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Biomedical subjects

E Iván

Publications and source records attributed to E Iván.

At least 19 recordsLinked to original sources

Analysis of cataract and keratotic damage induced by 4-diethylaminoethoxy-alpha-ethyl-benzhydrol (RGH-6201) in rats.

RGH-6201 (4-diethylaminoethoxy-alpha-ethyl-benzhydrol) in the first dose-range finding study on rats produced severe, irreversible ophthalmic damage. The underlying mechanism was studied in a series of experiments with daily doses of 50, 100 and 200 mg/kg in rats by gavage. Lenticular damage appeared as a moderate nuclear degeneration during Week 4 of treatment with 50 mg/kg RGH-6201. This could be detected in the isolated eye and in histological examination but not by ophthalmoscopy. Keratitis and iridocyclitis developed about the 2nd week of treatment followed by epithelial proliferation in the lens under the anterior capsule in the higher dose groups. Nuclear and total cataract developed from the 2nd week on in the 200 mg/kg group and from the 3rd week on in the 100 mg/kg group. Further gross pathological changes in the high dose group were characterized by marked hairloss, desquamation in the cardiac region of the stomach and diarrhoea. It has to be emphasized that fine lenticular changes were unrelated to keratitis and iridocyclitis. Since other benzhydrol derivatives such as 2,5-dimethyl-alpha-ethylbenzhydrol and 3-trifluoro-methyl-alpha-ethyl-benzhydrol do not induce similar changes, the diethyl-amino-ethoxy group was assumed to be the toxic part of the molecule. Intravenous studies with equimolar doses of diethyl-aminoethanol revealed no similar symptoms.

Alopecia↗

Preclinical toxicity studies with two thymopoietin-like peptides.

Differentiation of T-lymphocytes is regulated by thymopoietin, a 49 amino acid polypeptide chain. The site of immunological activity is in the 32-36 (Arg-Lys-Asp-Val-Tyr) fragment. This pentapeptide can be reduced to a tetrapeptide (RGH-0206: Arg-Lys-Asp-Val) and further to a tripeptide (RGH-0205: Arg-Lys-Asp) which still retains immunological activity. To prepare Phase I and II clinical trials preclinical toxicity studies were duly performed. Mice, rats and dogs tolerated a single 1000 mg/kg dose i.v. without any symptom. In a 14-day i.v. test on Lati:Han:WISTAR rats daily doses of 10,25, 62.5, 150, 400 and 1000 mg/kg of either test compound were tolerated without symptom or damage. In a 28-day i.v. toxicity test on Wobe:BEAGLE dogs given daily doses of 6, 20 and 60 mg/kg of either test compound, no adverse reaction occurred. The low toxicity of both RGH-0205 and RGH-0206 are probably attributable to their short half-life, as half-life of the pentapeptide fraction is less than 30 sec in humans. It was concluded that the planned clinical dose of 1 mg/kg i.v. was safe for both peptides for short-term administration.

Animals↗

Lysosomes in anterior pituitary corticotrophs of the rat. A combined immunocytochemical and enzyme cytochemical study.

E600 resistant non-specific esterase activity or acid phosphatase activity were localized in corticotrophic cells identified by postembedding immunocytochemistry (PAP of protein A-immunogold techniques). The lysosomal system of this cell type consists of dense bodies, of a population of small lysosomes mostly situated at the cell periphery in the vicinity of secretory granules as well as of tubular structures. These latter were located either in the central part of the cytoplasm and probably belonged to the Golgi apparatus or at the cell periphery, partly in the extensions. Small lysosomes occurred to be in continuity with enzyme-containing tubules. In a few structures lysosomal enzyme activity and ACTH immunoreactivity overlapped. Some autophagic vacuoles seemed to contain secretory granule matrix. It is suggested that the concept of crinophagy can be extended to the corticotrophs, though the lysosomal system may be involved in the specific function of this cell type by other mechanisms as well.

Acid Phosphatase↗

[Treatment of urinary tract infections after prostatectomy].

Patients subjected to transvesical prostatectomy were given before and after the operation Nebcin (Tobramycin) intramuscularly in daily doses of 160 mg for 8 days to prevent infections of the urinary tract which develop almost without fail after operations of this type. The urine of the patients participating in the trials was sterile before operation. Two hours before the operation the patient was given his full daily dose and the serum and urine levels, as well as the concentration of the antibiotic in the tissue were determined. The removed organs were processed under aseptic conditions. Bacteriological assay ensured the measurement of the biologically effective quantity of the drug, in contrast to chemical methods. The 18-hour slanting agar culture of the strain of the species susceptible to the antibiotic under investigation was used. The optical density of the suspension of the culture washed with physiological saline was photonephelometrically adjusted to that of a standard barium sulphate suspension. Compared to the controls the results indicate that the pre- and postoperatively administered antibiotic has a favourable effect on the healing of the wound, and on the progress of the postoperative phase.

Anti-Bacterial Agents↗

Bacteriological, clinical, and pharmacological investigations with tobramycin in patients with serious urinary tract infection.

In studies of tobramycin an excellent effect was noted against many strains of bacteria of the family Enterobacteriaceae and of Pseudomonas aeruginosa and Staphylococcus derived from clinical sources. When the susceptibility of the strains to tobramycin was compared with susceptibility to other aminoglycoside antibiotics, tobramycin was clearly the most effective antibiotic of this group. Therapy of chronic urinary tract infection with tobramycin resulted in good clinical effects with no (or only slight) adverse reactions. When the parameters of recovery in patients treated with tobramycin were compared with those in other patients who had the same diseases but were treated with gentamicin, tobramycin yielded clinical results that were as good as (and occasionally better than) those produced by gentamicin. Studies of the pharmacokinetics of tobramycin showed a high rate of absorption from the muscles, a high rate of renal excretion, and effective therapeutic concentrations (higher than the minimal inhibitory concentration for the infecting strains) in renal tissue homogenates.

Adolescent↗