Altered cAMP Response after Isoprenaline Stimulation of Mononuclear Leucocytes from Insulin-Dependent Diabetic Patients with Hypoglycaemia Unawareness

Abstract: Loss of adrenergic hypoglycaemic symptoms is the most distinctive feature in insulin-dependent diabetes mellitus (IDDM) patients with hypoglycaemia unawareness. Previous reports from in vivo studies show reduced heart rate responsiveness both to adrenergic agonists and antagonists in these patients. This study was carried out to investigate whether the reduced adrenergic sensitivity in IDDM patients with hypoglycaemia unawareness (IDDM-unaware) also could be demonstrated as reduced increase in cAMP production in mononuclear leucocytes induced by isoprenaline stimulation, or reduced inhibition by ICI-118551 (a selective β₂-adrenergic receptor blocker) of isoprenaline induced cAMP production. We found that the slope of the concentration-response curves of isoprenaline/cAMP and the maximal cAMP concentrations obtained after isoprenaline stimulation were reduced in IDDM-unaware compared to control and IDDM patients with normal hypoglycaemia awareness (IDDM-aware). We did not find any significant differences in the response to ICI-118551 between control, IDDM-aware and IDDM-unaware. This study supports the reports of reduced sensitivity of adrenergic agonists as a part of the pathophysiological changes in hypoglycaemia unawareness, but we have not been able to confirm the reports of an association between hypoglycaemia unawareness and reduced effect of adrenergic antagonists.     

Das kleinzellige Bronchialkarzinom – neue Entwicklungen nach ASCO 2007

Wiener Medizinische Wochenschrift - Aggressives Tumorwachstum, frühe Metastasierung und hohe Assoziation mit intensivem Nikotinkonsum sind die Charakteristika des kleinzelligen...     

A transient granulocyte killing defect secondary to a varicella infection

A varicella infection in a previously healthy young girl was complicated by bacterial sepsis, arthritis, and osteomyelitis in multiple locations. This secondary complication caused by Staphylococcus aureus was associated with a transient defect in granulocyte function and an alteration in the representation of CD4 and CD8 positive lymphocyte subpopulation. The mechanism responsible for secondary bacterial infections following varicella may be due to transient defects in granulocyte function.     

Untersuchung zur Morbidität der indigenen Volksgruppen der Chiquitanos im südlichen Amazonasgebiet

The Chiquitano-tribe lives in the southern Amazonas region in Bolivia, remote from larger towns. A study (n=1514) on morbidity over an one year period (April 1995 till March 1996) and its relation to general and social medicine is given. Most frequently, childreh under 15 years and women in parity age (15–45 years) sought consultation (34,1 %, 42,7 %). Gastrointestinal, respiratoral and gynecological-obstetric diseases were predominant (22,4 %, 16,2 % and 15,7 %). In the dry season, common colds and respiratoral infections represented the major health problem. In the rainy season, infectious diarrhea diseases caused by polluted water as a consequence of extended floods were most frequent. Typical tropical diseases (malaria, Dengue fever, Chagas’ disease, leprosy a.o.) and socially caused diseases (AIDS, dependencies on drugs and alcohol, consequencies of crime) were rarely seen. With respect to severity, 55,8 % of the patients showed mild disorders. More serious diseases were observed in 39, 8 %. 4,6 % of the patients were diagnosed severly ill and needed hospitalization. Epidemiological data on general and social medicine of minorities in developing countries and their actual degree of medical care are important in a shrinking world. The data are useful to estimate medical needs and plan improvements to the health care system especially in rural areas.     

Rapid chemical kinetic techniques for investigations of neurotransmitter receptors expressed in Xenopus oocytes

Xenopus laevis oocytes have been used extensively during the past decade to express and study neurotransmitter receptors of various origins and subunit composition and also to express and study receptors altered by site-specific mutations. Interpretations of the effects of structural differences on receptor mechanisms were, however, hampered by a lack of rapid chemical reaction techniques suitable for use with oocytes. Here we describe flow and photolysis techniques, with 2-ms and 100-μs time resolution, respectively, for studying neurotransmitter receptors in giant (≈20-μm diameter) patches of oocyte membranes, using muscle and neuronal acetylcholine receptors as examples. With these techniques, we find that the muscle receptor in BC₃H1 cells and the same receptor expressed in oocytes have comparable kinetic properties. This finding is in contrast to previous studies and raises questions regarding the interpretations of the many studies of receptors expressed in oocytes in which an insufficient time resolution was available. The results obtained indicate that the rapid reaction techniques described here, in conjunction with the oocyte expression system, will be useful in answering many outstanding questions regarding the structure and function of diverse neurotransmitter receptors.     

Cotinine determination by immunoassays may be influenced by other nicotine metabolites

Polyclonal rabbit anticotinine antiserum, which can be used for biomonitoring nicotine uptake by the determination of cotinine in body fluids, was checked by a competitive ELISA for its cross-reactivity with nine nicotine metabolites. The highest percentage of relative crossreactivity (about 30%) was observed with trans-3-hydroxycotinine, a metabolite which is known to be excreted in 3-fold higher amounts than cotinine in the urine of human smokers. Therefore, it is possible that cotinine determinations performed by immunochemical methods — especially in urine — may yield overestimated cotinine concentrations.     

CGP 6809 — A new nitrosoureido-sugar derivative with activity in human tumor xenografts

Summary CGP 6809 [ethyl-6-deoxy-3,5-di-O-methyl-6-(3-methyl-3-nitrosoureido)--d-glucofuranoside] is a new methylnitrosoureido-sugar derivative that has been shown to be active against a broad spectrum of transplantable tumours in mice and rats [14]. We investigated the anti-tumour effect of CGP 6809 in ten selected, human tumour xenograft lines growing s. c. in nude mice. The p. o. administration of 125 mg/kg per day for 10–15 days was less toxic (lethality 12% in tumour-bearing nude mice) than the i. p. injection of 62.5 mg/kg per day (lethality 22%). The anti-tumour effect was similar for both application routes; two large bowel cancers responded to treatment with CGP 6809, rectal cancer CXF 158 showed a remission, and the rapidly growing, undifferentiated colonic cancer CXF 280 exhibited a transient no-change. Furthermore, remissions were observed in the epidermoid lung cancer LXF 322 and in thyroid cancer 117. Tumour progression was found in another epidermoid lung cancer and in three stomach cancers, one melanoma, and one soft tissure sarcoma. CGP 6809 is a promising new agent for clinical trials, especially for large bowel and epidermoid lung cancer.Supported in part by grant PTB 8467 from the Bundesminister für Forschung und Technologie, Bonn, FRG     

Organization of cyclic AMP-dependent connexin 43 in Swiss 3T3 cells attached to a cellulose substratum.

We have previously shown that the adenylyl cyclase, which produces cyclic AMP (cAMP) in Swiss 3T3 cells, is activated by their attachment to a cellulose substratum (Cuprophan, CU). This substratum adsorbs vitronectin poorly, prevents cell spreading and causes them to aggregate. By contrast, cells spread out on polystyrene and contain low concentrations of cAMP. We have found that Connexin 43 (Cx 43) gap junction plaques are involved in this cell aggregation. MDL 12330 A, a specific inhibitor of adenylyl cyclase, prevented cell aggregation on CU and abolished Cx 43 channel clustering. But forskolin, a direct activator of adenylyl cyclase, and SBr cAMP, a cell-permeable analogue of cAMP, caused Cx 43 channel clustering in cells attached to polystyrene. Hence, Cx 43 channel clustering is regulated by cAMP in Swiss 3T3 cells. In addition, neither brefeldin A nor monensin (inhibitors of transit through the endoplasmic reticulum and Golgi apparatus), abolished Cx 43 channel clustering in cells aggregated on CU. Thus, the Cx 43 that form clusters in cells attached to CU are not dependent upon the trafficking of Cx 43 from intracellular storage sites, but are probably reorganised from the plasma membrane.