Embedding Windows

Not content with dominating the desktop, Microsoft is now testing the Windows standard against the taxing requirements of the embedded systems market. The author outlines the implications for developers     

Homologous desensitization of the D1A dopamine receptor: efficacy in causing desensitization dissociates from both receptor occupancy and functional potency

The role of drug efficacy in agonist-induced desensitization was studied in C-6 glioma cells transfected with the monkey dopamine D1A (mD1A) receptor. Dopamine pretreatment for 2 hr produced greater than 80% loss of responsiveness in the stimulation of cAMP accumulation that was blocked by the D1 antagonist SCH23390. A series of full and partial D1 agonists from structurally dissimilar classes were then examined. Three full agonists (dihydrexidine, SKF82958, A77636) desensitized the receptor to the same extent as dopamine, whereas two other full agonists (dinapsoline and A68930) and all the partial agonists tested (SKF38393, pergolide and d-lysergic acid diethylamide tartrate) produced only partial desensitization (i.e., 50% that of dopamine). Whereas partial agonists (i.e., SKF38393, pergolide and d-lysergic acid diethylamide tartrate) caused no alteration in ligand-accessible mD1A receptors, four of the full agonists (dopamine, dihydrexidine, dinapsoline, A68930) caused a 30 to 40% reduction in receptor number. One full agonist, A77636, caused nearly an 80% decrease in receptor number, despite the fact that the degree of functional desensitization was similar to the other full agonists. The desensitization of the D1 receptor was homologous, not affecting beta-2 adrenergic receptors endogenous to C-6 cells. Neither incubation with cAMP analogs, nor inhibition of protein kinase A, affected dopamine-induced desensitization, suggesting a cAMP-independent mechanism in this cell line. Together, these data suggest that functional desensitization of the mD1A receptor expressed in C-6 glioma cells is a cAMP-independent mechanism, cannot be predicted reliably from agonist efficacy for stimulating adenylate cyclase and can occur in the absence of changes in receptor number.     

Fas-induced apoptosis of T cells occurs independently of ceramide generation

The Fas receptor is one of a number of important physiological inducers of programmed cell death (apoptosis). Current models for regulation of this process involve rapid conversion of sphingomyelin to ceramide by cellular sphingomyelinases. Induced changes in cellular levels of such sphingosine-based ceramides are normally extrapolated from measurements of sphingomyelinase activity or following their conversion to ceramide phosphate by treatment of cellular lipid extracts with bacterial diacylglycerol kinase (DAGK). To allow direct study of cellular sphingosine- and sphinganine-based ceramide levels, we developed a mass spectrometric technique capable of determining inducible changes in both overall ceramide levels and species distribution in cellular lipid preparations. Contrary to current models, we detected no changes in cellular ceramide levels up to 2 hr poststimulation of Jurkat T cells with an anti-Fas IgM, although this treatment did induce apoptosis. We also determined in the same system that, when utilizing the DAGK assay, increased phosphorylation of substrates that comigrated with ceramide standards was apparent but that this effect was due to an enhancement of DAGK activity rather than increases in levels of cellular ceramides as substrates per se. Thus, the first direct measurement of ceramides present in cells undergoing apoptosis indicates that, insofar as it can be measured, the induction of apoptosis does not involve the generation of sphingosine-based ceramides, contrary to many published accounts.     

Education, occupation and health status of people of age five years or more living in a high density urban area in Zimbabwe

OBJECTIVE: To find out the education, occupation and health status of people aged five years or more living in a high density urban area in Zimbabwe. DESIGN: Cross sectional. SETTING: Households in Chitungwiza. SUBJECTS: Persons of age five years or more available in a household at the time of the survey. In 1990 and 1993, 822 and 1,023 people were surveyed, respectively. MAIN OUTCOME MEASURES: Educational level, employment, rate of smoking, nutritional status, blood pressure level, and rate of disability. RESULTS: After the age of 24 years, more males than females were observed in both periods. A much higher proportion (x2 = 20.34, df = 1, p < 0.001) of women were in informal employment in 1993 (28.6%) than in 1990 (12.9%). Meanwhile, about an equal proportion of men were in the informal sector in both periods (12.0% and 10.4% in 1990 and 1993, respectively). For females of age 15 years or more, fewer (40.8%) had attained secondary education than males (76.4%) in 1990 (x2 = 50.2, df = 1, p < 0.001). Overall, 208 (36.1%) men and eight (1.3%) women of age 15 years or more smoked. Raised blood pressure for both sexes increased significantly with age (x2 for linear trend = 20.21 for men and 65.81 for women, df = 1, p < 0.001 for both sexes). More women of age 45 years or more had raised blood pressure than men (x2 = 4.67, df = 1, p = 0.031). Many more women (8.0%) than men (0.7%) had a Ponderal Index of greater than 27 (x2 = 19.33, df = 1, p < 0.001). A total of 12 (1.5%) persons were disabled. CONCLUSION: Raised blood pressure and obesity mainly affected women and interventions to improve their health is recommended.     

Treatment of osteoporosis with bisphosphonates

Several bisphosphonates are effective for preventing bone loss associated with estrogen deficiency, glucocorticoid treatment, and immobilization, and for at least partially reversing bone loss in patients with postmenopausal osteoporosis and steroid-induced osteoporosis. The most promising of these agents are etidronate, alendronate, risedronate, and ibandronate. These drugs should have an important role in the prevention and treatment of osteoporosis; however, more research is needed regarding optimal doses and regimens (continuous versus intermittent, oral versus parenteral), comparisons with other agents, and their use in combination with other agents.     

Effect of nitrous oxide on cerebral blood flow velocity after induction of hypocapnia

Triphasic waves (TWs) can be recorded on EEG in the course of several metabolic disorders, mainly hepatic encephalopathy. A case of acute encephalopathy due to naproxen intoxication is reported, in the course of which diffuse, bilateral and symmetrical TWs were recorded. Biochemical mechanisms that might determine both a complex encephalopathy and TWs are discussed.