New D-modified androstane derivatives as aromatase inhibitors.

Starting from a 16-oximino derivative of 5-androstene the newly-synthesized 16-oximino-17-hydroxy-17-substituted derivatives 2-4 gave by the Beckmann fragmentation reaction the corresponding D-seco derivatives 6-9. Besides, in the case of the 17-hydroxy-17-methyl-16-oximino derivative 2, as a result of the rearrangement, the hydrolysis product 5 of the 16-oximino group with the opposite configuration at the C-17 was obtained. By the Oppenauer oxidation and/or by dehydration of 7 with 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ), the corresponding derivatives 12, 13, and 14 were obtained. The structures of 6 and 12 were unambiguously proved by the appropriate X-ray structural analysis. Kinetic analysis for anti-aromatase activity showed that compound 12 expressed the highest inhibition in the denucleated rat ovarian fraction in comparison to other androstene derivatives (IC(50) was 0.42 microM). In comparison to aminoglutethimide (AG) activity, it was 3.5 times lower. The inhibition was competitive, with K(i) of 0.27 microM. Introduction of additional units of unsaturation (compounds 13 and 14) in D-seco derivatives did not increase anti-aromatase activity.

Gadolinium chloride-induced macrophage blockade prevents rejection of human insulinoma cell xenograft in rats.

The effect of gadolinium chloride (GdCl3)-induced Kupffer cell blockade on the survival of discordant insulinoma cell xenografts was investigated. Insulinoma cells isolated by means of collagenase from human insulinoma and subsequently cultured were transplanted through the portal vein into the liver of streptozotocin-induced diabetic, male, CFY inbred rats. In the control, streptozotocin-treated rats, the decrease in blood glucose level was only transitory, in contrast with the GdCl3-pretreated diabetic rats, which remained normoglycemic during the 2-week observation period. Histologically, in the liver and lung of rats pretreated with GdCl3, large areas of extensively proliferating insulinoma cells were seen, whereas no insulinoma cells were seen in either the liver or the lung of diabetic control rats, not treated with GdCl3. These studies suggest that the Kupffer cells play significant roles in the recognition of xenoantigens and the induction of xenograft rejection.

[Langerhans cell granulomatosis of the lung (morphological studies of lung biopsy specimens from patient with histiocytosis X]. / A tüdó Langerhans-sejtes granulomatosisa (morfológiai vizsgálatok histiocytosis X-ben szenvedö betegekból származó tüdóbiopsiás anyagokon).

Morphologic studies, including conventional histology, electronmicroscopy and immunohistochemistry were performed on biopsies from 5 patients with pulmonary Langerhans's cell granulomatosis (LCG). In all cases we were able to identify the CD la antigen on paraffin section supporting the diagnosis of LCG.

[Lymphoid infiltrates in the lung]. / A tüdö lymphoid infiltratumairól.

The authors reviewed material of 10 year period (1980-1990) of the Department of Pulmonology, Albert Szent-Györgyi University of Medicine, Deszk, Hungary, and selected 14 patients from the files who considered to belong in one of the lymphoproliferative conditions (4 low grade and 4 high grade lymphomas of B-cell type, 1 angiocentric, 1 mediastinal lymphoblastic non-Hodgkin's lymphoma, 3 Hodgkin's lymphoma cases and 1 pleural pseudolymphoma). Every patient admitted with prominent pulmonary symptoms. The diagnoses were based on histology and immunohistochemistry of tissue samples and autopsy. One high grade B-cell and the angiocentric malignant lymphoma proved to be primary pulmonary process. No specific radiomorphological signs were found, which could be characteristic for the pulmonary lympho-reticular infiltrations and also to distinct the primary and secondary ones. The lung infiltrations in the most of the non-Hodgkin's lymphoma cases with low grade malignancy appeared imitating tuberculosis, while the high grade group and Hodgkin's lymphomas displayed confusion with any primary or multiple tumors.

[Barrett esophagus]. / Barrett oesophagus.

There are a lot of contradiction and uncertainty related to Barrett's esophagus. Authors review the literature about the incidence, the aetiology, the pathology of the ailment, the possibility of diagnosis and treatment. 25 Barrett's esophagus were observed in the course of controlling of patients after antireflux operations and investigations of patients suffering from gastroesophageal reflux disease. X-ray examination, endoscopy, biopsy, 24-hour pH monitoring of the distal esophagus and esophageal manometry were performed. Because of the possibility of malignant transformation Barrett's esophagus requires yearly endoscopic surveillance and biopsy at least. Antireflux procedure does not protect against the development of adenocarcinoma.

[Cancer metastasis causing superior vena cava syndrome in the right heart]. / Vena cava superior syndromát okozó rákáttét a jobb szívfélben.

In a 60-years-old woman, 1,5 year later of the diagnosis of the inoperable endocervical carcinoma vena cava superior syndrome developed. At autopsy mainly intracavital metastatic tumour mass was found in the right atrium of the heart. To the authors knowledge, intracavital heart metastatic tumor as cause of vena cava superior syndrome has not been described previously.

The Bellagio Declaration: overcoming hunger in the 1990's.

PIP: In November 1989, 23 leading hunger experts met in Bellagio, Italy, issues a document called the "Bellagio Declaration: Overcoming Hunger in the 1990s." The report lists 4 achievable goals: eliminate famine deaths; end hunger in half of the world's poorest households; reduce by half malnutrition of mothers and small children; and eradicate iodine and vitamin A deficiencies. Famine deaths can be eliminated by setting up early-warning systems and longer-term relief objectives. The only remaining obstacle is how to prevent warring nations from blocking food deliveries and destroying food. Hunger can be eliminated in half the world's poor households by giving the poor access to resources and credit, rehabilitating degraded ecosystems, using sustainable farming, and using existing markets to distribute food equitably. Malnutrition can be halved by sustained breastfeeding, and supplementation of food and micronutrients. Iodine and vitamin A deficiencies can be eliminated by giving iodized oil injections, vitamin A capsules and iodized salt. Ways of dealing with obstacles such as population, deforestation, soil and water shortages, pollution, global warming and capital deficits in the South are discussed. There is hope that these goals can be attained because of the outbreak of peace and democracy, freeing up substantial portions of the 1 trillion US dollars spent on defense; abatement of feat of worldwide economic collapse; and evolution of a worldwide logistic system to provide emergency food aid.^ieng

13C NMR study of actinoidins: carbohydrate moieties and their glycosidic linkages.

The configuration of the glycosidic linkages and the conformation of the carbohydrate moieties in the molecules of the glycopeptide-type antibiotics actinoidins A and B (1a, 1b) have been determined by means of two-dimensional 13C/1H correlation NMR technique and with the application of model compounds 2-4.

Non-specific drug-metabolizing enzyme activity in Gilbert disease.

Gilbert disease was diagnosed in a 15-year-old boy on the basis of the clinical pattern and the changing drug-metabolizing capacity of the liver-enzyme apparatus, which was drug-induced.