Effect of in vivo desensitization to leukotriene B4 on eosinophil infiltration in response to C5a in guinea-pig skin.

1. The effect of in vivo desensitization to leukotriene B4 (LTB4) on eosinophil infiltration in response to recombinant C5a was examined in guinea-pig skin. 2. LTB4 (10-300 ng) and C5a (1-10 micrograms) caused a dose-dependent increase in the levels of eosinophil peroxidase activity (a measure of eosinophil infiltration) 4 h after injection into guinea-pig skin. Leukotriene B4 and C5a were approximately equipotent on a molar basis. Platelet activating factor (0.01-10 micrograms) also caused eosinophil accumulation but was much less active than LTB4 or C5a. 3. 20-Hydroxy-LTB4 caused a dose-dependent desensitization of eosinophil responses to LTB4 (ED50 = 1.6 micrograms kg-1, s.c.) and partially reduced responses to C5a. At a dose of 20-hydroxy-LTB4 (10 micrograms) which inhibited responses to LTB4 completely, responses to C5a were reduced by 56.5 +/- 1.8% (n = 5). The structurally related metabolite of 20-hydroxy-LTB4, 20-carboxy-LTB4, which does not cause desensitization to the effects of LTB4, did not inhibit eosinophil infiltration in response to C5a. 4. The LTB4 receptor antagonist, SC-41,930 (10 mg kg-1, p.o.), also inhibited eosinophil accumulation in response to C5a by 63.0 +/- 3.9% (n = 5) at a dose which inhibited responses to LTB4 by 86.5 +/- 1.9% (n = 5). 5. These data indicate that eosinophil infiltration in response to C5a may, in part, be mediated by the generation of secondary chemotactic factors such as LTB4.     

Abolition of flow-dependent EDRF release before that evoked by agonists in hypercholesterolaemic rabbits.

1. We have used a pulsatile cascade bioassay system to investigate the effects of dietary-induced hypercholesterolaemia on EDRF release evoked by acetylcholine and by the oscillatory and time-averaged components of flow, in isolated segments of rabbit abdominal aorta. 2. Flow pulsatility (frequency range 0.1-10 Hz) was studied with constant flow (9 ml min-1) at a pulse pressure amplitude of 2 mmHg. Frequency-related EDRF release, maximal at 6 Hz, was slightly attenuated after 4 weeks and abolished after 8 weeks of cholesterol feeding. 3. Time-averaged shear stress was manipulated with dextran (1-4% w/v, 80000 mol. wt.), to increase perfusate viscosity. EDRF release induced by increased perfusate viscosity was unaffected after 4 weeks but abolished after 8 weeks of cholesterol feeding. 4. Endothelium-dependent relaxations to acetylcholine (0.1-10 microM) were not influenced after 4 weeks and only partially attenuated (by 60% of the maximal response, EC50 unchanged at 6.45 +/- 0.04 vs. 6.4 +/- 0.1 microM) after 8 weeks of cholesterol feeding. 5. Blood cholesterol levels were significantly (P < 0.001) increased after 4 weeks (26 +/- 3.6 vs 2.6 +/- 0.6 mmol l-1) and 8 weeks (56.2 +/- 3.8 vs 1.3 +/- 0.1 mmol l-1) of cholesterol feeding but after 8 weeks plasma L-arginine levels were not significantly different from the age-matched controls (0.2 +/- 0.05 vs. 0.19 +/- 0.04 mmol l-1). 6. We conclude that hypercholesterolaemia impairs flow-related (pulsatile- and time-averaged shear-induced) EDRF release earlier than acetylcholine-induced relaxation in rabbit aorta.(ABSTRACT TRUNCATED AT 250 WORDS)     

Contractile properties of synthetic cationic polypeptides in guinea-pig isolated trachea.

1. Purinoceptor agonist-induced currents in untreated (proliferating) and lipopolysaccharide- (LPS; 100 ng ml-1) treated (non-proliferating) rat microglial cells were recorded by the whole-cell patch-clamp technique. 2. In non-proliferating microglia, adenosine (0.01-100 microM), 2-methylthio ATP (3-3000 nM), ATP (0.1-1000 microM), and ATP-gamma-S (1-10 microM), but not alpha,beta-methylene ATP (alpha,beta-MeATP; 100 microM) produced a slow outward current at a holding potential of 0 mV. When K+ was replaced in the pipette solution by an equimolar concentration of Cs+ (150 mM), the 2-methylthio ATP- (300 nM) induced outward current disappeared. The effect of 2-methylthio ATP (300 nM) did not depend on the presence of extracellular Mg2+ (1 mM). The outward current response to 2-methylthio ATP (300 nM) was larger in proliferating than in non-proliferating microglia. 3. ATP (1-1000 microM) evoked a fast inward current at a holding potential of -70 mV in nonproliferating microglia, while adenosine (100-1000 microM) was inactive. When the effects of ATP were compared at 0 and -70 mV, it became evident that ATP is much more potent in evoking the outward current. 4. The 2-methylthio ATP- (300 nM) induced outward current was blocked by suramin (300 microM), but not by 8-(p-sulphophenyl)-theophylline (100 microM), while the adenosine- (1 microM) induced outward current had the reverse sensitivity to these antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nitric oxide as a mediator of the laxative action of magnesium sulphate.

1. Magnesium sulphate was studied for its effects on diarrhoea, fluid secretion, gastrointestinal transit and nitric oxide (NO) synthase activity in rats. 2. At a dose of 2 g kg-1 orally magnesium sulphate produced diarrhoea that was delayed in onset and intensity in a dose-related manner by the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). This was prevented by the NO precursor, L-arginine and the NO donating compound, isosorbide-5-mononitrate (IMN). 3. Nitric oxide synthase activity was stimulated in gut tissue from rats given magnesium sulphate and this was inhibited by L-NAME. Dexamethasone (1 mg kg-1, i.p.), an inhibitor of inducible NO synthase, had no effect on magnesium sulphate-induced diarrhoea. 4. Magnesium sulphate stimulated fluid and electrolyte accumulation in the intestinal lumen; these effects were prevented by L-NAME but not D-NAME. 5. Gastrointestinal transit of a non-absorbable marker (charcoal suspension) was increased by oral magnesium sulphate from a mean value of 54.1% to 72.9% (P < 0.01), and this was prevented by pretreatment with L-NAME. 6. The results demonstrate that oral magnesium sulphate produces diarrhoea in rats by increasing the accumulation of fluid in the intestinal lumen and enhancing flow from the proximal to distal intestine. The mechanism involves release of NO, probably through stimulation of the constitutive form of NO synthase. Whether or not the effects of magnesium sulphate are due to an osmotic action or an intrinsic effect of the magnesium or sulphate ions cannot be determined from these experiments.     

Natriuretic peptide-induced cyclic GMP accumulation in adult guinea-pig cerebellar slices.

1. Second messenger responses to natriuretic peptides were studied in guinea-pig cerebellar slices by use of radioactive precursors. 2. The rank order of potency of the different natriuretic peptides in generating [3H]-guanosine 3':5'-cyclic monophosphate (cyclic GMP) was atrial natriuretic peptide (ANP) > brain natriuretic peptide (BNP) >> C-type natriuretic peptide (CNP) with EC50 values of 19.5 +/- 8.8 nM for ANP and 169 +/- 41 nM for BNP. CNP induced [3H]-cyclic GMP accumulation only at concentrations greater than 1 microM. 3. An additive response to ANP (1 microM) was observed in the presence of the adenosine receptor agonist, 5'-N-ethylcarboxamidoadenosine (NECA, 10 microM) or the soluble guanylyl cyclase activator, sodium nitroprusside (SNP, 100 microM) for [3H]-cyclic GMP accumulation. 4. ANP, BNP and CNP (all at 1 microM) failed to alter significantly either basal-, forskolin- (10 microM), isoprenaline- (100 microM), or NECA- (10 microM) induced [3H]-cyclic AMP generation. Natriuretic peptides also did not change the [3H]-cyclic AMP steady-state reached after 10 min of treatment with 10 microM forskolin. 5. Natriuretic peptides failed to elicit significant accumulation of [3H]-inositol phosphates at concentrations up to 10 microM. 6. These data are consistent with the presence of ANPA, rather than ANPB or clearance receptors (C-receptors), linked to second messenger cascades in guinea-pig cerebellar slices.     

The electrophysiological effects of dicentrine on the conduction system of rabbit heart.

1. The electrophysiological effects of dicentrine, an aporphine alkaloid isolated from the root of Lindera megaphylla, were examined in the Langendorff perfused rabbit heart and rabbit isolated cardiac cells. 2. Standard electrophysiological characters were measured in the Langendorff perfused rabbit heart (control study) and after 5 min exposure to 1, 3 and 9 microM of dicentrine and during the subsequent recovery phase sequentially (n = 7). The same study protocols were performed in 0.5 to 4.5 microM quinidine (n = 7), 18 to 162 microM procainamide and N-acetylprocainamide (n = 7) for comparison. 3. The results showed that the spontaneously beating heart rate and the sinoatrial (SA) and atrioventricular nodal (AH) conduction time were not significantly affected by dicentrine but were significantly suppressed by the higher doses of quinidine (4.5 microM) and procainamide (162 microM). 4. The His-Purkinje conduction time was significantly increased by the higher dose of dicentrine, quinidine and procainamide. 5. The ventricular repolarization time and its effective refractory period were significantly increased by the higher dose of dicentrine and the other agents. 6. The effective refractory period of the atrium, AV node and His-Purkinje system were also significantly increased by dicentrine and the other agents. 7. A voltage clamp study revealed that the prolongation of atrial action potential duration by dicentrine (9 microM) was associated with a significant inhibition of the transient potassium outward current. As well as inhibition of the transient outward current, a significant inhibition of the sodium inward current by dicentrine was found.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of chronic infusions of alpha-trinositol on regional and cardiac haemodynamics in conscious rats.

1. Male, Long Evans rats (350-450 g) were chronically instrumented for the measurement of renal, mesenteric and hindquarters haemodynamics, and were given three consecutive, 24 h infusions of vehicle (sterile saline at 0.3 ml h-1, n = 8) or alpha-trinositol (D-myo-inositol-1,2,6-triphosphate) at 5, 20 and 80 mg kg-1 h-1 (0.3 ml h-1; n = 9). During infusion of alpha-trinositol at 5 or 20 mg kg-1 h-1, cardiovascular changes were little different from those seen during saline infusion. However, during infusion of alpha-trinositol at 80 mg kg-1 h-1 there were increases in hindquarters vascular conductance, renal flow and vascular conductance, that were all significantly different from the changes seen in the saline group. Infusion of alpha-trinositol at the high dose in naive rats (n = 8) had even more marked vasodilator effects. 2. Two groups of rats (n = 8 in each), chronically instrumented for the measurement of cardiac haemodynamics, were given 48 h infusions of saline (0.3 ml h-1) or alpha-trinositol (2 mg kg-1 bolus, 80 mg kg-1 h-1 infusion at 0.3 ml h-1). During the infusion of saline, there were slight reductions in heart rate, cardiac index, peak aortic flow, dF/dtmax and central venous pressure. In the animals receiving alpha-trinositol, with the exception of central venous pressure, all the above variables, together with total peripheral conductance, increased. 3. These results, collectively, indicate that incremental infusions of alpha-trinositol do not reveal its full vasodilator potential, possibly due to concurrent activation of counter-regulatory vasoconstrictor mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)     

广东省梅县乡(镇)卫生院卫生人力资源的现状调查分析

乡(镇)卫生院是农村三级医疗预防保健网的中心环节,是我国农村实现“2000年人人享有卫生保健”的关键。本文通过对广东省梅县乡(镇)一级卫生院卫生人力状况的调查分析,结果表明,目前该县乡镇卫生院的机构稳定,卫技人员占编比例合理,年龄较轻,成为今后农村卫生院发展的优势。但存在着卫生技术人员的总体数量不足,素质较差,各类专业技术人员的构成比例失调和层次分布不合理等问题,同时提出了如何加以改善的对策措施。     

大气中不同粒径颗粒物诱导人羊膜FL细胞UDS的研究

本研究以诱导人羊膜细胞ＵＤＳ为指标，对太原市大气不同粒径的颗粒物提取液进行了致突变性检验，结果表明，不同粒径颗粒物的提取液均可产生一定的遗传毒性，尤以３．３μｍ以下的颗粒物的遗传毒性较强。     

复治矽肺结核化疗效果观察

我们自１９８０～１９８８年对７９例复治矽肺结核进行化疗。其中绝大多数为慢性纤维化空洞性病例，均经细菌学证实，并由尘肺诊断组认定为矽肺合并结核。本组病例分别以ＫＭ、ＩＮＨ、ＲＦＰ、ＰＺＡ，或ＳＭ、ＩＮＨ、ＲＦＰ、ＥＢ联合，分两阶段治疗１８个月，获痰菌阴转７９．２％，其中ＫＨＲＺ与ＳＨＲＥ组分别为９３．９％与６８．２％（Ｐ＜０．０５）。自疗程结束追踪２～８年，其细菌复阳率分别为６．４５％和１０．０％（Ｐ＞０．１）。并对影响其过去治疗失败的原因及对策进行了讨论。