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Biomedical subjects

W Zheng

Publications and source records attributed to W Zheng.

At least 307 records · Page 17Linked to original sources
PubMed1991

Interactions of analogs of the 1,4-dihydropyridine tiamdipine in cardiac and smooth muscle.

Two series of 1,4-dihydropyridines related to tiamdipine, 2-(2-aminoethylthio)methyl-3-carboethoxy-5-carbomethoxy-6- methyl-4-(3-nitrophenyl)-1,4-dihydropyridine, have been evaluated for their pharmacologic and radioligand binding properties in smooth and cardiac muscle. In the tiamdipine series the influence of phenyl ring substitution, 3-Cl, 3-MeO and 3-CF3, was greatly reduced relative to the N-formyl and neutral nifedipine derivatives. Consistent with our previous observations onset and offset of action were greatly reduced by the presence of the amine side chain. In tiamdipine analogs also bearing an asymmetric substituent at C-2, chirality at C-4 was determinant for activity.

Animals↗
PubMed1991

Choroid plexus protects cerebrospinal fluid against toxic metals.

Although heavy metal ions are known to be toxic to the central nervous system (CNS), the mechanisms by which the CNS may protect itself from initial challenges of such toxic ions is unknown. The choroid plexus is the principal site of formation of the cerebrospinal fluid (CSF) which bathes the brain. We have determined in rats and rabbits that after intraperitoneal administration of lead, cadmium, mercury, and arsenic compounds, these toxic metal ions accumulated in the lateral choroid plexus at concentrations of Pb, Hg, and As that were 70-, 95-, and 40-fold higher, respectively, than those found in the CSF. Cd was not detected in the CSF. In addition, concentrations of these heavy metal ions were found to be many fold greater in the choroid plexus than in the brain or blood. The accumulation of Pb in the choroid plexus was dose-dependent and time-related. When the choroid plexus was preincubated, in vitro, with ouabain (1.5 mM), the uptake of Cd from the CSF side of the choroid plexus was inhibited 57%. Cadmium metallothionein was not found in the choroid plexus. Whereas the concentration of reduced glutathione in the choroid plexus was less than that in the brain cortex, the concentration of cystine was fourfold greater. The lateral choroid plexus sequesters Pb, Cd, As, and Hg. It appears to be one of the important mechanisms that protects the CSF and the brain from the fluxes of toxic heavy metals in the blood.

Animals↗
PubMed1991

Pharmacological, radioligand binding, and electrophysiological characteristics of FPL 64176, a novel nondihydropyridine Ca2+ channel activator, in cardiac and vascular preparations.

The pharmacological, radioligand binding, and electrophysiological properties of FPL 64176, a new nondihydropyridine Ca2+ channel activator, were studied in rat tail artery, cardiac membranes, and A7r5 smooth muscle cells. FPL 64176 induced a contractile response, with an EC50 value of 2.11 x 10(-7) M. The maximum tension response to FPL 64176 was approximately 2-fold higher than that to (S)-Bay K 8644. FPL 64176 showed no significant inhibitory activity at concentrations up to 10(-5) M. The Ca2+ channel antagonists nifedipine, verapamil and diltiazem noncompetitively antagonized and completely relaxed the responses induced by FPL 64176. IC50 values of these three drugs were 5.22 x 10(-9), 1.31 x 10(-7), and 1.95 x 10(-7) M, respectively, for relaxing submaximum contractile responses to FPL 64176 (5 x 10(-7) M). The washout time for FPL 64176 was about 40 min, which was much longer than that for (S)-Bay K 8644 (within 1 min). FPL 64176 weakly inhibited (+)-[3H]PN 200-110, [3H]D888, and [3H]TA-3090 binding in rat cardiac membranes, with IC50 values of 1.04 x 10(-5) M and 7.03 x 10(-6) M for inhibition of (+)-[3H]PN 200-110 and [3H]TA-3090 binding, respectively, and with 23% inhibition of [3H]D888 binding at a FPL 64176 concentration of 1 x 10(-5) M. Dissociation kinetics of the three radioligands were allosterically accelerated by FPL 64176. Electrophysiological studies on the A7r5 smooth muscle cell line directly confirmed a large (approximately 14-fold) stimulatory effect on L-type Ca2+ current amplitude. The results suggest that FPL 64176 is a new type of Ca2+ channel activator with higher efficacy and a mechanism and site of action that are distinct from those for (S)-Bay K 8644.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

Tobacco smoking and its effect on health in China.

Production and sales of manufactured cigarettes are increasing in China; furthermore, the proportion of filtered cigarettes is still low, and the tar yield thus remains high. The prevalence of smoking in the general population aged 20 and over is estimated to be 68.9% of men and 8.3% of women. Case-control studies carried out in major cities in China all showed a close relationship between lung cancer incidence and smoking. In Shanghai, the population attributable risks for lung cancer due to smoking were 0.69 in men and 0.24 in women. A limited number of case-control studies indicate that the incidences of cancers of the bladder, oesophagus and pancreas are also associated with smoking. Some studies on coronary heart disease reveal unequivocally a significant risk for this disease associated with smoking. Cancer, chronic obstructive lung diseases and coronary heart disease are now important causes of death in some large cities in China. More comprehensive investigations are needed in order to evaluate thoroughly the effect of smoking on health in China.

China↗
PubMed1990

Determination and metabolism of dithiol chelating agents. VII. Biliary excretion of dithiols and their interactions with cadmium and metallothionein.

N-(2,3-Dimercaptopropyl) phthalamidic acid (DMPA), meso-dimercaptosuccinic acid (DMSA), and 2,3-dimercapto-1-propanesulfonic acid (DMPS) are dithiol chelating agents with antidotal activity for lead, mercury, arsenic, and other heavy metals. The biliary excretion of these compounds was studied in male Sprague-Dawley rats. After iv administration of DMPA, 72% of the injected dose was recovered in the bile. Half of the recovered DMPA was in the unaltered form (parent compound) and the other half was in the altered form (parent compound recovered after chemical reduction by DTT). An altered, presumably disulfide, form of DMPS was found in the bile. Neither unaltered nor altered DMSA was detected in the bile. DMPA (0.10 mmol/kg), given to rats 3 days after exposure to Cd, elicited within 30 min a 20-fold increase in biliary Cd excretion. The increase of biliary Cd by DMPA was dose-related and not due to an increase of bile flow rate. DMSA and DMPS did not significantly affect the biliary excretion of Cd. Incubation of DMPA or DMSA with Cd-saturated metallothionein (MT) resulted in the removal of Cd from MT. DMPA was more active than DMSA in this respect. The evidence strongly supports the mechanism that the increase of biliary cadmium following DMPA administration is the result of DMPA entering cells and mobilizing and removing the cadmium from MT. The removal of cadmium from metallothionein by dithiol chelating agents provides another dimension to their mechanisms of action and may provide an important new tool for the study of cadmium as well as metallothionein.

Animals↗
PubMed1989

Determination and metabolism of dithiol chelating agents. VIII. Metal complexes of meso-dimercaptosuccinic acid.

Metal complexes of meso-dimercaptosuccinic acid (DMSA) with Pb2+, Cd2+, and Hg2+ were studied by potentiometric and infrared methods. This dimercapto metal-binding agent was found to form complexes whose structures are dependent on the metal ion to be complexed. In the cases of Pb2+ and Cd2+, one oxygen and one sulfur act as the donor atoms; in the case of Hg2+, two sulfur atoms act as the donors. The solubilities of all metal chelates were found to be pH dependent. Complexes of cadmium and lead are insoluble in the pH range 1.0 to 7.1, but are solubilized when the noncoordinated sulfhydryl and carboxylic acid groups are ionized. The mercury complex is insoluble in the pH range 1.0 to 3.0. It dissolves when one of the noncoordinated carboxylic acid groups is ionized. The dimethyl ester of meso-DMSA (DiMe-meso-DMSA) was synthesized and its acid dissociation constants were determined (pK1 = 6.38 and pK2 = 8.00). Esterification of the carboxyl groups of meso-DMSA changes its coordination properties in that the two sulfur atoms of DiMe-meso-DMSA are used to coordinate with Hg2+, Cd2+, or Pb2+. Esterification of meso-DMSA also changes its biological properties. DiMe-meso-DMSA, when given to rats 3 days after Cd administration, greatly increased the excretion of Cd via bile. In contrast, meso-DMSA was devoid of such activity.

Animals↗
PubMed1988

A population-based case-control study of childhood leukemia in Shanghai.

A population-based case-control interview study of 309 childhood leukemia cases and 618 healthy population control children was conducted in urban Shanghai, China. Like some studies in other countries, excess risks for both acute lymphocytic leukemia (ALL) and acute nonlymphocytic leukemia (ANLL) were associated with intrauterine and paternal preconception diagnostic x-ray exposure, and with maternal employment in the chemical and agricultural industries during pregnancy. ANLL was linked to maternal occupational exposure to benzene during pregnancy, whereas both ALL and ANLL were significantly associated with maternal exposure to gasoline and the patient's prior use of chloramphenicol. New findings, previously unsuspected, included an association of ANLL with younger maternal age at menarche (odds ratio [OR] = 4.3; 95% confidence interval (CI) = 1.3-13.9); a protective effect for long-term (greater than 1 year) use of cod liver oil containing vitamins A and D for both ALL (OR = 0.4; 95% CI = 0.2-0.9) and ANLL (OR = 0.3; 95% CI = 0.1-1.0); and excess risks of ANLL among children whose mothers were employed in metal refining and processing (OR = 4.6; 95% CI = 1.3-17.2) and of ALL associated with maternal occupational exposure to pesticides (OR = 3.5; 95% CI = 1.1-11.2). No relationships were found with late maternal age, certain congenital disorders, or familial occurrence, which have been related to childhood leukemia in other studies. In contrast with other reports, an excess of leukemia, primarily ANLL, occurred among second or later-born rather than firstborn children.

Child↗
PubMed1988

Lung cancer and smoking in Shanghai.

A case-control study involving interviews with 733 male and 672 female incident lung cancer patients and 1495 population-based controls revealed that cigarette smoking is the dominant cause of lung cancer among men in urban Shanghai. All of the principal cell types were affected, with clear trends of rising risk with increasing intensity and duration of smoking. Far fewer women smoked cigarettes, but the overall risk patterns resembled those among males. Among women, however, smoking accounted for only about one-quarter of all lung cancers and less than 10% of lung adenocarcinomas. The findings lay to rest any doubts about the health hazards of smoking Chinese cigarettes, although smoking is not responsible for the high rates of adenocarcinoma reported among Chinese women.

Adenocarcinoma↗
PubMed1988

Potential-dependent interactions of nitrendipine and related 1,4-dihydropyridines in functional smooth muscle preparations.

Interaction of nitrendipine and other Ca2+ channel antagonists including nifedipine, diltiazem, and D600 with intestinal smooth muscle was shown to depend on membrane potential. In the absence of extracellular Ca2+, guinea pig ileal longitudinal muscle does not contract and can be incubated at various K+ concentrations in the presence or absence of antagonist. Preincubation with elevated K+ prior to admission of Ca2+ and challenge with K+ to a total of 100 mM increased the activity of the antagonist. The IC50 for nitrendipine incubated in the presence of 5 mM K+ was 5.36 X 10(-9) M and in the presence of 40 mM K+ was 0.53 X 10(-9) M. Other 1,4-dihydropyridines showed similar potency shifts.

Animals↗
PubMed1988

Occupation and lung cancer in Shanghai: a case-control study.

Occupation was evaluated as a potential risk factor for lung cancer as part of a large population based case-control study conducted in the ten urban districts of Shanghai. A total of 733 newly diagnosed cases of male lung cancer and 760 controls selected from the general population was interviewed to obtain lifetime occupational histories and information on smoking and other factors. Of the approximately 25 major industrial titles examined, significantly raised risks, adjusted for smoking, were found for employment in agricultural production (odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.0-2.6). A concomitant increase was detected for farmers (OR = 1.6, 95% CI = 1.0-2.5) when 35 major occupational titles were examined. There was a 70% excess among workers in the chemical industry (OR = 1.7, 95% CI = 0.9-3.1) and a significant decrease among textile industry workers (OR = 0.7, 95% CI = 0.5-1.0). Raised risks of 30% to 80% were associated with reported job exposures to wood and coal dusts, smoke from burning fuels, and chemical fumes. Employment categories were also examined for 672 cases and 735 controls among women, but small numbers in many of the industrial and occupational categories precluded detailed analyses. The largest excess risk among women (OR = 5.1, 95% CI 1.3-23.5) was among glass products workers. Although cigarette smoking was the dominant cause of lung cancer among men and a significant risk factor among women in Shanghai, these findings suggest the importance of certain workplace exposures and offer leads to occupational carcinogens.

Adult↗