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Biomedical subjects

K Weismann

Publications and source records attributed to K Weismann.

At least 55 records · Page 3Linked to original sources
PubMed1993

Correlation of myosin heavy chain expression in the rat with cAMP in different models of hypertension-induced cardiac hypertrophy.

Both genetically determined and artificially-induced hypertension lead to cardiac hypertrophy and shift the myosin heavy chain (MHC) expression to the beta-MHC form. The cause of this change in gene expression is unknown. To contribute to the understanding of this phenomenon, we correlated the MHC expression in the left ventricle with basal, Forskolin- and isoprenaline-stimulated adenylate cyclase activity (cAMP production of membrane fractions). We used two control rat strains [Wistar-Hagemann (WH), Wistar-Kyoto (WKY)] and several rat models of hypertension: one clip-one kidney (1C-1K), desoxycorticosterone-treated rats (DOCA), rats with reduced renal mass (RRM) and spontaneously hypertensive rats (SHR). The level of hypertension correlated positively with the degree of cardiac hypertrophy (P < 0.01) and negatively (P < 0.05) with cAMP production, e.g. the higher the degree of hypertension, the lower both basal and stimulated cAMP levels. In addition we found that the lower the basal, isoprenaline- and Forskolin-stimulated cAMP production the lower was the expression of the alpha-MHC isoenzyme (P < 0.05). Thus, our data suggest that the decreased alpha-MHC expression upon hypertension-induced cardiac hypertrophy could be mediated via decreased adenylate cyclase activity and thus decreased intracellular cAMP production.

Adenylyl Cyclases↗
PubMed1993

Conversion of acitretin to etretinate in psoriatic patients is influenced by ethanol.

Acitretin has recently been introduced to replace etretinate in the treatment of severe psoriasis due to a considerable shorter terminal half-life. The previously recommended 2-month anticonceptive period after acitretin treatment has been extended to 2 years after the detection of etretinate in certain acitretin recipients. In the present study, 10 patients with severe psoriasis were treated with 30 mg acitretin daily for 3 months. Seven patients had detectable mean steady-state plasma etretinate concentrations in the range of 2.5 to 56.7 ng/ml. Four of the patients showed teratogenic levels of plasma etretinate. Consumption of alcohol appeared to be an important contributing factor for the formation of etretinate. As judged from the dose- and body-weight-normalized AUC values (AUCcor) there was a great inter-individual variation (sixfold) in the systemic availability of acitretin. After discontinuation of therapy, the rate of elimination of both acitretin (t1/2 range 1.0 to 25.4 d) and 13-cis-acitretin (t1/2 range 1.5 to 25.7 d) was found to be related to the observed mean steady-state level of etretinate as evidenced by a longer terminal t1/2 of patients with high levels of etretinate in plasma. A mean terminal elimination half-life of etretinate was found to be 45.7 d +/- 10.6 (mean +/- SD; range 27.0 to 59.3 d). The risk of metabolic formation of etretinate in acitretin recipients makes it impossible to draw any definite conclusion with regard to recommendation of length of anticonceptive period following acitretin therapy in psoriatics. Monitoring of plasma etretinate levels in acitretin-treated fertile women is advisable.

Acitretin↗
PubMed1993

Cardiac adenylyl cyclase, beta-adrenergic receptors, and G proteins in salt-sensitive hypertension.

The present study investigated whether high salt intake (8%) in Dahl salt-sensitive and salt-resistant rats with and without hypertension produces a heterologous desensitization of cardiac adenylyl cyclase as observed in various types of hypertension and human heart failure. In membranes from Dahl salt-sensitive rats on a high-salt diet (8%) basal, isoproterenol-, 5'-guanylylimidodiphosphate-, and forskolin-stimulated adenylyl cyclase was reduced compared with the low-salt (0.4%) group and Dahl salt-resistant rats on either 0.4% or 8% sodium chloride. The activity of the catalyst was depressed, and the expression of the immunodetectable inhibitory G proteins Gi alpha was increased in Dahl salt-sensitive rats on 8% sodium chloride, whereas the density of beta-adrenergic receptors and the activity of the stimulatory G protein Gs alpha reconstituted into Gs alpha-deficient S49 cyc- mouse lymphoma cell membranes were unchanged in any condition studied. We conclude that high salt intake in salt-sensitive hypertensive Dahl rats produces hypertension, cardiac hypertrophy, and heterologous desensitization of cardiac adenylyl cyclase. The latter alteration is due to an increase of Gi alpha proteins and a depressed catalyst activity of adenylyl cyclase. The results demonstrate that heterologous adenylyl cyclase desensitization can precede the development of contractile dysfunction in later stages and can occur independently of changes in beta-adrenergic receptors.

Adenosine Diphosphate Ribose↗
PubMed1993

Atypical varicella-zoster infection in AIDS.

A case of atypical varicella zoster in a 33-year-old AIDS patient is reported. The patient had had two attacks of herpes zoster within a year and was given high-dose acyclovir several times. Thereafter he developed small keratotic pellucid papules on fingers, wrists and face, which were found to contain varicella-zoster antigen by the ELISA test. Skin biopsy showed acanthosis and lack of vesication, as is usually seen in herpes infections. The atypical varicella-like lesions persisted despite repeated doses of acyclovir but cleared temporarily when the patient was given foscarnet. We believe that the prolonged therapy may have allowed selection of acyclovir-resistant varicella-zoster strains, resulting in the atypical clinical course.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Interferon alpha-2b treatment of symptomatic chronic vulvodynia associated with koilocytosis.

In an open study with identical criteria for diagnosis, 16 female patients with typical symptoms of chronic vulvodynia associated with acetowhitening of the vestibular epithelium and koilocytosis in biopsy specimens received recombinant interferon alpha-2b 5 MIU intralesionally 3 times weekly for 3 weeks or subcutaneously 3 times weekly for 8 weeks. Three months after end of therapy, clinical symptoms had disappeared in 7 (70%) of the 10 patients treated intralesionally, compared with only one (16%) of the 6 patients treated subcutaneously. In addition, the last 3 (30%) patients in the first group had a partial response to therapy. The acetowhitening persisted in all patients. The koilocytosis remained unchanged in 13 (81%) of the 16 patients. Our results indicate that recombinant interferon alpha-2b administered intralesionally seems to be efficacious in reducing clinical symptoms in vulvodynia with suspected human papillomavirus infection but does not eliminate the infection. Subcutaneous administration had neither symptomatic nor antiviral effect. A placebo-controlled study is needed, but with our present knowledge we recommend intralesionally administered interferon as a symptomatic treatment of vulvodynia.

Adult↗
PubMed1993

Topical tromantadine in the treatment of genital herpes. A double-blind placebo controlled study.

A randomised double-blind placebo controlled trial was performed to assess the efficacy and safety of tromantadine ointment 1% in male patients with genital herpes. 45 patients with penile genital herpes of less than three days duration were randomised to local treatment with tromantadine ointment 1% or placebo (ointment base alone) five times daily up to 12 days. No difference in time of healing could be detected between the two groups (p = 1.0). Both the objective signs (vesicles, pustules, ulceration, and glandular swelling) and the subjective symptoms (itching, burning, pain and dysuria) all diminished simultaneously in the two groups.

Administration, Topical↗
PubMed1992

Role of altered G-protein expression in the regulation of myocardial adenylate cyclase activity and force of contraction in spontaneous hypertensive cardiomyopathy in rats.

OBJECTIVE: The question of this study was whether alterations in the inhibitory guanine-nucleotide binding protein alpha-subunits (G(i)alpha) contribute to alterations in adenylate cyclase regulation in hypertensive cardiomyopathy of spontaneously hypertensive rats (SHR). DESIGN AND METHODS: G(i)alpha was measured by pertussis toxin-catalysed 32P-adenosine 5'-pyrophosphate (ADP)-ribosylation and radioimmunochemically by competition of rat myocardial membrane extracts to DS 4 antiserum binding to the 125I-radiolabelled C terminus of retinal transducin alpha (125I-KENLKDCGLF). Cardiac beta-adrenoceptors, m-cholinoceptors as well as isoprenaline-, guanine-nucleotide [Gpp(NH)p]- and forskolin-stimulated adenylate cyclase activity and inotropic responses to isoprenaline and carbachol were studied in SHR and age-matched Wistar-Kyoto (WKY, control) rats. RESULTS: In native membranes of SHR there was an increase in pertussis toxin substrates, but a larger increase in the presence of non-ionic detergent Lubrol PX. The radioimmunological quantification of G(i)alpha revealed an increase in membrane extracts of SHR. In addition, myocardial beta-adrenoceptors and myocardial m-cholinoceptors were reduced in SHR compared with in WKY rats. Basal adenylate cyclase, isoprenaline-, Gpp(NH)p- and forskolin-stimulated adenylate cyclase activities were also reduced. However, in the presence of 5 mmol/l MnCl2 no differences in adenylate cyclase activities between SHR and WKY rats were detected under either condition. CONCLUSIONS: The present study shows that the amount of G(i)alpha-proteins and not only pertussis toxin substrates are increased in membranes of hypertrophic hearts from SHR without heart failure. The results obtained with pertussis-labelling depended strongly on the substrate quality of G(i)alpha. Increased G(i)alpha expression and reduced beta-adrenoceptor number might have functional relevance in the regulation of adenylate cyclase activity and force of contraction in SHR. An increase in G(i)alpha expression might play a pathophysiological role, not only in terminal heart failure, but also in hypertrophic cardiomyopathy.

Adenylate Cyclase Toxin↗
PubMed1992

Desensitization of adenylate cyclase and increase of Gi alpha in cardiac hypertrophy due to acquired hypertension.

The present study investigated whether reduced adenylate cyclase activity and an increase in inhibitory guanine nucleotide binding proteins (Gi alpha), which have been observed in the failing human heart, already occur in myocardial hypertrophy before the stage of heart failure. In membranes of hypertrophic hearts from rats with different forms of experimentally induced hypertension without heart failure (one-kidney, one clip rats, deoxycorticosterone-treated rats, and rats with reduced renal mass), basal as well as isoprenaline-, 5'-guanylylimidodiphosphate-, and forskolin-stimulated adenylate cyclase activity was reduced. The activity of the catalyst was depressed in deoxycorticosterone but unchanged in one-kidney, one clip and reduced renal mass compared with controls. The number of beta-adrenergic receptors was similar in all groups. Radioimmunological quantification of Gi alpha proteins revealed an increase by 73% in one-kidney, one clip, 67% in reduced renal mass, but only 20% in deoxycorticosterone compared with sham-operated, age-matched control rats. The increase of Gi alpha was accompanied by smaller changes of pertussis toxin-induced [32P]ADP-ribosylation of a 40-kd membrane protein. It is concluded that Gi alpha contributes to the reduced adenylate cyclase activity in cardiac hypertrophy in one-kidney, one clip and reduced renal mass and to a smaller extent in deoxycorticosterone. It is suggested that an enhanced expression of Gi alpha could occur not only in severe heart failure but also in cardiac hypertrophy and could, therefore, contribute to myocardial depression and progression of disease in heart failure. In addition, Gi alpha might represent an important regulatory mechanism for cardiac adenylate cyclase activity and thus, might play an important role in various cardiac diseases.

Adenylyl Cyclases↗
PubMed1992

Pharmacokinetics and therapeutic efficacy of retinoids in skin diseases.

The retinoids are a class of compounds that includes the natural forms and synthetic analogues of vitamin A. Isotretinoin, often referred to as a first generation retinoid, may be of considerable benefit to patients with severe, recalcitrant acne. Etretinate and acitretin, 2 aromatic compounds representing the second generation, have found their major success in the treatment of psoriasis, particularly in combination with more traditional therapies. Retinoid therapy is associated with a distinctive adverse effect profile typical of hypervitaminosis A; thus, it is especially important that fertile women undergoing retinoid therapy adhere to a contraceptive regimen. These drugs are extensively metabolised and only traces of unchanged drugs are eliminated in urine. The terminal elimination half-lives of isotretinoin, etretinate and acitretin after long term treatment are up to 20h, 120 days and 48h, respectively. Because of lack of definite correlation between plasma concentration and desired pharmacological effects, in conjunction with the very pronounced inter- and intraindividual variation in systemic availability (15 to 90%) after oral administration of these drugs, initial dosages in individual patients can only be roughly judged on the basis of the general pharmacokinetics of the agents. Later dosage adjustments should be made on the basis of monitoring of both plasma drug (and possible metabolite) concentrations, and the efficacy and tolerability of the drugs.

Drug Interactions↗
PubMed1992

The relation between lichen planus and hepatitis C: a case report.

A case of simultaneous occurrence of lichen planus (LP) and hepatitis C in the same patient is presented. The patient had received treatment with interferon alpha for her chronic liver disease, and the association between LP, hepatitis C and interferon alpha treatment is discussed.

Female↗
PubMed1990

[Zinc deficiency in a premature infant].

A premature infant with a birth-weight of 1,218 g developed severe zinc depletion about two months after birth. He had received his mother's breast-milk which was found to have a low zinc content of about 5 mumol/l. The clinical symptoms of zinc deficiency included stunted growth, catarrhal symptoms and a characteristic eczematous eruption on the face and diaper region known as acrodermatitis. Serum zinc was lowered (6.8 mumol/l) and so was serum alkaline phosphatase activity. Oral zinc sulphate supplementation, initially 22.5 mg daily and subsequently 11 mg zinc daily, had a prompt effect on the patient's well-being and the skin was restored to normal after about a week.

Humans↗
PubMed1990

[Human papillomavirus (HPV) vulvitis].

Human papilloma virus vulvitis with flat elements resembling leucoplakia may be diagnosed by application of a 5% acetic acid solution and subsequent biopsy and histological examination. The condition causes irritation with dyspareumia and is so frequent that the diagnosis and initial treatment may be undertaken by the general practitioner.

Adult↗
PubMed1990

Histopathology of acute human immunodeficiency virus exanthema.

Acute exanthema occurs in patients who are human immunodeficiency virus (HIV) positive before they become seropositive. The patients have influenza like symptoms and a macular skin rash on the upper trunk. Histopathological investigation of skin punch biopsy specimens from four patients with acute HIV exanthema showed a normal epidermis and a sparse dermal, mainly perivascular, lymphocytic/histiocytic infiltrate around vessels of the superficial plexus. Histopathological changes of the exanthema of acute HIV infection are non-specific and resemble those of other acute viral exanthema, but when both the histopathological features and the clinical picture are suggestive, the clinician should take into consideration the possibility of HIV infection.

Acquired Immunodeficiency Syndrome↗