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Biomedical subjects

C D Fan

Publications and source records attributed to C D Fan.

16 recordsLinked to original sources

Stimulation of guanosine-5'-o-(3-[35S]thio)triphosphate binding in digitonin-permeabilized C6 rat glioma cells: evidence for an organized association of mu-opioid receptors and G protein.

The guanosine-5'-O-(3-[35S]thio)triphosphate ([35S]GTPgammaS) binding assay for the determination of relative opioid efficacy has been adapted to measure G protein activation in digitonin-permeabilized C6 rat glioma cells expressing a cloned mu-opioid receptor. The mu-agonist [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) caused a 3-fold increase in [35S]GTPgammaS binding over basal in a naloxone-sensitive manner. Relative mu-agonist efficacy was DAMGO > fentanyl > or = morphine > buprenorphine. Nalbuphine showed no efficacy. G protein activation by receptors has been predicted to occur by random encounter. In this model a reduction in the number of receptors will decrease the rate of G protein activation but not the maximum number of G proteins activated. To test this model C6 mu cells were treated with the irreversible mu-antagonist beta-funaltrexamine (10 nM) prior to permeabilization. This reduced the number of mu-opioid receptors determined with [3H]diprenorphine to 23 +/- 3% of control with no change in affinity. A commensurate reduction (to 29 +/- 10% of control) in the level of [35S]GTPgammaS binding stimulated by DAMGO was observed, but the t(1/2) for [35S]GTPgammaS binding remained unchanged. Thus, random encounters of receptor and G protein failed to occur in this permeabilized cell preparation. A model that assumes an organized association of G proteins with receptors better describes the activation of G proteins by opioid mu-receptors.

Analgesics, Opioid↗

Antifibrillatory effect of esmolol alone and in combination with lidocaine.

The primary objective of this study was to determine the effect of esmolol, administered alone and in combination with lidocaine, on ventricular fibrillation threshold (VFT) in pigs. A secondary objective was to determine the relationship between blood esmolol concentrations and VFT. We determined VFT using a train of electrical stimuli delivered to the right ventricle after eight paced beats at a basic cycle length of 285 ms. Current was increased in 2-mA increments until VF occurred. VFT determinations were performed during administration of esmolol 1,000 mu g/kg/min, during a continuous infusion of lidocaine, and during infusion of esmolol and lidocaine in combination. Mean increases in VFT from baseline during infusion of esmolol and lidocaine alone were 32.3 +/- 12.9 and 8.5 +/- 7.2 mA, respectively (p < 0.05, each drug compared with baseline; p < 0.05, esmolol vs. lidocaine). Mean increase in VFT from baseline during infusion of the combination was 52.0 +/- 22.0 mA (p < 0.05 as compared with baseline and with esmolol or lidocaine alone). The relationship between blood esmolol concentrations and VFT was described by a counterclockwise hysteresis curve, suggesting delay in equilibration of esmolol between blood and site of effect. The antifibrillatory efficacy of esmolol is significantly greater than that of lidocaine in this model. Administration of the two agents in combination resulted in significantly greater antifibrillatory efficacy than that associated with either drug administered alone.

Adrenergic beta-Antagonists↗

Resistance to erythropoietin: immunohemolytic anemia induced by residual formaldehyde in dialyzers.

Because of inadequate renal synthesis of erythropoietin, the anemia associated with chronic renal failure has been treated successfully in most patients on hemodialysis with recombinant human erythropoietin. Hemolysis due to anti-Nform antibody in dialysis patients with the reused dialyzer may be one of the factors that cause refractoriness to erythropoietin therapy. Patients who do not respond to erythropoietin administration should be screened for anti-Nform antibody.

Anemia↗

Mesangial overload in experimental membranous nephropathy.

1. The distribution and amount of ferritin in the glomeruli following intravenous injection of radiolabeled ferritin (125I-ferritin) was studied in 25 normal rats and in 25 rats with membranous nephropathy. The animals used were male Sprague-Dawley rats weighing 180-200 g at the beginning of the experiment. Membranous nephropathy was induced by repeated iv injections of 1.0 mg cationic bovine serum albumin during 28 days. 2. At the end of the experiment the animals received 125I-ferritin iv and were sacrificed 2, 6, 12, 24 and 36 h later, and the glomeruli were isolated. 3. Mean (+/- SEM) levels of 125I-ferritin in the glomeruli reported as cpm/mg protein in rats injected with cationic bovine serum albumin were: 731.8 +/- 155.6 after 2 h, 946.4 +/- 268.2 after 6 h, 565.4 +/- 143.5 after 12 h, 251.8 +/- 26.5 after 24 h, and 202 +/- 29.1 after 36 h. Mean (+/- SEM) 125I-ferritin in normal rats were: 2 h: 256.2 +/- 44.6; 6 h: 214.2 +/- 8.78; 12 h: 198.2 +/- 32.2; 24 h: 51.5 +/- 3.57; 36 h: 40.6 +/- 5.48. 125I-ferritin levels in the glomeruli isolated from rats injected with cationic bovine serum albumin were significantly higher than in control rats at 2, 6, 24 and 36 h. 4. The distribution of ferritin in the glomeruli was studied by a direct immunofluorescence technique. Normal and nephrotic rats showed ferritin in the glomerular mesangium only, with similar pattern and intensity. 5. These data show that rats with membranous glomerulonephritis induced by cationic bovine serum albumin presented an increased macromolecule uptake by the glomerular mesangium. However, the mechanism underlying this mesangial overloading is still unknown.

Animals↗

Simple and rapid high-performance liquid chromatographic assay for esmolol.

A procedure for determining esmolol concentrations in blood is described. Dichloromethane was used to extract esmolol from the blood and to inhibit the activity of blood esterases. Blood esmolol concentrations were determined by high-performance liquid chromatography using 3-methoxy-O-demethylencainide as the internal standard. The limit of detection of this assay was 5 ng/ml. The relationship between the peak-height ratio of esmolol and the internal standard was linear in the concentration ranges 10-30,000 ng/ml. The mean absolute and relative recoveries of esmolol from blood were 84 and 89%, with coefficients of variation less than 3%. This method has been used in our laboratory for pharmacokinetic and pharmacodynamic studies.

Adrenergic beta-Antagonists↗

Assessment of proteinuria by using the protein/creatinine ratio of single-voided urine.

Quantitative 24-hour urine protein excretion is used in the diagnosis, the monitoring of therapeutic effects and the prognosis of renal disease. However, this method is time-consuming, cumbersome and often inaccurate. Many studies have shown that the single voided urine protein/creatinine (Pr/Cr) ratio relates well with 24-hour urine protein excretion and can be substituted for evaluating some conditions. In our study, 41 patient with renal disease (25 men, 16 women) with a mean age of 43 years (range, 20-79 years), not only collected 24-hour urine, but also collected single voided urine at four different times. There was an excellent correlation between 24-hour urine protein excretion and the single voided urine Pr/Cr ratio at various degrees of creatinine clearance and ranges of proteinuria. The highest correlation was found in urine specimens collected at 16:00 hours with a correlation coefficient (r) of 0.91. Other urine specimens also showed a good relation with a correlation coefficient of above 0.80. The creatinine clearance (Ccr) greater than or equal to 70 ml/min group showed a better relationship than the Ccr less than 70 ml/min group. The proteinuria more than 1.0 g/day group also showed a better relationship than the group with proteinuria of less than 1.0 g/day. However, these differences were not statistically significant. No significant differences between the different age groups or sexes, using the single voided urine Pr/Cr ratio to estimate the 24-hour urine protein excretion were found. It is concluded that the single voided urine Pr/Cr ratio correlates highly with 24-hour urine protein excretion and could be an alternative means for disease monitoring and screening.

Adult↗

Focal glomerulosclerosis: a clinico-pathological analysis of 36 adult patients with idiopathic nephrotic syndrome.

A retrospective study was conducted to determine the clinicopathological correlation of focal glomerulosclerosis in 36 adult patients with idiopathic nephrotic syndrome. All cases were divided into two groups, focal segmental glomerulosclerosis (FSGS, 23 cases) and focal global glomerulosclerosis (FGBG, 13 cases), on the basis of pathological findings. Most patients with FSGS were non-responsive/partial-responsive (22/22) to the corticosteroid treatment. By contrast, those with FGBG gave a relatively high responsive rate of 7/12 to the same therapy. The 5 non-responders with FGBG, however, were noted to have intensive interstitial fibrosis/mononuclear cell infiltrate of the renal lesions (4 cases), or diffusely glomerular Clq deposition without other coexisting immune deposits (1 case). Most cases of FSGS (20/23) became steroid dependent or remained heavy proteinuria resistant to corticosteroids/other immunosuppressive agents over a mean of 3.4 (ranged, 1 to 7) years after renal biopsy. Three of the 5 patients of FGBG initially non-responsive/partial-responsive to corticosteroids turned out to have protein-free urine (less than 4 mg/hr/m2) (2 patients) 1 month after leaving the hospital and became mildly proteinuric (1 patient) two months after discharge, respectively. The remainders of FGBG (10/13) were free of protein in their urine sample or had occasional episodes of proteinuria over a mean duration of 4.1 (ranged, 1 to 7) years. In addition, chronic renal insufficiency on discharge was noted in 2 cases of FSGS (2/23) and 1 case of FGBG (1/13). Only two cases of FSGS (2/23) progressed into a uremic status 3 and 5 years, respectively, after the time of the presumed clinical onset of their disease. These findings suggest that FGBG clinically behaves similar to a minimal change disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗