Induction Of Endothelin-1 Expression By Glucose: An Effect Of Protein Kinase C Activation

Enhanced actions or levels of endothelin-1 (ET-1), a potent vasoconstrictor, have been associated with decreased blood flow in the retina and peripheral nerves of diabetic animals and may be related to the development of pathologies in these tissues. Hyperglycemia has been postulated to increase ET-1 secretion in endothelial cells. We have characterized the mechanism by which elevation of glucose is increasing ET-1 mRNA expression in capillary bovine retinal endothelial cells (BREC) and bovine retinal pericytes (BRPC). Elevation of glucose, but not mannitol, from 5.5 to 25 mmol/l for 3 days increased membranous protein kinase C (PKC) activities and ET-1 mRNA in parallel levels by 2-fold in BREC and BRPC. These effects were reversed by decreasing glucose levels to 5.5 mmol/l for an additional 2 days. Glucose-induced ET-1 overexpression was inhibited by a general PKC inhibitor, GF109203X, and a mitogen-activated protein kinase kinase inhibitor, PD98059, but not by wortmannin, a phosphatidylinositol 3-kinase inhibitor. By immunoblot analysis, PKC-beta 2 and -delta isoforms in BREC were significantly increased relative to other isoforms in the membranous fractions when glucose level was increased. Overexpression of PKC-beta 1 and -delta isoforms but not PKC-zeta isoform by adenovirus vectors containing the respective cDNA enhanced in parallel PKC activities, proteins, and basal and glucose-induced ET-1 mRNA expression by at least 2-fold. These results showed that enhanced ET-1 expression induced by hyperglycemia in diabetes is partly due to activation of PKC-beta and -delta isoforms, suggesting that inhibition of these PKC isoforms may prevent early changes in diabetic retinopathy and neuropathy.     

Knowledge of rural nurses' aides about end-of-life care

Currently, little is known about the role of nurses' aides (NAs) in rural long-term care facilities or their impact on the process of death and dying in rural healthcare environments. Focus groups with NAs were held in 6 rural counties located in 5 states to assess attitudes and perceptions about end-of-life care and training needs. Key informants from 8 states and the District of Columbia added to the understandings. Nurses' aides (N = 63) and key informants (N = 21) worked in a variety of rural settings that provide end-of-life care (ie, nursing homes, hospitals, hospices, home healthcare agencies). Five themes about the needs of rural NAs around end-of-life care were identified in the focus groups, and 4 themes emerged from key informant interviews. A prototype computer-based training module on communication about end-of-life issues was developed, tested, and found useful and compelling.     

PROGRESSIVE SUPRANUCLEAR PALSY PRESENTING WITH PSYCHIATRIC FEATURES

SUMMARY A patient with progressive supranuclear palsy who presented with psychiatric features is reported. His case illustrates the difficulty of early diagnosis of this condition. Associated psychiatric symptoms are common and may precede the occurrence of gaze palsy. Our patient's behavioural problems responded to fluoxetine.     

Hyperkalemia Associated With High-Dose Trimethoprim-Sulfamethoxazole in a Patient With the Acquired Immunodeficiency Syndrome

When given in standard dosages to treat bacterial respiratory and urinary tract infections, trimethoprim-sulfamethoxazole (TMP-SMX) is not commonly associated with hyperkalemia. However, the emergence of the acquired immunodeficiency syndrome has led to increased numbers of patients with Pneumocystis carinii pneumonia (PCP) who require high-dose TMP-SMX therapy. A 25-year-old man with human immunodeficiency virus infection developed hyperkalemia while receiving high-dose TMP-SMX for PCP. His baseline serum potassium of 3.0 mEq/L, which increased to 4.2 mEq/L after potassium replacement therapy, rose to 6.9 mEq/L after 8 days of TMP-SMX. No other etiology was found for the hyperkalemia, and the disorder resolved when TMP-SMX was stopped. It recurred when the patient was rechallenged with high doses of TMP-SMX during a second treatment course for PCP. This case and a review of previous reports highlight the importance of monitoring serum potassium concentrations in patients receiving high-dose TMP-SMX.     

Cytotoxicity of a BIS-GMA dental composite before and after leaching in organic solvents.

Cell culture techniques were used to determine the source of cytotoxic agents in a commercial BIS-GMA composite. The material was polymerized according to the manufacturer's directions and leachable components were removed by room temperature extraction in ethanol, chloroform, or toluene. The leachable components in the extracts were identified using infrared spectrographic analysis. Thin layer chromatographic analysis was used to determine the number of constituents. These constituents were separated by gas chromatography and then identified by mass spectrographic analysis. Succinic dehydrogenase activity and radioactive labeling with tritiated leucine were used to evaluate cell metabolism and protein synthesis, respectively. The infrared analysis of the extracts showed that the primary component was unreacted BIS-GMA. Trace amounts of 2-hydroxy-4-methoxy-benzophenone, a light stabilizer, as well as a phenyl ester of benzoic acid which was probably degraded from BIS-GMA, were detected by the mass spectrographic method. The removal of leachable components caused a 90% decrease in toxicity compared to the nonextracted BIS-GMA samples. The extracted BIS-GMA samples showed no cellular response compared to the Teflon negative control.