Pharmacokinetics of orally administered norethisterone enanthate in rabbit, monkey, and women

Norethisterone enanthate (NET-En), an established intramuscular long-acting contraceptive agent, has previously been shown to be effective in inhibiting fertility in two rodent species even 4 days after oral ingestion. Pharmacokinetics of NET and NET-En were studied after oral and intramuscular doses in two animal species and a few women. The results suggest that the NET-En was absorbed within a day in all the species after oral dose. The estimates of relative bioavailability ranged from 13 to 51% in rabbits, monkeys, and women. The elimination half-life was 5–10 days. The presence of the active component, NET, in the circulation over the experimental period of 15 days suggests that NET-En could be useful as a long-acting oral pill. The suppression of progesterone levels during the luteal phase of menstrual cycle in women also supports this finding.     

Lymphangiomatosis presenting with bronchial cast formation.

Lymphangiomatosis is a rare disorder of the lymphatic system that is known to cause chylothorax. Chyloptysis may occur but chylous bronchial cast formation is rare. A case is reported of lymphangiomatosis in a 34 year old woman whose initial manifestation was cough productive of bronchial casts. Two years later the patient developed a chylothorax. Ligation of the thoracic duct through a low thoracotomy was curative.     

Metastatic renal carcinoma: rare cause of outflow obstruction (a case report).

A case of bladder tumour arising as a metastasis of renal carcinoma and presenting as obstruction to urinary outflow is described. The possible mechanism of spread to bladder is also suggested.     

Effect of dietary protein on Masheri-induced drug metabolising enzymes

The modulation of drug metabolising enzymes by Masheri extract (ME) and Benzo(a)Pyrene [B(a)P] was studied in male Sprague Dawley rats fed different dietary protein levels. Two groups of 21 days old male Sprague Dawley rats were put on a high protein diet (SHP) with 20% Casein, and a low protein diet (SLP) with 3% Casein semisynthetic based diets for 12 weeks. The SLP fed animals showed lower basal levels of the Phase I activating enzymes viz. Cytochrome P450, Benzo(a)Pyrene hydroxylase, Benzphetamine demethylase and Phase II glutathione detoxification system viz. Glutathione (GSH) and Glutathione-S-transferase. ME and B(a)P treatment significantly depleted the glutathione detoxification system in the SLP group whereas an opposite effect was observed in the SHP group. Interstingly, ME and B(a)P treated rats in the SLP group showed a higher percent increase in the hepatic and pulmonary Phase I enzyme activities than those observed in the treated ME/B(a)P treated SHP rats. Furthermore, both ME and B(a)P significantly decreased the hepatic pool of vitamin A while a concomittant increase in that of vitamin C was observed.     

Do symptoms reflect a change in left ventricular function after aortocoronary bypass grafting in patients with depressed left ventricular function?

Seventy-nine patients with moderate to severe left ventricular dysfunction who underwent aortocoronary bypass grafting between 1971 and 1977 had follow-up heart catheterization at a mean interval of 3 years. Thirty-three patients (42%) had angiographic improvement in left ventricular function at follow-up and 18 (25%) had a decrease in left ventricular end-diastolic pressure. Fifty-eight patients (73%) had improvement in angina of at least one New York Heart Association class at follow-up. There was no correlation between late improvement in left ventricular function and improvement in angina. Improvement in left ventricular function did not correlate with preoperative indices of severity of coronary disease or with indices of completeness of surgical repair.     

Development and implementation of an innovative intern training programme

The quality of medical education during internship is a cause for concern. This paper describes a structured educational programme for interns that was based around learning modules, clinical attachments and bedside teaching. The programme was incorporated into the term rotation of interns within an Area Health Service, and evaluated. Learning modules were timetabled by a Programme Coordinator and interns were reminded to attend. Clinical attachments were organized by the interns from a list of willing supervisors. Attendance at timetabled learning modules averaged 67%, which was greater than the 27% attendance at clinical attachments. Both sessions received high ratings for quality and clinical relevance. This structured education programme was based upon adult learning methods and was both feasible and well received by interns. Intern training programmes need to be programmed into the working week to ensure attendance, and modified following evaluation by interns. Such programmes should be considered by all hospitals to which interns are allocated.     

Heroin-Induces Differential Protein Expression by Normal Human Astrocytes (NHA)

Heroin use is postulated to act as a cofactor in the neuropathogenesis of human immunodeficiency virus (HIV-1) infection. Astrocytes, integral components of the CNS, are reported to be susceptible to HIV-1 infection. Upon activation, astrocytes release a number of immunoregulatory products or modulate the expression of a number of proteins that foster the immunopathogenesis of HIV-1 infection. However, the role of heroin on HIV-1 infectivity and the expression of the proteome of normal human astrocytes (NHA) have not been elucidated. We hypothesize that heroin modulates the expression of a number of proteins by NHA that foster the neuoropathogenesis of HIV-1 infection. We utilized LTR amplification and the p24 antigen assay to quantitate the effect of heroin on HIV-1 infectivity while difference gel electrophoresis (DIGE) combined with protein identification through high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to analyze the effects of heroin on the proteomic profile of NHA. Results demonstrate that heroin potentiates HIV-1 replication in NHA. Furthermore, heroin significantly increased protein expression levels for protein kinase C (PKC), reticulocalbin 1 precursor, reticulocalbin 1, tyrosine 3-monooxgenase/tryptophan 5-monooxgenase activation protein, chloride intracellular channel 1, cathepsin D preproprotein, galectin 1 and myosin light chain alkali. Heroin also significantly decreased protein expression for proliferating cell nuclear antigen, proteasome beta 6 subunit, tropomyosin 3, laminin receptor 1, tubulin alpha 6, vimentin, EF hand domain family member D2, Tumor protein D54 (hD54), ATP synthase, H+ transporting, mitochondrial F1 complex and ribosomal protein S14. Identification of unique, heroin-induced proteins may help to develop novel markers for diagnostic, preventative and therapeutic targeting in heroin using subjects.