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).     

Hepatic histological findings after transplantation for chronic hepatitis B virus infection, including a unique pattern of fibrosing cholestatic hepatitis

Long-term follow-up of 27 patients with hepatitis B virus-related chronic liver disease treated by transplantation showed that 23 had hepatitis B virus recurrence. In 13 patients late changes in the grafts were similar to those described in other series: minor abnormalities in five cases, chronic active hepatitis in five cases and non-hepatitis B virus-related graft dysfunction in three cases. Three patients had incomplete histological follow-up. Analysis of the histological changes and viral antigen expression in six cases revealed a distinct and novel pattern termed fibrosing cholestatic hepatitis. Development of fibrosing cholestatic hepatitis was associated with rapidly progressive graft dysfunction. It is postulated that this pattern of fibrosing cholestatic hepatitis develops because of a high cytoplasmic expression of viral antigens, including HBsAg. The remaining case had some features of fibrosing cholestatic hepatitis. The main histological features of this unique syndrome include thin, perisinusoidal bands of fibrosis extending from portal tracts to surround plates of ductular-type epithelium; prominent cholestasis; ground-glass transformation; and ballooning of hepatocytes with cell loss and mild mixed inflammatory reaction.     

Role of thermal trauma in experimental oral mucosal Candida infections in rats

A model of candidosis in experimental rats was used to study the role of trauma in the aetiology of oral mucosal infections caused by Candida albicans. Standardised thermal trauma was delivered to the dorsum of the tongue of Sprague-Dawley rats and experimental candidosis was induced. Histologically. the site of trauma was invaded by hyphae earlier and more extensively than in control animals, leading to the conclusion that trauma facilitated the establishment of the C. alhicana infections.     

Cellular interactions determining the production of collagenase by a rat mammary carcinoma cell line

The cellular interactions regulating the production of collagenase by a cell line derived from a spontaneously arising rat mammary carcinoma have been studied. The cell line, BC1, was grown permanently under defined serum-free conditions, so that the poorly characterized and variable effects of serum on collagenase expression were avoided. Two stable subpopulations of cells present in BC1 cultures were defined as epithelioid cells ("E-cells") and myoepithelioid cells ("M-cells"). These subpopulations differed in their morphology, pattern of growth and susceptibility to detachment from culture vessels by trypsin. Seven clones of M-cells and 7 clones of E-cells, obtained by the limiting dilution technique, were used to determine the cellular source of collagenase and the interactions which led to its expression. M-cells displayed an absolute dependence on a soluble factor produced by E-cells for their survival in vitro. The presence of both cellular types in culture was necessary for collagenase secretion to occur, E-cells being the major source of enzyme in mixed cultures. A soluble factor produced by M-cells was largely, if not completely, responsible for the induction of collagenase secretion by E-cells. Clones representative of both subpopulations were tumorigenic in syngeneic host animals. These results suggest that the phenotypic diversity which occurs within populations of neoplastic cells may give rise to subpopulations of cells which display a more aggressive phenotype in coexistence than in isolation.     

Presence of pro-opiomelanocortin peptides and corticotropin-releasing factor in human placenta

Immunoreactive adrenocorticotropin (ACTH), beta-endorphin (BEP) and corticotropin-releasing factor (CRF) were detected in human term placenta obtained from elective Caesarian surgery. The concentrations of ACTH, BEP and CRF in placenta detected by radioimmunoassay (RIA) were 2.83 +/- 0.36, 0.52 +/- 0.05 and 0.56 +/- 0.15 ng/g wet weight of tissue respectively. Pro-opiomelanocortin (POMC) peptides were also detected in the amnion and chorion membranes and in the decidua. The concentrations of ACTH were 1.72 +/- 0.20, 4.43 +/- 0.39 and 5.80 +/- 0.17 ng/g and the levels of BEP were 0.42 +/- 0.18, 0.65 +/- 0.20 and 3.66 +/- 1.10 ng/g in the amnion, chorion and decidua respectively. In contrast to placenta, immunoreactive CRF was not detected in the amnion, chorion and decidua. Immunoreactive N-acetylated BEP was also not detected in all the placental subfractions. Comparison of the amounts of both ACTH and BEP in the various placental components indicated the following distribution: decidua > chorion > placenta > amnion. In decidua, POMC peptides were present in an equi-molar ratio but in the other three placental fractions, ACTH levels were three to five-fold higher than BEP. In immunohistochemical studies, only a positive staining for ACTH was obtained for decidua. Our results confirm the presence of POMC peptides and CRF in placenta and their physiological roles in pregnancy and parturition.     

Role of lymphocytes in silicosis: regulation of secretion of macrophage-derived mitogenic activity for fibroblasts.

We investigated the role of pulmonary lymphocytes in regulating the secretion by alveolar macrophages (AM) of mitogenic activity for lung fibroblasts, in an experimental model of the initial stages of silicotic inflammation and fibrosis. Following intratracheal instillation of silica, pulmonary parenchymal lymphocytes produced a lymphokine(s) that caused modest stimulation of the secretion of mitogenic activity by normal AM. Co-culture of small numbers of lymphocytes from silica-injected animals with AM induced enhanced secretion of fibroblast growth factor activity which was comparable to the maximal response elicited by recombinant interferon-gamma. Lymphocytes from animals given non-fibrogenic titanium dioxide exhibited no such effects. The stimulatory effect of lymphocytes from silica-treated animals in co-culture with macrophages was abrogated when the cells were separated by a microporous membrane. Our findings demonstrate that lymphocytes participating in the response to pulmonary deposition of silica are able to induce the secretion of a growth factor(s) for fibroblasts by pulmonary macrophages, possibly via lymphokines expressed on the cell surface or secreted at sites of cell-to-cell contact.