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Biomedical subjects

C D Brown

Publications and source records attributed to C D Brown.

At least 19 recordsLinked to original sources
PubMed1992

Hypo-osmolar stimulation of transepithelial Cl- secretion in cultured human T84 intestinal epithelial layers.

Intact epithelial monolayers of T84 human colonic adenocarcinoma cells were exposed from the basolateral surfaces to hypo-osmotic media; in responsive tissues this resulted in a transient stimulation of inward short-circuit current (SCC) to a peak of 12.9 +/- 1.5 (S.E., n = 10) microA/cm2 which declined to prestimulation values of SCC (2.1 microA/cm2) within 5 min. Exposure of T84 cells to hypo-osmotic media results in an increase in cytosolic [Ca2+]i, dependent on extracellular Ca2+ influx. The cell-swelling activated SCC is abolished upon medium Cl- replacement and by 100 microM bumetanide applied to the basal-surfaces, consistent with the inward SCC resulting from transepithelial Cl- secretion. 100 microM DIDS (4,4'-diisothiocyanantostilbene-2,2'-disulphonic acid) also abolished the cell-swelling activated increase in SCC; DIDS is without effect upon the VIP-stimulated SCC, suggesting distinct Cl- channels are involved in the two responses.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1992

Effects of alloxan-induced diabetes on hemorheology in rabbits.

Plasma viscosity (PV), apparent whole blood viscosity (WBV), relative blood viscosity (RV) and erythrocyte deformability (filterability) (EDF) were determined in 13 New Zealand White (NZW) rabbits with alloxan induced-diabetes (AID) and 8 normal NZW rabbits, matched for age, sex and weight. AID rabbits were divided into two groups depending on the duration of hyperglycemia (long-term, greater than 6.0 months (n = 7), and short-term, less than or equal to 3.0 months of hyperglycemia, n = 6). Comparing long-term AID rabbits to normal animals, we found significant increases in WBV (P less than 0.001, 0.005 for high and low rates of shear, respectively), and a marked reduction in EDF (P less than 0.001). There was no significant difference in PV between long-term AID and normal rabbits. Conversely, PV was significantly increased in rabbits with short-term diabetes (P less than 0.01) while there was a concurrent significant increase in WBV measured at high and low rates of shear (P less than 0.001, 0.001, respectively). No difference was detected in EDF between normal and short-term AID rabbits. Furthermore, in long-term AID rabbits there was a strongly positive correlation between RV and reduced erythrocyte deformability (r = 0.94, P = 0.006) while WBV strongly correlated with PV (r = 0.92, P = 0.004) in the short-term AID subgroup. We conclude from these data: (1) elevated blood viscosity in long term AID rabbits is associated with reduced erythrocyte filterability; and (2) elevated WBV in short-term AID rabbits is associated with increased PV.

Animals↗
PubMed1992

Drug interactions in dermatologic surgery.

Intravenous sedation is a popular method of anesthesia in outpatient cosmetic surgery. To ensure a successful surgical outcome, awareness of potential interactions between intravenous agents and patient medications is essential. The more commonly used intravenous drugs are reviewed, with particular emphasis on their side-effects and potential for drug interactions.

Anesthetics↗
PubMed1992

A Cl- conductance sensitive to external pH in the apical membrane of rat duodenal enterocytes.

1. The pH dependence of a chloride conductance in the apical membrane of rat duodenal enterocytes was examined. 2. A stepwise reduction of both internal and external pH from 7.4 to 6.8 resulted in a significant stimulation of 36Cl flux driven by an inside-positive membrane potential. 3. A stepwise reduction in pH had no significant effect upon other parameters such as the initial rate of D-[3H]glucose or voltage-independent 36Cl uptake, suggesting a specific effect upon the chloride conductance. 4. The pH-dependent stimulation of 36Cl uptake exhibited saturation kinetics, with an apparent Vmax (maximum velocity) of 5.5 nmol (mg protein)-1 (4 s)-1 and an apparent Km (Michaelis-Menten constant) of 88 nM H+ ions. 5. To determine the site of action of protons upon the conductance the effect of asymmetrically reducing either the internal or external pH was examined. 6. A step reduction of extracellular pH from 7.8 to 6.8 significantly stimulated the rate of 36Cl uptake. In contrast, a step reduction of internal pH from 7.8 to 6.8 was without effect upon the rate of 36Cl uptake. 7. These results suggest that the chloride conductance on the apical membrane of rat duodenal enterocytes is allosterically regulated by protons at an external site.

Animals↗
PubMed1991

Arginine vasopressin stimulation of chloride secretion in Madin-Darby canine renal epithelial layers.

Arginine vasopressin (AVP) at a concentration of 0.1 microM stimulates an inward short-circuit current (SCC) in voltage-clamped Madin-Darby canine kidney epithelial layers with a mean peak of 3.1 +/- 0.8 microA cm-2 (n = 6). The response to AVP is markedly attenuated when inward SCC is stimulated with forskolin or prostaglandin E1, in Cl(-)-free media and by the Cl(-)-transport inhibitors, bumetanide and 5-nitro-2-(3-phenylpropylamino)-benzoic acid, consistent with an AVP-stimulated basal to apical Cl- secretion. Endogenous release of prostaglandins may contribute to AVP stimulation of Cl- secretion.

Adenylyl Cyclases↗
PubMed1991

Treatment of azotemic, nonoliguric, anemic patients with human recombinant erythropoietin raises whole-blood viscosity proportional to hematocrit.

It has been reported that patients with azotemia have reduced red blood cell (RBC) deformability. Since this is a major determinant of whole-blood viscosity (WBV) and rigid RBCs increase WBV disproportionately relative to the level of hematocrit, it is conceivable that sustained improvement of hematocrit with recombinant human erythropoietin (rhEPO) therapy in azotemic patients might result in abnormally raised WBV. To address this concern, WBV and plasma viscosity (PV) were measured in 9 adult patients (4 men, 5 women) with anemia (mean hematocrit 29.2 +/- 2.7%) and azotemia [mean serum creatinine concentration 339.85 +/- 102.44 mumol/l (3.8 +/- 1.1 mg/dl)] before and after 6 months of treatment with rhEPO (50-175 U/kg given intravenously thrice weekly). Baseline and post-treatment hematocrit, WBV and PV were compared to values derived in 50 normal adult subjects with normal renal function [25 women, 25 men; mean serum creatinine concentration 79.56 +/- 8.84 mumol/l (0.9 +/- 0.1 mg/dl), mean hematocrit 42.4 +/- 3.7%]. To compare rheologic factors at subnormal hematocrits, blood from subjects with normal renal function was diluted with autologous plasma to achieve a range of hematocrits from 20 to 50%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Lipid and lipoprotein profiles relate to peak aerobic power in spinal cord injured men.

The relationship between peak VO2 and serum lipids, lipoproteins, and apolipoproteins was assessed in nine traumatic spinal cord injured (SCI), active, male volunteers. Mean (SD) age, height, and weight were 30.6 (11.6) yr, 171.1 (11.3) cm, and 74.2 (12.5) kg, respectively. Peak VO2 (X = 2.13 l.min-1) was assessed by a graded arm-crank test to maximum, percent body fat (X = 28.7%) by densitometry, and lipid profile by measures of serum triglycerides, total cholesterol (TC), high and low density lipoprotein cholesterol (HDL-C and LDL-C, respectively), apolipoproteins (apoA-1, apoB), and various ratios of lipids, lipoproteins, and apolipoproteins. Significant inverse relationships emerged between peak VO2 and TC/HDL-C (r = -0.86; P less than 0.01), apoB/apoA-1 (r = -0.75; P less than 0.05), triglycerides (r = -0.73; P less than 0.05), and LDL-C/HDL-C (r = -0.72; P less than 0.05). Direct correlations (P less than 0.05) were demonstrated between peak VO2 and apoA-1/apoB (r = 0.71) and HDL-C/apoA-1 (r = 0.64). The present results indicate that, for active, mid-to-lower thoracic SCI men, the putative atherogenic and antiatherogenic lipid, lipoprotein, and apolipoprotein indices are significantly related to peak VO2 in a manner similar to that described for the able-bodied. These findings indicate the relevance of aerobic fitness assessment in planning CHD prevention strategies for the SCI.

Adult↗
PubMed1990

Primary rat Sertoli and interstitial cells exhibit a differential response to cadmium.

Two cell types central to the support of spermatogenesis, the Sertoli cell and the interstitial (Leydig) cell, were isolated from the same cohort of young male rats and challenged with cadmium chloride to compare their susceptibility to the metal. Both cell types were cultured under similar conditions, and similar biochemical endpoints were chosen to minimize experimental variability. These endpoints include the uptake of 109Cd, reduction of the vital tetrazolium dye MTT, incorporation of 3H-leucine, change in heat-stable cadmium binding capacity, and production of lactate. Using these parameters, it was observed that the Sertoli cell cultures were adversely affected in a dose-and time-dependent manner, while the interstitial cell cultures, treated with identical concentrations of CdCl2, were less affected. The 72-hr LC50's for Sertoli cells and interstitial cells were 4.1 and 19.6 microM CdCl2, respectively. Thus, different cell populations within the same tissue may differ markedly in susceptibility to a toxicant. These in vitro data suggest that the Sertoli cell, in relation to the interstitium, is particularly sensitive to cadmium. Because the Sertoli cell provides functional support for the seminiferous epithelium, the differential sensitivity of this cell type may, in part, explain cadmium-induced testicular dysfunction, particularly at doses that leave the vascular epithelium intact.

Animals↗
PubMed1990

Effects of different exercise training intensities on lipoprotein cholesterol fractions in healthy middle-aged men.

Exercise training has been associated with decreases in total cholesterol and increases in high-density lipoprotein (HDL) cholesterol. The effect of the intensity of the exercise on alterations in cholesterol and lipoprotein fractions has not been defined and is the subject of this study. We divided 49 healthy men (aged 44 +/- 8 years) into four groups and evaluated them before and after 12 weeks of cycle ergometer exercise training at (1) an intensity of 65% of maximal achieved heart rate, (2) 75% maximal heart rate, (3) 85% maximal heart rate, and (4) a 12-week nonexercise control period. Pre- and post-training evaluations included maximal ergometer exercise ECG examinations with measurement of maximal minute oxygen consumption and serum total cholesterol, HDL cholesterol, and triglyceride levels. Low-density (LDL) and very low-density lipoprotein (VLDL) cholesterol levels were calculated. Dietary histories were obtained before and after the training period, and body weight and percentage of body fat were measured. Post-training oxygen uptake was significantly increased (training effect) in the groups exercising to 65%, 75%, and 85% maximal heart rate. Results of within-group analysis showed significant increases in the HDL cholesterol fractions in the 75% and 85% groups but not in the 65% group or the control group. Significant decreases in calculated LDL fractions occurred only in the 75% exercise-trained group with maximal heart rate. Aerobic exercise training favorably alters plasma lipoprotein profiles. A minimum training intensity equal to 75% maximal heart rate is required to the increase HDL cholesterol level.

Adult↗
PubMed1990

Clinical and blood rheologic stability in erythropoietin-treated predialysis patients.

We assessed human recombinant erythropoietin (rHuEPO) as treatment for anemia in azotemic patients who did not require dialytic therapy. The study group consisted of 5 azotemic men and 5 women (mean serum creatinine concentration 5.2 +/- 3.2 mg/dl) whose mean hematocrit was 27.4 + 3.0%. Of these, 5 subjects had diabetic nephropathy. The study was a 12-month rHuEPO maintenance (open label) trial in which a previously established median i.v. dose of 50 U/kg was given three times each week. The rHuEPO was temporarily discontinued when the target hematocrit of 37% was achieved, and after the hematocrit decreased below 35%, it was restarted at half the initial dose. Of the 10 subjects who started the trial, 2 (both nondiabetic) deteriorated early in the study, and before a hematocrit rise was attained commenced maintenance hemodialysis. All subjects completed the year of study and achieved the target hematocrit. Mean hematocrit rose 42% (p less than 0.001) in a mean period of 3.3 +/- 1.3 months. When treatment was interrupted at a hematocrit of 37%, mean absolute reticulocyte count fell from 1.21 +/- 0.59% to 0.38 +/- 0.14% within one week. After rHuEPO was withdrawn, the increase in hematocrit persisted for a mean of 13.0 +/- 6.0 days and patients were able to sustain hematocrits above 35% for a mean of 1.44 +/- 0.6 months. Coincidentally with the rise in hematocrit during rHuEPO treatment, whole-blood viscosity increased significantly (p less than 0.001) but remained within the range for individuals with normal renal function at an equivalent hematocrit (p greater than or equal to 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Stimulation of Cl/HCO3 exchange in rat duodenal brush border membrane vesicles by cAMP.

Brush border membrane vesicles have been used to study the regulation of rat duodenal HCO3 secretion. When vesicles were loaded with cAMP and ATP SITS-sensitive Cl/HCO3 exchange (unidirectional 36Cl influx in response to an outward-facing OH/HCO3 gradient) was stimulated by approximately 25%. In contrast, there was no effect of cAMP upon SITS-insensitive 36Cl uptake. The stimulation of Cl/HCO3 exchange caused by cAMP was abolished in the presence of a specific heat-stable cAMP-dependent protein kinase inhibitor. These results suggest that Cl/HCO3 exchange, and hence HCO3 secretion, is regulated by cAMP via phosphorylation of some component of the membrane associated with the transport protein.

Animals↗
PubMed1989

Cl-HCO3 exchange and anion conductance in rat duodenal apical membrane vesicles.

Transport mechanisms for Cl and HCO3 anions in the apical membrane of rat duodenal enterocytes have been characterized using brush-border membrane vesicles. 36Cl uptake was stimulated by outwardly directed gradients of OH, HCO3, and Cl anions. The anion exchanger was sensitive to inhibition by 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS) (Ki, 1.3 mmol/l), 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), and furosemide. The process was electroneutral, since voltage clamping the membrane potential to 0 mV or applying a large inside-positive potential had no effect on the magnitude of uptake. The kinetic properties of the exchanger were measured and an apparent Km of 9.8 mM Cl and a Vmax of 134 nmol.mg protein-1.4 s-1 were found. In addition, an electrogenic conductive component of 36Cl uptake was found. This component was dependent on an inside-positive membrane potential and was inhibited by the Cl channel blocker diphenylamine-2-carboxylate. SITS, DIDS, and furosemide had no effect on the electrogenic component of 36Cl uptake. An apparent anion selectivity of SCN greater than I greater than Br greater than Cl greater than HCO3 greater than SO4 greater than Glu greater than PO4 was found. These results support the presence of both Cl-HCO3 exchange and a conductive anion channel in the apical membrane of rat duodenal enterocytes.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1987

Variations of susceptibility to alloxan induced diabetes in the rabbit.

The variations of susceptibility to alloxan induced Diabetes in a total of seventeen rabbits was described. Our study was designed to explore dosage schedules which might improve rabbit responsiveness to and survival after alloxan treatment. A wide range of response to intravenously administered alloxan was observed. Permanent diabetes (blood glucose 350 mg/dl) was found in three rabbits after a single injection (60 mg/kg in one, 100 mg/kg in two). This effect has persisted for eight months. By contrast, two other rabbits injected with a single dose of alloxan (60 mg/kg) developed only transient hyperglycemia. Similarly, four other rabbits either did not respond or had an incomplete response after receiving a total dose of 120 mg/kg. These data suggest that there is extreme variability in individual rabbits susceptibility to the diabetogenic affects of alloxan.

Alloxan↗
PubMed1987

Fatigue, acid-base and electrolyte changes with exhaustive treadmill exercise in hemodialysis patients.

Aerobic conditioning exercises have been shown to be beneficial for maintenance hemodialysis patients, but biochemical changes during exhaustive exercise in these functionally anephric patients have been less thoroughly studied. We evaluated serum biochemical changes in 7 patients during and after treadmill exercise to patient exhaustion. Duration of exercise was limited by lower leg fatigue without claudication. At exhaustion, only mild changes from baseline rest values were noted in arterial pH (7.39 +/- 0.03-7.33 +/- 0.04) and lactate (0.94 +/- 0.3-5.73 +/- 2.68 mmol/l) despite normal exercise-induced intracellular fluid shifts as evidenced by albumin concentration increases (44.9 +/- 2.8-49.3 +/- 3.1 g/l). Increases in serum K+ concentrations are also modest (change in K from baseline = 0.87 +/- 0.22 mmol/l). An explanation for these minimal biochemical alterations at exhaustion is unclear, but could relate to exercise being limited well below estimated maximum cardiac output and muscle O2 extraction levels by early, unexplained muscle fatigue. Fatigue in hemodialysis patients does not appear to be due to muscle hypoxia.

Acid-Base Equilibrium↗
PubMed1987

Heterogeneity of cholesterol homeostasis in man. Response to changes in dietary fat quality and cholesterol quantity.

Studies were carried out to examine the effects of dietary fat and cholesterol on cholesterol homeostasis in man. 75 12-wk studies were carried out during intake of 35% of calories as either saturated or polyunsaturated fat, first low and then high in dietary cholesterol. Dietary fat and cholesterol intakes, plasma lipid and lipoprotein levels, cholesterol absorption and sterol synthesis in isolated blood mononuclear leukocytes were measured during each diet period. In 69% of the studies the subjects compensated for the increased cholesterol intake by decreasing cholesterol fractional absorption and/or endogenous cholesterol synthesis. When an increase in plasma cholesterol levels was observed there was a failure to suppress endogenous cholesterol synthesis. Plasma cholesterol levels were more sensitive to dietary fat quality than to cholesterol quantity. The results demonstrate that the responses to dietary cholesterol and fat are highly individualized and that most individuals have effective feedback control mechanisms.

Cells, Cultured↗