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Biomedical subjects

N Agarwal

Publications and source records attributed to N Agarwal.

At least 145 records · Page 8Linked to original sources

Production of bovine rhodopsin by mammalian cell lines expressing cloned cDNA: spectrophotometry and subcellular localization.

Cloned cDNA encoding bovine rhodopsin has been recombined into an expression vector and cotransfected with an antibiotic resistance plasmid into cultured human embryonic kidney cells. The resulting cell lines produce 100-200 micrograms of bovine opsin per liter of saturated tissue culture medium (10(9) cells). Incubation in vitro with 11-cis retinal produces a photolabile pigment the absorbance spectrum of which is indistinguishable from that of bona fide bovine rhodopsin. Expressed rhodopsin accumulates in the plasma membrane as determined by immunoelectron microscopy.

Animals↗

Prevention of postischaemic lipid peroxidation and liver cell injury by iron chelation.

Liver ischaemia was induced by cross clamping the hilar pedicle for 30 minutes in groups of rats with or without treatment with the iron chelating agent desferrioxamine (deferoxamine, DFR). The groups included eight animals each and were divided into the following treatment categories: control; ischaemia alone; ischaemia with subsequent reperfusion; ischaemia preceded by DFR, 60 mg/kg body weight; and reperfusion preceded by 20, 40, or 60 mg/kg DFR. The drug was given intravenously five minutes before either ischaemia or reperfusion. Malondialdehyde (MDA), a product of lipid peroxidation, and histopathological changes of liver tissue samples were used as indicators of hepatocellular injury. Lipid peroxidation (MDA concentration in mumol/kg liver tissue) was highest (4.76 (1.19] after ischaemia without reperfusion and less pronounced (2.87 (0.34] after reperfusion. Both concentrations, however, were significantly (p less than 0.05) higher than basal (control) values (1.78 (0.27]. At 60 mg/kg body weight, DFR treatment reduced MDA to basal or even lower concentrations in both situations (1.98 (0.08) and 1.26 (0.06), respectively) with a corresponding improvement in liver histopathology. Lower DFR doses were less protective. The data suggest that liver ischaemia is associated with free radical initiated, and apparently iron catalysed lipid peroxidation, which can be significantly decreased by iron chelation.

Animals↗

Binding properties of diethylcarbamazine.

Diethylcarbamazine (DEC) reacted with liver cell plasma membrane of rodent hosts-cotton rat, albino rat and Mastomys natalensis exhibiting the presence of both saturable and unsaturable components. The presence of lectins or sugar derivatives did not affect the binding significantly. The drug showed similar binding pattern with serum but the saturation was reached at a much lower concentration of the ligand. Data obtained with a variety of macromolecules, particularly with the homopolymers of amino acids indicate that DEC does not require any specific constituent of the membrane for binding. The nonspecific nature of DEC binding does not provide any convincing clue for the accumulation of microfilariae specifically in the liver following the drug treatment.

Animals↗

Pelvic fibromatoses--a rare gynecological entity.

A rare case of pelvic fibromatoses is reported. This condition is rarely encountered in gynecological practice but when encountered, creates a diagnostic and therapeutic challenge. The reported patient highlights the difficulties encountered in surgical excision (done twice) and illustrates the local aggressive growth behavior of this entity.

Adult↗

Overinflation of pneumatic antishock garments in the elderly.

The hemodynamic effects of pneumatic antishock garment application in high-risk elderly patients were examined in 10 preoperative patients (mean age 66.5 +/- 6.4 years) with the pneumatic antishock garments uninflated, after 15 minutes of inflation to 50 mm Hg, and after 15 minutes of inflation to 75 mm Hg. After inflation, significant increases in right atrial pressure (89 percent), pulmonary capillary wedge pressure (34 percent), and mean pulmonary artery pressure (21 percent) were noted. Mean peripheral arterial pressure increased 11.2 percent. Depression of the cardiac index (18 percent), left ventricular stroke work (20 percent), and right ventricular stroke work (16.4 percent) with associated increases in total peripheral resistance (26 percent) and pulmonary vascular resistance (18 percent) occurred in 5 of 10 patients. Left ventricular function curves revealed a progressive decrease in ventricular function at 50 mm Hg and 75 mm Hg. We have concluded that the effect of the pneumatic antishock garment on myocardial function is variable and unpredictably dangerous in the elderly patient with diminished myocardial reserve. As no significant benefit was derived from inflation pressures greater than 50 mm Hg in these patients, the lowest combination of pressures producing the most efficacious results should be used.

Aged↗

Pharmacologically different Na/H antiporters on the apical and basolateral surfaces of cultured porcine kidney cells (LLC-PK1).

Proximal tubule cells of the kidney contain, on their apical surface, an amiloride-sensitive Na/H antiporter that functions in Na reabsorption and proton secretion. We have investigated the localization of the antiporter in a cloned cell line of porcine renal origin, LLC-PK1/Cl4, which is often considered to be a useful model of the proximal tubule. Transport measurements were performed with differentiated monolayers grown on Nuclepore filters, permitting independent access to the apical and basolateral cell surfaces. In control experiments with LLC-PK1/Cl4 monolayers, three marker transport systems showed the expected polarity: 87% of ouabain-sensitive Rb uptake was at the basolateral surface, and 99% of Na-dependent alpha-methylglucoside transport and 93% of Na-dependent D-aspartate (L-glutamate) transport were at the apical surface. By contrast, the monolayers displayed significant Na/H antiporter activity (assayed as ethylisopropylamiloride-sensitive 22Na uptake) at both cell surfaces, with an apical uptake rate amounting to 44% and a basolateral rate amounting to 56% of the total. Significantly, the apical and basolateral antiporters could readily be distinguished from one another on the basis of ethylispropylamiloride sensitivity. The apical system had an IC50 of 13 microM, close to that reported for kidney brush border vesicle preparations, whereas the basolateral system had an IC50 of 44 nM, similar to values seen in undifferentiated LLC-PK1 cells and other cultured cell lines. The PKE20 mutant, previously selected from LLC-PK1/Cl4 on the basis of resistance to ethylisopropylamiloride, was found to overexpress the more resistant antiporter both during rapid growth and on its apical cell surface at confluence; normal amounts of the more sensitive antiporter were seen on the basolateral surface of confluent PKE20 cells. Taken together, these results suggest that there are two distinct forms of the Na/H antiporter, which are under separate genetic control.

Animals↗

Predictive ability of various nutritional variables for mortality in elderly people.

Nutritional indices (percentage ideal body weight [IBW], serum albumin, serum transferrin, total lymphocyte count [TLC] and delayed cutaneous hypersensitivity [DH] response) were assessed in 80 consecutive patients (aged 85-100 y) within 24 h of admission to determine their predictive value for mortality. Nine patients died. Pearson correlation analysis demonstrated that death was significantly (p less than 0.05 to less than 0.01) associated with sepsis, serum albumin less than 30 g/L, TLC less than or equal to 1500 cells/mm3, and percentage IBW less than or equal to 90%. However, when serum albumin was controlled for, logit regression analyses demonstrated that the impact of other nutritional indices on death was insignificant. The effect of serum albumin remained significant (p less than 0.05 to less than 0.01) even when age and physician's diagnosis were held constant. With the logit model, serum albumin greater than or equal to 30 g/L had a sensitivity of 0.33, specificity of 0.99, and overall predictive power of 0.91. Serum albumin is thus the simplest and best single predictor of mortality and can provide early identification of elderly people at increased risk of death.

Aged↗

Manipulation of ascitic fluid pressure in cirrhotics to optimize hemodynamic and renal function.

Intra-abdominal pressure (IAP), measured via a transurethral catheter, hemodynamic, and renal functions were evaluated in 25 cirrhotic patients admitted to ICU with variceal bleeding, tense ascites, and peripheral edema. In patients with an IAP greater than 25 cm H2O, a paracentesis was performed to decrease the IAP by 10 cm H2O. After paracentesis, a decrease in the IAP from 33.47 to 19.06 cm H2O (p less than 0.001) resulted in a decrease in total peripheral resistance (TPR) (p less than 0.01) and a significant increase in cardiac index (CI) (p less than 0.001), stroke index (p less than 0.001), left ventricular stroke work (LVSW) (p less than 0.01), and right ventricular stroke work (p less than 0.01). The therapeutic effects of paracentesis on renal function were: a decrease in BUN and serum creatinine (p less than 0.001) and an increase in the creatinine clearance (Ccr) (p less than 0.001), urine volume (p less than 0.001), osmolar clearance (Cosm) (p less than 0.001), and urine creatinine (p less than 0.001) values. The IAP correlated directly with the TPR (r = +0.35, p less than 0.01) and inversely with the CI (r = -0.39, p less than 0.001) and LVSW (r = -0.37, p less than 0.001) in the 126 studies of IAP performed with the 25 patients. IAP also correlated directly with BUN (r = 0.40, p less than 0.001), serum creatinine (r = 0.28, p less than 0.01), and free water clearance (CH2O) (r = 0.3, p less than 0.001); IAP correlated negatively with Ccr (r = -0.54, p less than 0.001) and Cosm (r = -0.43, p less than 0.001). In critically ill cirrhotic patients, IAP, when measured noninvasively via a bladder catheter, is an accurate and useful method to follow manipulation of ascitic fluid pressure quantitatively in order to optimize hemodynamic and renal function.

Abdomen↗

LLC-PK1 mutant with increased Na+-H+ exchange and decreased sensitivity to amiloride.

LLC-PK1 cells contain a well-characterized Na+-H+ antiporter that is sensitive to ethylisopropylamiloride (EIPA) in the submicromolar range. Using a modification of the method of Franchi et al. (J. Biol. Chem. 261: 14614-14620, 1986), we have selected mutants that can recover from an acid load in the presence of 100 microM EIPA. One such mutant, designated PKE20, has been studied in detail. The maximal velocity (Vmax) for the Na+-H+ antiporter, assayed as EIPA-sensitive 22Na+ uptake, has increased from 44 nmol.min-1.10(6) cells-1 in the parent cells to 106 nmol.min-1.10(6) cells-1 in PKE20. No detectable change has occurred in the Km for Na+ (118 mM in the parent, 111 mM in the mutant) or in the dependence of Na+ uptake on intracellular pH. However, the PKE20 antiporter exhibits a greatly decreased sensitivity to amiloride and its derivatives, with drops in inhibitory potency ranging from 25-fold (amiloride) to 100-fold (EIPA). The mutation is specific for the antiporter; measurements of Na+-K+ pump and Na+-dependent amino acid uptake show only small changes, which appear to result from minor antiporter-induced alterations in internal Na+ concentration. PKE20 cells should prove useful in experiments to identify and isolate the antiporter protein.

Amiloride↗

Pharmacokinetics of centperazine: a new antifilarial agent.

Blood concentration compared with time profile of centperazine, obtained after intravenous injection of a 5 mg/kg dose in male albino rats, was analysed for various parameters. The data could be interpreted best in terms of the three compartment open model system. The drug exhibited 4.4 h of half-life, with an elimination constant of 1.65. Values for the area under curve and distribution volume were determined as 14.62 micrograms h/ml and 438 ml respectively. Only 10% of centperazine present in the central compartment was available for elimination at any one time. Mean plasma clearance value was found to be 72.87 ml/h/kg body weight.

Animals↗