烟酰胺类和吡啶丙烯酰胺类衍生物的合成及扩血管活性

Eighteen nicotinamides(I_1～12)and pyridylacrylamides(II_1～15)have beensynthesized. All synthesized amides were submitted to phannacological screening and 0.1um·L^-1(10^-7M)-noradrenaline induced contraction of the rat aortic strip was taken aS criterion,The amidesI_3,4 and II_1,2 showed more potent vasodilating activity than compounds I_12,13 and II_3,4.     

广西HIV-1首次流行的分子流行病学分析

目的　广西自1996年4月起在静脉吸毒者和卖血者中发现HIV感染者,为了解其传染来源和判断其流行趋势,对广西流行的HIV进行分子流行病学分析。方法　选取HIV抗体阳性血清标本44份,分别采用多肽酶免疫法(PEIA)和经逆转录PCR扩增作cDNA序列分析,分别确定其HIV-1基因亚型并加以比较。结果　结果表明广西存在4种HIV-1M组基因亚型,即B’(泰国B亚型)、C、D、E亚型。在静脉吸毒人群和性混乱者中存在HIV-1E亚型流行和C亚型感染者;而在卖血者中发现HIV-1B’和D亚型感染。结论　HIV-1D亚型感染和E亚型流行已在国内出现,E亚型病毒已由东南亚传入流行并将在我国南部形成新的流行区域。提出血清学分型方法可作为HIV-1基因亚型分析的筛选技术推广应用。     

In vitro release of immunoreactive substance P from putative afferent nerve endings in bovine pia arachnoid

The release of substance P-like immunoreactivity was examined using bovine pia arachnoid and its attendant blood vessels in vitro. At concentrations of 20,51, and 100 mM, potassium ions evoked the release of substance P-like immunoreactivity in a dose-dependent manner. The drug capsaicin released substance P at concentrations greater than 10(-8) M. Both potassium- and capsaicin-induced release were abolished by omitting calcium ions from the superfusion buffer. When subjected to separation by reverse phase high performance liquid chromatography, the superfusate from capsaicin perfused tissues contained a peak of immunoreactivity which migrated at the retention time corresponding to substance P. During basal and stimulated states, the percent endogenous substance P released ranged between 0.4-6.5 X 10(-2) and 1.3-11.6 X 10(-2) per minute, rates comparable to those previously reported by others using slices of dorsal horn or spinal cord segments. The immunoreactivity measurable in the conditioned buffer probably reflected release from afferent nerve endings in as much as most of the substance P immunoreactivity in pia arachnoid arises from trigeminal ganglia. Release of substance P, a cerebrovasodilating peptide from perivascular nerve endings in pia arachnoid suggests a possible role for substance P in the pathophysiology of disorders associated with pain of cerebrovascular origin.     

Depletion of secretory granules from the feline parotid gland: action of NANC transmitters per se

Ekstrom , J., Asztély , A., Helander , H. F. & Tobin , G. 1994. Depletion of secretory granules from the feline parotid gland: action of NANC transmitters per se. Acta Physiol Scand 150, 83–88. Received 5 May 1993, accepted 30 July 1993. ISSN 0001–6772. Department of Pharmacology, University of Goteborg, and Astra Hassle AB, Molndal, Sweden. A parotid acinar degranulation of approximately 60 and 40% was observed in cats under pentobarbitone anaesthesia after a 90-min period of continuous stimulation of the parasympathetic auriculo-temporal nerve at 10 Hz in the absence and presence of atropine, respectively. Atropine completely abolished the large fluid response of the gland to the nerve stimulation. In the non-atropinized cats, bethanechol, infused into the carotid artery at a dose rate evoking a salivary flow similar to that in response to parasympathetic nerve stimulation, caused an acinar degranulation of approximately 25% and acinar vacuolation. Vasoactive intestinal peptide (VIP; 0.5 μg kg^-1 min^-1 also infused into the carotid artery for 90 min) caused an acinar degranulation of the same magnitude as the parasympathomimetic drug but the peptide did not give rise to any fluid secretion or vacuole formation. The experiments were performed in the presence of α- and β-adrenoceptor blockers. Thus, in parotid glands of the cat, producing no overt secretion of fluid, non-adrenergic, non-cholinergic (NANC) mechanisms may be at work causing exocytosis of the acinar granules. These mechanisms are also likely to contribute to the secretion of granules in response to parasympathetic nerve activity in the absence of blockade of the classical autonomic receptors.     

N-methylacetamide analog of salvinorin A: a highly potent and selective kappa-opioid receptor agonist with oral efficacy

Several preclinical studies indicate that selective kappa-opioid receptor (KOR) antagonists have antidepressant-like effects, whereas KOR agonists have opposite effects, suggesting that each might be useful in the treatment of mood abnormalities. Salvinorin A (salvA) is a valuable KOR agonist for further study due to its high potency and receptor selectivity. However, it has short lasting effects in vivo and limited oral bioavailability, probably due to acetate metabolism. We compared the in vitro receptor binding selectivity of salvA and four analogs containing an ethyl ether (EE), isopropylamine (IPA), N-methylacetamide (NMA), or N-methylpropionamide (NMP) at C-2. All compounds showed high binding affinity for the KOR (K(i) = 0.11-6.3 nM), although only salvA, EE, and NMA exhibited KOR selectivity. In a liver microsomal assay, salvA was least stable, whereas NMA and IPA displayed slower metabolic transformations. Intraperitoneal (i.p.) administration of salvA, NMA, and NMP dose-dependently elevated brain reward thresholds in the intracranial self-administration (ICSS) test, consistent with prodepressive-like KOR agonist effects. NMA and NMP were equipotent to salvA but displayed longer lasting effects (6- and 10-fold, respectively). A dose of salvA with prominent effects in the ICSS test after i.p. administration (2.0 mg/kg) was inactive after oral administration, whereas the same oral dose of NMA elevated ICSS thresholds. These studies suggest that, although salvA and NMA are similar in potency and selectivity as KOR agonists in vitro, NMA has improved stability and longer lasting actions that might make it more useful for studies of KOR agonist effects in animals and humans.     

Telehealthcare for chronic obstructive pulmonary disease: Cochrane Review and meta-analysis

Background

Chronic obstructive pulmonary disease (COPD) is common. Telehealthcare, involving personalised health care over a distance, is seen as having the potential to improve care for people with COPD.

Aim

To systematically review the effectiveness of telehealthcare interventions in COPD to improve clinical and process outcomes.

Design and setting

Cochrane Systematic Review of randomised controlled trials.

Methods

The study involved searching the Cochrane Airways Group Register of Trials, which is derived from the Cochrane Central Register of Controlled Trials, MEDLINE®, embase™, and CINAHL®, as well as searching registers of ongoing and unpublished trials. Randomised controlled trials comparing a telehealthcare intervention with a control intervention in people with a clinical diagnosis of COPD were identified. The main outcomes of interest were quality of life and risk of emergency department visit, hospitalisation, and death. Two authors independently selected trials for inclusion and extracted data. Study quality was assessed using the Cochrane Collaboration’s risk of bias method. Meta-analysis was undertaken using fixed effect and/or random effects modelling.

Results

Ten randomised controlled trials were included. Telehealthcare did not improve COPD quality of life: mean difference –6.57 (95% confidence interval [CI] = –13.62 to 0.48). However, there was a significant reduction in the odds ratios (ORs) of emergency department attendance (OR = 0.27; 95% CI = 0.11 to 0.66) and hospitalisation (OR = 0.46; 95% CI = 0.33 to 0.65). There was a non-significant change in the OR of death (OR = 1.05; 95% CI = 0.63 to 1.75).

Conclusion

In COPD, telehealthcare interventions can significantly reduce the risk of emergency department attendance and hospitalisation, but has little effect on the risk of death.     

Clinical characteristics and risk factors for peripartum cardiomyopathy

Background

Peripartum cardiomyopathy (PPCM) is a potentially fatal form of heart failure and the recognition of its risk factors is important for prevention and treatment.

Objective

To explore the clinical characteristics and the risk factors for PPCM.

Methods

Echocardiographic was used to examine the left ventricular ejection fraction (LVEF). Blood level of troponin I (cTNI), high sensitive C-reaction protein (hs-CRP), NT-proBNP was measured. All PPCM occurred within weeks following delivery.

Results

Fifty-two PPCM patients and 52 normal delivery subjects (control group) were included in this study. Compared with the control group, PPCM patients were older, with a higher level of blood pressure, and a higher rate of suspected respiratory infection. The level of leucocytes, hs-CRP, cTNI and NT-proBNP in PPCM patients were higher than in the control. Multivariate logistic regression analysis showed that elevated plasma hs-CRP (OR =1.86, p<0.05), respiratory infection (OR = 2.87, p<0.01), and hypertension (OR =1.68, p < 0.05) were independent risk factors for PPCM. During the follow up of 21.6±5.4 d, one patient (1.9%) died probably of heart failure but other patients remained well.

Conclusion

Hypertension, respiratory infection, and elevated plasma hs-CRP seem to be associated with the pathogenesis of peripartum cardiomyopathy in this patient population.     

Advances and challenges in biosensor-based diagnosis of infectious diseases

Rapid diagnosis of infectious diseases and timely initiation of appropriate treatment are critical determinants that promote optimal clinical outcomes and general public health. Conventional in vitro diagnostics for infectious diseases are time-consuming and require centralized laboratories, experienced personnel and bulky equipment. Recent advances in biosensor technologies have potential to deliver point-of-care diagnostics that match or surpass conventional standards in regards to time, accuracy and cost. Broadly classified as either label-free or labeled, modern biosensors exploit micro- and nanofabrication technologies and diverse sensing strategies including optical, electrical and mechanical transducers. Despite clinical need, translation of biosensors from research laboratories to clinical applications has remained limited to a few notable examples, such as the glucose sensor. Challenges to be overcome include sample preparation, matrix effects and system integration. We review the advances of biosensors for infectious disease diagnostics and discuss the critical challenges that need to be overcome in order to implement integrated diagnostic biosensors in real world settings.