[Analysis on the incidence of influenza-like syndromes and related health behavior factors among Beijing residents].

Objective: The objective was to identify the incidence of influenza-like syndromes and related health behavior factors among Beijing residents. Methods: From December 6, 2013 to January 16, 2014, we selected 150 villages or communities from 30 towns or streets as survey locations using a multi-stage random sampling method, and then conducted a cross-sectional study among 7 354 residents who aged 18 years or above and had live in Beijing for more than a half year using self-administered anonymous questionnaires, and totally 7 327 valid questionnaires are collected. The questionnaire consisted of demographic information, self-reported influenza-like syndromes in the past two weeks, and health behaviors. Multiple logistic regression models were used to identify the factors associated with self-reported influenza-like syndromes. Results: The mean (SD) age of the partcipants was 44.6 (15.2) years. Among them, 6.9% (506 cases) reported having influenza like illness during the past two weeks. The multiple logistic regression analysis indicated that regular physical exercise, optimal hand hygiene, and avoidance of going to the crowded places during respiratory infectious disease epidemics were significantly associated with a lower likelihood of reporting influenza-like syndromes, compared with those without regular physical exercises, without optimal hand hygiene, and not avoiding going to the crowded places, and the OR(95%CI) were 0.80 (0.66-0.97), 0.75 (0.57-0.99) and 0.80 (0.65-0.98), respectively. Conclusion: Personal health behaviors were associated with the incidence of respiratory infectious diseases such as influenza in Beijing, and future interventions to improve personal hygiene behaviors are needed to prevent the spread of respiratory infectious diseases.

[Human exposure to live poultry among residents during the second wave of avian influenza A (H7N9) epidemic in Beijing, 2013-2014].

Objective: To investigate human exposure to live poultry (poultry feeding and purchasing) in the residents in Beijing and related factors during the second wave of avian influenza A(H7N9) epidemic during 2013-2014, and provide scientific evidence for avian influenza prevention and control. Methods: A total of 7 366 adults aged ≥18 years were selected through multi-stage stratified sampling in Beijing for a questionnaire survey. Logistic regression model was used to analyze the influence factors of human exposure to live poultry. Results: The live poultry feeding rate and live poultry purchasing rate in residents in Beijing in the past year were 5.3% (95%CI: 4.8%-5.8%) and 6.0% (95%CI: 5.5%-6.5%) respectively. Logistic regression analysis indicated that lower educational level of primary school and below, (OR=1.82, 95%CI: 1.22-2.72); being farmer (OR=2.49, 95%CI:1.89-3.29) or being unemployed (OR=1.65, 95%CI: 1.08-2.52); being non local resident (OR=1.54, 95%CI: 1.10-2.16); living in suburban area (OR=2.36, 95%CI: 1.77-3.16); having one child (OR=1.76, 95%CI: 1.42-2.17) or ≥2 children (OR=2.15, 95%CI: 1.43-3.22) in the family were the risk factors associated with feeding poultry compared with higher educational level of college and above, being employed, being local resident, living in urban area and having no child. And being farmer (OR=1.61, 95%CI: 1.27-2.02); being non local resident (OR=1.76, 95%CI: 1.31-2.35); living in suburban area (OR=2.05, 95%CI: 1.61-2.61); having one child (OR=1.24, 95%CI: 1.02-1.52) or ≥2 children (OR=1.78, 95%CI: 1.21-2.63) were the risk factors for purchasing live poultry. Conclusion: Some residents living in Beijing still have exposure to live poultry, and targeted measures should be taken to reduce the exposure to poultry.

[Survey on a public health emergency event caused by norovirus].

Objective: To study the epidemiological characteristics of an outbreak caused by norovirus infection in a school in Haidian district, Beijing. Methods: Basic information of the school and data related to patients in the fields survey were collected and analyzed descriptively. Laboratory tests were performed to test the stool and anal swab specimens of both patients and cooks as well as the environmental specimens. Risk factors related to the incidence were analyzed through a case-control study. Results: A total number of 119 patients were identified in the school. Clinical symptoms were mild, mainly involving vomiting (94.1%, 112/119), abdominal pain (46.2%, 55/119), but no need of hospitalization. The average age of the student patients was 6.38, with minimum and maximum between 5 and 11. Patients were found in 22 classes, but mainly in grade 1 and class 7 where 35 patients were found (30.17%). A total of 134 specimens of rectal swabs and stool were collected, with 7 positive for norovirus and 6 for sappovirus. Salmonella, Shigella, lapactic Escherichia coli and Vibrio parahaemolyticus were not found in on dinner sets, residual foods, bottled water or in drinking fountains. Index on water hygiene was unsatisfactory in classrooms or dormitories where more cases were found. Accommodation, north-facing-classrooms, abnormal water hygiene indexes were found related to the occurance of the disease (P<0.05). Conclusions: The outbreak was identified a gastroenteritis infection, caused by norovirus with symptoms as vomiting and abdominal pain. This event reached the reporting standards of public health emergencies-level Ⅳ. Discovery and isolation of the first case was not timely while transmission of the disease might be water-borne. Surveillance programs on symptoms, disinfection of vomit and stool in places like nurseries and schools should be strengthened to prevent the norovirus outbreak.

Pharmacokinetics, safety and tolerability of pirfenidone and its major metabolite after single and multiple oral doses in healthy Chinese subjects under fed conditions.

BACKGROUND AND OBJECTIVE: Pirfenidone is a promising antifibrotic agent with therapeutic potential for idiopathic pulmonary fibrosis. This study aimed to evaluate the pharmacokinetics and urinary excretion of pirfenidone and its major metabolite 5-carboxy-pirfenidone in healthy Chinese subjects under fed conditions. METHODS: 20 healthy subjects of either sex were recruited in this randomized, single-center, and open-label, single ascending doses (200, 400, and 600 mg) and multiple doses (400 mg, 3 times daily) study. Safety was assessed by adverse events, ECGs, vital signs, and clinical laboratory parameters. Blood and urine samples were analyzed with a validated LC/MS method. RESULTS AND CONCLUSIONS: Pirfenidone was safe and well tolerated. After single-dose administration, pirfenidone was rapidly absorbed with a mean Tmax of 1.8-2.2 h and a mean t1/2 of 2.1-2.4 h. 5-carboxy-pirfenidone was rapidly formed with a mean Tmax of 1.5-2.2 h and a mean t1/2 of 2.1-2.6 h. Cmax and AUC for both parent and metabolite were dose proportional over the 200-600 mg dose range. No gender effect was found. In the steady state, the accumulation index (R) estimated for the 3 dosing intervals ranged from 1.1 to 1.5 for both pirfenidone and 5-carboxy-pirfenidone, indicating that the exposure of pirfenidone and 5-carboxy-pirfenidone increased slightly with repeated dosing, but t1/2 and CL/F remained unchanged. Metabolism is the primary mechanism of drug clearance of pirfenidone. About 87.76% of the administered pirfenidone was excreted in urine in the form of 5-carboxy-pirfenidone, while only 0.6159% of the administered pirfenidone was detected as the unchanged form in urine.

Synthesis and biological evaluation of substituted phenylpyrazole[4,5-b]oleanane derivatives as inhibitors of glycogen phosphorylase.

A series of substituted phenylpyrazole[4,5-b]oleanane derivatives have been synthesized and biologically evaluated as inhibitors of glycogen phosphorylase (GP). The structure of phenylpyrazole moiety in compound 17 was determined by ROESY. All of the synthesized oleanane derivatives were biologically evaluated against rabbit muscle GPa. Within this series of compounds, pyrazole triterpene 7 (IC(50) = 10.8 µM) exhibited slightly more potent activity than its parent compound 1. Preliminary SAR analysis of the pyrazoleoleanane derivatives as GP inhibitors is discussed.

Tumor necrosis factor alpha enhances the cytotoxicity induced by nitric oxide in cultured cerebral endothelial cells.

It has been shown that independent sources of nitric oxide (NO) and the inflammatory cytokine tumor necrosis factor alpha (TNFalpha) contribute to the breakdown of the blood-brain barrier (BBB) in the pathogenesis of a number of brain disorders. However, the interaction of NO and TNFalpha has not been elucidated. The present study was designed to determine whether the toxicity induced by NO is altered by TNFalpha in brain capillary endothelial cells (BCECs), and if so, whether it is related to the generation of superoxide. TNFalpha (50-400 U/ml) did not produce toxicity until at a concentration of 800 U/ml. This toxic effect was completely blocked by copper-zinc superoxide dismutase (SOD)/catalase or N(omega)-nitro-L-arginine methyl ester (L-NAME) or oxyhemoglobin (HbO2). Sodium nitroprusside (SNP) reduced with 0.4 mM ascorbate (SNP/Vc) significantly increased Lactate dehydrogenase (LDH) efflux in a concentration-dependent manner. This cytotoxicity of SNP/Vc was also completely inhibited by SOD/catalase or HbO2. When SNP/Vc used in combination with 400 U/ml TNFalpha, a more remarkable LDH efflux was induced than SNP/Vc alone, even as little as 0.01 mM SNP/Vc was toxic, although a dose of 400 U/ml TNFalpha alone had no effect on LDH efflux. In addition, either 0.4 mM SNP/Vc and 800 U/ml TNFalpha alone or 0.4 mM SNP/Vc and 400 U/ml TNFalpha in combination significantly increased malondialdehyde (MDA) content, but nitric oxide synthase (NOS) activity was inhibited only by SNP/Vc and TNF in combination. These results suggest that TNFalpha enhances the toxicity of NO in BCECs and that at least part of this enhancement involves the generation of superoxide.

Design and synthesis of amidino-tyrosine derivatives as non-peptide fibrinogen receptor antagonists.

The design, synthesis and antiaggregation activity of amidino-tyrosine derivatives based on Arg-Gly-Asp (RGD) tripeptide sequence as non-peptide fibrinogen receptor antagonists is described. Optimization of the spacer and the substituent at the C-terminal is reported.

[Synthesis and antiarrhythmic activity of some (erythro)-phenylpropanediolamine compounds].

For the purpose of searching for new drug with high potency and simple chemical structure, the dominant conformation and structural parameters of Guan-Fu base (GFA) molecule were modelled and calculated with a SGI-4D 25G computer. The propanediolamine chain in GFA might be considered to be a pharmacophore responsible for the bioactivity and the configuration of the chain seemed important. Thus, thirteen compounds of (erythro)-p-x-PhCHOHCHOHCH2NHR(x = H, I1-7; X = NO2, II1-6) were prepared. Among them, 10 compounds showed antiarrhythmic effect on aconitine-induced arrhythmia in rats. The ED50(to stop VT) of I2 and ED50(to stop VP) of I3 were shown to be comparable with those of GFA. In the synthesis, no stereoselectivity was found in the Prevost reaction with allylamine analogues (a1-7). After a1-7 were acetylated, the erythro type products(I1-7) were obtained.

[Synthesis and bioactivity of some 3,4-diacyloxybenzopyrans].

Considerable attention is now being given to the potassium channel openers of benzopyrans as potential therapeutical agents for hypertension. In order to search for novel antihypertensive with high efficacy and low toxicity, integrating structural features of cromakalim and praeruptorin C, twenty-four compounds of 3,4-diacyloxybenzopyrans were designed and synthesized. Some of them exhibited hypotensive activity in Sprague Dawley rats.

[Synthesis and biological activity of substituted benzyl/naphthylmethylisoquinolines and related quaternary ammonium derivatives].

In an attempt to search for novel antihypertensive or antiarrhythmic agents, especially compounds mainly acting on calcium or potassium channels, with the isoquinoline alkaloids which possessed cardiovascular effects as lead compounds, and on the basis of previous works of our laboratory as well as integration of the structural feature of certain potassium channel blockers, 28 compounds (I1-6 and II1-22) were designed and synthesized among which 24 were not reported previously. 3,4-Dihydroisoquinolines were first synthesized by the Bischler-Napieralski cyclization with 3,4-disubstituted phenethylamine and aromatic acetic acid as starting materials. N-alkyl substituted tetrahydroisoquinolines were prepared by the alkylation of tetrahydroisoquinolines with corresponding substituted benzyl halides, or by the reduction of dihydroisoquinoline quaternary ammonium derivatives. Preliminary pharmacological studies in vivo showed that most of these compounds exhibited various degrees of hypotensive and bradycardial effects except I4 which exhibited hypertensive activity. The hypotensive effect of II1 was the most potent among these compounds in anaesthetized normotensive Sprague-Dawley rats. Analysis of the QSAR between hypotensive/bradycardial activities of certain compounds and their structural parameters of molecular mechanics (MM2) showed that the hypotension/bradycardia increased with the increase/decrease of the charge of the nitrogen atom in the isoquinoline nucleus. Thus, the charge of the nitrogen atom might be one of the important factors which could enhance the selectivity of the compounds acting on blood vessels or cardiac tissues.

[Structural congeners of guanfu base A and their antiarrhythmic activity].

Guanfu base A (GFA) is an alkaloid isolated from the root of Aconitum coreanum and is effective in several experimental arrhythmia models. GFA can effectively antagonize aconitine-induced arrhythmia, significantly reduce CaCl2-induced incidence of ventricular fibrillation in rats and markedly raise the ventricular fibrillation threshold to electrical stimulation in rabbits and cats. It would be valuable in clinic to treat ventricular fibrillation. Thus, we chose GFA as lead compound for chemical modification. From the view point of stereochemistry, GFA is a rigid structure and can be considered as composed of two layers. The first layer is a hydrogenated phenanthrene ring; the second is the alkylamino chain containing hydroxy and acetoxy groups [formula: see text]. It was speculated that the skeleton of such chain might play as pharmacophore contributing to the biological activity. In order to reduce the size of the molecule and simplify the chemical structure of GFA, the hydrogenated phenanthrene was removed and an aryl residue commonly occurred in the structure of antiarrhythmic agents was introduced. Thus, fourteen derivatives of phenylpropanediolamine were designed and synthesized. There is a hydrogenated indolizine ring in the structure of GFA and a indolizine ring in the structure of class III antiarrhythmic agent--butoprizine. By combing the structural feature of GFA with that of butoprizine, nine indolizine derivatives were also designed and synthesized. Screening test of 23 compounds indicated that phenylpropanediolamine derivatives--I1, I2, I3, I7, I8, I14, and indolizine derivatives--II2 markedly antagonized chloroform-induced arrhythmias in rats. Among them I2, I3, I7 and I8, appeared to be more potent than GFA.