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Biomedical subjects

G Beck

Publications and source records attributed to G Beck.

At least 127 records · Page 7Linked to original sources

Comparison of betaxolol with verapamil in hypertensive patients: discrepancy between office and ambulatory blood pressures.

The purpose of this study was to compare in the individual hypertensive patient the blood pressure lowering effect of a beta-blocking agent i.e. betaxolol with that of a calcium entry blocker, i.e. verapamil. The antihypertensive efficacy of the drugs was evaluated both at the physician's office and by monitoring ambulatory daytime blood pressure using a portable blood pressure recorder (Remler M2000). Seventeen patients with uncomplicated essential hypertension (aged 35-67 years) were treated for two consecutive 6-week periods with either betaxolol, 20 mg/day or a slow-release formulation of verapamil, 240-480 mg/day. The sequence of treatment phases was randomly allocated and a 2-week wash-out period preceded each treatment. Both betaxolol and verapamil had a significant blood pressure lowering effect when assessed at the physician's office. However, ambulatory recorded blood pressures were significantly reduced only with betaxolol. In the presence of a physician, the best responders to betaxolol tended to be also the best responders to verapamil, whereas there was no relationship between the fall in ambulatory recorded blood pressure observed during betaxolol and the corresponding fall during verapamil administration. The blood pressure response to both betaxolol and verapamil was not related to age.

Adult↗

Effects of leukotriene C4 on pancreatic secretion and circulation in dogs.

In the present study the effects of leukotriene C4 (LTC4) on exocrine pancreatic secretion and pancreatic blood flow were determined. LTC4 given intravenously in various doses ranging from 0.35 to 2.8 nmol.kg-1.h-1 in conscious dogs caused a dose-dependent inhibition of pancreatic HCO-3 and protein responses to exogenous hormones such as secretin, cholecystokinin octapeptide (CCK-8), and bombesin and to endogenous stimulants including meat feeding and duodenal perfusion with oleate. In tests with pancreatic secretion induced by secretin plus CCK, maximal inhibition by LTC4 occurred at a dose of 1.4 nmol.kg-1.h-1 and reached approximately 70% of the control value for HCO-3 output and 45% for protein output. In tests with separate secretin- or CCK-induced secretion, maximal inhibition occurred at a dose of 1.4 nmol.kg-1.h-1 and reached 38 and 66% of the control HCO-3 and protein secretion, respectively. The same dose of LTC4 reduced the postprandial HCO-3 secretion by approximately 80% and protein output by approximately 70%. After administration of indomethacin, the pancreatic secretion declined, but the inhibitory effects of LTC4 remained unchanged. Pancreatic tissue generated two to three times more LTC4 than the gastrointestinal mucosa, and indomethacin caused further increase in this generation, suggesting that LTC4 may contribute to indomethacin-induced pancreatic inhibition. (ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗

Influence of the thromboxane synthetase inhibitor HOE 944, prostacyclin and indomethacin on reperfusion arrhythmias, cardiodynamics and metabolism in isolated ischemic rat hearts.

We investigated the influence of the thromboxane (TX) synthetase inhibitor HOE 944 (6-(5-Methylimidazol-1-yl)methyl-2-naphthoic acid-Hydrochloride), prostacyclin (PGI2) and indomethacin on reperfusion arrhythmias in isolated perfused ischemic rat hearts. HOE 944, PGI2 and indomethacin were perfused in a concentration of 1 x 10(-6), 5 x 10(-8) and 1 x 10 (-6) mol/l respectively (in vitro). In another set up rats were pretreated p.o. with a daily dose of 30 mg/kg for 7 days (ex vivo). Acute regional myocardial ischemia was induced in isolated working rat hearts by occlusion of the left coronary artery. Reperfusion commenced upon release of this occlusion which was invariably associated with ventricular fibrillations (VF). Perfusion with 1 x 10(-6) mol/l HOE 944 did not affect these arrhythmias. In contrast hearts from HOE 944 pretreated rats were protected against fibrillations (p less than 0.01). PGI2 perfusion was also protective against VF (p less than 0.01) whereas indomethacin perfusion aggravated VF. In the ischemic period cardiodynamics like left ventricular pressure (LVP), dp/dt max and coronary flow (CF) were improved in HOE 944 pretreated rat hearts. In the venous effluent the enzyme activities of lactate dehydrogenase (LDH) and creatine kinase (CK) as well as lactate production were decreased in the ischemic and reperfusion period. Myocardial tissue levels of ATP were distinctly increased and lactate levels decreased in HOE 944 pretreated rats, whereas glycogen and creatine phosphate did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A new model for studying bacterial adherence to the respiratory epithelium.

The frog palate mucosa was used as a new model for studying bacterial adherence to the respiratory epithelium. The main advantage of this model is that the mucus blanket, normally present on airway mucosa, can be preserved during the assays. The adherence of radiolabeled pneumococci to mucus-coated mucosa was five times higher (P less than 0.001) than the adherence to mucus-depleted mucosa. In the latter case, bacteria were never seen attached to ciliated cells but could be detected on small remaining patches of mucus. These results demonstrate that respiratory mucus plays a major role in bacteria-mucosa interactions.

Animals↗

Synthesis and biological activity of new leukotriene antagonists (racemates and enantiomerically pure compounds).

Two series of structural analogues of leukotrienes C4, D4 and E4 (LTC4, LTD4, LTE4) were prepared. The compounds were evaluated for their ability to antagonize leukotriene-induced contractions of guinea pig lung strips. In comparison to FPL-55712, compounds 1a and 2h were more potent antagonists against LTC4 (2- and 3fold, respectively) and LTD4 (6- and 60fold respectively). Moreover, in vivo compounds 1a and 2h exhibited antagonism against leukotrienes (C4, D4, E4) and PAF, the most potent mediators in bronchial asthma. 2h also showed antagonistic activity when tested by inhalation.

Animals↗

Vasoactive and metabolic effects of leukotriene C4 and D4 in the intestine.

The effects of intra-arterial administration of leukotrienes (LT) C4 and D4 upon total intestinal and mucosal blood flow, intestinal oxygen consumption and motor activity were measured in anesthetized dogs. Blood flow to a segment of distal ileum was measured with an electromagnetic blood flow meter, and arteriovenous oxygen difference (AVO2) was determined spectrophotometrically. Oxygen consumption was calculated as the product of AVO2 and total blood flow. Intestinal mucosal blood flow was determined by a local H2-gas clearance technique. Motor activity was monitored on the basis of changes in intraluminal pressure. LTC4 and LTD4 induced a dose-related decrease in total intestinal blood flow, mucosal blood flow and in oxygen consumption, and an increase in intestinal motor activity. Both LT produced a redistribution of blood flow into the muscular compartment of the intestinal circulation. The results of these studies indicate that LTC4 and LTD4 are potent vasoconstrictors in the intestinal microcirculation, and that endogenous LT may contribute to the microvascular changes leading to the intestinal damage.

Animals↗

[Treatment of aluminum-induced osteopathy with desferrioxamine in dialysis-dependent renal failure].

Presenting two patients on long-term dialysis with marked osteopathy due to aluminium intoxication we described the symptoms, pathogenesis and therapy of the disease. Two patients were treated with the chelating agent desferrioxamine which lead to a striking improvement in clinical symptoms and removal of aluminium from bone. Osteopathy due to aluminium intoxication is refractory to Vitamin D and its metabolites. Using reversed osmosis in dialysis the high aluminium levels in bone result mainly from the long-term use of phosphate binders. Therapy of choice is the treatment with desferrioxamine.

Adult↗

Integrity of the C-terminal part of tyrosine aminotransferase revealed by an anti-peptide serum.

A synthetic peptide corresponding to the seven carboxy-terminal amino acids of tyrosine aminotransferase was coupled to ovalbumin or keyhole limpet haemocyanin, and the resulting conjugates were used to raise anti-peptide antibodies by immunization of rabbits. The crude sera were purified and tested for recognition of the whole enzyme by enzyme-linked immunosorbent assay and immunoprecipitation in extracts from [35S] methionine labeled hepatoma cells. Our results support the existence of an intact C-terminus. If processing takes place, it will rather occur at the N-terminus of this hepatic enzyme.

Antigen-Antibody Complex↗

C1q inhibits the expression of B lymphoblastoid cell line interleukin 1 (IL 1).

Although the existence and ubiquity of the C1q receptor is well established, its role in health and disease is largely unknown. Interleukin 1 (IL 1) is the major immunoregulatory molecule produced by macrophages and B lymphoblastoid cell lines. In this paper we present evidence that occupancy of C1q receptors by C1q on B lymphoblastoid cell lines inhibits "IL 1-like" activity, which is constitutively produced by these cells. When 5 X 10(6) Raji cells were cultured (24 hr at 37 degrees C) in the presence or absence of various concentrations of C1q (final concentration; 5 to 50 micrograms/ml) and the cellfree supernatants were analyzed for their effect on thymocyte proliferation by using the concanavalin A co-mitogenesis assay for IL 1, a statistically significant dose-dependent reduction of 3H-TdR incorporation was observed. Similar results were obtained when Daudi and Wil2WT cells were used, whereas Molt4, which is a T cell lymphoblastoid cell line, neither produced "IL 1-like" activity nor was affected by C1q. When immune complex-bound C1q was used instead of free C1q, inhibition of B cell IL 1 activity was also observed. Mixing experiments showed that Raji cells incubated with C1q released an inhibitor of IL 1-induced thymocyte proliferation. C1q alone had no effect on thymocyte proliferation in the presence or absence of human IL 1. In addition, the effect of C1q on IL 1 activity was abrogated either when the C1q was heat inactivated (56 degrees C, 60 min) or when the C1q was incubated with the cells in the presence of F(ab')2 anti-C1q. On the basis of these data, it is concluded that B cell receptor-bound C1q may play an important role in immunoregulation.

Antigen-Antibody Complex↗

Effects of leukotrienes on gastric acid and alkaline secretions.

This study was designed to determine the influence of leukotriene C4 on gastric acid and alkaline secretion. Leukotriene C4 was found to be a potent inhibitor of gastric acid secretion induced in vagally innervated and denervated portions of the stomach of conscious dogs by a variety of stimulants such as histamine, pentagastrin, and meat feeding. Leukotriene C4 was also an effective inhibitor of acid formation in the isolated gastric glands stimulated by histamine or dibutyryl cyclic adenosine monophosphate without or with addition of indomethacin, indicating that this compound acts directly on the parietal cells without mediation of endogenous prostaglandins. Leukotriene C4 was also an effective stimulant of gastric alkaline secretion. However, this effect was probably mediated by an increase in the generation of endogenous prostaglandin, as it was accompanied by an increase in the luminal release of prostaglandin E2 and indomethacin prevented both the stimulation of alkaline secretion and luminal prostaglandin E2 release by leukotriene C4.

Animals↗

Lyme disease.

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Arachnid Vectors↗

Factors interfering with the 1 mg dexamethasone suppression test in depression.

The 1 mg dexamethasone suppression test (DST) was performed in 50 depressive inpatients in order to investigate factors which might interfere with its sensitivity and specificity for endogenous depression: improvement within one week after the test, recent admission to a psychiatric ward, and weight loss. Four out of five endogenous depressive patients whose depression improved within one week after the test had normal suppression, thus supporting the assumption that normalization of the DST may precede the improvement in depression. Nonendogenous depressive patients had an accumulation of pathologic test results on the day after admission that may be due to "admission stress". However, in endogenous depressives this effect was not observed. An influence of weight loss on the percentage of suppressors and nonsuppressors was not demonstrable. It is concluded that in the evaluation of DST results time parameters should be considered to a greater degree.

Adult↗

Cysteinyl leukotrienes as mediators of staphylococcal enterotoxin B in the monkey.

The role of cysteinyl leukotrienes (LTs) in the action of staphylococcal enterotoxin B (SEB) was investigated in unsensitized monkeys using inhibitors of prostanoid synthesis and LT action and by measuring generation of LT in vivo. LY 171883, a selective LTD4/LTE4 receptor antagonist, proved highly efficient in inhibiting immediate-type hypersensitivity reactions in the skin and protecting against the emetic response provoked by SEB in a concentration-dependent manner. Inhibition of prostanoid formation by pretreatment of monkeys with indomethacin or aspirin did not influence SEB responses. Based on chromatographic and radioimmunologic analysis, the generation of endogenous cysteinyl LTs was demonstrated in vivo. The concentration of LTE4, the major biliary cysteinyl LT detected, increased ten-fold and a novel cysteinyl LT metabolite in urine indicated strongly enhanced LT generation upon challenge with SEB. Cysteinyl LTs are important mediators in the pathophysiology of SEB-induced enteric intoxication. Therefore, cysteinyl LT antagonists may be of therapeutic value in the treatment of this intestinal disorder.

Acetophenones↗

Staphylococcal enterotoxin B as a nonimmunological mast cell stimulus in primates: the role of endogenous cysteinyl leukotrienes.

The immediate-type skin reaction and the emetic response in unsensitized monkeys on challenge with staphylococcal enterotoxin B (SEB) were studied to define the role of cysteinyl leukotrienes (LTs) in the action of the toxin. LY 171883, a selective LTD4/LTE4 receptor inhibitor, antagonized SEB-induced skin reactions and emetic responses completely. Inhibition of prostanoid formation by indomethacin, however, and pretreatment with BW 755C, a dual lipoxygenase and cyclooxygenase inhibitor, did not influence these reactions. The generation of endogenous cysteinyl LTs upon intragastric SEB administration was established in vivo. There was a tenfold increase in LTE4, the major biliary cysteinyl LT, and a novel cysteinyl LT metabolite in urine occurred, indicating strongly enhanced LT generation on SEB challenge. These results provide the first evidence that cysteinyl LTs may be important mediators in the pathophysiology of SEB-induced effects, as a model for pseudo-allergic reactions.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗