Comparison of the hypotensive and diuretic effects of 1,4-dimorpholino-7-phenylpyrido[3,4]pyridazine (DS-511) and hydrochlorothiazide in Doca, renal and spontaneously hypertensive rats

The hypotensive and diuretic activities of a new diuretic, 1,4-dimorpholino-7-phenylpyrido[3,4-d] pyridazine (DS-511), were compared with those of hydrochlorothiazide (HC) in DOCA, renal and spontaneously hypertensive rats. The results obtained were: 1. During the developing stage of DOCA-hypertension the daily treatment of rats with DS-511 and HC showed significant hypotensive action. During this period the diuretic activity of both agents was clear. 2. During the equilibrium stage of DOCA-hypertension the hypotensive action of DS-511 was indistinct despite its diuretic activity. The hypotensive and diuretic action of HC was not clear. 3. In renal-hypertensive rats the daily treatment of DS-511 and HC caused significant, but weaker hypotension than that in the developing stage of DOCA-hypertension. In these animals the diuretic activity of both agents was clear. 4. In spontaneously hypertensive rats the daily treatment with DS-511 and HC exhibited a similar hypotensive and diuretic action. 5. In all three kinds of hypertensive rats the diuretic activity of DS-511 was similar to that of HC in the excretion of urine and sodium, but the former was less kaliuretic than the latter.     

Enhanced interleukin production after long-term administration of erythromycin stearate

The effects of erythromycin stearate (10 mg/kg/day) were studied on productions of interleukin (IL)-1 and -2 in mice after a long-term treatment. A 28-day treatment resulted in higher levels of IL-1 production by macrophages and of IL-2 production by splenocytes, while a 7-day treatment did not increase them. T-cell growth factor activity of IL-2 preparation prepared on day 28 of treatment as determined by HT-2 cell proliferation was reduced by about 40% in the presence of anti-murine IL-4 monoclonal antibodies, while control IL-2 activity was not reduced. Furthermore, a 28-day treatment with erythromycin stearate increased concanavalin A-induced blastogenesis of splenocytes significantly. These results suggest that long-term treatment with erythromycin stearate can stimulate host defense by increasing interleukin production.     

Complement-fixing pemphigus antibodies.

The serum of a patient with a typical case of pemphigus vulgaria contained complement-fixing intercellular autoantibodies (pemphigus antibodies). Complement-fixing pemphigus antibodies were demonstrated only during the untreated active stage of the disease and titrated lower than corresponding IgG autoantibodies, which paralleled well with the disease activity. Pemphigus lesional skin, which contained in-vivo-bound IgG, showed the capability of further binding C3 in vitro from normal human serum. It was suggested from these findings that the complement system may play an active role in pemphigus acantholysis through complement-fixing pemphigus antibodies.     

Combined treatment of tardive dyskinesia with clonidine and neuroleptics: A follow-up study of three cases for three years

Three cases of tardive dyskinesia with psychotic symptoms (one presenile psychosis; two schizophrenia) were successfully treated with both clonidine and neuroleptics for 3 years. The dyskinesia abolished or reduced by clonidine returned several months after discontinuation of clonidine. During the follow-up study, it was observed that combining neuroleptics with clonidine was superior to thioridazine, levomepromazine, or sulpiride for controlling the dyskinesia. These findings suggest that noradrenergic involvement is important in tardive dyskinesia and that other subtypes of dyskinesia might exist.     

Altered behavioral responses to intense foot shock in socially-isolated rats

Male Wistar rats were isolated immediately after weaning for 12 weeks and exposed to electric foot shock of various intensities. The shock-elicited jumping behavior was measured every ten minutes for one hr. The frequency of jumping in isolated rats was lower than that in grouped and the difference between two groups was the greatest with the most intense shock. In these experimental situations, there was no significant difference in monoamine turnover rate between the two groups while noradrenaline turnover markedly increased in both groups. Chlorpromazine suppressed the jumping in a dose-dependent manner in both groups with stronger suppression in isolated rats. Methamphetamine facilitated the jumping in grouped rats dose-dependently while the drug rather depressed it in the isolated. From these results and the behavioral similarity between the isolated and 6-hydroxydopamine treated rats under foot shock situation, it was suggested that the receptor supersensitivity of central catecholaminergic neurons was involved in the behavioral change in isolated rats.     

Clinical Response to Busramustine (KM-2210) in Chronic Lymphocytic Leukemia: A Pilot Evaluation of Estrogen Receptor in Relation to Its Therapeutic Effect

Busramustine (KM-2210), the benzoate of a 17ß-estradiol-chlorambucilconjugate,$$$ was administered to 11 patients with chronic lymphocyticleukemia (CLL) which included eight cases of B-cell CLL andthree cases of T-cell CLL. Four patients had received priorchemotherapy. Busramustine was given orally at an initial dailydose of 50–100 mg continuously, and the dose was modifiedaccording to hematological improvement. Two cases of B-cellCLL achieved clinical complete responses, six cases includingtwo of T-cell CLL and four of B-cell CLL achieved partial responsesand one case of B-cell CLL achieved improvement. The partialand complete response rate was 72.7%. Four patients showed estrogenreceptor activity of CLL cells ranging from 3.5 to 57.5 fmol/mgcytosol protein, but there seemed to be no correlation betweenthe estrogen receptor activity of the CLL cells and the therapeuticeffects of busramustine. Toxic effects included diarrhea (2/11)and estrogen-related symptoms including breast pain (4/11),genital bleeding (2/5), gynecomastia (2/6) and loss of libido(2/6). The findings of this preliminary study suggest that busramustineis effective in the treatment of CLL, irrespective of the presenceof the estrogen receptor.