V/VI-R pacemakers undergoing therapeutic atrioventricular nodal ablation were studied. Preablation patients underwent two 30 min observation periods in a randomized, blinded fashion during which they were either in baseline AF (pacer set to default V/VI 50/min) or being paced using a rhythm stabilizing algorithm (RSA) designed to regularize rhythm without changing baseline ventricular rate. Six weeks after ablation, patients were again observed during the two following 30 min periods: pacing at a low clinically indicated rate (69+/-9 beats/min), and pacing at the rapid, mean preablation rate. During all observation periods, left ventricular function was measured continuously using a nuclear vest that provided validated measures of heart rate, ejection fraction, and normalized end-systolic volume (ESV) and end-diastolic (EDV) volume. RESULTS: Before ablation, RSA successfully regularized rhythm, decreasing the coefficient of variation of interbeat intervals 20+/-5% to 10+/-4% (P<0.001). The heart rate with RSA (105+/-19 beats/min) was not significantly different from the baseline AF rate (102+/-21 beats/min). Increased rhythm regularity achieved by RSA significantly improved left ventricular function, decreasing ESV from 62+/-12 units to 57+/-11 units (P=0.03), and increasing the ejection fraction from 31+/-11% to 36+/-11% (P=0.03). After ablation, at the clinically indicated low pacing rate of 69+/-9 beats/min, a much greater improvement in ejection fraction was observed, increasing to 44+/-13% (P=0.005 compared with preablation). However, rapid regular pacing at the mean preablation rate of 110+/-18 beats/min eradicated this improvement, decreasing the ejection fraction to 31+/-8% (P=0.003), and increasing ESV from 53+/-13 units to 62+/-8 units (P=0.006). CONCLUSIONS: Rhythm regularity achieved by a regularizing pacing algorithm can significantly, albeit modestly, improve left ventricular function in AF. However, more marked improvements in left ventricular function seen after ablation are primarily due to rate reduction alone.     

The anti-leishmanial drug miltefosine causes insulin resistance in skeletal muscle cells in vitro

Aims/hypothesis Miltefosine, the first oral anti-leishmanial drug, is reported to inhibit phosphatidylinositol 3-kinase (PI3K)/Akt activity in carcinoma cell lines. Inhibition of the PI3K/Akt pathway is known to result in insulin resistance. Therefore, we investigated whether miltefosine has any deleterious effect(s) on insulin sensitivity in L6E9 skeletal muscle cells.Materials and methods L6E9 myotubes were treated with miltefosine and its effect was observed on insulin-signalling proteins such as Akt, PI3K, insulin receptor-β, IRS-1, c-Jun N-terminal kinase, p38 and glycogen synthase kinase β, as well as on glucose uptake.Results Miltefosine caused skeletal muscle insulin resistance in vitro by interfering with the insulin-signalling pathway and inhibiting insulin-stimulated glucose uptake.Conclusions/interpretation Miltefosine may contribute to the risk of type 2 diabetes and needs further clinical exploration.NIPER Communication no. 370     

Effects of pioglitazone and metformin on plasma adiponectin in newly detected type 2 diabetes mellitus

OBJECTIVE: This prospective study evaluates the effect of insulin sensitizers, pioglitazone (PGZ) and metformin (MET) on plasma adiponectin and leptin levels in subjects newly diagnosed with type 2 diabetes mellitus (T2DM). DESIGN: Double blind, randomized, active control, dose escalation study of 12 weeks treatment duration. PATIENTS: Thirty apparently healthy, treatment-naive T2DM patients diagnosed within the past 6 months. MEASUREMENTS: Plasma adiponectin and leptin levels were estimated by enzyme-linked immunosorbent assay (ELISA), and insulin resistance by the homeostasis model of assessment (HOMA-IR). RESULTS: Baseline plasma levels of adiponectin were lower in diabetic (n = 30) subjects than matched controls (n = 10, 6.6 +/- 1.1 vs 10.4 +/- 4.2 microg/ml, P = 0.021). The 12-week treatment with PGZ significantly increased adiponectin concentrations (6.6 +/- 1.1-17.9 +/- 7.4 microg/ml, P < 0.001) with no alteration in the MET treated group (6.8 +/- 1.5-6.7 +/- 2.8 microg/ml, P = 0.9). A significant decrease in plasma leptin levels was observed in the MET treated group (32.0 +/- 28.9-21.4 +/- 23.3 ng/ml, P = 0.024) but not in the PGZ treated group (23.9 +/- 24.1-22.4 +/- 25.4 ng/ml, P = 0.69). The alterations in plasma adiponectin and leptin levels were not associated with any change in body mass index (BMI). PGZ therapy improved insulin sensitivity to a greater degree (P = 0.007 and P = 0.001 for fasting plasma insulin (FPI) and HOMA-IR, respectively) than MET (P = 0.75 and P = 0.02 for FPI and HOMA-IR, respectively) but this improvement was not significantly different from that of MET at the end of 12 weeks (P = 0.146 and P = 0.09 for FPI and HOMA-IR, respectively). However, improvement in insulin sensitivity with PGZ was not commensurate with the increase in adiponectin. Better control of postbreakfast plasma glucose (PBPG) as well as decrease in serum triglycerides (TGs) were also seen with PGZ (PBPG, P < 0.001; TGs, P = 0.013). The rest of the parameters were comparable. Adverse reactions reported were minor and did not result in treatment discontinuation. CONCLUSIONS: Pioglitazone therapy appears to be better in achieving glycaemic control and increasing plasma adiponectin and insulin sensitivity in newly detected type 2 diabetics.