The effects of up to 240 days of tacrolimus therapy on the gingival tissues of rats – a morphological evaluation

Background:  Tacrolimus, an immunosuppressive drug used in organ transplantation, has been reported not to induce gingival overgrowth. However, prevalence studies are limited, and the methods used for assessing gingival overgrowth varies among studies.
Objective:  The purpose of this study was to evaluate the effects of up to 240 days of tacrolimus therapy on gingival tissues of rats.
Materials and methods:  Rats were treated for 60, 120, 180 and 240 days with daily subcutaneous injections of 1 mg/kg body weight of tacrolimus. After histological processing, the oral and connective tissue, volume densities of fibroblasts ( V _f), collagen fibers ( V _cf) and other structures ( V _o) were assessed in the region of the lower first molar.
Results:  After 60 and 120 days of treatment with tacrolimus, gingival overgrowth was not observed. The gingival epithelium, connective tissue, as well as the values for V _f, V _cf, and V _o were similar to those of the control rats ( P  > 0.05). After 180 and 240 days of the treatment, gingival overgrowth was associated with a significant increase in the gingival epithelium and connective tissue as well as an increase in the V _f and V _cf ( P  < 0.05).
Conclusions:  Within the limits of the experimental study, it may be concluded that the deleterious side effects of tacrolimus on the gingival tissues of rats may be time-related.     

Smaller aortic dimensions do not fully account for the greater pulse pressure in elderly female hypertensives

This study examined the importance of aortic dimensions in determining pulse pressure in elderly hypertensives participating in the 2nd Australian National Blood Pressure Study, including a substantial number not previously receiving blood pressure lowering medication. Aortic dimensions were determined by ultrasound at the transverse arch and at the insertion of the aortic valve. Unadjusted data showed negative (P<0.001) correlations between central (carotid) and (brachial) peripheral pulse pressure and both arch (-0.200, -0.181) and outflow tract (-0.238, -0.238) diameters. Correlations were similar in those previously treated with blood pressure lowering medication and in the treatment na?ve. Central pulse pressure (84+/-26 versus 75+/-28 mm Hg, P<0.001) was higher and aortic dimensions (transverse arch 2.56+/-0.31 versus 2.88+/-0.35 mm, P<0.001) smaller in women than men. Women had greater aortic stiffness (beta index 29.4+/-36.1 versus 22.1+/-21.3, P<0.03). Other bivariate correlates of central pulse pressure were age, mean arterial pressure, height, heart rate, augmentation index, aortic stiffness (all P<0.001), and weight (P=0.027). In multivariate analyses gender remained a predictor of central pulse pressure (P<0.001) even with inclusion of aortic dimensions (P=0.013) height and weight. Other significant terms were age, heart rate, mean blood pressure, and aortic stiffness (all P<0.001). These findings demonstrate an independent inverse relation between aortic size and pulse pressure in older hypertensive subjects. Differences in aortic dimensions and stiffness between genders do not fully account for the observed blood pressure differences, suggesting that a contributory factor to gender differences in pulse pressure is an increased age-related mismatch in ventricular function and aortic stiffness in women compared with men.     

婴幼儿血管瘤的发病机制：新的分子与细胞学认识

幼年性血管瘤是婴幼儿最常见的肿瘤，但对其病因仍存在争论，且对其演变周期知之甚少。过去10年间对幼年性血管瘤的许多新的认识逐渐显现，但都在基础研究领域对之进行讨论，包括细胞起源、非随机分布及肿瘤快速增殖和消退的调控机制等方面。由于在研究模型的建立方面面临困难，从而限制了其治疗方法的研究。     

Feasibility of conducting a primary prevention trial of low-dose aspirin for major adverse cardiovascular events in older people in Australia: results from the ASPirin in Reducing Events in the Elderly (ASPREE) pilot study

AIM: To determine the feasibility of performing a large clinical trial of the use of aspirin for the primary prevention of cardiovascular disease in older participants--the ASPirin in Reducing Events in the Elderly (ASPREE) trial. DESIGN AND PARTICIPANTS: A randomised double-blind placebo-controlled pilot trial of 100 mg of enteric-coated aspirin tablets daily, in men and women aged 70 years and over who did not have overt cardiovascular disease, and who were followed for 12 months. Participants were identified from the computer databases of general practitioners who were co-investigators in a previous trial. SETTING: The Melbourne metropolitan area between March 2003 and June 2005. MAIN OUTCOME MEASURES: The level of response to participation by GPs; the level of response from potential trial participants; the screening-to-randomisation rate to ensure the recruitment target could be achieved; and the retention of participants in the trial after 12 months. RESULTS: Forty-two GPs (23% of 180 mailed) expressed interest in participating in the pilot trial. Nineteen became co-investigators, of whom six were not required to meet recruitment targets. Letters were sent to 2614 patients, of whom 243 were screened and 209 (86%) were randomly allocated to receive aspirin or placebo. At 12 months,192 (92%) returned for follow-up, and 153 of these (80%) were still taking trial medication. There was a significant reduction in mean haemoglobin level in those taking aspirin. CONCLUSIONS: The recruitment strategy for ASPREE, based on methods developed for the conduct of a previous large-scale trial conducted in general practice, was successfully redeployed in this pilot study, with improved efficiency resulting from computerised database searching, telephone pre-screening, a simpler run-in phase and participant familiarity with the trial drug. We conclude that conducting ASPREE in Australian general practice with 18 000 participants is feasible. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number Register ISRCTN83772183.     

Antibody to Hepatitis B Surface Antigen in Vaccinated Health Care Workers

Background

Health care workers (HCWs) in Armed Forces are immunised against Hepatitis B virus (HBV), however they are not subjected to anti-HBs (antibody to Hepatitis B surface antigen) assessment after primary vaccination. The present study was undertaken to determine the protection offered by HBV vaccine in HCW.

Methods

Cross-sectional study was carried out at tertiary care hospital. A total 146 HBV vaccine compliant HCW were evaluated for quantitative anti-HBs by enzyme immune assay.

Result

129 (88.4%) subjects had protective levels of anti-HBs. Higher age at vaccination was an important risk factor in low vaccine response. Decline in anti-HBs with time was evident. Anti-HBs levels were more than 10mIU/ml in subjects even after 11 years of primary vaccination. There was no difference in protection in booster and non booster groups.

Conclusion

Age is the most important factor in HBV vaccine response. Booster dose of HBV vaccine is not necessary in healthy HCW for atleast ten years after primary vaccination. The study recommends early primary vaccination of HCW and ‘initial’ anti-HBs assay for confirmation of vaccine response.Key Words: Anti-Hepatitis B surface antigen, Health care workers, Hepatitis B virus vaccine     

Let’s talk about sex: Development and evaluation of a sexual history and counseling curriculum for internal medicine interns

Objective

We developed a curriculum to increase internal medicine interns’ proficiency in sexual history taking and sexually transmitted illness (STI) counseling.

Extended storage of AS-1 and AS-3 leukoreduced red blood cells for 15 days after deglycerolization and resuspension in AS-3 using an automated closed system

BACKGROUND: The utilization of cryopreserved red blood cell (RBC) units had been limited by a maximum postdeglycerolization storage of 24 hours at 1 to 6 degrees C until the recent development of a closed system for the glycerolization and deglycerolization process. STUDY DESIGN AND METHODS: Sixty leukoreduced additive solution (AS), AS-1 (n = 30) and AS-3 (n = 30) RBC units from 500-mL whole blood (WB) collections were stored for 6 days, glycerolized, frozen at -70 +/- 5 degrees C for at least 14 days, thawed, deglycerolized, and stored for 15 days at 1 to 6 degrees C. Glycerolization and deglycerolization were performed with the ACP 215. In-vitro variables were tested before glycerolization, on Day 0, and Day 15 after deglycerolization storage. Forty donors were assessed for double-label 24-hour percent recovery, and T1/2 survival time was measured for 20 donors. RESULTS: Postdeglycerolization mean +/- standard deviation in-vitro RBC mass recoveries were 93 +/- 5 percent for AS-1 and 95 +/- 4 percent for AS-3. Mean hemoglobin +/- standard deviation after deglycerolization was 50.5 +/- 5.5g for AS-1 and 50.1 +/- 3.5g for AS-3. Mean hemolysis (Day 15) was 0.36 +/- 0.11 percent for AS-1 and 0.38 +/- 0.13 percent for AS-3. Double-label 24-hour in-vivo recoveries were 82.5 +/- 7.8 percent for AS-1 and 81.4 +/- 7.1 percent for AS-3. The 51Cr T1/2 value was 41.8 +/- 3.97 for AS-1 and 40.6 +/- 7.11 for AS-3. Other in-vitro variables were as expected. CONCLUSION: Leukoreduced AS-1 and AS-3 RBCs after frozen storage at -70 +/- 5 degrees C can be stored for up to 14 days when processing is performed with the ACP 215 system with resuspension of deglycerolized RBCs in AS-3.     

Clopamide: plasma concentrations and diuretic effect in humans

Clopamide pharmacokinetics were determined after oral doses of 5, 10, and 20 mg in normal volunteers. Maximum plasma concentrations occurred within 2 hours and were followed by a monoexponential decline with an elimination half-life of approximately 10 hours. There was an approximately linear relationship between dose and the AUC. Urinary sodium, chloride, and potassium excretion rates indicated that the peak diuretic activity corresponded with peak plasma drug concentrations and probably continued for 12 to 24 hours. There was little difference between the total sodium and chloride output after each dose of clopamide, suggesting that 5 mg may have been close to the top of the dose-response curve. Chlorothiazide, 500 mg, caused less sodium and chloride output with similar potassium loss. During chronic administration to patients with hypertension, hypokalemia was more marked with clopamide, 10 mg daily, than with clopamide, 5 mg, or chlorothiazide, 500 mg daily.     

Galpha13 mediates a signal that is essential for proliferation and survival of thymocyte progenitors

G protein signaling via the Galpha12 family (Galpha12 and Galpha13) has not been well studied in T cells. To investigate whether Galpha12 and Galpha13 are involved in thymopoiesis, we expressed the regulator of G protein signaling domain of p115RhoGEF to inhibit Galpha12 and Galpha13 during thymopoiesis. Fetal thymus organ cultures seeded with p115DeltaDH-expressing progenitor cells showed impaired thymopoiesis with a block at the CD4-CD8-CD44-CD25+ (DN3) stage. Using Galpha13 or Galpha12 minigenes, we demonstrated that Galpha13, but not Galpha12, is required for thymopoiesis. T progenitor cells expressing p115DeltaDH showed reduced proliferation and increased cell death. T cell receptor stimulation of the fetal thymus organ cultures did not rescue the block. Overexpression of the antiapoptotic gene Bcl2 rescued the defect in DN3 cells and partially rescued T cell development. Therefore, Galpha13-mediated signaling is necessary in early thymocyte proliferation and survival.