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Biomedical subjects

A Bhatnagar

Publications and source records attributed to A Bhatnagar.

At least 109 records · Page 6Linked to original sources
PubMed1996

Scintigraphic diagnosis of gastrointestinal bleeding with 99Tcm-dextran.

Intravenously administered dextran is used clinically as a plasma expander. The aim of this study was to assess the use of 99Tcm-dextran in the diagnosis of gastrointestinal (GI) blood leaks. Twenty-one patients with GI blood loss underwent 99Tcm-dextran scintigraphy, 17 of whom were found to be positive. Pathologic or 99Tcm-RBC (red blood cell) blood pool correlation was possible in 15 cases, while 2 were unconfirmed. No case had a positive 99Tcm-RBC blood pool study and a negative 99Tcm-dextran study. Images obtained with 99Tcm-dextran were generally better than those with 99Tcm-RBC. This agent may have several other advantages over 99Tcm-RBC blood pool and 99Tcm-sulphur colloid scintigraphy for detecting GI blood loss.

Adult↗
PubMed1996

A kit for the instant preparation of 99Tcm-citrate for tumour and inflammation scintigraphy.

A lyophilized kit has been developed to produce 99Tcm-citrate (99%) instantly when mixed with 99TcmO4-. The ingredients of the kit, citrate and stannous chloride, are in a ratio of 100:1 (w/w) and are bound to 700 MBq 99Tcm, sufficient for use in a single patient. The shelf life of the kit when kept refrigerated is at least 3 months. The blood clearance and organ distribution of 99Tcm-citrate have been studied in rabbits and mice respectively, showing its fast clearance (55% at 5 min) and low uptake by the reticulo-endothelial system and other organs. The main route of clearance is via the kidneys. Scintigraphic studies in experimental mice have demonstrated high levels of accumulation of 99Tcm-citrate in turpentine-induced abscess (target-to-non-target ratio 4.2:1) and EAT implanted tumour in mice (T/NT 5:1) 1 h after its administration. In keeping with these animal studies, low uptake of 99Tcm-citrate by normal organs and fast blood clearance have been demonstrated in human patients with infection and tumour as early as 5 min post-administration. This study documents a new kit developed for the preparation of 99Tcm-citrate suitable for the scintigraphic assessment of abscess, infection and tumour.

Abscess↗
PubMed1996

Attenuation of 4-hydroxynonenal-induced cataractogenesis in rat lens by butylated hydroxytoluene.

PURPOSE: We have previously shown that 4-hydroxynonenal (4-HNE) causes opacification of cultured rat lenses and that a novel group of glutathione S-transferases (GSTs) exhibit high specific activity towards 4-HNE. Previous studies have shown that t-butylated hydroxy toluene (BHT) induced GSTs in cultured rat lens. Therefore, the purpose of the present studies was to investigate if the opacification of rat lenses exposed to 4-HNE is ameliorated by pre-culturing the lenses in media containing BHT. METHODS: Rat lenses were divided into four groups. Group I and II were controls and groups III and IV were cultured in the presence of 100 microM 4-HNE. Groups II and IV were pre-cultured in the media containing 10 microM BHT for 24 hrs which was designated as 0 time point. Lenses were withdrawn at 24 and 72 h and evaluated for opacification by digital image analysis. Induction of the specific GST isozyme (gammaGST8-8) was studied in the lens epithelium by immunohistochemical studies. Results. Digital image analysis revealed amelioration in opacification induced by 4-HNE, when the lenses were precultured with BHT. Immunohistochemical studies show that BHT induced GST8-8 several folds in the epithelium. CONCLUSIONS: These studies indicate that pretreatment with BHT would increase the lens capacity to detoxify 4-HNE by conjugating it with GSH, thus assigning an important detoxication role to this specific GST isozyme in oxidative cataract.

Aldehydes↗
PubMed1996

Mechanism of calcium-induced disintegrative globulization of rat lens fiber cells.

PURPOSE: To study the role of calcium and calcium-dependent processes in the disintegrative globulization of isolated single rat lens cortical fibers. METHODS: The authors isolated viable and morphologically intact single fiber cells from rat lens cortex and studied the effect of 1 mM [Ca2+]o on the globulization of fiber cells from the outer and inner cortex. They investigated the effects of the calcium-channel blocker, verapamil; an inhibitor of calcium transport, lanthanum; various protease inhibitors; Na+ -free and K+ -free media; calcium ionophore, A23187; and calcium chelator, BAPTA, on the globulization of fiber cells exposed to 1 mM [Ca2+]o. RESULTS: Perfusion with Ringer's solution containing 1 mM [Ca2+]o, caused disintegration and globulization of the isolated fibers in 32.3 +/- 1 minute, and the addition of 10 microM A23187 to the superfusing solution reduced the time to complete globulization (tg) to 19.4 +/- 0.3 minutes. However, the addition of protease inhibitors, leupeptin, calpain inhibitor I, E-64, or pepstatin (0.5 mM each) to the superfusing solution, increased tg to 105 +/- 3.5, 84.2 +/- 7.8, 60.7 +/- 3.5, and 48.3 +/- 3.1 minutes, respectively. The tg also increased (96.4 +/- 3.5 minutes) when the fibers were preincubated with BAPTA-AM or when they were exposed to 1 mM [Ca2+]o in Na+ - or K+ -free Ringer's solution (tg = 66.7 +/- 5.3 and 58.9 +/- 3.9 minutes, respectively) or in Ringer's solution containing 1 mM [Ca2+]o + 50 microM verapamil (tg = 49.3 +/- 3.8 minutes). Single fibers isolated from the outer cortex of the lens were less susceptible to extracellular calcium than those isolated from the inner cortex. CONCLUSIONS: Increased calcium influx and the attendant elevation of [Ca2+]i are necessary for disintegrative globulizaiton of lens fiber cells. Calcium influx appears to be mediated partially by the L-type calcium channels and the background calcium leak. Protection by protease inhibitors suggests that membrane fragmentation, caused by elevated [Ca2+]i, results from proteolytic damage to the fiber cytoskeleton. Besides underscoring the central role of calcium homeostasis in preserving the morphologic integrity of the cortical fibers, this study suggests a possible cellular mechanism for the formation of supranuclear cataract.

Animals↗
PubMed1995

Lipid peroxidation product, 4-hydroxynonenal and its conjugate with GSH are excellent substrates of bovine lens aldose reductase.

There is increasing evidence that lipid aldehydes generated endogenously during the process of degradation of lipid peroxides, are causally involved in the pathophysiology effects associated with oxidative stress. We report here that 4-hydroxynonenal (HNE), which is one of the most abundant and toxic lipid aldehyde can be efficiently detoxified by the aldo-keto reductase, aldose reductase, purified from bovine lens. The enzyme displays a Km of congruent to 9 microM for HNE and 34 microM for the glutathione adduct of HNE (HNE-GS) assigning HNE and HNE-GS to be the best natural substrates of aldose reductase known so far and exposing a new efficient detoxification route of HNE.

Aldehyde Reductase↗
PubMed1995

Calcium-mediated disintegrative globulization of isolated ocular lens fibers mimics cataractogenesis.

Single viable fiber cells have been isolated from the cortex of rat ocular lens by proteolytic digestion of the intact lens in calcium-free media. In isomolar sucrose, the isolated cells maintain their fiber-shaped morphology and exclude trypan blue. The surface morphology of the isolated fiber cells appears to be largely unaffected by the isolation procedure. The concentrations of adenine nucleotides, GSH, GSSG and the rate of glycolysis in the isolated fiber cells were comparable to those in the cortex. Upon perfusion of the tissue chamber with Ringer's solution, the fiber cells undergo a series of transformations, beginning with cell swelling, periodic blebbing along the longitudinal cellular axis, and eventual disintegration of the fiber into a number of resealed globules or round cells which resemble light-scattering areas in human cortical and supranuclear cataract. This disintegrative globulization of the fiber cells appears to be mediated by calcium influx, as it was prevented or delayed by a reduction in extracellular calcium concentration, verapamil or lanthanum. Since disturbances in calcium homeostasis are associated with various forms of cataract, such Ca(2+)-mediated disintegrative globulization of the fiber cells may be responsible for the formation of light scattering centers during cataractogenesis.

Adenosine Monophosphate↗
PubMed1995

Efficacy of hepatobiliary scintigraphy in demonstrating cholangio-colic fistulae. Is formation of internal biliary fistula related to external leak closure?

The authors present four cases of internal biliary fistulae (IBF) identified on hepatobiliary scintigraphy. All of the cases share common history of external biliary leak closure. Scintigraphy in all four cases showed a similar pattern of direct visualization of transverse colon without any significant small bowel activity. This suggests an increased frequency of IBF formation in cases with external fistulous tract closure. Retrospectively, it appears that spontaneous closure of external leak may be pathological consequence of formation of IBF involving hepatic flexure.

Adult↗
PubMed1995

Diagnosis of uterine abnormalities with radionuclide imaging.

A pelvic hypervascular blush often creates a diagnostic dilemma during radionuclide abdominal imaging studies in females. This blush is shown to be due to uterine vascularity that is more prominent in the secretory and menstrual phases of the menstrual cycle. Significant uterine vascularity in the earlier phases is inappropriate and may be pathologic. Three such cases are presented in which increased uterine vascularity on radionuclide imaging during the proliferative phase either lead to a diagnosis or supported a clinical finding.

Adult↗
PubMed1995

Scintigraphic diagnosis of protein losing enteropathy using Tc-99m dextran.

The authors performed abdominal scintigraphy using intravenously administered Tc-99m dextran in a patient with protein losing enteropathy. The study revealed abnormal leakage of the radiotracer in the left lumber area that moved over time in a pattern suggestive of small intestinal transit. Besides being a nonprotein and having long stay in intravascular compartment, the macromolecule may have many advantages over Tc-99m human serum albumin, the current radiotracer of choice for imaging intestinal protein loss.

Adult↗
PubMed1995

Attenuation of reperfusion injury by the antioxidant n-propyl gallate.

We studied the effects of n-propyl gallate (n-PG) on Langendorff preparations of isolated rat hearts. Perfusion of the hearts with Krebs-Henseleit (KH) solution containing 20 microM n-PG did not cause a statistically significant change in either left ventricular systolic pressure (LVSP), end-diastolic pressure (LVEDP), developed pressure (LVDP), or heart rate (HR), indicating that n-PG has little acute myocardial toxicity. The effects of n-PG on the reperfused and ischemic myocardium were tested in hearts subjected to 15-min global P4 the ischemic hearts with KH buffer resulted in the recovery of the LVDP to 66 +/- 7% (mean +/- SEM, n = 11) and the recovery of the rate-pressure product (RPP) to 65 +/- 7% of their preischemic values. The LVEDP of the reperfused hearts was 30 +/- 5 mm Hg as compared with the preischemic LVEDP of 5.2 +/- 0.9 mm Hg. The difference between the coronary flow rate of the preischemic hearts (15.4 +/- 0.8 ml/min) and the reperfused hearts (13.9 +/- 0.9 ml/min) was not statistically significant (p > 0.05). Addition of n-PG, at the time of reperfusion, resulted in with KH buffer containing 20 microM n-PG had LVEDP of 6.2 +/- 0.4 mm Hg, and both LVDP and RPP recovered to 92 +/- 4% of the preischemic control.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Electrophysiological effects of 4-hydroxynonenal, an aldehydic product of lipid peroxidation, on isolated rat ventricular myocytes.

Aldehydic products of lipid peroxidation, such as 4-hydroxynonenal (4-HNE), have been implicated in the etiology of pathological changes under oxidative stress. To identify the mechanism by which 4-HNE alters cellular excitability, its effects on isolated rat ventricular myocytes were studied. Superfusion with 100 to 880 mumol/L 4-HNE led to a time- and concentration-dependent rigor shortening of myocytes. A reduction in [Ca2+]o and inhibition of transsarcolemmal Ca2+ transport by 1 mmol/L La3+ did not affect either the magnitude or the time course of 4-HNE-induced myocyte rigor. Superfusion of myocytes with 400 mumol/L 4-HNE led to an increase in the action potential duration, progressive depolarization of the resting membrane potential, and an increase in the input resistance (Rin) of the myocyte (phase I), followed by a loss of electrical excitability. Continued superfusion with 4-HNE resulted in membrane hyperpolarization and a prominent decrease in the Rin (phase II). The decrease in Rin coincided with myocyte rigor. In whole-cell voltage-clamp experiments, superfusion with 4-HNE inhibited current through the inward rectifier K+ channel (IK1). 4-HNE had no effect on either the magnitude or the rate of "rundown" of L-type Ca2+ currents. Exposure to 4-HNE led to an increase in the magnitude of the fast inward Na+ current (INa). The voltage dependence of the steady state parameters for activation and inactivation of INa shifted to more positive potentials, with a resultant increase in the window current. 4-HNE-induced myocyte rigor was accompanied by a large increase in time-independent currents that displayed linear dependence on the membrane potential and were inhibited by glibenclamide, suggesting activation of the ATP-sensitive K+ channel. Steady state currents recorded in Cs(+)-containing Ringer's solution with La3+ and tetrodotoxin and Cs(+)-containing internal solution (leak currents) were not affected by 4-HNE. Superfusion with 4-HNE resulted in a significant decrease in the cellular concentration of nonprotein thiols and a severe decrease in [ATP]i. The energy charge of the myocytes fell from 0.9 to 0.3. These observations indicate that 4-HNE-induced membrane depolarization may be due to an inhibition of IK1. Changes in voltage dependence of INa, inhibition of IK1, and membrane depolarization appear to contribute to the prolongation of the action potential, observed during phase I. Depletion of [ATP]i may be responsible for changes observed during phase II, ie, activation of the ATP-sensitive K+ channels, membrane hyperpolarization, decrease in Rin, and rigor shortening of the myocytes. These results suggest that stable products of lipid peroxidation, such as 4-HNE, are proarrhythmic and may contribute to the cytotoxic effects of oxidative stress.

Adenosine Triphosphate↗
PubMed1995

Efficacy of standard ten millicurie dose of radio-iodine in management of autonomously functioning toxic thyroid nodules.

Therapeutic effect of radio-iodine treatment on thyroid patients with autonomously functioning toxic thyroid nodule was evaluated. Fifty one patients were given a standard dose of 10 mci of radioiodine (I-131) and were followed up for 2-3 years. The failure rate (relapse after 10 mci of radioiodine) of this regime was 10%. It was found that the nodules less than or equal to 3 cms. in size were completely cured after a dose of 10 mic. of radio-iodine therapy, over a follow up period of next 6 months. Patients having nodules larger than 3 cms. relapsed after first dose of 10 mci of radio-iodine, but were cured completely after the second dose of 10 mci of radio-iodine therapy. Tri-iodothyronine (T3) and thyroxine (T4) values were both found to be high before giving treatment in all the cases. Only one case developed hypothyroidism after radioiodine therapy.

Female↗
PubMed1995

99Tcm-dextran: a potential inflammation-seeking radiopharmaceutical.

The aim of this study was to test whether 99Tcm-dextran can be used for imaging inflammation. An in vivo inflammation model was prepared by intramuscular (i.m.) injection of Freund's complete adjuvant to the thigh of five rabbits. Serial imaging of the animals was done with 99Tcm-dextran for 2 weeks following the onset of inflammation. The radiotracer was seen to concentrate selectively in the lesion, with a mean target-to-nontarget ratio of 3.01 (range 2.74-3.15) from day 4 onwards. The area of scintiscan abnormality increased with time and was more marked than the physical appearance of the lesion. In two rabbits, the tracer was also seen to localize at the site of injection of the anaesthesia in the normal thigh. The best time to image was found to be 2-4 h after 99Tcm-dextran administration. It would appear that abnormally increased capillary permeability in the inflamed area results in enhanced uptake of the macromolecule. We conclude that 99Tcm-dextran is a potential inflammation-seeking radiotracer, though it needs to be evaluated further.

Animals↗