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Biomedical subjects

G Chaudhuri

Publications and source records attributed to G Chaudhuri.

At least 91 records · Page 5Linked to original sources
PubMed1988

Pharmacological evidence that endothelium-derived relaxing factor is nitric oxide: use of pyrogallol and superoxide dismutase to study endothelium-dependent and nitric oxide-elicited vascular smooth muscle relaxation.

The principal objective of this study was to elucidate the influence of superoxide anion on both endothelium-dependent arterial relaxation elicited by acetylcholine and endothelium-independent arterial relaxation produced by nitric oxide (NO). Pyrogallol was used to generate superoxide in the oxygenated bathing medium, and superoxide dismutase was used to scavenge superoxide. Pyrogallol caused endothelium-dependent contractions of bovine intrapulmonary arterial and venous smooth muscle after precontraction of muscle by phenylephrine. Acetylcholine- and NO-elicited arterial relaxations were promptly converted to marked contractions upon addition of pyrogallol. Moreover, pyrogallol markedly inhibited the development of arterial relaxant responses to acetylcholine and NO. However, isoproterenol- and glyceryl trinitrate-elicited arterial relaxations were unaffected by pyrogallol. Both pyrogallol and oxyhemoglobin enhanced arterial contractile responsiveness to phenylephrine in an endothelium-dependent manner, whereas indomethacin was without effect. Similarly, both pyrogallol and oxyhemoglobin inhibited acetylcholine- and NO-elicited arterial cyclic GMP accumulation, whereas indomethacin was without effect. Uncontracted arterial rings maintained under tension showed endothelium-dependent contraction and decreased cyclic GMP levels in response to oxyhemoglobin but not pyrogallol. Superoxide dismutase enhanced arterial relaxation and cyclic GMP accumulation in response to both acetylcholine and NO. Using a bioassay superfusion cascade system in which intact perfused artery was the source of endothelium-derived relaxing factor (EDRF) and three endothelium-denuded arterial strips mounted in series served as the detector of EDRF, superfusion of strips with pyrogallol blocked relaxation caused by perfusion of artery with acetylcholine. Superoxide dismutase enhance the relaxations produced by arterial perfusion with acetylcholine and prevented the effects of pyrogallol.

Animals↗
PubMed1988

Endothelium-derived relaxing factor and nitric oxide possess identical pharmacologic properties as relaxants of bovine arterial and venous smooth muscle.

The principal objective of this study was to compare and contrast the vascular smooth muscle-relaxing properties of endothelium-derived relaxing factor (EDRF) and nitric oxide (NO) in two different assay systems. In one system, precontracted rings of bovine intrapulmonary artery and vein and coronary artery were used to compare the relaxant effects of endothelium-dependent vasodilators, NO, S-nitroso-N-acetylpenicillamine, glyceryl trinitrate, prostacyclin and isoproterenol. In a second system, a bioassay superfusion cascade procedure was employed to compare the relaxant effects and biologic stability of EDRF and NO. Acetylcholine and bradykinin elicited concentration-dependent but transient relaxant responses in arterial and venous rings, respectively. NO and S-nitroso-N-acetylpenicillamine, which generates NO in solution, elicited similar transient relaxant responses in endothelium-denuded arterial and venous rings. Glyceryl trinitrate, however, produced sustained relaxations, as did isoproterenol and prostacyclin. Utilizing a bioassay superfusion cascade system in which intact perfused artery or vein was the source of EDRF and three endothelium-denuded arterial or venous strips mounted in series served as the detector of EDRF or NO, the relaxation profile and biologic stability of superfused EDRF were compared with those of superfused NO. Arterial or venous perfusion with acetylcholine or bradykinin, respectively, and superfusion of NO over the strips produced characteristic decremental relaxant responses in the three vascular strips and revealed the highly unstable nature of EDRF and NO (T1/2 = 3-5 sec for both). The relaxation profile of EDRF was indistinguishable from that of NO.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1988

Influence of blood components on the tissue uptake indices of cyclosporin in rats.

The effect of blood components on the transfer of cyclosporin into brain, salivary gland, liver and kidney was measured in rats by an an vivo double isotope, tissue-sampling single injection technique. The brain-, salivary gland- and liver extraction of [3H] cyclosporine relative to [14C]butanol were studied with an intracarotid and a portal vein injection technique; the kidney extraction of [3H]cyclosporin relative to p[14C]aminohippuric acid was measured after a rapid injection in the aorta. The injection vehicles were a Ringer's solution [Ringer-4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid], rat plasma, human plasma, human red blood cells (RBC) suspension and human blood. The brain extraction (1-4%), the salivary extraction (25-74%) and the kidney extraction (8-47%) varied markedly depending on which blood components were added to the injection solution. The effect of RBC binding on tissue extraction was by far more pronounced than that of plasma protein binding. The binding of cyclosporin to RBC retards particularly the uptake of this drug by kidney. Moreover the kidney penetration of cyclosporin was confirmed by thaw-mount autoradiography after injection of the labeled drug in the aorta; the micrographs showed that the renal clearance of cyclosporin was restricted largely to the glomerular route. In contrast the hepatic extraction of [3H]cyclosporin was high (48-84%) and generally nonlimited by its binding to blood components; this could explain the high concentrations of drug observed in this tissue. In summary, cyclosporin binding to RBC and plasma proteins reduces drug uptake by brain, kidney and salivary gland, but causes little inhibition of hepatic uptake of cyclosporin.

Animals↗
PubMed1988

Computerized tomography head scans as predictors of functional outcome of stroke patients.

Preadmission computerized tomography (CT) scans of the head were used to help develop a clinical method for the prediction of outcome of stroke patients. The functional gains and discharge outcomes of 100 stroke patients after inpatient rehabilitation were considered. Reports of preadmission (acute care hospital) CT scans of the head were analyzed and placed into six groups representing progressive anatomic involvement. Functional status was measured at admission and discharge using the patient evaluation and conference system (PECS) and placed into four functional groups. The groups ranged from normal to totally dependent in self-care activities, ambulation, and bladder and bowel functioning. Admission CT head scans reported in two categories--"normal" or "small superficial infarct"--were associated with return to independent functioning. Bihemispheric infarcts were associated with discharge to nursing home (71%), rather than to independent living. Of all patients with functional gain as measured with PECS, 79% returned home.

Adolescent↗
PubMed1988

Aspiration in rehabilitation patients: videofluoroscopy vs bedside clinical assessment.

This paper reports the results of a blinded study comparing videofluoroscopy with bedside clinical evaluations by speech/language pathologists in the diagnosis of aspiration. One hundred and seven inpatients from a general rehabilitation hospital were evaluated over a four-month period. Of the total patient population, 43 (40%) aspirated at least one consistency of food during videofluoroscopy. Bedside evaluation identified only 18 (42%) of these patients. The positive predictive value of bedside assessment was 0.75; negative predictive value was 0.70. Aspirators on videofluoroscopy were more likely to have brainstem or multilobe central nervous system involvement than nonaspirators. However, there was no statistically significant difference in lesion sites between clinically detected and "silent" aspirators. While the significance of aspiration noted on videofluoroscopy is debatable, it is clear that bedside evaluation alone underestimates the frequency of aspiration in patients with neurologic dysfunction.

Adult↗
PubMed1987

Selective availability of protein bound estrogen and estrogen conjugates to the rat kidney.

Estrogen glucuronides are selectively cleared by the kidney as compared to estrogen sulfates. The selective trafficking of circulating serum estrogen conjugates to kidney and urine may arise from differential transport properties of the various estrogen conjugates in the renal microcirculation. In the present study, the effects of glomerular and peritubular permeability barriers, and plasma protein binding on the influx of unconjugated and conjugated estrogens into rat kidney were studied. Experiments were carried out utilizing an in vivo double isotope, single injection, timed tissue sampling technique. The extractions of these steroids by the renal cortex were examined utilizing inulin as the reference substance, as it is freely permeable through the glomerular and tubular capillary permeability barriers, but not extracted by tubular epithelial cells. The method was validated by studying the extraction of para-amino hippuric acid (PAH) before and after probenecid treatment. In the absence of plasma proteins, all the estrogens and estrogen conjugates readily diffused through both the glomerular and peritubular capillary permeability barriers and were extracted by tubular epithelia. The addition of 4% albumin to the injection solution led to significant inhibitions of extraction of estradiol (E2) and estrone sulphate (E1-S) only. The extraction of E1-S was reduced to a value less than that of inulin; the extraction of E2 was less than that of control value but significantly more than that of inulin. The addition to the injection solution of human pregnancy sera containing sex hormone binding globulin and albumin was associated with a reduction in the extraction of all estrogens and estrogen conjugates except estriol and E1-S to values approximating that of inulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Salvage of ischemic rabbit ear by BW-755C and steroids, but not by indomethacin.

The effects of anti-inflammatory steroids and BW-755C (both of which inhibit the formation of prostaglandins and leukotrienes) were studied in ischemia-induced edema and necrosis of the rabbit ear utilizing an occlusion reperfusion model. The results were compared with cyclooxygenase inhibitors which selectively block the synthesis of prostaglandins without affecting leukotriene production. Significant inhibition of the progression of necrosis was observed with both methyl prednisolone and BW-755C. The cyclooxygenase inhibitors, naproxen and low-dose indomethacin had no effect on the progression of ear necrosis. By contrast, high-dose indomethacin significantly inhibited edema but accelerated the progression of necrosis.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1987

The effects of membrane permeability and binding by human serum proteins on steroid influx into the rabbit uterus.

The effects of capillary membrane permeability and binding by human plasma proteins on the influxes of tritium-labeled steroids from the circulation into the uterus were measured in vivo in anesthetized rabbits with a tissue-sampling, single injection technique, and the results were compared with similar studies involving rats. Rabbits were used in this study because this species, unlike the rat, has a sex steroid-binding protein. The impact of capillary membrane permeability markedly varied with different steroids and did not completely parallel the lipid solubility of these compounds. The addition of plasma proteins to the injection vehicle had varied inhibitory effects on the in vivo extractions by the uterus. These in vivo extraction values could not be predicted from in vitro studies of steroid binding to plasma proteins and the results underscore the importance of performing in vivo studies so that we may have a better understanding of the bioavailability of steroids to tissues.

Animals↗
PubMed1987

Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide.

The objective of this study was to determine whether nitric oxide (NO) is responsible for the vascular smooth muscle relaxation elicited by endothelium-derived relaxing factor (EDRF). EDRF is an unstable humoral substance released from artery and vein that mediates the action of endothelium-dependent vasodilators. NO is an unstable endothelium-independent vasodilator that is released from vasodilator drugs such as nitroprusside and glyceryl trinitrate. We have repeatedly observed that the actions of NO on vascular smooth muscle closely resemble those of EDRF. In the present study the vascular effects of EDRF released from perfused bovine intrapulmonary artery and vein were compared with the effects of NO delivered by superfusion over endothelium-denuded arterial and venous strips arranged in a cascade. EDRF was indistinguishable from NO in that both were labile (t1/2 = 3-5 sec), inactivated by pyrogallol or superoxide anion, stabilized by superoxide dismutase, and inhibited by oxyhemoglobin or potassium. Both EDRF and NO produced comparable increases in cyclic GMP accumulation in artery and vein, and this cyclic GMP accumulation was inhibited by pyrogallol, oxyhemoglobin, potassium, and methylene blue. EDRF was identified chemically as NO, or a labile nitroso species, by two procedures. First, like NO, EDRF released from freshly isolated aortic endothelial cells reacted with hemoglobin to yield nitrosylhemoglobin. Second, EDRF and NO each similarly promoted the diazotization of sulfanilic acid and yielded the same reaction product after coupling with N-(1-naphthyl)-ethylenediamine. Thus, EDRF released from artery and vein possesses identical biological and chemical properties as NO.

Animals↗
PubMed1986

Enhanced hepatic extraction of estrogens used for replacement therapy.

Oral estrogen administration elicits greater effects on hepatic than on nonhepatic markers of estrogen action. This has important clinical implications, since the hepatic actions of estrogens are believed to account for several complications of this form of therapy. To date, the mechanism responsible has been attributed to the so-called first pass effect of the orally administered hormones. The present study was undertaken to examine the in vivo extraction from the circulation of all commercially available classes of estrogens used for replacement therapy. Influxes from the microcirculation into three important target organs of estrogen action, i.e. the brain, uterus, and liver, were assessed. This was accomplished by the use of previously described double isotope, single injection, timed tissue-sampling techniques. For the brain, two patterns of influx were found using different injection vehicles. The first was characterized by high extraction (80-100%) in the absence of plasma proteins. The only inhibitory effects on influx were exerted by plasma proteins. Estrogens displaying this pattern were estradiol, estrone, and ethinyl estradiol. The second pattern was characterized by very restricted influx in the absence of plasma proteins, and plasma protein binding had little or no additional effect. In the absence of plasma proteins, the percentages extracted of estrone sulfate (E1S) and diethylstilbestrol were 6.5% and 38.5%, respectively. For the uterus, the patterns of extraction of all five estrogens were similar to those found for the brain. In contrast, the hepatic microvasculature was freely permeable to all estrogens including E1S and diethylstilbestrol. Albumin binding had little or no effect on hepatic uptake. Significant reductions in the influx of estradiol and E1S were found only when the injection vehicle was human pregnancy serum (high sex hormone-binding globulin concentration). In the presence of plasma proteins, the hepatic extraction of all of the estrogens studied significantly exceeded that in the brain and uterus. We conclude that enhanced delivery of circulating estrogens to the liver compared to that to the brain and uterus provides a further explanation for the enhanced hepatic actions of these preparations when used for oral replacement therapy.

Animals↗
PubMed1986

Serum bioavailability and tissue metabolism of testosterone and estradiol in rat salivary gland.

The concentration of testosterone in saliva is probably in equilibrium with the concentration of cellular exchangeable testosterone in salivary gland, and these pools are a function of hormone transplant from the plasma compartment, and hormone metabolism in salivary gland cells. Both of these processes were examined in the present study using the carotid injection technique in normal and pilocarpine-stimulated ketamine-anesthetized rats. Both testosterone and estradiol were rapidly transported across salivary gland capillaries in vivo from the circulating albumin-bound pool. Estradiol, but not testosterone, was also rapidly transported into salivary gland from the circulating human sex hormone-binding globulin-bound pool. Hormone transport was several-fold greater than the capillary transport of [3H]bovine albumin, indicating that bound hormone was available for transport across salivary gland capillaries via an enhanced dissociation mechanism, with the plasma protein primarily residing in the plasma compartment. This result was confirmed by thaw-mount autoradiography, which showed diffuse distribution of [3H]testosterone in salivary gland, but vascular retention of [3H]bovine albumin. The concentration of exchangeable cellular testosterone in rat saliva was less than 4% of the total or plasma exchangeable testosterone in the rat. This marked discrepancy between the concentration of plasma and cellular exchangeable hormone suggested that there was rapid metabolism of androgen by salivary gland in vivo. This was confirmed by chromatographic separation of [3H] testosterone and labeled metabolites in homogenates of salivary gland. By 60 sec after injection, approximately 30% of the radioactivity in the salivary gland was in the form of androgen metabolites, which primarily comigrated with an androstenedione standard. The data indicate that albumin-bound testosterone, albumin-bound estradiol, and sex hormone-binding globulin-bound estradiol are all exchangeable in salivary gland capillaries. The low concentration of cellular exchangeable testosterone in salivary gland appears to be due to rapid tissue metabolism of this hormone. Thus, changes in androgen metabolism may alter salivary gland hormone concentrations independent of any change in the concentration of biologically active hormone in plasma.

Adult↗
PubMed1986

The role of thyroxine (T4)-binding serum proteins in oleic acid-induced increase in free T4 in nonthyroidal illnesses.

We studied the effects of various concentrations of oleic acid (0.1-3.3 mM), such as are often found in the serum of patients with nonthyroidal illness, on the dialyzable (free) fraction of T4 (DFT4) in three types of serum samples: pooled normal serum (PNS), pooled pregnancy serum (PPS), and pooled serum of hospitalized patients (PSHP). The samples were extracted with diethyl ether to remove endogenous fatty acids before being tested in the DFT4 assay. Oleic acid caused only a moderate increase in DFT4 in PNS; a significant (greater than 2 SD above control) increase (15%) was found with 2.0 mM oleic acid, and the maximal dose of oleic acid (3.3 mM) caused a 33% increase in DFT4. However, the DFT4-increasing effect of oleic acid was enhanced (increase in DFT4 of 33% caused by 0.9-1.2 mM oleic acid) when the serum tested had low (0.5 times normal) albumin and prealbumin concentrations with either normal (50% PPS) or half-normal TBG (50% PNS). The effect of oleic acid in 100% PSHP was significantly (P less than 0.005) greater than that in 100% PNS, and it was close to that in 50% PNS (increase in DFT4 with 3.3 mM oleic acid, 118% in PSHP vs. 98% in 50% PNS). Normalization of serum albumin in PSHP by adding exogenous albumin markedly reduced the DFT4-increasing effect of oleic acid; the maximal increase in DFT4 of 64% with 3.3 mM oleic acid in albumin-normalized PSHP was equalled with 1.3 mM oleic acid in unmodified PSHP. The data suggest that the serum concentrations of albumin and other T4-binding proteins are important in modulating the DFT4-increasing effect of oleic acid and that oleic acid may contribute to the reduced serum binding of T4 in nonthyroidal illness.

Dialysis↗
PubMed1985

Inhibition by indomethacin of increased estradiol extraction by the IUD-containing rat uterine horn.

The role of prostaglandins on the extraction of estradiol (E2) by the rat uterine horn in the presence of the intrauterine device (IUD) was evaluated. Increased extraction of E2 by the IUD horn compared to the contralateral control horn was consistently observed irrespective of the estrogen status of the animals. This increased extraction was abolished by indomethacin, an inhibitor of prostaglandin synthesis, suggesting a role of prostaglandin in this process.

Animals↗