血管细胞粘附分子调控造血的研究进展

本文简述了血管细胞粘附分子 (Vascularcelladhesionmolecule 1,VCAM 1)的结构和生物学功能 ,总结了VCAM 1在恶性血液病骨髓基质中的表达和意义 ,探讨了VCAM 1在造血干细胞动员和归巢中的作用 ,指出VCAM 1作用机制的深入研究将对恶性血液病的治疗提供更为有效的方法。     

Noradrenaline reuptake and plasma dihydroxyphenylglycol during sustained changes in sympathetic activity in rabbits

The effects of sustained changes in sympathetic activity, produced by intracisternal (i.c.) infusion of yohimbine or clonidine, on the formation of the intraneuronal noradrenaline metabolite, dihydroxyphenylglycol (DHPG), and on the efficiency of noradrenaline reuptake were examined in conscious rabbits. Noradrenaline spillover was estimated by radiotracer dilution analysis of i.v. infused [3H]noradrenaline. Noradrenaline reuptake was estimated from the amount of DHPG derived from recaptured neurotransmitter and the effects of desipramine-induced neuronal uptake blockade on noradrenaline clearance and plasma [3H]DHPG. The efficiency of neuronal reuptake was assessed from relationships between noradrenaline reuptake and spillover. Sustained sympathetic activation with i.c. yohimbine increased the amount of plasma DHPG that was derived from recaptured noradrenaline as well as that derived from other sources. Acute administration of desipramine decreased both components so that the decrease in plasma DHPG overestimated the amount derived from recaptured noradrenaline. Thus, estimation of the component of plasma DHPG that was derived from recaptured noradrenaline was most accurately achieved by examination of relationships between plasma noradrenaline and DHPG. Noradrenaline reuptake and spillover into plasma were decreased by i.c. infusion of clonidine and increased by i.c. infusion of yohimbine. Neither i.c. infusion of clonidine nor yohimbine altered relationships between noradrenaline reuptake and spillover indicating that the efficiency of neuronal reuptake was unaltered by sustained changes in sympathetic activity.     

Estimation of normal lumbar flexion with surface inclinometry. A comparison of three methods.

The purpose of this study was to determine the magnitude and clinical significance of surface measurement error in the determination of lumbar spinal flexion. Intrarater, inter-rater and intermethod reliability estimates were obtained using single inclinometry, double inclinometry and back range-of-motion inclinometry methods. Eight healthy subjects were examined independently by two experienced observers and three replicates of each measurement were obtained by each observer in a random sequence. In addition, three replicates of lumbar flexion angles were obtained for each subject by a single observer using the B-200. Reliability estimates were determined by intraclass correlation coefficients and were further compared by paired t tests between observation series. The median range of error was 8.5 degrees using the single inclinometer, 10.5 degrees using the double inclinometer and 16 degrees using the back range-of-motion. The intrarater reliability was generally higher than inter-rater reliability and intermethod reliability was low in most cases reflecting the poor cross-validity across inclinometry methods and between each inclinometry method and the B-200. In conclusion, significant measurement error in estimating lumbar flexion by inclinometry may be expected to occur even in a "controlled" setting using experienced observers, standard examination techniques and asymptomatic healthy subjects. These findings appear to undermine the expectation that the clinician can reliably apply surface inclinometry to estimate loss of spinal mobility for purposes of impairment determination.     

Sympathetic nerve activity and neurotransmitter release in humans: translation from pathophysiology into clinical practice

AIM: There has been a revolution in cardiovascular neuroscience in recent years with, in some cases, translation into clinical practice of the knowledge of pathophysiology gained through application of sympathetic nerve recording and catecholamine isotope dilution methodology. OBESITY-RELATED HYPERTENSION: An earlier hypothesis, based on findings in most models, was that weight gain in obesity is due in part to sympathetic nervous underactivity reducing thermogenesis. Microneurography and regional noradrenaline spillover measurements in human obesity have disproven this hypothesis, weakening the case for the use of beta3-adrenergic agonists to stimulate thermogenesis. Sympathetic nerve firing rates in post-ganglionic fibres directed to the skeletal muscle vasculature are increased, as is renal sympathetic tone, with a doubling of the spillover rate of noradrenaline from the kidneys. Given these findings, antiadrenergic antihypertensive drugs may be the preferred agents for obesity-related hypertension, but this has not been adequately tested. ESSENTIAL HYPERTENSION: Whether stress causes high blood pressure, previously hotly debated, has been under recent review by an Australian Government body, the Specialist Medical Review Council. Despite medicolegal implications, the ruling was that stress is one proven cause of hypertension. The judgment was reached after consideration of the epidemiological evidence, but in particular the described neural pathophysiology of essential hypertension: (a) persistent sympathetic nervous stimulation is commonly present, (b) suprabulbar projections of noradrenergic brainstem neurones are activated and (c) adrenaline is released as a cotransmitter in sympathetic nerves. These were taken to be biological markers of stress. CARDIAC FAILURE: At one time, the failing heart was thought to be sympathetically denervated. Longterm administration of inotropic adrenergic agonists, to provide the cardiac catecholamine stimulation thought to be lacking, increased mortality. Noradrenaline isotope dilution methodology subsequently demonstrated that the sympathetic outflow to the heart was preferentially activated, cardiac noradrenaline spillover being increased as much as 50-fold. The level of stimulation of the cardiac sympathetic nerves was the most powerful predictor of death. These observations provide the theoretical foundation for the very successful introduction of beta-adrenergic blockers for treatment of heart failure.     

Glycoproteins present in human follicular fluid that inhibit the zona- binding capacity of spermatozoa

Previous studies have suggested that human follicular fluid contains factors that reduce the zona-binding capacity of spermatozoa. The present study provides further evidence of the existence of such factors. Using the hemizona binding assay (HZA), we have shown that the inhibitory effect of human follicular fluid on the zona-binding capacity of spermatozoa is concentration-dependent, an inhibitory effect being detected when the concentration of human follicular fluid was > or = 10%. A 1% concentration of human follicular fluid did not possess this inhibitory activity. Heating human follicular fluid at 56 degrees C for 30 min did not affect its inhibitory properties; treatment with proteinase-K abolished such inhibition. Human follicular fluid was fractionated sequentially by concanavalin-A affinity chromatography, Mono Q ion-exchange chromatography and Superose-12 gel filtration. The zona binding inhibitory activity resided in the fraction which bound to the lectin and Mono Q column and contained molecules with native molecular weights of 32 and 192 kDa. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis suggested that the 192 kDa glycoprotein was a tetramer, while the 32 kDa glycoprotein remained as a single molecular species under denaturing conditions. We conclude that two glycoproteins were responsible for the zona binding inhibitory activity of human follicular fluid. The physiological role of these factors remains unclear.      

Response from lieberman and colleagues

Respond on comments on Lieberman's article: Cyclosiloxanes Produce Fatal Liver and Lung Damage in Mice. Environ Health Perspect 107:161-165     

Effects of Tadalafil on Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia and on Erectile Dysfunction in Sexually Active Men with Both Conditions: Analyses of Pooled Data from Four Randomized,Placebo‐Controlled Tadalafil Clinical Studies

IntroductionErectile dysfunction (ED) and lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) are common in aging males and frequently occur together. Tadalafil has demonstrated efficacy in treating both conditions.AimThe study aims to evaluate the efficacy and safety of tadalafil 5 mg once daily vs. placebo over 12 weeks in treating both LUTS/BPH and ED in sexually active men. We also assessed relationships of baseline disease severity and prostate specific antigen (PSA) to outcomes.MethodsData were pooled from four multinational, randomized studies of men ≥45 years with LUTS/BPH, with analyses restricted to sexually active men with ED. Randomization (baseline) followed a 4‐week placebo run‐in; changes from baseline were assessed vs. placebo using analysis of covariance.Main Outcome MeasuresInternational Prostate Symptom Score (IPSS), IPSS subscores, Quality‐of‐Life Index (IPSS‐QoL), BPH Impact Index (BII), and International Index of Erectile Function‐Erectile Function (IIEF‐EF) Domain score were used in this study.ResultsTadalafil (N = 505) significantly improved total IPSS vs. placebo (N = 521); mean changes from baseline were ?6.0 and ?3.6, respectively (P < 0.001). Improvements in IIEF‐EF Domain score (tadalafil, 6.4; placebo, 1.4) were also significant vs. placebo, as were the IPSS storage and voiding subscores, IPSS‐QoL, and BII (all P < 0.001).No significant impact of baseline ED severity or PSA category on IPSS response was observed (interaction P values, 0.463 and 0.149, respectively). Similarly, improvement in IIEF‐EF Domain score was not significantly impacted by baseline LUTS/BPH severity or PSA category (interaction P values, 0.926 and 0.230, respectively). Improvements in IPSS and IIEF‐EF Domain score during treatment were weakly correlated (r = ?0.229). Treatment‐emergent adverse events were consistent with previous reports.ConclusionsTadalafil was efficacious and well tolerated in treating ED and LUTS/BPH in sexually active men with both conditions. Improvements in both conditions were significant regardless of baseline severity. Improvements in the total IPSS and the IIEF‐EF Domain score were weakly correlated. Porst H, Roehrborn CG, Secrest RJ, Esler A, and Viktrup L. Effects of tadalafil on lower urinary tract symptoms secondary to benign prostatic hyperplasia and on erectile dysfunction in sexually active men with both conditions: Analyses of pooled data from four randomized, placebo‐controlled tadalafil clinical studies. J Sex Med 2013;10:2044–2052.