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Biomedical subjects

H Kuhn

Publications and source records attributed to H Kuhn.

At least 91 records · Page 5Linked to original sources
PubMed1994

Prolactin lowering activity of the retinoid Ro 14-9706 affecting lactation and pup survival.

The arotinoid Ro 14-9706, though devoid of any teratogenic potential, was found to reduce dose dependently the survival of pups when their mothers were treated with toxic doses during days 6-15 of gestation. The increased mortality was primarily seen during early lactation. When pups derived from treated mothers were nursed by control foster mothers unexposed to the drug, their survival was significantly improved indicating that the increased mortality was not solely due to fetal drug exposure. When pups derived from untreated mothers were fostered by dams that were exposed to the arotinoid during pregnancy, a significant pup mortality (p < 0.01) was observed, suggesting that the nursing behaviour of lactating dams was seriously affected. This impairment could be linked to a prolactin-suppressive activity of the arotinoid during lactation which was also seen during pregnancy. Other pituitary hormones, however, were not affected by the compound. Although the drug induced pronounced structural alterations in mitochondria of adrenocortical cells, visualized by light microscopy as extended vacuolization in the zona fasciculata and reticularis, this pathological finding did not translate into functional impairment of steroidogenesis. Thus, the arotinoid Ro 14-9706 exhibits in rats a prolactin-suppressive activity which affects lactation and subsequently pup survival. This particular endocrinological interference is a new phenomenon and uncommon for retinoids.

Adrenal Cortex↗
PubMed1994

[Sagittal burst fracture of the talus].

Fractures of the talus have a relatively low incidence, accounting for 0.3% of all bone fractures and 3.4% of fractures of bones in the foot. These injuries affect the neck of the talus more frequently than its head or body. Because of the combined traumatic mechanism, sagittal fracture of the talar body is extremely rare; the literature contains only a few case reports, all with severe dislocation of the fragments. Plain film radiographs and CT pictures recorded in a rare case of nondisplaced fracture of the talar body are presented.

Adult↗
PubMed1994

Hyperinsulinism in patients with coronary artery disease.

AIM: To assess the clinical impact of hyperinsulinism and major coronary risk factors in patients with angiographically documented or excluded coronary artery disease (CAD), a clinical study was carried out in 268 men admitted for left heart catheterization. METHODS: Fasting immunoreactive insulin (IRI) levels were correlated to all major cardiovascular risk factors and to the presence and degree of CAD. RESULTS: IRI levels were correlated significantly with the degree of CAD (one-vessel disease: mean IRI 9.45 microU/ml +/- 0.43 SEM; two-vessel disease: mean IRI 10.4 microU/ml +/- 0.71 SEM; three-vessel disease: mean IRI 11.88 microU/ml +/- 0.98 SEM) and inversely to the high-density lipoprotein level (P < 0.05). In patients with arterial hypertension, IRI levels were elevated, without a significant difference between those with and those without CAD, whereas the IRI levels of non-hypertensive men with CAD (n = 81; mean IRI 9.85 microU/ml +/- 0.51 SEM) differed significantly (P < 0.05) from those of non-hypertensive men without CAD (n = 59; mean IRI 7.76 microU/ml +/- 0.43 SEM). IRI levels were significantly higher (P < 0.05) in obese patients (n = 65; mean IRI 11.68 microU/ml +/- 0.70 SEM versus n = 203; mean IRI 9.32 microU/ml +/- 0.34 SEM), in patients with elevated triglycerides (n = 58 mean IRI 11.59 microU/ml +/- 0.81 SEM versus n = 210; mean IRI 9.42 microU/ml +/- 0.33 SEM), and in patients with lowered HDL cholesterol (n = 178; mean IRI 11.06 microU/ml +/- 0.63 SEM versus n = 90; mean IRI 9.29 microU/ml +/- 0.34 SEM). Diabetic patients on angiotensin converting enzyme inhibitor therapy (n = 11; mean IRI 7.91 microU/ml +/- 0.91 SEM) had significantly (P < 0.05) lower IRI levels than those not treated with ACE inhibitors (n = 25; mean IRI 12.96 microU/ml +/- 1.47 SEM). IRI levels exceeding 8 microU/ml were associated with a 1.98-fold risk for CAD compared with IRI levels below 8 microU/ml. Stepwise logistic regression showed that insulin was an independent determinant of CAD. CONCLUSION: Knowledge of the fasting insulin level is an important contribution to the identification of patients with, or at risk of, CAD.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Synovial tissue implants from patients with rheumatoid arthritis cause cartilage destruction in knee joints of SCID.bg mice.

OBJECTIVE: To establish in SCID.bg mice a model in which joint destruction is initiated by human inflammatory cells from patients with rheumatoid arthritis (RA). METHODS: Development of a surgical technique and immunohistologic analysis. RESULTS: Initial experiments with single cell suspensions failed because more than 70% of the cells injected intraarticularly left the mouse knee joint within 16 h without causing destruction. This was observed with peripheral blood mononuclear cells, T cell lines reactive to mouse or rat collagen type II, and synovial mononuclear cells. Cell immigration was reduced but not prevented by preactivation with mitogens. In contrast, small tissue implants from human synovial membrane which were transferred by surgical intervention into mouse knee joints remained at the site of injection and could be easily localized within the mouse joint (observation period up to 8 weeks). The human synovial membrane implants induced pannus formation and erosion of cartilage and bone while only a mild and transient synovitis was observed with normal synovial membrane and control tissues like human thymus. The predominant cells at the site of destruction were human (CD68+) and murine (Mac-2+) monocytes/macrophages. CONCLUSION: The human/murine SCID arthritis is a useful model for studying pathogenetic aspects of joint destruction as well as effects of new drugs or novel treatment strategies.

Animals↗
PubMed1993

ACE inhibition and the vascular intima in hypertension.

Both the function and the morphology of the vascular intima are altered during hypertension. In spontaneously hypertensive rats, endothelium-dependent relaxation is decreased, and the subendothelium becomes infiltrated with monocyte macrophages. It is not known if these two features are secondary to high blood pressure and what their consequences are; however, both can be reversed by angiotensin-converting enzyme (ACE) inhibition. The present paper summarizes the effects of a chronic treatment with the ACE inhibitor cilazapril on endothelial function and subendothelial morphology in spontaneously hypertensive rats.

Animals↗
PubMed1993

Protective effect of cilazapril on the cerebral circulation.

The goal of an antihypertensive treatment is to prevent "end-organ" damage. Cerebral vascular complications are among the most important because they are life threatening and can occur even at an early stage of the disease. Recently, it has been shown that cilazapril can decrease the mortality of stroke-prone rats, suggesting a decrease in the incidence of strokes, which occur spontaneously in these animals. The present article reviews the different functional and morphological changes that may explain the cerebral protective effects of cilazapril, such as the normalization of cerebral vascular reserve, decrease in the media, increase in the external diameter, and normalization of the mechanics and endothelial function of cerebral arterioles. In addition, the inhibition by cilazapril of injury-induced proliferation of smooth muscle cells and the infiltration of the endothelium by macrophages could prevent the development of atherosclerosis.

Animals↗
PubMed1993

Ro 44-9883, a new nonpeptide glycoprotein IIb/IIIa antagonist, prevents platelet loss during experimental cardiopulmonary bypass.

Extensive contact between blood and artificial surfaces causes platelet activation and depletion. The aim of the study was to test the efficacy of Ro 44-9883, a new nonpeptide, reversible, glycoprotein IIb/IIIa antagonist in preventing platelet count drop in dogs undergoing cardiopulmonary bypass during 2 hours. Twenty-two heparinized dogs were divided into three groups, one control group (n = 9) not treated, one group treated with a low dose of Ro 44-9883 (145 micrograms/kg intravenously, n = 6), and one group treated with a high dose of Ro 44-9883 (870 micrograms/kg intravenously, n = 7). In the control group, platelet counts declined to 53% +/- 15% of initial levels at the start of cardiopulmonary bypass and remained lower than 80% of initial levels during follow-up. Platelet count drop was completely prevented in the Ro 44-9883 high-dose group, whereas it was only partially prevented in the low-dose group. Blood loss was similar in the three groups despite the fact that bleeding times were longer in the Ro 44-9883 high-dose group than in the control group. We conclude that Ro 44-9883, together with heparin as a standard anticoagulant, is highly effective in preventing platelet count drop during cardiopulmonary bypass without causing excessive bleeding.

Acetates↗
PubMed1993

Effects of heparin, aspirin and a synthetic platelet glycoprotein IIb-IIIa receptor antagonist (Ro 43-5054) on coronary artery reperfusion and reocclusion after thrombolysis with tissue-type plasminogen activator in the dog.

Adjuncts to thrombolytic agents have improved coronary patency and prevented early reocclusion after thrombolysis in acute myocardial infarction. The aim of this study was to compare in a canine thrombolysis model the effects of Ro 43-5054 = N-(N-[N-(p-amidinobenzoyl)-beta-alanyl]-L-alpha-aspartyl)-3- phenyl-L-alanine-trifluor-acetate, a new glycoprotein IIb-IIIa receptor antagonist with aspirin or heparin. Six groups of 10 dogs each were studied. A platelet-rich coronary thrombus was induced in open-chest dogs by electrical stimulation. In addition to recombinant tissue-type plasminogen activator (30 micrograms/kg.min during 60 min), the dogs received 1) saline, 2) heparin 200 U/kg + 50 U/kg.hr i.v., 3) aspirin 10 mg/kg i.v., 4) heparin+aspirin, 5) Ro 43-5054 (3 micrograms/kg.min) and 6) heparin+Ro 43-5054. The overall reperfusion rate was 70% (range, 60-90%) and comparable in all the six groups. During the 120-min observation period, episodes of reocclusion were observed in the absence of antiplatelet therapy (group 1 and 2) irrespective of heparin treatment. Aspirin prevented coronary reocclusion in half of the reperfused dogs (group 3 and 4). However, after reinforcement of the thrombogenic stimulus, 80% of the reperfused dogs treated with aspirin showed reocclusion, whereas none of them reoccluded when treated with Ro 43-5054. Thus, inhibition of platelet activation by the selective, nonpeptidic glycoprotein IIb-IIIa receptor antagonist Ro 43-5054, although without effect on the time to reperfusion, better protected than aspirin against early reocclusion after thrombolytic therapy.

Amino Acid Sequence↗
PubMed1992

Left ventricular outflow tract obstruction in patients with hypertrophic cardiomyopathy: increase in gradient after exercise.

To define alterations in the magnitude of the left ventricular outflow tract gradient during supine exercise, 10 patients with hypertrophic obstructive cardiomyopathy were studied under basal conditions and during exercise and recovery with simultaneous invasive hemodynamic measurements, particularly of the peak to peak systolic pressure gradient across the left ventricular outflow tract. Basal outflow pressure gradient ranged from 0 to 89 mm Hg (average 37.4 +/- 9.6). No increase was observed during 5 min of exercise (average 29.6 +/- 10 mm Hg, range 0 to 91; p = NS), even though arterial blood pressure, heart rate and cardiac index increased significantly in association with a decrease in peripheral vascular resistance. However, a rapid and highly significant increase in left ventricular outflow gradient occurred after exercise was completed (average 83.5 +/- 11.4 mm Hg, range 10 to 130; p less than 0.001), while arterial blood pressure, heart rate and cardiac index closely approached basal levels and total peripheral vascular resistance increased. In contrast to previous assumptions regarding the behavior of the outflow gradient in hypertrophic cardiomyopathy, obstruction to left ventricular outflow increases after rather than during supine exercise. Rapid changes in preload during recovery represent the most likely explanation for the postexercise development of outflow obstruction. New considerations regarding the mechanisms of sudden cardiac death and the therapeutic approach in patients with hypertrophic cardiomyopathy may result from this pathophysiologic observation.

Adult↗
PubMed1992

Specific inflammatory cytokines regulate the expression of human monocyte 15-lipoxygenase.

Arachidonate 15-lipoxygenase (arachidonate:oxygen 15-oxidoreductase, EC 1.13.11.33) is a lipid-peroxidating enzyme that is implicated in oxidizing low density lipoprotein to its atherogenic form. Monocyte/macrophage 15-lipoxygenase is present in human atherosclerotic lesions. To pursue a basis for induction of the enzyme, which is not present in blood monocytes, the ability of relevant cytokines to regulate its expression was investigated. Interleukin 4 (IL-4), among 16 factors tested, specifically induced 15-lipoxygenase mRNA and protein in cultured human monocytes. Interferon gamma and hydrocortisone inhibited this induction. High-performance liquid chromatography analysis of lipid extracts from IL-4-treated monocytes detected 15-lipoxygenase products esterified to the cellular membrane lipids, indicating enzymatic action on endogenous substrates. Stimulation of IL-4-treated monocytes with calcium ionophore or opsonized zymosan A enhanced the formation of 15-lipoxygenase products. These data identify IL-4 and interferon gamma as physiological regulators of lipoxygenase expression and suggest an important link between 15-lipoxygenase function and the immune/inflammatory response in atherosclerosis as well as other diseases.

Arachidonate 15-Lipoxygenase↗
PubMed1992

Effects of chronic aortic coarctation on atherosclerosis and arterial lipid accumulation in the Watanabe hereditary hyperlipidemic (WHHL) rabbit.

The effects of high blood pressure on atherosclerosis were examined in the Watanabe heritable hyperlipidemic (WHHL) rabbit. For this purpose, the subdiaphragmatic aorta of rabbits was partially ligated (coarctation) to increase blood pressure. Atherosclerosis was assessed 4 months later by morphometric analyses and quantitation of arterial lipids. Results were compared to control WHHL rabbits with matched plasma triglycerides and cholesterol levels. A marked increase in atherosclerotic lesions was observed in the thoracic aorta of the hypertensive rabbits without qualitative changes in its morphometric features. The cross sectional area of the atherosclerotic plaques of the ascending and descending aorta in the hypertensive rabbits was two- and six-times larger than in normotensive rabbits, respectively. Lesions represented 12.0% +/- 3.5% of the total medial cross sectional area of the descending aorta of normotensive rabbits, versus 45.0% +/- 5.7% in hypertensive rabbits. No lesions were observed downstream of the coarctation in hypertensive rabbits, nor in the normotensive rabbits. Accumulation of cholesterol and choline-containing phospholipids in the descending aorta of hypertensive rabbits was increased 3.2- and 1.5-fold, respectively, when compared to normotensive rabbits. Hypertension did not change the unesterified cholesterol/total cholesterol and sphingomyelin/lecithin + lysolecithin molar ratios. In conclusion, chronic coarctation enhances the atherosclerotic response in WHHL rabbits in the high blood pressure compartment, and reduces the variability of this response.

Animals↗
PubMed1992

Isoproterenol impairs the rat coronary vasculature: effects of angiotensin-converting enzyme inhibition.

The purpose of the present study was to evaluate whether in addition to its myocardial effects, chronic beta-adrenergic stimulation with isoproterenol could modify the coronary vasculature. For this purpose, rats were treated for 2 weeks with isoproterenol, and the hearts were isolated for determination of the minimal coronary vascular resistance under maximal vasodilation and then perfused-fixed for morphometry of the coronary arteries. In addition, because isoproterenol stimulates the renin-angiotensin system (RAS), the effects of angiotensin-converting enzyme (ACE) inhibition on the coronary vasculature were assessed. Isoproterenol increased heart weight by 65% and minimal coronary resistance by 55%. This effect was associated with medial thickening in intermediate (32%) and large coronary arterioles (26%). Cilazapril, a long-acting ACE inhibitor, completely prevented the medial thickening induced by isoproterenol and normalized the minimal coronary resistance. We conclude that impairment of the rat coronary vasculature induced by chronic beta-adrenergic stimulation might be in part mediated by activation of the RAS.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Protective effect of cilazapril on the cerebral circulation.

The goal of an antihypertensive treatment is to prevent "end-organ" damage. Cerebral vascular complications are among the most important because they are life threatening and can occur even at an early stage of the disease. Recently, it has been shown that cilazapril can decrease the mortality of stroke-prone rats, suggesting a decrease in the incidence of strokes, which occur spontaneously in these animals. The present article reviews the different functional and morphological changes that may explain the cerebral protective effects of cilazapril, such as the normalization of cerebral vascular reserve, decrease in the media, increase in the external diameter, and normalization of the mechanics and endothelial function of cerebral arterioles. In addition, the inhibition by cilazapril of injury-induced proliferation of smooth muscle cells and the infiltration of the endothelium by macrophages could prevent the development of atherosclerosis.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Physiological asymmetry in etiolated pea epicotyls: relation to patterns of auxin distribution and phototropic behavior.

Etiolated pea seedlings require transformation of Pr phytochrome to Pfr before they display optimal phototropic response to unilateral blue light. This study investigates the possible role of auxin transport in explaining these phenomena. Labeled [2-14C]IAA applied to the intact terminal buds of dark-grown and red light-treated pea seedlings was measured 210 min later on the shaded and illuminated sides of the epicotyl as a function of direction and duration of irradiation with blue light. Totally darkened epicotyls show an asymmetry in distribution of radioactivity in the upper growth zone of the epicotyl, in favor of the side under the concave part of the apical hook. Red light, which greatly potentiates curvature toward subsequent unilateral blue light, lowers this asymmetry. Blue light directed to the epicotyl of red-pretreated plants in a plane parallel to the hook and from the side bearing the convex portion of the hook induces positive phototropic curvature as well as a surplus of radioactivity on the illuminated side of the upper epicotyl and on the shaded side of the lower growth zone of the epicotyl. Light directed to the side bearing the concave part of the hook also causes an accumulation of counts in the upper part of the lighted side but produces neither curvature of the epicotyl nor accumulation of counts in the lower shaded side. Because of this built-in physiological asymmetry in the growth zone just below the apical hook, it is difficult to explain the effects of red and blue light on curvature in terms of patterns of auxin distribution alone.

Indoleacetic Acids↗
PubMed1992

Vascular protection with cilazapril in hypertension.

Anatomical changes of arteries and arterioles secondary to hypertension explain most of the late complications of this disease. Therefore, a series of experiments was performed to characterize the vascular protective effects of cilazapril in experimental hypertension. These experiments aimed to answer three types of questions: (a) In which vascular bed is cilazapril effective? (b) Are the vascular changes induced by cilazapril associated with functional effects? (c) Is the effect of cilazapril only preventive or can cilazapril also be effective when hypertension is already present? Our results show that cilazapril is acting on nearly every vascular bed. Its vascular morphological effects (decrease of vascular hypertrophy) are associated with functional changes such as improvements of coronary or cerebral vascular reserves. Cilazapril is active either as a preventive treatment or given when hypertension is already present.

Angiotensin-Converting Enzyme Inhibitors↗