摘要:

Summary—Effects of 4 progestogens at equal dosages (5 mg/kg/day) on lipid metabolism and plasma glucose levels of adult female rats were compared. The 4 progestogens studied were progesterone (P) by SC injection, and megestrol acetate (MEG), norethindrone acetate (NOR), and nomegestrol acetate (NOM) PO.MEG, a 17α‐hydroxyprogesterone derivative, induced significant increases in glucose, total and high‐density lipid (HDL) cholesterol, triglyceride, and phospholipid plasma levels. Treatment with NOR, a 19‐nortestosterone derivative, resulted in a reduced gain in body wt and in a marked decrease in all plasma lipid parameters. The 19‐norprogesterone derivative NOM, like P, did not alter lipid or glucose metabolism, despite a significant increase in body wt gain. In particular, no reduction in the HDL cholesterol level occurred. Plasma and tissue lipolytic activities remained unchanged.The results of this study confirm interest in the therapeutic class of 19‐norprogesterone‐derived progestogens, exemplified by NOM, with respect to their lack of metaboli

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1987.tb00562.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Summary—The effects of modafinil and adrafinil, 2 drugs that induce locomotor hyperactivity, and those of the parent compounds CRL 40467 and CRL 40385, were studied on the external pancreatic secretion of anaesthetized and conscious rats. In anaesthetized rats modafinil, adrafinil, and CRL 40385 antagonized the central vagal stimulation of protein output induced by 2‐deoxy‐D‐glucose in the pancreatic juice. In conscious rats, modafinil and adrafinil inhibited the output of protein in the basal interdigestive pancreatic secretion. Modafinil was more active than adrafinil as an inhibitor of pancreatic secretion. The effects of modafinil and adrafinil were different from those of sympathetic amines and dopamine: they did not stimulate the output of bicarbonate in anaesthetized rats, and pancreatic inhibition observed in conscious rats was not inhibited by either yohimbine or p

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1987.tb00563.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Summary—Submaximal exercise heart rate was measured after oral administration of placebo, tertatolol 5 mg, propranolol 80 mg, and atenolol 100 mg to 12 subjects in a double‐blind cross‐over study. The peaks of beta‐blocking activity, observed at 2 hr, were of similar extent for the 3 drugs. The duration of activity of tertatolol, a beta blocker with a short elimination half‐life, extended up to 24 hr as did that of atenolol, but was longer than that of propranolol which reached only 18 hr. These results support once‐daily administration of tertatolol

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1987.tb00564.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Summary—The arterial baroreceptor reflex (BR; aortic and carotid sinus BR) and the cardiopulmonary BR are the most important reflexes acting as buffer systems for the maintenance of arterial pressure around a fixed physiologic value. They act as permanent inhibitory systems on the central cardiovascular structures and they can be either activated or deactivated by using selective techniques. During chronic hypertension there are structural alterations of the peripheral and/or central components of the BR that become «reset», with a shift in the function curve relating BR activity to blood pressure (BP) in the direction of higher pressure values. As a consequence of the hypertension‐induced resetting phenomenon, both the threshold pressure and sensitivity of BR are disturbed. However, if BR resetting during hypertension clearly decreases the sensitivity of BR control of heart rate (HR), BR control of peripheral resistance and arterial pressure as a whole is preserved and even increased when hypertension develops. Thus, this apparent discrepancy between BR control of HR and BP during hypertension demonstrates that evaluation of an antihypertensive therapy on reflex control of HR alone cannot predict what will happen to BR control of the whole cardiovascular system. Regarding BR control of HR, in contrast to the classical arteriolar vasodilators such as hydralazine and its derivatives, the majority of the modern antihypertensive drugs do not evoke reflex tachycardia in response to lowering of BP in normotensive or hypertensive subjects. Although the intrinsic pharmacologic mechanisms of action of these drugs on BR may be quite different (e.g., α1,‐or β‐adrenoreceptor blocking agents, converting enzyme inhibitors, certain calcium‐channel blockers of the phenyldihydropyridine group, and so on), they all shift in a parallel manner the set‐point of the BR response curve towards lower pressures, with no change in HR or R‐R interval. Generally, this resetting phenomenon occurs after several weeks or months of antihypertensive therapy, but it can also occur acutely (e.g.after IV injection) after administration of drugs such as prazosin or ketanserin. Finally, antihypertensive agents such as clonidine and methyldopa can simultaneously reset the BR and increase its sensitivity, thus leading to almost complete restoration of control of HR response despite the concomitant decrease in BP.Regarding BR control of blood pressure, only captopril and especially celiprolol (a β1‐adrenoreceptor blocking drug with vasodilating properties) are able to restore almost normal BR control

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1987.tb00565.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Summary—The current status and future prospects of the immunotherapy of cancer, infection, and autoimmunity are reviewed briefly. Progress in treating the immunodeficiency of cancer with thymic hormones and drugs such as levamisole and lentinan has produced some degree of remission stabilization. Interferon, interleukin II, and LAK cells have inhibited active, progressive cancer. New approaches with monoclonal antibodies, immunotoxins, tumor necrosis factors, and so on are under rapid development. Future prospects focus on combined approaches yielding synergy. Treatment of infections in animals and man either prophylactically or therapeutically, with thymic hormones, interferons, and thymomimetic drugs such as levamisole and isoprinosine, demonstrate the efficacy of this approach. The use of these agents in conjunction with antimicrobial therapy in immunosuppressed hosts is warranted. In immunodeficiency associated with AIDS virus infection, interleukin II, thymic hormones, isoprinosine, and imuthiol have shown effect in partially restoring immune function, although with little clinical benefit. Their use with antiviral therapy is advocated. Finally, thymic hormones, isoprinosine, levamisole, and other sulfur‐containing compounds have ameliorated murine and human autoimmune disease presumably through effects in improving cellular immune function. Continued development of this type of therapy is warranted. The continued progress of immunopharmacology as the science of immunotherapy portends the future successful development of many therapeutic approaches to these disea

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1987.tb00566.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY