Brain natriuretic peptide enhances the endothelium-independent cAMP and vasorelaxant responses of calcitonin gene-related peptide in rat aorta

Calcitonin gene-related peptide (CGRP) causes vasorelaxation in rat aorta involving endothelium/nitric oxide (NO)-dependent elevations of both cAMP and cGMP levels. When endothelium is removed, preincubation with exogenous NO uncovers and potentiates direct (endothelium-independent) cAMP elevations and vasorelaxations caused by CGRP. This enhancing effect of NO potentially involves elevation of cGMP and inhibition of Type III (cGMPinhibitable) phosphodiesterase, causing accumulation of cAMP. However, NO may have other actions. The aim of the present study was to determine if brain natriuretic peptide (BNP), which elevates cGMP levels independent of NO, could enhance cAMP accumulations and vasorelaxations induced by CGRP in rat aortic rings denuded of endothelium. When added separately, neither CGRP (100 nM) nor BNP (10 nM) altered cAMP levels. When added in combination, CGRP (100 nM) and BNP (10 nM) significantly elevated cAMP levels (from control of 0.95 ± 0.08 to 1.53 ± 0.09 pmol/mg protein) at 2 min. BNP (10 nM) elevated cGMP levels 10-fold at 2 min and this response was not altered by co-administration of CGRP (100 nM).Pretreatment with BNP at concentrations as low as 1 nM in endothelium-denuded aortic rings greatly enhanced the direct vasorelaxant effects of CGRP (100 nM) (from control of 0% to 57.6 ± 6.8% relaxation of phenylephrineprecontractions). Our findings indicate that BNP enhances direct (endothelium-independent) cAMP elevations and vasorelaxations caused by CGRP in rat aorta, thus supporting the concept that cGMP inhibits cAMP metabolism and enhances CGRP-induced responses in aortic smooth muscle cells.     

神经肽Y对免疫细胞活性的影响

神经肽Y（NPY）是广泛分布于中枢神经系统和外周神经各部位的神经肽类物质。本实验观察NPY在体外对几种免疫细胞活性的直接作用。结果表明，NPY对小鼠T淋巴细胞丝裂原反应性和NK细胞的杀伤活性均无明显影响（P＞0．05），对巨噬细胞分泌溶菌酶有明显抑制作用（P＜0．05）；而对B淋巴细胞丝裂原反应性则有明显的促进作用（P＜0．05）。上述结果提示，NPY对部分免疫细胞功能的影响因细胞种类而异。     

雌酮对蟾蜍神经—肌接头传递的影响

在蟾蜍离体坐骨神经－缝匠肌制备的肌细胞终板进行细胞内记录，研究了雌酮对神经－肌接头传递的影响。结果表明：雌酮加于浸浴液能增加１０μｇ筒箭毒处理组和１０ｍｍｏｌ／Ｌ ＭｇＣｌ２处理组制备的终板电位振幅，但前者的增加更显著；雌酮加入浸浴液３０分钟后引起小终板电位的振幅和频率明显增加，但波形不改变，静息膜电位也不改变。这些结果提示，雌酮能增加神经－肌接头传递，且主要通过突触前机理的作用。     

Apolipoprotein E—associated risk for Alzheimer's disease in the African-American population is genotype dependent

As a part of our ongoing study on Alzheimer's disease (AD) in elderly African Americans, we obtained clinical assessment and apolipoprotein E (ApoE) genotype data on 288 individuals (including 60 with AD). The ApoE σ4 allele frequency was significantly increased in AD patients compared with controls. The age-adjusted odds ratio (OR) for AD in σ4 homozygotes was 4.83 (95% confidence interval [CI], 1.71–13.64) compared with the σ3/σ3 genotype, but the OR for AD with the σ3/σ4 genotype did not reach significance (1.20; 95% CI, 0.58–2.45). These findings suggest that the association between ApoE σ4 and AD is weaker in African Americans than in whites.     

Lyme disease presenting as urinary retention

We report a case of Lyme disease that presented with urinary retention. The individual then experienced lower extremity paralysis. Paralysis and urinary retention resolved with intravenous ceftriaxone antibiotic. To our knowledge this is the first report of a urological manifestation as the initial clinical presentation of Lyme disease. Recognition of clinical symptoms and urological complications of Lyme disease also are discussed.     

Pathobiology of canine cyclic hematopoiesis (review)

Canine cyclic hematopoiesis (CH) was first described in Gray Collies as the lethal gray syndrome, and was subsequently shown to be a counterpart of human cyclic neutropenia (CN). The disease is characterized by a recurrent cyclic change in the levels of neutrophils and other blood elements at approximately 12-day intervals. It is caused by an autosomally recessive gene with pleiotropic effects or a CH gene which is closely linked to a gray color gene. The infectious insult on affected animals is periodic but its clinical and pathologic effects are continual and cumulative Affected dogs die after weaning and rarely survive over 6 months of age. There is evidence of immunoregulatory defects in these dogs. Reciprocal bone marrow transplantation indicates that the defect resides in the bone marrow, but the actual site and mechanism of the defect has not been established. The disease in Gray Collies represents a unique model system for studying the mechanism of cyclic hematopoiesis and hematopoietic regulation. Studies of the disease have made conceptual contributions toward understanding and treatment of human cyclic neutropenia.