The in vitro pharmacological profile of KR31080, a nonpeptide AT1 receptor antagonist

Summary— KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b] pyridine) is a potent inhibitor of angiotensin type 1 (AT₁) receptors in rabbit aorta and human recombinant AT₁ receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration-response curves to angiotensin II (All) with decreased maximal response (pD'₂ = 10.1 ± 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific [¹²⁵I]AII binding to rabbit aortic membranes (AT, receptors) and [¹²⁵I][Sar¹, Ile⁸]AII binding to human recombinant AT₁ receptors in a concentration-dependent manner with IC₅₀ values of 0.84 ± 0.08 nM and 1.92 ± 0.15 nM, respectively, but did not inhibit specific [¹²⁵I)AII binding to bovine cerebellum membranes (ÀT₂ receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT₁ receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT₁ selective angiotensin receptor antagonist which exerts a competitive antagonism in the [¹²⁵I]AII binding assay and insurmountable AT₁ receptor antagonism in the functional study.     

A Chinese adolescent girl with Fechtner-like syndrome

We describe a 15-y-old girl with Fechtner-like syndrome, who is the first Chinese reported to have this rare syndrome. She presented with left homonymous hemianopia and neuroimaging revealed haemorrhage in both parietal and occipital lobes. Peripheral blood smear showed macrothrombocytopenia and intracytoplasmic inclusion bodies inside leucocytes. Thrombocytopenia and proteinuria responded to intravenous immunoglobulin and pulsed methylprednisolone. This case illustrates that life-threatening haemorrhage can occur in patients with Fechtner syndrome. Although there was no effective treatment reported in the literature, high dose steroid and immunoglobulin seemed to be useful in our patient. Our patient also had nephritic-nephrotic syndrome with renal insufficiency, which is unusual in adolescent female patients.     

无溶剂体系合成1,3-甘油二酯用脂肪酶的筛选及其酯化性质

对不同来源的脂肪酶进行了系统的筛选,并根据位置专一性的差别将脂肪酶分为1,3 特异的、1,3 选择性和非选择性的3类.采用LipozymeRMIM在无溶剂系统中催化甘油、脂肪酸合成1,3 sn 甘油二酯.研究表明脂肪酸、底物醇种类、温度、水分活度对LipozymeRMIM的活力有明显的影响.     

低氧及运动致大鼠骨骼肌形态学改变的实验研究

目的观察低氧及低氧复合运动时,大鼠体重及腓肠肌显微、超微结构的变化,旨在探讨低氧状态下适当运动对骨骼肌的影响。方法建立大鼠低氧及低氧复合运动模型,运用光镜及透射电镜观察大鼠腓肠肌显微、超微结构的变化。结果低氧复合运动组较低氧安静组大鼠体重差异有显著性意义(P<0.05)。低氧复合运动组骨骼肌结构正常,线粒体数量增加,骨骼肌纤维增粗,毛细血管增生。结论低氧复合适当的运动能够维持骨骼肌的正常形态,增强骨骼肌的有氧代谢,起到保护骨骼肌的作用,从而提高骨骼肌的低氧适应能力,促进低氧习服。     

PCR-SSP法HLA-A、B基因分型与血清学分型的比较

目的比较聚合酶链反应-序列特异性引物(PCR-SSP)进行HLA-Ⅰ类A、B抗原位点分型的准确性,并探讨血清学分型错误发生的原因。方法用PCR-SSP以及单克隆抗体血清学分型技术对HLA-A、B分型并比较。结果34例样本PCR-SSP基因分型无假阳性和假阴性出现。PCR-SSP法与血清学比较,血清学检出错误或漏检率分别为HLA-A位点23.5%,B位点26.5%。血清学发生错误或易混淆的抗原有:A2和A68、A32和A33,B5、B60和61。结论PCR-SSP法进行HLA-A、B抗原等位基因分型具有分辨率高、特异性强、重复性好、实验过程简捷快速、分型结果较血清学更加准确可靠的优点。     

Neurally Augmented Sexual Function in Human Females: A Preliminary Investigation

Objective. Neurally augmented sexual function (NASF) is the production of pleasurable genital stimulation and subsequent orgasm through the application of electrical energy to provide stimulation of the spinal cord or peripheral nerves. The purpose of this paper is to demonstrate the reproducibility of this phenomenon. Materials and Methods. Eleven otherwise healthy women, ages 32–60 years, were selected for this study. Through standard techniques, quadripolar (octopolar in the final patient) leads were placed in the epidural space percutaneuously. The lead was maneuvered initially to an L1–L2 position and then repositioned based on feedback from the patient. The patients were allowed to utilize the device ad libitum for up to 9 days. Results. Successful stimulation was achieved in 91% (10/11) of patients. These women described a greater frequency in sexual activity, increased lubrication, and overall satisfaction. A smaller subset had substantial improvement in sexual function as measured by orgasmic capacity. This subset consisted of women with secondary anorgasmia. A return of orgasmic capacity was found in 80% (4/5) of patients having secondary anorgasmia with an average intensity of ≥ 3/5 while using the device. Once the device was removed, the patients returned to their previous anorgasmic status. Conclusions. Pleasurable genital stimulation of the spinal cord is a consistently reproducible phenomenon. In a subset of the population studied, improvement in orgasmic function was noted. This was noted in the group with secondary orgasmic dysfunction.     

Solid and papillary epithelial neoplasms of the pancreas: CT findings

Five female patients and one male patient with solid and papillary epithelial neoplasms of the pancreas were examined with computed tomography (CT). The mean age of the patients was 27 years (range, 13-46 years). All cases showed well-encapsulated, round or lobulated masses consisting of both cystic and solid areas. Cystic portions showed CT numbers that suggested hemorrhagic necrosis. There were no internal septations within the masses. In three tumors located in the head of the pancreas, dilatation of the biliary tree was absent or minimal, although the masses were large. Two tumors contained calcifications. One tumor demonstrated metastatic deposits in liver and lymph nodes. Metastatic masses appeared similar to the primary pancreatic mass. Solid and papillary neoplasm of the pancreas should be the primary diagnostic consideration when characteristic CT findings are detected in a young female patient.     

A survey of newborn screening for cystic fibrosis in Europe.

BACKGROUND: Cystic fibrosis (CF) is a recessively inherited condition caused by mutation of the CFTR gene. Newborn infants with CF have raised levels of immuno-reactive trypsinogen (IRT) in their serum. Measurement of IRT in the first week of life has enabled CF to be incorporated into existing newborn screening (NBS) blood spot protocols. However, IRT is not a specific test for CF and NBS therefore requires a further tier of tests to avoid unnecessary referral for diagnostic testing. Following identification of the CFTR gene, DNA analysis for common CF-associated mutations has been increasingly used as a second tier test. The aim of this study was to survey the current practice of CF NBS programmes in Europe. METHOD: A questionnaire was sent to 26 regional and national CF NBS programmes in Europe. RESULTS: All programmes responded. The programmes varied in number of infants screened and in the protocols employed, ranging from sweat testing all infants with a raised first IRT to protocols with up to four tiers of testing. Three different assays for IRT were used; in the majority (24) this was a commercially available kit (Delfia). A number of programmes employed a second IRT measurement in the 4th week of life (as the IRT is more specific at this point). Nineteen programmes used DNA analysis for common CFTR mutations on samples with a raised first IRT. Three programmes used a second IRT measurement on infants with just one recognised mutation to reduce the number of infants referred for sweat testing. Referral to clinical services was prompt and diagnosis was confirmed by sweat testing, even in infants with two recognised mutations in most programmes. Subsequent clinical pathways were less uniform. Multivariate analysis demonstrated a relationship between the age of diagnosis and the timing of the first IRT. More sweat tests were undertaken if the first IRT was earlier and the diagnosis was later. CONCLUSIONS: Annually these programmes screen approximately 1,600,000 newborns for CF and over 400 affected infants are recognised. The findings of this survey will guide the development of European evidence based guidelines and may help new regions or nations in the development and implementation of NBS for cystic fibrosis.