Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells.

Histone deacetylases (HDACs) play important roles in transcriptional regulation and pathogenesis of cancer. Thus, HDAC inhibitors are candidate drugs for differentiation therapy of cancer. Here, we show that the well-tolerated antiepileptic drug valproic acid is a powerful HDAC inhibitor. Valproic acid relieves HDAC-dependent transcriptional repression and causes hyperacetylation of histones in cultured cells and in vivo. Valproic acid inhibits HDAC activity in vitro, most probably by binding to the catalytic center of HDACs. Most importantly, valproic acid induces differentiation of carcinoma cells, transformed hematopoietic progenitor cells and leukemic blasts from acute myeloid leukemia patients. More over, tumor growth and metastasis formation are significantly reduced in animal experiments. Therefore, valproic acid might serve as an effective drug for cancer therapy.

HIV induces modulation of functionally important cellular antigens.

Infection of T lymphoblastoid CEM cells with the IIIB isolate of HIV-1 results in modulation of the expression of several cellular antigens in addition to the CD4 molecule. The intercellular adhesion receptor LFA-1 (CD11a/CD18) and HLA-DR are markedly induced in the cytoplasm and at the cell surface, and the CD7 antigen is down-regulated, being virtually undetectable by sensitive immunocytochemical techniques in the infected cell population. These modulatory effects are to some degree dependent on the virus isolate examined, as the CBL-1 British isolate did not induce comparable phenotypic changes in the CEM cell line. Furthermore, these effects are not reproduced by recombinant gp120 (IIIB isolate) or p24 added exogenously to uninfected CEM cells. The CD7 molecule appears to play a regulatory role in T cell proliferation, and the LFA-1 integrin molecule is involved in a wide range of immunologically important cell-cell interactions, as well as HIV-induced syncytium formation. The possible contributions of such effects to the pathogenesis of HIV infection are considered.

Influence of different experimental recreation treatments on sympathoadrenergic and metabolic regulation mechanisms in repeated exercises.

The influence of different recreation treatments on the sympathoadrenergic regulation, heart rate, mean blood pressure, plasma lactate, and glucose levels was investigated in a study in which the 1000 m distance was performed twice by top middle- and long-distance runners. Between the two runs, executed three times in an interval of 1 week, different regeneration strategies such as active or passive recreation as well as progressive muscle relaxation (PMR) with cognitive skill (Cl) were applied. The best running times in the second run were achieved after the PMR with Cl. After this treatment heart rate (HR) and mean arterial blood pressure (MBP) were not higher than in the other forms of regeneration, although the norepinephrine (NE) and epinephrine (EPI) increase was significantly higher after the second run compared with other treatments. The lactate and glucose levels in plasma were significantly higher after PMR with Cl than after active and passive regeneration. After the recovery period both metabolites decreased faster after PMR with Cl. The percentage of catecholamine sulfates of the total amount decreased after the first and the second run without significant differences between the three recreation treatments.

Laboratory investigations in patients with generalized psoriasis under oral retinoid treatment. A multicenter study of computerized data.

Numerous laboratory parameters were examined 235 patients with generalized psoriasis treated orally with retinoid and in 35 patients treated topically with anthralin as control. Computer evaluation of the obtained data revealed statistical trends to elevation of the total serum bilirubin level and increasing number of blood monocytes after long-term oral treatment. No other statistically significant changes of the laboratory data were found. Particularly, the liver function tests (transaminases, prothrombin and alkaline phosphatase) showed no significant alterations. Only in a few cases did the retinoid compound have an influence on the GPT and GOT levels. The reasons for this individual sensitivity to the drug remain unknown. No significant alterations were found in the control group treated topically with anthralin.

[Clinical experiences with terracortril ointment and cream]. / Klinische Erfahrungen mit Terracortril Salbe und Creme

The results of a clinical trial using a new preparation of Terracortril ointment and Terracortril cream without preservatives are reported. Apart from oxytetracycline 30 mg/g and 10 mg hydrocortisone alcohol/g, each drug contains polymyxin B 10,000 I.U./g. Of a total of 85 patients with primary and secondary pyodermias, 41 were completely or almost completely cured after application of ointment or cream respectively, 13 were largely, and 31 cases satisfactorily improved (see tables 1 and 2). The bacteriological findings are discussed. No skin irritations such as contact dermatitis were observed.

Serum IgE-concentrations in patients with contact sensitization.

In 123 patients with contact sensitization (cs), of whom 23 had positive histories of atopy and/or positive prick tests (csa), the serum IgE-concentrations were determined and the following results were obtained: 1. A remarkable dispersal of IgE-concentrations was noted in cs--patients (1-3080 U/ml); 12% of them displayed IgE-concentrations of more than 1000 U/ml, even though they had no histories of clinical manifestations of atopy, liver of kidney diseases, or parasitic infestations. Their mean IgE-value of 396 U/ml +/- 60 differed considerably from the one of a comparable control group of healthy individuals. No statistically significant differences were noted between the IgE-levels, the age of our patients, the type and number of contact allergens, and the duration of skin lesions. 2. On an average, there were higher IgE-levels noted in cases of acute and extensive skin lesions than in cases of subacute to chronic, localised skin lesions. Controls of the serum IgE-concentrations and histologic examinations by means of immunofluorescence suggested that, depending on the individual patient, skin lesions might lead to an (unspecific?)activation of IgE-synthesising round cells. 3. In csa-patients with sensitization to metal, the skin lesions were of localised subacute to chronic character, while skin lesions of acute and extensive character were exceptional (5.9%).