The lipophilic properties of angiotensin I-converting enzyme inhibitors do not influence their diffusion through cultured endothelium

The background for these investigations was the discovery that formation of angiotensin II by the renin angiotensin system can take place in extravascular tissues (e.g., cardiomyocytes and neurons) and within single cells. Consequently, the question arose about whether such tissue-based systems might be differentially influenced by angiotensin I-converting enzyme (ACE) inhibitors with distinct physicochemical properties. Therefore, the aim of this study was to investigate how the membrane penetration of various ACE inhibitors depends on their lipophilia. All diacid forms of ACE inhibitors are dissociated at a pH of 7.4 and scarcely extractable into octanol (extraction coefficient < 10%). In contrast, the extraction coefficients of the parent substances showed marked differences in the following order of increasing lipophilia: enalapril = perindopril < captopril = ceranapril < ramipril < quinapril < HOE288 = zofenopril < fosinopril < HOE065. For selected substances, the kinetics of diffusion through a monolayer of cultured bovine aortic endothelium were determined. The diffusion rates (expressed as half lives) of captopril (59.6 min), enalapril (53.4 min), enalaprilat (50.8 min), ramipril (56.9 min) and ramiprilat (51.1 min) are similar indicating: 1) that penetration is independent on lipophilia and 2) that endothelium constitutes no specific barrier for the passage of ACE inhibitors into the vessel wall.     

Serostatus and counseling

Seroconcordance and serodiscordance are important issues in counseling for both HIV-positive and HIV-negative gay men. Just as gay psychotherapists have used self-disclosure as a tool to help clients feel understood, serostatus disclosure by therapists could also be beneficial. By serving as role models, counselors can help gay men remain uninfected and help men with AIDS take care of themselves. At the same time, counselors can aid both infected and affected men in maintaining a sense of hope and intimacy. Role modeling has been useful for many HIV-negative gay men, who often feel abandoned by communities and social services that focus on the needs of the HIV-positive community. As a result, mental health and social service providers have begun developing services, including support groups, particularly for HIV-negative gay men.     

Computed cranial tomographic findings in cerebral sinovenous occlusion.

Eleven patients with angiographically and/or pathologically verified cerebral sinovenous occlusions not directly caused by trauma were studied by computed cranial tomography (CCT). Static radionuclide brain scans and dynamic radionuclide flow studies were also obtained in four patients; in two, findings diagnostic of lateral sinus thrombosis were noted. These comprised a "negative on dynamic, hot on static" image, as well as a "hot on static with nonfilling on angiography." Computed cranial tomography findings included visualization of the thrombosed vein ("cord sign") or sinus ("empty triangle" or "delta sign"), multiple focal bilateral parasagittal hemorrhages, intense tentorial enhancement, gyral enhancement indistinguishable from infarct, solitary intracerebral hematoma, small ventricles, and normal scan. Excluding the patients with underlying meningioma, all three of whom survived, seven of the remaining eight patients expired during the acute phase of their illness, an 88% mortality. This group includes one patient who had normal CCT findings, albeit without contrast enhancement, who was diagnosed as pseudotumor cerebri. The need for full neuroradiological evaluation, including angiography, is thus stressed if this highly fatal yet treatable condition is not to remain undiagnosed.     

Ambulance services: a logical, effective and economic solution

Ambulance services tend to be over-manned and under-productive. Metropolitan services, run by regions, cost more and are less sensitive to local needs than those run by areas. In offering his strictly personal views, Terry Ball, staff officer, West Yorkshire Metropolitan Ambulance Service, suggests that in future DHAs should run the ambulances.     

Development of a new controlled-release formulation of chlorpheniramine maleate using in vitro/in vivo correlations

Development of a controlled-released formulation of chlorpheniramine maleate is described, using in vitro/in vivo correlates, according to a process that has been termed "biorelevant dissolution". The process begins with simulations using several possible input rates combined with known disposition parameters of chlorpheniramine maleate. Based on desired plasma concentrations, an input rate is selected for further development which consists of a combination of clinical bioequivalence studies and further in vitro testing and simulations. The method is designed to reduce the requirements for trial and error clinical bioequivalence testing of a new controlled-release formulation.     

蝙蝠葛中的新生物碱——蝙蝠葛新林碱

防已科植物蝙蝠葛(Menispermum daurioum DC.)的根茎,即北豆根,是一种重要的中药,具有清热解毒、消肿止痛等功效。已知含有近二十种生物碱,其中五种属双苄基四氢异喹啉类,即蝙蝠葛碱(dauricine,Ⅰ)、蝙蝠葛诺林碱(daurinoline,Ⅱ)、蝙蝠葛新诺林碱     

Very mild Alzheimer's disease: informant-based clinical, psychometric, and pathologic distinction from normal aging

We compare clinicopathologic data from 10 subjects identified in the very mild stage of senile dementia of the Alzheimer type with findings from similar studies in four cognitively normal subjects. We based the diagnosis of very mild dementia in the 10 subjects on informant reports and the judgment of experienced clinicians. Deficits of some psychometric measures of memory, language, and speeded psychomotor performance were observed for these subjects. The histologic markers of Alzheimer's disease, including neurofibrillary tangles and both the "diffuse" and classic subtypes of senile plaques, were present in the neocortex in all 10 subjects but essentially were absent in the four controls. These findings indicate that even "questionable" dementia can be diagnostic for Alzheimer's disease. Furthermore, because truly normal aging may be unaccompanied by neocortical senile plaques and neurofibrillary tangles, the presence of these lesions should suggest the possibility of clinically undetected Alzheimer's disease.