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Biomedical subjects

J Ahrens

Publications and source records attributed to J Ahrens.

54 records · Page 3Linked to original sources
PubMed1984

Treatment of experimental murine candidiasis with liposome-associated amphotericin B.

Mice were challenged intravenously with Candida albicans, and then treated either with nothing (controls), amphotericin B-desoxycholate (AMB), or amphotericin B associated with liposomes (AMB-lipo). AMB-lipo permitted larger doses of amphotericin B to be given, and also appeared to have no severe toxicity in the animal model. High doses of AMB-lipo were protective, but at equal doses, AMB-lipo was not as effective as commercial AMB.

Amphotericin B↗
PubMed1984

R 51211 (itraconazole) therapy of murine cryptococcosis.

A new antifungal triazole, itraconazole (R51211), was compared with ketoconazole in treatment of murine cryptococcosis. Itraconazole is sparingly soluble in water, and must be administered orally in solvents such as polyethylene glycol. Serum concentrations are lower than those achieved with ketoconazole, but sustained for longer periods. Itraconazole was more effective than ketoconazole by MIC, but was similar to ketoconazole by minimum fungicidal concentration. Both drugs prolonged equally survival after intraperitoneal or intracerebral challenge with Cryptococcus neoformans. Tissue counts of C. neoformans were similar in mice treated with either drug. Neither drug sterilized brains of mice challenged intracerebrally. Itraconazole appears equally potent as ketoconazole, but in this model does not appear to offer any therapeutic advantage over ketoconazole.

Administration, Oral↗
PubMed1983

Pulmonary cryptococcosis in the rat.

We evaluated a rat model of pulmonary cryptococcosis. Rats immunized subcutaneously with cryptococcal antigen developed peritoneal but not pulmonary macrophage migration inhibition factor (MIF) to cryptococcal cell extract antigens. They did not develop MIF to capsular polysaccharide antigens. Conversely, when rats were immunized subcutaneously with heat-killed cryptococcus neoformans, migration inhibition factor was detected in alveolar but not in peritoneal macrophages. Finally, rats given viable cryptococci subcutaneously developed both pulmonary and extrapulmonary cell-mediated immune responses. When viable C. neoformans were administered directly into bronchi of the right lung, immunologically intact rats developed hard nodular lesions in the ipsilateral lung. These contained caseous centers with numerous cryptococci seen on histologic examination. Over the course of 9 months, the lesions shrunk and disappeared. In contrast, congenitally athymic (nude) rats developed progressive cryptococcosis with widespread dissemination. The rat appears to be a useful model for study of pulmonary cryptococcosis.

Animals↗
PubMed1982

[The renaissance of theophylline therapy].

Deeper insight into the pharmacodynamics and pharmacokinetics of theophylline during the past 10 years led to the wide-spread use of the substance in the treatment of obstructive airway diseases. The effect of theophylline can be explained by different mechanisms of action, namely increase in cAMP and prostaglandins, redistribution of calcium, and blockade of purinergic receptors. Besides the known antiobstructive activity of theophylline ethylenediamine, its influence on the respiratory muscles is an essential clinical quality. The results of pharmacokinetic studies and routine determination of theophylline levels contributed to greatly improve the efficacy of theophylline therapy. At adequate doses, theophylline or theophylline ethylenediamine in sustained-release form constitutes the most effective long-term treatment of chronic asthma today. The pharmacological properties of ethylenediamine reinforce some of the more important effects of theophylline and improve tolerance. Combining the substance with beta-sympathomimetics elicits additive effects, while side effects are kept low.

Calcium↗
PubMed1982

Pharmacokinetics of theophylline in patients following short-term intravenous infusion.

Serum theophylline concentrations after intravenous administration of a new short-term infusion (Euphyllin Kurzzeitinfusion) were measured in 50 out-patients with chronic obstructive airways disease (COAD). An intravenous infusion of theophylline ethylenediamine 480 mg (corresponding to approximately 350 mg anhydrous theophylline) in 50 ml isotonic solution was given in 20 min. Blood samples were taken beforehand and 25 to 30 min and 1, 3 and 6 h after starting the infusion. 86% of the patients had a one-hour serum level in he therapeutic range of 8.20 mg/l, and 2 h later, this was true of 64% of the patients. The short-term infusion was well tolerated, even in cases with unknown high pre-infusion serum levels. Pertinent pharmacokinetic parameters were determined, such as total body clearance, apparent volume of distribution, and half-life of elimination. Geometric mean an 95%-confidence limits, derived from the log-normal distribution of these parameters, were: Cl = 0.044 (0.018-0.190) l/h/kg ideal body weight, Vd = 0.451 (0.258-0.789) l/kg ideal body weight, and t 1/2(el) = 7.1 (2.6-19.1) h.

Adolescent↗
PubMed1982

Host defense against experimental paracoccidioidomycosis.

An experimental model for the study of paracoccidioidomycosis was established in BALB/c mice. Both normal and athymic nu/nu animals were challenged intraperitoneally and intratracheally with yeastlike cells of Paracoccidioides brasiliensis. After challenge, all immunologically intact (+/+) mice survived, whereas nu/nu mice gradually succumbed. The latter had focal peritoneal, liver, spleen, and lung lesions consisting of P. brasiliensis with inflammation, polymorphonuclear leukocytes, monocytes, and histiocytic reactions, but no granuloma formation. Thymus transplantation heightened resistance of nu/nu mice to P. brasiliensis. These studies indicate that the nu/nu mouse develops progressive lethal paracoccidioidomycosis after intraperitoneal and intratracheal challenge, and that thymus-dependent immune mechanisms mediate host defense.

Animals↗
PubMed1980

[Euphyllin retard and "exercise-induced" asthma].

In a double blind crossover experiment the protective effect of theophylline slow-releasing coated tablets (Euphyllin retard) on exercise-induced asthma has been compared with that of a placebo. Sixteen patients with bronchial asthma (mean age 23 years, range 16-49 years) who were selected in a preliminary test exhibited an FEV1 decrease greater than 15% 10 minutes after an exhausting 6 minute run on the treadmill. Euphyllin retard and placebo were given 6 hours before the exercise test. Venous blood was sampled 6 hours prior to and immediately before exercise in order to determine the plasma concentrations of theophylline by a tritium radioimmunoassay method. FEV1 was measured prior to and immediately after exercise, 10 and 20 minutes later and after a final orciprenaline inhalation. A group of 9 patients (group 1) has plasma concentrations of theophylline lower than 6.2 microgram/ml (4.8 +/- 0.9 microgram/ml), and a group of 7 patients (group 2) had concentrations higher than 10.0 microgram/ml (13.8 +/- 3.3 microgram/ml). Compared with placebo, a protective effect of Euphyllin retard could be observed in group 2 only (p < 0.025). In group 1 the asthma protection was indistinguishable form that of placebo. Hence, plasma concentrations higher than 10 microgram/ml appear to be required to protect asthmatics from exercise-induced asthma. Although in some patients an effective concentration can be achieved by the recommended dose of one tablet of Euphyllin retard (350 mg aminophylline) every 12 hours, the importance of measuring plasma concentrations must be emphasized in view of the variable absorption and elimination of theophylline. Side effects may occur at concentrations higher than 15 microgram/ml.

Asthma↗
PubMed1980

[The effect of aminophylline (Euphyllin) on the mechanics of breathing and the gaseous exchange in persons with bronchial asthma (author's transl)].

The physiological effect of intravenous application of aminophylline on the mechanics of breathing and the gaseous exchange in persons with bronchial asthma was studied in 7 out-patients before, during and up to 90 minutes after intravenous injection of 0,48 g of Euphillin, and the data were related to the respective serum levels of the drug. The patients suffered from long-standing bronchial asthma, generally associated with moderate airways obstruction. The bronchodilating effect of Euphyllin could be substantiated for the whole time of the trial solely in respect of the changes in oscillatory impedence; the other parameters showed only temporary changes which had disappeard by the end of the trial although the serum levels of aminophylline were in the therapeutic range (mean +/- SD: 12,5 +/- 3,0 microgram/ml). The data indicate that in some patients with bronchial asthma the effect of Euphyllin on lung function is unpredictable. The suggestion is made to measure the responsiveness of the patient to aminophylline by means of simple lung function tests in order to decide whether or not other bronchodilatory substances should be aded to the therapy.

Adult↗
PubMed1977

[Theophylline blood levels after administration of Euphyllin retard (author's transl)].

The plasma theophylline concentration gradually increases after oral administration of Euphyllin retard, followed by a slower fall, than is the case after Euphyllin tablets have been taken, in which case maximal theophylline levels are reached 1 1/2 hours after administration. When Euphyllin retard is given, one to two tablets (350-700 mg) eight or twelve hours apart, there is a progressive rise of theophylline plasma levels to a plateau. This plateau can be maintained and is dependent upon dosage and the half-life of theophylline, which varies amongst individuals. Patients with obstructive airway disease treated with one tablet of Euphyllin retard every twelve hours for several weeks had a mean plasma theophylline level of about 6 microng/ml. In these patients the airway resistance, measured by body-plethysmography, improved by about 30%, without any side-effects. Six and twelve hours after administration of two tablets of Euphyllin retard the mean plasma concentration was 13 and 9 microng/ml, respectively. About half the patients receiving the larger dose of two tablets every twelve hours had gastro-intestinal or CNS disturbances. Long-term administration of Euphyllin retard provides a constant blood level of the drug.

Adolescent↗
PubMedDate not supplied

Interaction of rifampin with other antifungal agents in experimental murine candidiasis.

A murine model of systemic candidiasis was used for evaluation of the interaction of rifampin with ketoconazole and amphotericin B. In vitro studies with a clinical isolate of Candida albicans showed that rifampin modestly potentiated the antifungal activity of both of these drugs. When mice were challenged iv with C. albicans, therapy with rifampin plus ketoconazole or rifampin plus amphotericin B significantly reduced counts in kidney tissue from levels in untreated controls. However, rifampin plus amphotericin B was no more effective than amphotericin B alone, and rifampin plus ketoconazole was no more effective than ketoconazole alone. In challenges with lethal numbers of organisms, amphotericin B or ketoconazole alone increased the rate of survival from 0% to approximately 50%, and the addition of rifampin to the regimen conferred no further benefit. Therefore, the use of rifampin with either of these antifungal agents resulted in minimal, if any, increase in efficacy.

Animals↗