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V S Warty

Publications and source records attributed to V S Warty.

30 records · Page 2Linked to original sources
PubMed1991

Cyclosporine enhances the growth of carcinogen-induced enzyme-altered foci in rat liver.

Cyclosporine, a powerful immunosuppressant, has been used successfully for organ transplantation. Its efficacy on liver transplants of patients with primary hepatic tumors remains controversial because of a high rate of recurrence of the original tumors in the transplanted livers. In this study, we experimentally tested whether cyclosporine exerts any effects on the growth of carcinogen-initiated liver cells using the short-term assays of rat liver carcinogenesis. Dietary cyclosporine, which maintained sufficient levels of blood cyclosporine and suppressed host immune functions, enhanced the development of the glutathione S-transferase, placental form-positive hepatocyte foci in the liver of male F-344 rats treated with a single weekly dose of diethylnitrosamine (75 mg/kg) for 3 wk. Dietary cyclosporine also accelerated the growth of preformed glutathione S-transferase, placental form-positive foci induced by a single dose of diethylnitrosamine (250 mg/kg) followed by the promoting regimen of a choline-deficient diet. It is possible that the enhancement of the size of hepatocyte foci by cyclosporine could be due to stimulation of growth or inhibition of regression. The mechanisms by which cyclosporine modifies the growth of preneoplastic lesions in the liver are not yet fully understood. Possible involvement of immunologically relevant cells in the liver, Kupffer cells and pit cells in the process is suggested.

Animals↗
PubMed1990

Experimental determination and mathematical model of the transient incorporation of cholesterol in the arterial wall.

Experimental data of the radial incorporation of labeled cholesterol [14C-4] into the artery wall is regressed against a mathematical model that predicts macromolecular transport in this biological system. Data is obtained using excised canine carotid arteries that are perfused in vitro under pulsatile hemodynamic conditions for 2 hr. Vessels are exposed to either normotensive hemodynamics, hypertensive hemodynamics, or simulations in which the rate of flow or vessel compliance is deliberately altered. Several arteries are studied under normotensive conditions following balloon catheter deendothelialization. Transmural concentration profiles of [14C-4] activity are determined by microcryotomy of longitudinal sections of perfused vessels. Nonlinear Marquardt regression on 12 experimental cases yields parameter estimates of effective diffusivity, D and solute filtration velocity, V. Results of this experimental investigation support our hypothesis that hemodynamics and the endothelial lining influence wall flux in intact vessels. Exposure to altered (vs normotensive) hemodynamics is associated with increased incorporation of labeled cholesterol. A similar observation is made for deendothelialized vessels (e.g. a greater accumulation of label and a rise in convective flux). Based upon our companion measurements of vessel wall forces and endothelial cellular morphology accompanying hemodynamic simulations, we suggest that hemodynamically induced alterations to endothelial structures lead to the increased permeability, convection and incorporation that we observe in this work.

Animals↗
PubMed1989

Hemodynamics alter arterial low-density lipoprotein metabolism.

We have investigated the role of hemodynamic factors on low-density lipoprotein transport and metabolism in the intact arterial wall. Freshly excised canine carotid blood vessels were exposed to well-defined pulsatile flow in vitro for continuous periods up to 20 hours. We chose to impose the following hemodynamic conditions on our test carotid arteries: normotension, hypertension (at physiologic flow conditions), and hypertension coupled with elevated flow of canine serum perfusate. In several experiments the effect of endothelial denudation was examined in carotid arteries exposed to normotensive pulsatile flow. A trapped ligand method was used for quantitating low-density lipoprotein uptake and metabolism in the arterial wall. The distribution of both intact and degraded low-density lipoprotein fractions was determined from measurements of radiolabelled low-density lipoprotein activity within thin radial sections of perfused arteries. Our results suggest that both hypertensive hemodynamic simulations exacerbate the uptake of low-density lipoprotein within the arterial wall (by a factor of three to nine). The percentage of low-density lipoprotein that undergoes irreversible degradation falls from 41% under normotensive conditions to below 30% when hypertensive conditions are imposed, indicating that degradative processes are not proportionally elevated with the accelerated influx. A similar pattern is observed for deendothelialized vessels.

Animals↗
PubMed1987

Hemodynamics and the vascular endothelial cytoskeleton.

Although there is considerable evidence to suggest that hemodynamics play an important role in vascular disease processes, the exact mechanisms are unknown. With this in mind, we have designed a pulsatile perfusion apparatus which reproducibly delivers pulsatile hemodynamics upon freshly excised canine carotid arteries in vitro. Quantifiable simulations included normotension with normal or lowered flow rates (120/80 mmHg, 120 and 40 ml/min), normotension with lowered or elevated transmural pressures (40-170 mmHg), and elevated pulse pressure (120 and 80 mmHg) with normal (150 ml/min) or elevated rates of flow (300 and 270 ml/min). Arterial biomechanical stresses and cellular behaviors were characterized biochemically and morphologically under all these stimulations which continued for 2-24 h. We found that increased pulse pressure alone had little effect on the total amount of radiolabeled [4-14C]cholesterol present within the medial compartment. However, normotension when coupled with altered transmural pressure yielded a three- to fourfold increase. Combinations of increased pulse pressure and flow potentiated cholesterol uptake by a factor of 10 when compared with normotension control values. Simulations that enhanced carotid arterial cholesterol uptake also influenced the endothelial cytoskeletal array of actin. Stress fibers were not present within the carotid endothelial cells of either the sham controls or the normotension and increased pulse pressure (normal flow) simulations. Endothelial cells lining carotids exposed to elevations in flow or those present within vessels perfused as per simulation b above assembled stress fibers (x = 4 and 10 per cell, respectively) within the time course of these studies. When endothelial cells were subjected to hemodynamic conditions that potentiated maximally cholesterol transport, no diffuse or stress fiber staining could be seen, but the cortical array of actin was intact. These results suggest that those biomechanical stresses that alter endothelial permeability and intimal integrity may do so via cytoskeletal actin signaling.

Animals↗
PubMed1987

Biopharmaceutical aspects of FK-506.

FK is a potent immunosuppressive agent. FK can be analyzed in biologic fluids by EIA. The oral absorption of FK is rapid but variable in dogs. After intramuscular administration, FK is slowly and continuously absorbed. FK is primarily eliminated by metabolism. Less than 1% of the administered dose is excreted in the bile or the urine. After chronic intramuscular administration FK inhibits drug metabolism. Monitoring of FK levels in plasma is essential for the proper interpretation of efficacy and toxicity studies.

Administration, Oral↗
PubMed1986

Cardiovascular depression secondary to ionic hypocalcemia during hepatic transplantation in humans.

Cardiovascular function, serum ionized calcium (Ca+2), and serum citrate were measured intraoperatively in patients (n = 9) undergoing orthotopic hepatic homotransplantation. Serum citrate increased 20-fold (P less than 0.0006) following transfusion of citrated blood products in the absence of a functional liver. Serum ionized calcium decreased (P less than 0.003) with concomitant decreases in cardiac index (P less than 0.005), stroke index (P less than 0.004), and left ventricular stroke work index (P less than 0.001). Hemodynamic depression and ionic hypocalcemia were reversed following the administration of CaCl2. In contrast to patients with normal hepatic function, who may tolerate large amounts of citrated blood, patients with end-stage liver disease demonstrate acute ionic hypocalcemia with concomitant hemodynamic depression when receiving citrated blood products during the course of hepatic transplantation.

Calcium Chloride↗
PubMed1984

A kit for citrate in foodstuffs adapted for assay of serum and urine.

A kit method for rapid analysis of citrate in foodstuffs, based on use of citrate lyase (EC 4.1.3.6), has been adapted and evaluated for use with clinical samples. Membrane filters removed serum proteins, which interfere with the analysis, and reagent and sample volumes were decreased from those in the manufacturer's protocol, thereby decreasing the cost of the assay. Using gravimetrically prepared citrate standards, we determined that assay results varied linearly with concentration up to sixfold the upper reference limit for serum citrate. Intra- and interassay variation were within acceptable limits (CVs less than 3% and less than 8.5%, respectively). Kit reagents were stable for four weeks at -20 degrees C. Assay results were unaffected by hemolysis or other biochemical interferences. The method evidently provides a rapid, convenient microassay for citrate in clinical samples.

Bilirubin↗
PubMedDate not supplied

Lipid and volume analysis of neck drainage in patients undergoing neck dissection.

PURPOSE: We seek to establish normative values for the volume of postoperative neck drainage from patients undergoing ablative oncologic procedures that include a neck dissection and to analyze neck drainage for lipid content to establish guidelines that may be helpful in identifying chylous fistula when this diagnosis is not clinically straightforward. PATIENTS AND MATERIALS: Neck drainage obtained through continuous suction percutaneous drainage catheters was evaluated following 23 neck dissections performed on 19 patients. In every case, either radicle or modified type I neck dissection was performed. The volume of drainage was quantitated on a day-to-day basis. In a separate group of 27 patients undergoing neck dissection, neck drainage was compared with serum levels of triglyceride, cholesterol, and chylomicron content. RESULTS: The mean duration of neck drainage was 5 days. Maximum drainage (160 mL) was noted on the first day and dropped daily to less than 10 mL by the fifth postoperative day. A statistically significant difference between serum and neck drainage triglyceride and cholesterol content was observed in nearly all cases. Neck drainage fat content was lower than that noted in serum in nearly all cases. Chylomicron content of 4% was encountered in neck drainage. CONCLUSIONS: This study provides normative data on lipid content of neck drainage. With only a rare exception, the triglyceride and cholesterol levels are higher in the serum than in the neck drainage. A triglyceride level of 100 mg/dL seems to be the upper limit of normal (mean plus 1 standard deviation). A low level of chylomicron (> 4%) is consistent with normal healing and may be due to breakdown of fatty tissue.

Aged↗
PubMedDate not supplied

Hemodynamics and low density lipoprotein metabolism. Rates of low density lipoprotein incorporation and degradation along medial and lateral walls of the rabbit aorto-iliac bifurcation.

We have investigated whether arterial wall low density lipoprotein (LDL) metabolism in areas of disturbed flow differs from the metabolism in adjacent regions of undisturbed flow. Using the rabbit aorto-iliac bifurcation as a model, we examined the rates of LDL incorporation and catabolism in vivo and correlated them to the arterial flow patterns in these regions. The trapped ligand method was used to quantitate the rates of LDL incorporation and degradation over a 20-hour period in three hemodynamic zones of the daughter iliac branch: 1) a region of flow separation where the shearing forces are elevated along the medial wall and reduced along the lateral wall, 2) a transition region where the flow patterns begin to approach the fully established situation, and 3) a unidirectional flow region with symmetric fluid shearing forces along the medial and lateral walls. Our results indicate an elevated rate of LDL incorporation into the lateral versus the medial wall in the proximal zone of flow separation (5.2 +/- 0.8 nl/mg/hr vs. 3.7 +/- 0.5 nl/mg/hr, p less than 0.01). A similar elevation in the degradation rate of the lateral over the medial wall of this most proximal zone was also observed (2.1 +/- 0.4 vs. 1.4 +/- 0.2, p less than 0.05). No such differences were observed regarding LDL incorporation and degradation in the transitional or unidirectional hemodynamic zones. These results suggest that modifications in arterial wall LDL incorporation and catabolism are induced by hemodynamic forces. The implications of these findings for the formation of the atherosclerotic lesion are discussed.

Animals↗