2-甲酰(乙酰)取代喹啉缩氨基硫脲的合成

缩氨基硫脲类化合物有抗肿瘤、抗病毒和抗菌等多种药理活性。Barret等首次报道了乙二醛二缩氨基硫脲(Ⅰ)的抗疟活性。Klayman等研究了缩     

Pharmacokinetic interaction of antimicrobial agents with levomethadon in drug-addicted AIDS patients

Summary Morphine and its derivatives are metabolized by the liver microsomal enzyme system with a high first-pass effect after oral application. In four of 44 HIV-infected i.v. drug abusers who participated in a levomethadon maintenance program, we observed sustained symptoms of under-dosage and loss of effect of there to fore well-tolerated substitution therapy during rifampin treatment or therapy with zidovudine or fucidic acid. As a pharmacological model substance for cytochrome p 450 enzymes, measurement of antipyrine in serum by high pressure liquid chromatography revealed induction of cytochrome p 450 isoenzymes. The half-life of antipyrine decreased (patient 1 from 11.3 to 8.4 h and patient 2 from 10.7 to 7.6 h after rifampin, patient 3 from 12.2 to 8.6 h after fucidic acid, and patient 4 from 10.6 to 8.6 h after zidovudine). In i.v. drug abusers on levomethadon maintenance programs, adjustment of the levomethadon dosage may be necessary when specific therapy for HIV infection and associated diseases requires the use of drugs known to be potent inducers of the liver microsomal enzyme system.Abbreviations IVDA intravenous drug abusers - C total body clearance - PCP pneumoncystis carinii pneumonia - INH isonazid - EMB ethambutol - PZA pyrazinamide - t_1/2 half-life     

Granulocyte colony-stimulating factor treatment in AIDS patients

Summary Frequent complications of human immunodeficiency virus infection are hematopoietic failure and poor tolerance of myelosuppressive drugs. Reasons for neutropenia resulting from hematopoietic failure are infection of the bone marrow and hematotoxicity of treatment with zidovudine, ganciclovir, sulfonamides, and interferons. Moreover, tumor necrosis factor-, transforming growth factor- and interferon- have been shown to suppress proliferation of bone marrow cells. Both granulocyte (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) increase neutrophil counts and ameliorate phagocytic and bactericidic function of neutrophils. We report eight cases of AIDS patients with serious infections and neutropenia (< 750 cells/l), who were treated concomitantly with recombinant human G-CSF (3–4 g subcutaneously per kilogram body weight daily). G-CSF treatment was well tolerated in all patients and showed no side effects or disturbances of other lineages than neutrophils. Life-threatening bacterial infections were treated successfully by stimulating the neutrophil immune system. This therapy shortened the duration of subsequent treatment with antibiotics. Since human immunodeficiency virus infects CD4-positive monocytes and macrophages, which are stimulated by GM-CSF, G-CSF seems to be the cytokine of choice, if stimulation of the neutrophil lineage is warranted.Abbreviations G-CSF granulocyte colony-stimulating factor - GM-CSF granulocyte-macrophage colony-stimulating factor - HIV human immunodeficiency virus     

Sexually transmitted infections

In no other medical field former rare infections of the 1980^th and 1990^th occur again as this is seen in the field of venerology which is as well based on the mobility of the population. Increasing rates of infections in Europe, and increasing bacteriological resistances face health professionals with new challenges. The WHO estimates more than 340 million cases of illnesses worldwide every year. Diseases caused by sexually transmitted infections (STI) in a strict sense are syphilis, gonorrhea, lymphogranuloma venereum, granuloma inguinale, and chancroid. In a wider sense, all illnesses are included which can mainly be transmitted through sexual contact. The term “sexual contact” has to be seen widely, from close physical contact to all variants of sexual behavior. This CME article is an overview of the most common occurring sexually transmitted infections in clinical practice. Both, basic knowledge as well as recent developments are discussed below.     

Activated protein C decreases plasminogen activator-inhibitor activity in endothelial cell-conditioned medium

Confluent cultures of endothelial cells from human umbilical cord were used to study the effect of activated human protein C (APC) on the production of plasminogen activators, plasminogen activator-inhibitor, and factor VIII-related antigen. Addition of APC to the cells in a serum-free medium did not affect the production of tissue-type plasminogen activator (t-PA) or factor VIII-related antigen; under all measured conditions, no urokinase activity was found. However, less plasminogen activator-inhibitor activity accumulated in the conditioned medium in the presence of APC. This decrease was dose dependent and could be prevented by specific anti-protein C antibodies. No decrease was observed with the zymogen protein C or with diisopropylfluorophosphate-inactivated APC. APC also decreased the t-PA inhibitor activity in endothelial cell-conditioned medium in the absence of cells, which suggests that the effect of APC is at least partly due to a direct effect of APC on the plasminogen activator- inhibitor. High concentrations of thrombin-but not of factor Xa or IXa-- had a similar effect on the t-PA inhibitor activity. The effect of APC on the plasminogen activator-inhibitor provides a new mechanism by which APC may enhance fibrinolysis. The data suggest that activation of the coagulation system may lead to a secondary increase of the fibrinolytic activity by changing the balance between plasminogen activator(s) and its (their) fast-acting inhibitor.