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Biomedical subjects

H Hoffmann

Publications and source records attributed to H Hoffmann.

At least 217 records · Page 12Linked to original sources

Conditioning of aversion to alcohol orosensory cues in 5- and 10-day rats: subsequent reduction in alcohol ingestion.

Two experiments examined in 5- and 10-day-old rat pups the impact of alcohol olfactory aversions upon subsequent alcohol intake. In Experiment 1 it was observed that at both ages, animals given a single pairing of alcohol odor and LiCl subsequently consumed less alcohol than those in any of 4 control conditions (alcohol odor unpaired with LiCl, alcohol odor exposure, lemon odor paired with LiCl, and untreated animals). In Experiment 2, pups of both age groups were given LiCl following exposure to alcohol odor, the infusion of an alcohol solution or both stimuli simultaneously. Rats given explicitly unpaired presentations of the different conditioned stimuli and internal malaise served as controls. It was observed that equivalent aversions to alcohol ingestion were expressed whether the infants had experienced the alcohol odor, the alcohol infusion, or both, paired with toxicosis. These experiments extend the ontogenetic spectrum of circumstances in which olfactory experiences affect subsequent ethanol ingestion and also may indicate an early nondifferentiated processing of odorant and gustatory cues arising from an ethanol stimulus.

Aging↗

Overproduction of the proFhuA outer membrane receptor protein of Escherichia coli K-12: isolation, properties, and immunocytochemical localization at the inner side of the cytoplasmic membrane.

The fhu operon of Escherichia coli K-12 comprises four genes, termed fhuA,C,D,B, which are involved in the uptake of iron-hydroxamate compounds. The fhuA gene encodes the outer membrane receptor protein. Cells that contained three copies of the fhuACD fragment on the thermoamplifiable plasmid pHK232 accumulated at 37 degrees C large amounts of the proFhuA protein. Most of the overproduced proFhuA protein was not translocated into the outer membrane but instead precipitated at the cytoplasmic side of the inner membrane, presumably at the sites of synthesis. Despite inhibition of export proFhuA synthesis continued. The precipitate formed was sedimented by centrifugation at 8,000 x g. The proFhuA protein could be solubilized in 1% sodium dodecyl sulfate. Replacement of sodium dodecyl sulfate by Triton X-100 resulted in a proFhuA protein which exhibited 10% of the phage T5 binding activity of renatured mature FhuA protein. Binding of the phage T5 was inhibited by the FhuA-specific ligands ferrichrome, albomycin and colicin M. Limited proteolysis of the isolated pro- and mature form of the FhuA protein with trypsin yielded similar oligopeptide patterns. Addition of ferrichrome affected trypsin cleavage of both proteins in the same way. The common proteolytic intermediates together with phage inactivation indicate a similar conformation of the pro- and mature form.

Bacterial Outer Membrane Proteins↗

Results of the Austrian celiprolol postmarketing surveillance study.

This study was initiated to assess the efficacy and safety of celiprolol in a large number of hypertensive patients. Patients received a once-daily dose of 200 mg celiprolol for the first 3 weeks. If blood pressure was not lowered satisfactorily, the investigator was asked to raise the dose to 300 mg celiprolol or add a diuretic for the next 3 weeks. The study included 2,694 patients, 2,311 of whom were evaluable over a period of 3 weeks, 1,876 over 6 weeks. On admission 10% had isolated systolic hypertension, 38% mild diastolic hypertension, 35% moderate diastolic hypertension, and 17% severe diastolic hypertension. Concomitant diseases were diabetes mellitus, chronic obstructive airway disease, and peripheral arterial disease. BP was lowered in patients with hypertension of all degrees of severity. There was no obvious relation between efficacy and age or with duration of disease. Only 229 patients received 300 mg celiprolol; 223 patients additionally received a diuretic. Heart rate decreased by a mean of 8 beats/min and was lowered mostly in patients with tachycardia. In no case did heart rate fall below 50. Side effects were rare and in most cases not serious. Treatment was discontinued owing to suspected adverse effects in 58 patients (2.15%). In conclusion, celiprolol administered for up to 6 weeks appeared to be safe in the management of hypertension.

Celiprolol↗

The effect of the cardioselective beta blocker celiprolol on pulmonary function in asthmatic patients.

The influence of single oral doses of 200 mg celiprolol, 100 mg atenolol, and 200 mg metoprolol on airway resistance (Raw) FEV1, VC, and MEF 50 was studied in a randomized double-blind crossover trial. Eighteen patients with hypertension and asthma, 14 men and 4 women, aged 43-75 years, took part. Pulmonary function tests were performed in the morning before treatment and 2 and 5 h after each treatment in the whole-body plethysmograph. The use of bronchodilators was not allowed during the 3 days. There was no significant change in airway resistance, FEV1, and MEF 50 after celiprolol and a slight increase of vital capacity at 2 h. After atenolol there was a decrease of FEV1 and MEF 50 at 5 h. Metoprolol caused an increase in resistance at 2 and 5 h and a fall in FEV1, VC, and MEF 50 at 2 and 5 h. Two patients required bronchodilator therapy after metoprolol and were excluded from evaluation. We conclude that celiprolol appears to be a safe drug in the treatment of asthmatic patients.

Adrenergic beta-Antagonists↗

Preparation of the FhuA (TonA) receptor protein from cell envelopes of an overproducing strain of Escherichia coli K-12.

A rapid and simple method for purification of the FhuA receptor protein from cell envelopes of a FhuA-overproducing strain of Escherichia coli K-12 was developed. The overproduction of FhuA was programmed by the thermoamplifiable plasmid pHK232, which carried the fhuACD genes of pLC19-19 of the Clarke and Carbon collection. At low temperature (27 degrees C), pHK232 specified the overproduction of FhuA to levels comparable to those of major outer membrane proteins OmpF, OmpC, and OmpA. The amount of these proteins in the outer membrane was reduced along with overproduction of FhuA. Upon runaway replication of pHK232 at 37 degrees C, the precursor of the FhuA protein, proFhuA, was also accumulated in the cell envelope in amounts similar to FhuA. For extraction of the FhuA protein, crude cell envelopes were washed with 2% Triton X-100-6 M urea to remove less tightly bound proteins. Then FhuA but not proFhuA was solubilized by treating Triton X-100-urea-washed membranes with 1% octylglucoside-1 mM EDTA. This procedure yielded FhuA protein free from other membrane proteins. The amount of lipopolysaccharide and phospholipids was low and ranged from 5 to 15% and 10 to 25% of the weight of the FhuA protein, respectively. As shown by direct inactivation and by competition assays, the isolated FhuA protein retained receptor activity for ferrichrome, albomycin, colicin M, and phages T5 and T1.

Bacterial Outer Membrane Proteins↗

[Uricosuric action of a new beta receptor blocker-diuretic drug combination].

The influence of a once daily dose of 200 mg celiprolol alone and in combination with 12.5 mg chlorthalidone on uric acid and electrolyte metabolism was investigated in 22 hypertensive patients with gout in a randomized trial. All patients were treated with allopurinol and diet. A four weeks treatment with celiprolol (11 patients) showed no influence on uric acid metabolism, electrolytes, blood glucose, cholesterol and triglycerides. Under treatment with celiprolol plus chlorthalidone (11 patients) only a small rise in serum uric acid was observed after four weeks but at the same time uric acid clearance and excretion increased significantly. There was no obvious change in serum electrolytes but an increase in sodium, potassium and chloride urine excretion. Serum uric acid, uric acid clearance and excretion decreased during a 6 months treatment period. A small decrease in cholesterol and triglycerides was observed. Blood pressure decreased in both treatment groups but there was only a small change in heart rate.

Adrenergic beta-Antagonists↗

[Treatment of hypertension with a new beta blocker-diuretic combination under long-term control].

161 hospitalized hypertensive patients of all degrees of severity were treated with a dose of once daily 200 mg celiprolol for 3 weeks. The data of 143 patients were evaluated. After 3 weeks of therapy with 200 mg celiprolol 67,8% of the patients showed to be responders. 42 non responders were treated under double blind conditions for the following 3 weeks with 2 different dosages of chlorthalidone (12,5 mg or 25 mg CT) in combination with 200 mg celiprolol once daily. After 3 weeks of therapy 80,9% of the patients showed a satisfying reduction of blood pressure. There was no difference in terms of the extent of blood pressure reduction between the 2 combination treatment groups. A total of 73 patients who responded to celiprolol monotherapy or one of the combination therapies were treated up to 12 months. The data of 43 patients, who came to all monthly controls, could be evaluated. During the whole period of treatment a constant reduction of elevated blood pressure levels was obtained under treatment with 200 mg celiprolol or in combination with 12,5 mg or 25 mg CT. There was no negative influence on laboratory parameters under celiprolol or combination (12,5 mg CT) therapy. There was a slight increase of uric acid and in 3 cases a decrease of serum potassium under combination therapy with 25 mg CT.

Adrenergic beta-Antagonists↗

Toxicity of the alkylating agent bendamustin.

In acute toxicity studies the maximum tolerated dose (MTD), the LD50 and the LD100 of Bendamustin were determined in rats and mice after i.v. and oral administration. In a subchronic study male rats were given Bendamustin for 28 days at oral dose levels of 5, 10, 20 or 40 mg/kg/day. Chlorambucil was used as a standard at dose levels of 1, 5 and 10 mg/kg/day. Bodyweight gain, food and water intake, hematology, clinical chemistry and histopathology were evaluated. With quantitative differences the main target organs for both compounds were the bone marrow, the kidney, the intestine and the lymphatic system. Additionally, Chlorambucil caused a significant atrophy of the testes and a slight atrophy of the pancreas at a dose of 5 mg/kg/day. In conclusion, the data obtained may be used as a base to evaluate the therapeutic range of Bendamustin compared to Chlorambucil for the oral route.

Alkylating Agents↗

[The effect of celiprolol on driving ability. An experimental psychological and comparative clinical study].

In this open study 21 hypertensive patients (WHO I + II) received after a one-week placebo period a 4-week treatment with a once daily dose of 300 mg celiprolol hydrochloride (Selectol). 21 normotensive subjects receiving placebo during the whole trial period and 20 normotensives receiving no treatment at all served as comparative groups. Prior to the treatment the hypertensive subjects showed a marked lack in acquisition and reproduction of complex visual information and their subjective emotional condition was more negative than that of the healthy subjects. A one-week placebo treatment had no influence on the parameters under test. One single dose of celiprolol had no influence on the specific capacity of driving a motor vehicle and on the emotional condition. Long-term medication of celiprolol did not impair the driving ability. The subjective emotional condition improved as desired.

Adult↗

[Transport of antibiotics to the endocardium following administration into the pericardial cavity--experimental study].

After injection of diverse antibiotics (penicillin G, tetracycline, cephalosporin) into the pericardial cavity of miniature swine higher antimicrobial activities in the subendocardial layers (mitral valve) were observed than after the intravenous application. Additional experimental studies should succeed these preliminary results. The intrapericardial application could be discussed than as a last measure in conservative treatment of the therapy-resistant endocarditis.

Absorption↗