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Biomedical subjects

H Luo

Publications and source records attributed to H Luo.

At least 19 recordsLinked to original sources
PubMed1992

Role of cholecystokinin in mediating GRP-stimulated gastric, biliary and pancreatic functions in man.

To explore the mechanisms of gastrin-releasing peptide (GRP)-induced gut functions in man, we investigated the effect on gallbladder contraction, exocrine pancreatic secretion and gastric acid secretion of a recently developed CCK receptor antagonist, loxiglumide, on GRP-stimulated effects in six healthy human subjects. Intravenous infusion of graded doses of synthetic human GRP (1-27 pmol/kg per h) caused significant and dose-dependent increases in pancreatic enzyme and gastric acid secretions and in gallbladder contraction. Intravenous administration of loxiglumide (10 mg/kg per h) abolished GRP-stimulated gallbladder contraction, augmented gastric acid secretion, but did not affect exocrine pancreatic secretion. The results suggest that endogenously released CCK is (1) responsible for GRP-stimulated gallbladder contraction, and (2) involved in regulating gastric acid secretion. The results further suggest that GRP-stimulated pancreatic secretion is not mediated by CCK, but has a direct response of GRP on the exocrine pancreas.

Adult↗
PubMed1992

Protective effect of anisodamine on cultured bovine pulmonary endothelial cell injury induced by oxygen-free radicals.

Anisodamine, a Chinese traditional medicine herb, has been used for treatment of adult respiratory distress syndrome effectively, but little is known about its mechanism. We attempted to investigate if anisodamine could protect bovine pulmonary endothelial cell injury induced by exogenous oxygen-free radicals that were generated by xanthine/xanthine oxidase or opsonized zymosan-stimulated polymorphonuclear leukocytes. Results showed that with the addition of xanthine/xanthine oxidase into cultured bovine pulmonary endothelial cells, production of malondialdehyde and release of lactate dehydrogenase in supernatant increased, and synthesis of prostacyclin decreased. Damaged cellular membranes were revealed by scanning electron microscopy. The same was true for the addition of opsonized zymosan-stimulated polymorphonuclear leukocytes. While treatment with anisodamine greatly attenuated all of the above-mentioned parameters, results showed that (1) cultured bovine pulmonary endothelial cells could be damaged by oxygen-free radicals, (2) anisodamine had a protective effect on this injury as effective as that of superoxide dismutase and catalase, and (3) the membrane-stable action might contribute to the mechanism of protective effect against this injury.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Synthesis and characterization of quaternary ammonium-linked glucuronide metabolites of drugs with an aliphatic tertiary amine group.

A synthetic approach was developed to make the quaternary ammonium-linked glucuronide metabolites of compounds with an aliphatic tertiary amine group. The key step involved quaternization of the compound with methyl (2,3,4-tri-O-acetyl-alpha-D-glucopyranosyl bromide)uronate and sodium bicarbonate in a two-phase system of water and an organic solvent. The synthetic approach successfully yielded quaternary ammonium-linked glucuronides of 20 drugs and two of their phase I metabolites. The drugs were from various pharmacological classes: H1 antihistamines, antipsychotic agents, and tricyclic antidepressants. Physical data such as HPLC retention times, and diagnostic fast-atom bombardment mass spectra and 1H NMR spectra were obtained. These should aid in the characterization of compounds in samples isolated from biological media.

Amines↗
PubMed1992

Effects of rapamycin on human HLA-unrestricted cell killing.

Rapamycin (RAPA) is a potent immunosuppressant and can effectively prevent allograft rejection at a dosage 10- to 100-fold lower than that of cyclosporin A. RAPA strongly inhibits proliferation and function of T and B cells. In this study, we investigated the effect of RAPA on human HLA-unrestricted cell killing. It was shown that in vitro RAPA inhibited the cytolytic effect of natural killer cells and lymphokine-activated killer cells (LAK) and inhibited antibody-dependent cell-mediated cytotoxicity. The effective concentration of RAPA was 10- to 100-fold higher than that required for inhibiting T cell proliferation. These results suggest that there could be a therapeutic dose window at which RAPA inhibits T cell activity while it leaves HLA-unrestricted cell killing unaffected. We also demonstrated that while IL4 inhibited LAK activity, and RAPA inhibited IL4-promoted T cell proliferation, RAPA was not able to antagonize IL4's inhibitory effect on LAK. This indicates that the mechanism of interaction between RAPA and IL4 on LAK is different from that on T cells.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1992

Inhibition of in vitro immunoglobulin production by rapamycin.

Like FK506, rapamycin, a structural analog of FK506, is a strong immunosuppressant. The immunosuppressive effect of Rapa in in vitro IgG, IgM, and IgA production by human lymphocytes was examined in this study. To inhibit spontaneous or pokeweed mitogen-stimulated production of Ig by human peripheral blood lymphocytes, about one thousandfold lower concentrations of Rapa (IC50 = 0.3 nM-2 nM) were required than of cyclosporine (IC50 = 0.3 microM-2 microM). T cells were the direct targets of Rapa, because preincubation of T cells with Rapa abolished the T cells helper effect to T-dependent Ig production. Rapa also had direct suppressive effect on B cells, since Rapa suppressed IgG production by pure B cells stimulated with IL2 and Staphylococcus aureus Cowan I. Kinetic studies measuring IgG production and cell proliferation revealed that Rapa acted at the activation stage of T and B cells. Exogenous IL2 substantially reversed the inhibitory effect of CsA but not that of Rapa in Ig production. This study is the first report on the strong suppressive effect of Rapa on human humoral immune response with a quantitative comparison with that of CsA. The underlying mechanisms are also explored. The results indicate the potential usefulness of this drug in treatment of presensitized transplantation patients, with whom cytotoxic Ab is a major obstacle to a successful transplantation.

Antibody Formation↗
PubMed1992

Postprandial control of gallbladder contraction and exocrine pancreatic secretion in man.

To explore the interactions between cholecystokinin (CCK) and the cholinergic system, we compared the effect of cholinergic or peptidergic CCK blockade on gallbladder contraction and pancreatic enzyme secretion using atropine and loxiglumide (a specific CCK antagonist) as pharmacological tools. Gallbladder contraction was measured by sonography and pancreatic secretion by a marker perfusion and aspiration technique. Graded doses of exogenous CCK8 induced dose-dependent contractions of the gallbladder and increasing enzyme outputs. Loxiglumide (10 mg kg-1 h-1) abolished the gallbladder response and prevented an increase in pancreatic enzyme secretion to CCK8. Atropine (5 micrograms kg-1 h-1), however, only reduced gallbladder contraction and enzyme output to CCK8. Gallbladder volumes decreased maximally to 12 +/- 4% after oral food, whereas enzyme output and plasma CCK levels increased 6- to 8-fold. Loxiglumide completely abolished gallbladder contraction and inhibited enzyme secretion by 30%. Atropine caused a small reduction in gallbladder volumes, but essentially blocked postprandial enzyme secretion. The results indicate that CCK is the major regulator of gallbladder contraction with the cholinergic system modulating the response, while the exocrine pancreas is crucially dependent on a cholinergic background with CCK modulating the secretory response.

Adult↗
PubMed1992

Participation of protein kinase C in desensitization to bradykinin and to carbachol in MDCK cells.

To explore the possibility that protein kinase C (PKC) participates in desensitization to Ca(2+)-mobilizing hormones in MDCK cells, we measured intracellular free Ca2+ concentration ([Ca2+]i) using fura-2 and video microscopy. We first examined the response of MDCK cells grown on plastic dishes. Exposure of cells to bradykinin (BK) or to carbachol, followed by reexposure after washing off the hormone, revealed two features of hormone desensitization. First, the initial hormone-induced peak response of [Ca2+]i was transitory; [Ca2+]i returned to control levels despite continued presence of hormone. Second, cells remained refractory to hormone rechallenge for 5 min after washing off hormone; [Ca2+]i response on re-exposure was reduced 70% compared with initial hormone-stimulated peak. Subsequent experiments demonstrated involvement of PKC in both desensitization processes. Pretreatment with the phorbol ester, phorbol 12-myristate 13-acetate, significantly blunted initial response to BK and to carbachol by 70 and 86%, respectively. When hormone-stimulated C kinase activity was enhanced with the diglyceride lipase inhibitor, RG 80267, BK- and carbachol-induced increases in [Ca2+]i were blunted 50%. Pretreatment with sphingosine, an inhibitor of PKC, resulted in an amplification of initial hormone-stimulated increase in [Ca2+]i and restored the response to rechallenge. To examine the possible interaction between BK and carbachol,both of which use PKC to induce desensitization, we measured [Ca2+]i in cells grown as monolayers on permeable, collagen-coated supports. Both carbachol and BK induced desensitization to the other hormone (heterologous desensitization)provided that the two hormones were applied to the same side of the polarized monolayer (apical).(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

[Cardiovascular responses to microinjection of atrial natriuretic peptide into ventrolateral medulla of rat].

Application of atrial natriuretic peptides (alpha-ANP and AP III) to glutamate sensitive area of ventrolateral medulla produced a dose-dependent decrease in MAP and HR in anesthetized rats. Lower dosage of AP III induced hypotension without bradycardia, whereas the higher dosage of AP III decreased both blood pressure and heart rate. The results suggested that ANP may inhibit the medullary sympathetic center.

Animals↗
PubMed1992

[Relation between the occurrence of malignant arrhythmia during acute myocardial ischemia and the weight of ischemic myocardium in goats].

The coronary collateral circulation of goat is very spare, so myocardiac ischemia model of goat can simulate the patient previously with normal coronary circulation and suddenly developing complete occlusion of coronary arteries. In this study 80 Chengdu goats were used, and the branches of their left coronary artery were ligated. Ventricular tachycardia (VT) developed in 23 goats and ventricular fibrillation (VF) in 39 goats. VT and VF both occurred in the early phase of acute myocardial ischemia, and both had 6 min as the median time of onset. In 71 cases data on the weight of myocardiac ischemic area were collected, in which the weight percentage of ischemic area relating to the ventricles of 34 goats with VF was significantly higher than that of 37 goats without VF (35.4 +/- 2.4% vs 19.5 +/- 1.9%). After coronary ligation, 9 cases directly precipitated into VF which could not be defibrillated. In the remaining 62 cases, the weight percentage of ischemic area of 21 cases with VT was higher than that of 41 cases without VT (32.9 +/- 2.8% vs 20.9 +/- 2.1%). The relationships between the incidence of VT or VF and the weight percentage of ischemic area were fitted with logistic curve. The likelihood of occurrence of VT or VF is increased as the weight percentage of ischemia area goes up.

Animals↗
PubMed1992

[Effects of tian-ma injection on myocardial ischemia and lipid peroxidation in rabbits].

Lipid peroxidation initiated by oxygen free radicals played an important role in the pathogenesis of coronary heart disease. The purpose of this study was to explore the effects of Tian-Ma (Gastrodia elata Bl.) injection on myocardial infarct size and lipid peroxidation by observing serum malondialdehyde (MDA) levels. Twenty-six New Zealand rabbits were divided into control group (n = 6), ischemic group (n = 10), and Tian-Ma treated group (n = 10). Left ventricular branch (LVB) of coronary artery was ligated at its middle third in ischemic and treated groups. LVB was not ligated in control group. Tian-Ma injection was given intravenously (1 mg/kg) every 8 hours after ligation in treated group for 48 hours. Precordial 12-lead ECG mapping was recorded before operation and at 3, 24 and 48 hours after occlusion. Hemodynamic changes (HR, LVP) were monitored before and 0.5, 3 and 48 hours after ligation. Serum MDA levels were determined by thiobarbituric acid spectrophotometry before operation, and 0.5, 3, 9, 24, and 48 hours after ligation. Dual staining technique was used 48 hours after ligation to determine the area at risk and infarct size. The results showed that Tian-Ma injection did not decrease sigma ST elevation (P greater than 0.05), but NQ was significantly lower during ischemia in treated group (P less than 0.01), Tian-Ma injection reduced the area at risk by 23.5% (P less than 0.05) and infarct size by 34.5% (P less than 0.01). Tian-Ma injection significantly decreased the levels of serum MDA 24 and 48 hours after occlusion (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

[Circadian rhythm of blood pressure in renovascular hypertensive goats treated with captopril].

Blood pressure (BP) was recorded directly and automatically by a microcomputer aid system for 48 h in normotensive and Goldblatt hypertensive goats. By population-mean cosinor fitting, significant circadian rhythms were found for SBP and DBP in both groups of goats. The BP during nighttime was higher than that during daytime in our goats. An angiotensin converting enzyme inhibitor, captopril, was given to hypertensive goats with usual schedule of drug administration (25mg, t.i.d) or form of chronotherapy (62.5 mg, given before the acrophase of BP, q.n). BP significantly decreased throughout the whole day in both treated groups. But there was no statistical difference of cosinor parameters between the effects of BP in these two groups. BP could be decreased by the method of chronotherapy with less amount of drug and less frequency of drug administration.

Animals↗
PubMed1991

Inhibition of binding of [3H]metolazone to rat kidney membrane by stilbene disulfonates.

Thiazide diuretics inhibit an electroneutral chloride and sodium reabsorptive transport pathway in the renal distal convoluted tubule. [3H]Metolazone binds with high affinity to the drug recognition site on the thiazide-sensitive ion transporter. The molecular nature of this transporter is currently unknown. This report examines whether stilbene disulfonates [4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS)], agents that have been used to identify other anion-transporting proteins, could be useful in the identification of the thiazide receptor. We found that high concentrations of DIDS or SITS were required to inhibit binding of [3H]metolazone to rat kidney membranes, with apparent IC50 values of 380 and 940 microM, respectively. The inhibition was due to a decrease in the number of binding sites without alteration in the affinity of the binding. The inhibition was not reversible, as judged by the inability of the inhibition to be reversed by removal of the DIDS or SITS from the membranes prior to equilibration with [3H]metolazone. Addition of 100 mM NaCl to the incubation medium did not protect the [3H]metolazone binding site from inhibition by DIDS. We infer that DIDS and SITS irreversibly inhibit binding of [3H]metolazone by reaction with the thiazide receptor at a site other than the anion-transporting site.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1991

N(+)-glucuronidation of aliphatic tertiary amines, a general phenomenon in the metabolism of H1-antihistamines in humans.

1. Representative drugs of the various structural classes of H1 antihistamines were chosen for study. The drugs chosen (class name in parentheses) were chlorpheniramine maleate and pheniramine maleate (alkylamines), diphenhydramine hydrochloride and doxylamine succinate (ethanolamines), pyrilamine maleate and tripelennamine hydrochloride (ethylenediamines), promethazine hydrochloride (phenothiazine), cyclizine lactate (piperazine) and terfenadine (miscellaneous). In each case oral dose(s) were administered over no more than 6 h to two healthy volunteers and the total urine collected for 36 h. 2. Metabolites from urine were separated by h.p.l.c. and individually collected prior to mass spectrometric analysis in the fast atom bombardment mode. The structure of each metabolite identified as a quaternary ammonium-linked glucuronide metabolite was confirmed by direct comparison of its mass spectrum and chromatographic behaviour with that of a synthetic authentic compound. 3. For eight of the nine drugs studied, metabolism by the N(+)-glucuronidation pathway was observed in each of the volunteers. Terfenadine was the exception. 4. The amount of each N(+)-glucuronide in the urine was estimated by h.p.l.c. analysis. The mean proportion of dose excreted as the metabolite was 14.3%, 6.5% and 4.0% for cyclizine, tripelennamine and diphenhydramine, respectively. Promethazine was the only case where the N(+)-glucuronide accounted for less than 1.0% of the administered dose in both volunteers examined.

Adult↗
PubMed1991

[Central cardiovascular and renal effects of atrial natriuretic peptide].

In 54 anesthetized rats, the changes in arterial blood pressure, heart rate and/or urine volume, urinary sodium excretion were observed following intracarotid, intrathecal and intracerebroventricular (ICV) injection of atrial natriuretic peptide (ANP). The effects of ANP on the central actions of angiotensin II (AG II) were also examined. The results were as follows: (1) In the cross-circulation preparation of rat head, MAP of the recipient was unchanged and that of the donor was decreased in response to the administration of alpha-hANP (15 micrograms/kg) into the carotid artery of the recipient. (2) By injecting AP III (5 micrograms/kg) intrathecally, MAP, HR and urine volume (V) of the rats (n = 7) showed no change. (3) The ICV injection of AP III (20 micrograms/kg) did not result in changes in MAP, HR, and urinary sodium excretion (UNaV), but there was a transient and significant increase in V. (4) ICV injection of AG II (1 microgram/kg) resulted in an increase of MAP by 1.3 +/- 0.17 kPa (10 +/- 1.3 mmHg, n = 10, P less than 0.001), V by 106% (n = 6, P less than 0.01) and UNaV by 642% (P less than 0.01). (5) ICV injection of AP III 2 min prior to the injection of AG II by the same route, the central hypertensive effect induced by AG II was not affected, while the increments in V and UNaV were decreased significantly (P less than 0.05). The results indicate that (1) ANP is incapable of penetrating the blood-brain barrier owing to its large molecular size and therefore, the central mechanism is not involved in the hypotensive effect induced by intravenous injection of ANF and (2) the central diuretic and natriuretic actions of AG II may be markedly inhibited by ICV injection of ANP, thus indicating the existence of some central antagonistic interactions between AG II and ANP.

Angiotensin II↗