Renal hypertrophy is a common consequence of diabetes mellitus that precedes and possibly accounts for the increased glomerular filtration rate. We have postulated that the glucose-mediated increase in the intracellular concentration of sodium [Na]i initiates the chain of events leading to the increase in cell size and eventually cell number. Experiments were conducted on Sprague-Dawley rats made diabetic by the intravenous injection of 45 mg/kg body wt of streptozotocin dissolved in a 5 mM citrate buffer solution. Control animals were injected with the vehicle alone. Ninety-six hours and 11 weeks later, measurements of [Na]i were done by NMR spectroscopy on suspensions of proximal tubules, using dysprosium tripolyphosphate as an extracellular shift reagent. At 96 hours after the induction of the diabetes, there was a 60% increase in [Na]i compared to control (P less than 0.01). No further increase in [Na]i was observed during the subsequent 11 weeks of observation. Addition of ouabain (1.0 mM) resulted in a fourfold increase in [Na]i in tubules from control animals, and a 2.5-fold increase in tubules from 96-hour diabetic rats. Ouabain-inhibitable Na+-K+-ATPase activity was substantially higher in the renal tubules of diabetic rats, the increase being proportional to that of [Na]i. In order to ascertain the effect of hyperglycemia on [Na]i, proximal tubules prepared from kidneys of normal and diabetic rats were exposed to low (5 mM) and high (25 mM) concentration of glucose in the media.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
Twelve patients with frequent ventricular premature depolarizations (VPDs) received amiodarone, 600 mg/day, for up to 8 weeks. On days 0, 1, 4, 8, 15, 22, 36, and 57 of treatment, 24-hour ambulatory ECGs were obtained, and multiple blood samples were taken for determination of amiodarone and desethylamiodarone plasma concentrations. All patients had at least 75% suppression of VPDs. The mean duration of therapy before the onset of antiarrhythmic effect was 13.2 days (range 1 to 36 days). Trough amiodarone and desethylamiodarone plasma concentrations at the time of onset of antiarrhythmic effect were 0.86 +/- 0.48 mg/L and 0.23 +/- 0.15 mg/L, respectively. Sixty-seven percent of patients responded at amiodarone concentrations below 1.0 mg/L. For each patient there was a progressive decrease in frequency of VPDs as both amiodarone and desethylamiodarone concentrations increased. Regression modeling indicated that both amiodarone and desethylamiodarone plasma concentrations explained significant variability in the frequency of VPDs, and amiodarone and desethylamiodarone plasma concentrations were highly correlated with each other. There was a trend for desethylamiodarone to explain more variability in frequency of VPDs than amiodarone. 相似文献
Hyperlipidemia may play a role in the progression of diabetic and other renal diseases. Low density lipoprotein (LDL) and other proteins including extracellular matrix components undergo nonenzymatic glycation in vivo. We examined the effects of glycation of LDL as occurs in diabetes (4 to 8%) on binding and uptake by mesangial cells and their proliferation. The glycation of LDL (g-LDL) significantly decreased its binding and uptake by mesangial cells by 15 to 20%, indicating that glycated LDL binds to the LDL receptor, but with lower affinity than LDL. Both LDL and g-LDL modestly stimulated [3H] thymidine incorporation into mesangial cells at 5 to 10 micrograms/ml. Native, oxidized (Ox-LDL) and glycated LDL all bound to the extracellular matrix generated by rat mesangial cells in culture. The binding of LDL, Ox-LDL and g-LDL to mesangial matrix was two to four times higher than to mesangial cells. Binding of LDL and g-LDL was significantly higher to glycolaldehyde modified matrix, which serves as an in vitro model for nonenzymatic glycation end-product cross-linking of matrix which occurs in long-standing diabetes. Based on these findings, we propose that glycation of LDL decreases its binding and uptake by the LDL receptor of mesangial cells and may slow its catabolism. Furthermore, LDL bound to extracellular mesangial matrix can undergo oxidation and generate cytotoxic LDL components. This process may be further enhanced by advanced glycation of the mesangial matrix in diabetes, contributing to glomerular pathology. 相似文献
Background: Opioids are commonly used in conjunction with sedative drugs to provide anesthesia. Previous studies have shown that opioids reduce the clinical requirements of sedatives needed to provide adequate anesthesia. Processed electroencephalographic parameters, such as the Bispectral Index (BIS; Aspect Medical Systems, Newton, MA) and Auditory Evoked Potential Index (AAI; Alaris Medical Systems, San Diego, CA), can be used intraoperatively to assess the depth of sedation. The aim of this study was to characterize how the addition of opioids sufficient to change the clinical level of sedation influenced the BIS and AAI.
Methods: Twenty-four adult volunteers received a target-controlled infusion of remifentanil (0-15 ng/ml) and inhaled sevoflurane (0-6 vol%) at various target concentration pairs. After reaching pseudo-steady state drug levels, the modified Observer's Assessment of Alertness/Sedation score, BIS, and AAI were measured at each target concentration pair. Response surface pharmacodynamic interaction models were built using the pooled data for each pharmacodynamic endpoint.
Results: Response surface models adequately characterized all pharmacodynamic endpoints. Despite the fact that sevoflurane-remifentanil interactions were strongly synergistic for clinical sedation, BIS and AAI were minimally affected by the addition of remifentanil to sevoflurane anesthetics. 相似文献
Primary salivary gland carcinoma with neuroendocrine differentiation is of rare occurrence, especially so in the parotid gland.
Amongst the various reported primary tumors with neuroendocrine differentiation, acinic cell carcinoma (ACC) one such tumor.
A 48 year old lady presented with a gradually increasing right infra-auricular swelling for a period of 1 year which enlarged
suddenly in a short period. Contrast Enhanced Computed Tomography (CECT) suggested diagnosis of Pleomorphic Adenoma. Fine
Needle Aspiration Cytology (FANC) yielded a cystic fluid suggesting a possibility of Warthin’s tumor or Oncocytic lesion.
Intraoperative findings were suggestive of a Warthin’s tumor. Initial histopathological examination of the tumor was suggestive
of neuroendocrine carcinoma. However, extensive sectioning revealed peripheral islands of ACC. Immunoexpression of S-100,
Neuron specific Enolase (NSE), Chromogranin A and Synaptophysin confirmed the diagnosis. The possibility of neuroendocrine
differentiation in a primary salivary gland tumor should be kept in mind whenever a salivary gland tumor shows only neuroendocrine
histology. 相似文献
To identify the role of protein kinase C (PKC) isoforms in multidrug resistance in tumor cells, we examined the PKC isoform pattern in the multidrug resistant P388/ADR cell line and studied the effect of down regulation of PKC isoforms on intracellular daunorubicin accumulation and P-glycoprotein expression. Using monoclonal antibodies to PKC alpha, beta and gamma and flow cytometry technique we showed that P388/ADR cells overexpressed PKC alpha and beta as compared to drug sensitive P388 cells. Prolonged treatment of P388/ADR cells with phorbol myristate acetate (PMA), a procedure that is known to down regulate PKC, resulted in the down regulation of total PKC activity and the PKC beta isoform (at the protein level) that was accompanied by the correction of daunorubicin accumulation in P388/ADR cells. The level of expression of P-glycoprotein in PMA treated cells was similar to that of untreated cells. These results suggest that PKC beta regulates the drug efflux function of P-glycoprotein. 相似文献