The effect of some tricyclic antidepressants on the inhibition of mouse brain monoamine oxidase in-vivo by phenelzine

Four tricyclic antidepressants, amitriptyline, imipramine, desipramine and iprindole have been shown to partially protect mouse brain monoamine oxidase in-vivo from the irreversible enzyme inhibition produced by subsequent injection of phenelzine. Levels of protection were similar when the enzyme was assayed with selective substrates (5-hydroxytryptamine and phenethylamine) for both the A and B forms of the enzyme. Although other explanations cannot at this stage be ruled out, these observations are consistent with the tricyclic antidepressants acting as reversible inhibitors of brain monoamine oxidase in-vivo.     

Recognizing and managing mycobacterial diseases in clients with AIDS.

Mycobacterial diseases are common in people infected with human immunodeficiency virus. Mycobacterium tuberculosis (MTB) and Mycobacterium avium intracellulare (MAI), the specific pathogens most frequently involved, cause pulmonary tuberculosis and disseminated MAI infections. Pulmonary tuberculosis incidence was on the decline from 1950 to 1985, but since 1985 has been on the rise worldwide. Prior to the onset of AIDS, MAI infections were rare in humans. However, disseminated MAI seems to be associated with the terminal stage of AIDS. The symptomatology of MTB and MAI infections is similar, yet diagnosis and treatment vary. Pulmonary TB can be treated effectively with chemotherapy and isolation to prevent transmission. Because MAI infection is not a communicable disease, isolation is not necessary. Effective treatment for disseminated MAI remains under investigation; currently, a regimen of four to five drugs is recommended. There are however, significant side effects associated with this therapy. Because the number of AIDS patients is increasing, it is imperative for clinicians to understand the mycobacterial diseases and how best to manage them.     

Effects of low-dose prednisolone on cyclosporine pharmacokinetics in liver transplant recipients: radioimmunoassay with specific and non-specific monoclonal antibodies

The following study of cyclosporine pharmacokinetics was performed to investigate the effects of withdrawal of low-dose maintenance prednisolone (0.3-0.6 mg/kg body weight) from the routine immunosuppressive regimen given to 10 liver transplant recipients with stable liver function tests. After oral administration of cyclosporine (6.4-10.3 mg/kg) whole blood concentrations were measured by radioimmunoassay (RIA) with both a specific monoclonal antibody detecting parent drug and a non-specific antibody additionally detecting a cross-section of metabolites. Withdrawal of prednisolone produced no significant change in the mean time and concentration of maximum blood cyclosporine (3.3 h and 1160 micrograms/l, respectively), the initial and terminal elimination half-life (3.5 h and 18.4 h, respectively) and the area under the blood concentration versus time curve (AUC) measured with either the specific or non-specific monoclonal antibody. Measurements with these two antibodies indicated that the terminal elimination of cyclosporine metabolites was more rapid than for the parent drug (half-life: 14.5 vs 18.4, respectively).     

A novel 37-Kd adhesive membrane protein from cloned murine bone marrow stromal cells and cloned murine hematopoietic progenitor cells

The adhesion of hematopoietic progenitor cells to bone marrow stromal cells is critical to hematopoiesis and involves multiple effector molecules. Stromal cell molecules that participate in this interaction were sought by analyzing the detergent-soluble membrane proteins of GBI/6 stromal cells that could be adsorbed by intact FDCP-1 progenitor cells. A single-chain protein from GBI/6 cells having an apparent molecular weight of 37 Kd was selectively adsorbed by FDCP-1 cells. This protein, designated p37, could be surface-radiolabeled and thus appeared to be exposed on the cell membrane. An apparently identical 37- Kd protein was expressed by three stromal cell lines, by Swiss 3T3 fibroblastic cells, and by FDCP-1 and FDCP-2 progenitor cells. p37 was selectively adsorbed from membrane lysates by a variety of murine hematopoietic cells, including erythrocytes, but not by human erythrocytes. Binding of p37 to cells was calcium-dependent, and was not affected by inhibitors of the hematopoietic homing receptor or the cell-binding or heparin-binding functions of fibronectin. It is proposed that p37 may be a novel adhesive molecule expressed on the surface of a variety of hematopoietic cells that could participate in both homotypic and heterotypic interactions of stromal and progenitor cells.