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.     

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.     

Geometric requirements for membrane perturbation and anesthetic activity. Conformational analysis of alphaxalone and delta 16-alphaxalone and 2H NMR studies on their interactions with model membranes

2H NMR spectra were obtained for dimyristoylphosphatidylcholine multilamellar dispersions, perdeuterated in the fatty acid chains, in the presence and absence of two steroid analogs. The presence of the active anesthetic steroid alphaxalone results in consistently smaller 2H quadrupolar splittings (delta nu Q) for individual C2H2 segments of the fatty acid chains, indicating increased molecular disorder. In contrast, the inactive analog delta 16-alphaxalone causes no significant change in the 2H spectra of the phospholipid. The conformational analysis of alphaxalone and delta 16-alphaxalone in solution was carried out with the help of 1H and 13C high resolution NMR spectroscopy and the results were used to propose a molecular model for the interaction of the two steroids with membrane phospholipids. The model correlates the observed differences in the manner in which the two steroids interact with model membranes with differences in their respective conformations and provides a molecular basis for anesthetic steroid activity.     

Orthotopic liver transplantation in a patient with carbamyl phosphate synthetase deficiency and cystic fibrosis

A 15-year-old female with carbamyl phosphate synthetase deficiency, cystic fibrosis, and cystic fibrosis-related diabetes underwent orthotopic cadaveric liver transplantation. Metabolic control was maintained during the procedure with nutritional support and the use of intravenous sodium phenylacetate and benzoate. Her postoperative course was complicated by seizures and a transient decline in her pulmonary function tests, which returned to preoperative levels within one year of the transplant. Now, four years post-transplant, her quality of life has dramatically improved. There are only four Canadian centres with paediatric liver transplantation programs. However, expert medical care for adults with inborn error of metabolism is even more limited, suggesting that access to adult medical care is one of the many factors to be considered when liver transplantation is contemplated for patients with metabolically unstable conditions.     

Prognostic significance of HIV-associated oral lesions and their relation to therapy

The oral manifestations of HIV infection have been considered to be of value in assessing disease progression in the developed world. However, the potential use of oral lesions as prognostic markers in resource-poor countries has yet to be fully investigated. There is reasonably compelling evidence in the developed world for an association between oral lesions and viral load. However, the true nature of this association is less clear and there are few data available from the developing world. With the introduction of HAART, a change in prevalence of the oral manifestations of HIV infection has been observed, including regression of oral candidiasis, Kaposi's sarcoma and oral hairy leukoplakia. However, oral condylomata and herpes simplex virus infection appear to persist with HMRT therapy. Further research in partnership with resource-poor countries is required to document disease progression and the associated oral lesions in both adults and children.     

Treatment of lipomas assisted with tumescent liposuction

BACKGROUND: Lipoma is a common soft-tissue tumour of mature fat cells. Although surgical excision is effective, treatments that are less invasive and not associated with disfigurement of scar would be ideal for the treatment of lipomas. Recently, tumescent liposuction has been used for the treatment of lipomas. OBJECTIVE: To evaluate the efficacy of tumescent liposuction in lipoma treatment, we reviewed our experience of lipoma treatment by tumescent liposuction. METHODS: A total of 21 patients presenting with 31 lipomas were treated with tumescent liposuction. After liposuction, remaining stromas were removed by a haemostat through the small incision. Tumour size and post-operative complications were recorded before and after treatment. RESULTS: A total of 31 lipomas of 21 patients were treated by tumescent liposuction. The size of lipomas ranged between 1.2 and 11 cm (mean size, 4.1 cm). In 23 cases, there were no complications. However, remnant lipomas, bruise, haematoma and immediate dimpling were found as complications. CONCLUSION: Tumescent liposuctions with extracting remnant fat tissue and fibrous tissue through the opening for liposuction can be an effective treatment technique in lipoma treatment in the efficacy and cosmetic outcomes and this method can be a substitute for excision in treating large lipomas.