Evaluation of stimulus-induced acrosome reaction by two-colour flow cytometric analysis

Acrosome status in human spermatozoa from 20 normozoospermic men was evaluated by flow cytometry following the induction of the acrosome reaction with the ionophore A23187. Dual fluorescence staining of methanol fixed spermatozoa incubated with and without (control) the ionophore A23187 was performed with probes which targeted the outer acrosomal membrane (OAM) (rhodamine-labelled Arachis hypogaea agglutinin) or constituents of the acrosomal vesicle (fluorescein- labelled Pisum sativum agglutinin). Flow cytometry analysis revealed two major subpopulations of cells: acrosome-intact and acrosome-reacted spermatozoa after induction of the acrosome reaction. The intensity of green and red fluorescence in acrosome-reacted spermatozoa was significantly lower than that of the acrosome-intact control spermatozoa (P < 0.0001). The intensity of green fluorescence in the acrosome-intact subpopulation of spermatozoa was significantly higher than that of the control population (P < 0.002). Exposure of spermatozoa to the ionophore A23187 resulted in reliable enhancement of the number of spermatozoa with very high intensity of green and/or red fluorescence compared with the control (P < 0.03). An inverse correlation between the number of acrosome-reacted spermatozoa and spermatozoa with a very high intensity of green and/or red fluorescence was demonstrated (r = -0.631, P < 0.01). This method provides an objective and efficient procedure for quantitative estimation of the acrosomal status of human spermatozoa.      

Early referral to the nephrologist and timely initiation of renal replacement therapy: a paradigm shift in the management of patients with chronic renal failure

The high mortality rate among dialysis patients has spawned investigation into potentially correctable factors that are associated with an increased risk of death. Several studies have demonstrated a strong association between an increased risk of death in dialysis patients and suboptimal delivered dose of dialysis, malnutrition, and non-renal comorbidity. In addition, the use of unsubstituted cellulose dialyzers and reprocessed dialyzers also has been associated with an increased risk of death. Increased attention to these factors has resulted in a significant improvement in patient survival. Nonetheless, the mortality of dialysis patients remains unacceptably high and indicates that other factors may be operative. One of the factors that has thus far received scant attention, but could significantly affect morbidity and mortality in dialysis patients, is the timing and quality of care before initiation of dialysis. Optimal pre-end-stage renal disease care involves early interventions aimed at delaying progression of chronic renal failure, judicious management of uremic complications, timely placement of vascular access, timely initiation of renal replacement therapy, and implementation of educational programs targeted at maximum rehabilitation. Given the fact that early referral to the nephrologist is likely to result in optimal pre-dialysis care, the 1993 National Institutes of Health Consensus Statement on Morbidity and Mortality of Dialysis recommended that referral of a patient to a renal team should occur at a serum creatinine of 1.5 mg/dL in women and 2.0 mg/dL in men. Several investigators also have argued that patients with chronic renal failure who begin dialysis at a relatively "high level of residual renal function" (early start) may have lower morbidity and mortality compared with patients who begin dialysis at a more traditional "low level of renal function" (late start). This hypothesis is based on evidence that declining renal function is associated with malnutrition and that malnutrition at the start of dialysis is associated with poor clinical outcomes. Furthermore, patients are started on dialysis at an endogenous solute clearance that is lower than that accepted as optimum for patients on dialysis. Finally, limited clinical studies have demonstrated the benefit of early initiation of dialysis. Consequently, the Peritoneal Dialysis Adequacy Work Group of the National Kidney Foundation-Dialysis Outcomes Quality Initiative recommends that dialysis be initiated when the weekly renal Kt/Vurea decreases to below 2.0 unless all three of the following criteria are fulfilled: (1) stable or increased edema-free body weight, (2) normalized protein equivalent of total nitrogen appearance greater than 0.8, and (3) absence of clinical symptoms and signs attributable to uremia.     

Digital and conventional chest imaging: a modified ROC study of observer performance using simulated nodules

A modified receiver operating characteristic (ROC) study was performed in which five readers were asked to locate multiple nodules on images of an anthropomorphic phantom obtained with a prototype digital radiographic chest unit and with a conventional chest unit. Results indicate that when nodules were projected over the lungs, a significantly greater number (significant at the 5% level) were identified on conventional radiographs, whereas for nodules projected over the mediastinum, the digital images were notably superior (difference significant at the 2% level). An error analysis of the multiple nodule problem and pseudo-ROC curves are presented. The modified ROC study does not suffer from the positional ambiguity inherent in most ROC studies and is efficient in acquiring data.     

局部麻醉药利多卡因透皮吸收的研究

评价了局部麻醉药利多卡因的透皮吸收和制成压敏胶粘贴片皮肤局部给药麻醉的可能性。在考察利多卡因游离碱(分子型)和盐酸盐(离子型)从水和硅酮中透过无毛鼠皮肤的基础上,试制了利多卡因游离碱的橡胶型压敏胶粘贴片,对药物的体外释放和皮肤透过进行了考察,并与日本的利多卡因凝胶剂(xylocainejelly)的皮肤透过进行了比较,考察了10%～60%的利多卡因压敏胶粘贴片中药物浓度与皮肤透过之间的关系。     

紫堇灵、乙酰紫堇灵及原鸦片碱对小鼠实验性肝损伤的保护作用

研究了紫堇灵、乙酰紫堇灵及原鸦片碱对小鼠实验性肝损伤的保护作用及其作用机理。小鼠预先分别ｉｇ紫堇灵、乙酰紫堇灵或原鸦片碱５０及１００ｍｇ·ｋｇ－１２次，对ＣＣｌ４、硫代乙酰胺、扑热息痛所致的小鼠肝损伤均有保护作用，使ＳＧＰＴ显著降低，肝病理损伤程度减轻。此３种成分在体外均能抑制ＣＣｌ４引起的肝微粒体脂质过氧化及ＣＣｌ４转化为ＣＯ。在上述实验中乙酰紫堇灵的作用均强于另外两种成分。另外，此３种成分对肝药酶有先抑制后诱导作用。     

N-甲基(3,4-亚甲二氧基苯甲酰)甲基-乙酰胺(SY-640)对化学致癌剂苯并芘与小鼠肝细胞核DNA共价结合的抑制作用

用小鼠肝细胞核制备和肝微粒体制备，研究了化合物ＳＹ６４０对致癌剂苯并芘（ＢＰ）损伤肝细胞核的保护作用及与Ｐ４５０的关系。结果表明，ＳＹ６４０可显著抑制３ＨＢＰ与小鼠肝细胞核的ＤＮＡ共价结合。ＳＹ６４０连续ｐｏ３ｄ，可显著诱导小鼠肝微粒体细胞色素Ｐ４５０含量及氨基比林脱甲基酶活性；给药１次２ｈ内却只抑制氨基比林脱甲基酶活性。体外温孵实验表明，ＳＹ６４０对小鼠肝微粒体氨基比林脱甲基酶活性也具有明显的抑制作用。差示光谱分析表明，ＳＹ６４０可与细胞色素Ｐ４５０形成络合物。提示该化合物对肝微粒体细胞色素Ｐ４５０酶系的影响与其对化学致癌剂ＢＰ所致肝细胞毒性的保护作用有关。     

Both CD80 and CD86 co-stimulatory molecules regulate allergic pulmonary inflammation

We examined the roles of CD80 (B7-1) and CD86 (B7-2) in a model of allergic pulmonary inflammation and airway hyper-responsiveness (AHR) by selectively inhibiting either CD80 or CD86. Inhibition of co- stimulation by either CD80 or CD86 affected multiple parameters of the allergic response. Specifically, blockade of either CD80 or CD86 in ovalbumin-sensitized and challenged mice resulted in reduced expression of IL-2Ralpha (CD25) on CD4+ T lymphocytes, decreased airway eosinophilia, lower serum IgE production and diminished AHR. Importantly, blockade of CD80 and CD86 inhibited production of IL-4 and IL-2, and enhanced IFN-gamma production. Our observations support a role for both CD80- and CD86-mediated co-stimulation in development of allergic pulmonary inflammation.