Biomedical subjects
Publications and source records attributed to M Gandhi.
A 15 year old girl who was labelled as having MacLeod's syndrome on the basis of a chest radiograph was subsequently, at the age of 23 years, found to have an adenoid cystic carcinoma obstructing the left main bronchus. This case emphasises the need to exclude a central lesion in cases of unilateral hyperlucent lung.
This study compared the effects of adenosine (Ado) on the coupling of glycolysis and glucose oxidation and on mechanical function in normal hearts and in hearts subjected to transient ischemia. Isolated working rat hearts were perfused with Krebs containing 1.2 mM palmitate and 100 microU/ml insulin. After 15 min of aerobic perfusion, hearts underwent either two cycles of 10 min of ischemia and 5 min of reperfusion (stressed) or 30 min of aerobic perfusion (control). After 45 min, hearts underwent either aerobic perfusion for 35 min (series A) or 30 min of ischemia and 30 min of reperfusion (series B). In series A, left ventricular minute work (LV work) was similar in control and stressed hearts and was not affected by Ado (500 microM) or N6-cyclohexyladenosine (CHA 0.5 microM). Ado reduced glycolysis by 49% in control hearts but increased glycolysis by 74% in stressed hearts. CHA inhibited glycolysis in both groups by 50 and 62%, respectively. In series B, LV work during reperfusion recovered to a similar extent in untreated control and stressed hearts. In control hearts, Ado reduced glycolysis by 50% while enhancing LV work to 81% of preischemic values. In stressed hearts, Ado increased glycolysis by 34% and depressed LV work to 9%, whereas CHA inhibited glycolysis by 53% and LV work to 91%. These data indicate that coupling of glycolysis to glucose oxidation is a key determinant of mechanical function of the postischemic myocardium. They also show that the metabolic and protective effects of Ado depend on the status of the heart before sustained ischemia.
The effect of ischemic preconditioning (IPC) on glycolysis, glucose oxidation, adenine nucleotide and nucleoside levels, and mechanical function was studied in isolated paced working rat hearts under aerobic conditions or when reperfused following sustained ischemia. IPC inhibited glycolysis in aerobic hearts (4.48 +/- 0.66 vs. 3.18 +/- 0.39 mumol.min-1.g dry wt-1) and calculated proton production attributable to exogenous glucose (7.79 +/- 1.31 vs. 4.73 +/- 0.81 mumol.min-1.g dry wt-1). In hearts subjected to ischemia and reperfusion, IPC decreased, relative to controls, glycogen content before the onset of ischemia (116.6 +/- 4.3 vs. 158.0 +/- 8.4 mumol/dry wt) and decreased consumption of glycogen during ischemia (54 +/- 6 vs. 76 +/- 7 mumol/dry wt). During reperfusion, glycolysis was lower in IPC hearts (2.45 +/- 0.16 vs. 4.4 +/- 0.46 mumol.min-1.g dry wt-1), as was calculated proton production (3.57 +/- 0.30 vs. 8.38 +/- 0.93 mumol.min-1.g dry wt-1). Glucose oxidation was similar in control and IPC hearts. Adenosine and ATP content of IPC hearts, relative to controls, were higher at the end of ischemia, being 0.86 +/- 0.08 vs. 0.34 +/- 0.15 mumol/g dry wt and 11.3 +/- 0.8 vs. 5.0 +/- 1.6 mumol/g dry wt, respectively. IPC enhanced recovery of ventricular work during reperfusion of ischemic hearts from 37 to 68%. These results indicate that IPC is associated with a reduction in glycogen content, inhibition of glycolysis during ischemia and reperfusion, and a decrease in proton production from glucose. These changes may, in part, explain the enhanced recovery of mechanical function observed in IPC hearts.
Hepatocyte growth factor (HGF) has been implicated in branching tubulogenesis of the developing kidney and in response to renal injury. We therefore examined the effects of response to renal injury. We therefore examined the effects of HGF on a recently described murine inner medullary collecting duct epithelial cell line (mIMCD-3 cells) in comparison with Madin-Darby canine kidney (MDCK) cells. HGF induced mitosis, scattering, and tubulogenesis in both mIMCD-3 cells and MDCK cells. However, mIMCD-3 cells underwent branching tubulogenesis under matrix conditions that did not support these morphogenetic changes in MDCK cells, suggesting substantial differences in regulation of tubulogenesis in these two cell types. In quiescent mIMCD-3 cells, the high-affinity receptor for HGF, c-met, was expressed in a nonphosphorylated state. After stimulation with HGF, there was a > 10-fold increase in receptor tyrosine phosphorylation and selective association with at least two intracellular proteins, including the phosphatidylinositol-3-kinase. Thus mIMCD-3 cells, which undergo HGF-dependent mitosis, scattering, and branching tubulogenesis, express the c-met receptor in a highly regulated state and therefore should make an excellent model for examining the mechanisms of HGF-dependent tubulogenesis in the renal collecting duct.
Computed tomography (CT) scanning is an accepted first line investigation for suspected lumbar prolapsed intervertebral disc disease (PID). However, it does involve ionizing radiation and any possible reduction in the dose is desirable. A questionnaire was sent to a random selection of 60 CT centres in the UK to confirm that a routine scan of the three lower lumbar levels is current practice in a majority of centres, regardless of symptomatic presentation. All orthopaedic CT referrals over 2 years for suspected lumbar disc disease in Sheffield were studied retrospectively. Of 486 cases, 99 (20%) were shown to have disc disease, of which 16 (3.3%) had disease at the L3/4 level. Of these 16 cases, 11 were suspected clinically. Analysis of the long-term outcome of the five unsuspected cases showed that in none did the CT findings make any significant contribution to this outcome. These results have altered our practice. Two-level scanning is now performed routinely and three-level scanning is only performed when specified clinical or radiological indications are present.
Different preparations of Ruta graveolens were administered orally to female rats (Days 1-10 post coition) and female hamsters (Days 1-6 post coition). The powdered root (CDR), aerial parts (CDA) and the aerial parts aqueous extract (AEA) all showed potential anticonceptive activity in rats. Limited administration on selected days of CDA showed uniformly lesser activity than with 10-day treatment. Sequentially prepared petroleum ether and methanol extracts of CDA were as active as CDA itself. The benzene and chloroform extracts were toxic and inactive. Rutin, a known chemical constituent of the plant, was found to be inactive. None of the above preparations showed activity in hamsters.
The petroleum either extract and methanol extract of the bark of Alstonia scholaris were found to be devoid of antiamalarial activity in mice infected with Plasmodium berghei. However, a dose-dependent improvement of conditions and delayed mortality amongst animals receiving methanol extract of A. scholaris was noticed. Studies with A. constricta and alstonine shall help resolve the antimalarial status of the bark in question.
Trospectomycin (U-63366F), a 6'-propyl analogue of spectinomycin, was tested against aminoglycoside-resistant enterococci. The MIC90 for Enterococcus faecalis was 4 mg/l and that for E. faecium was 8 mg/l. Trospectomycin alone was not bactericidal for enterococci, with MBC90 4096 mg/l for both E. faecalis and E. faecium. The addition of commercially available polyvalent immunoglobulin decreased significantly both the MICs and the MBCs and the rendered trospectomycin bactericidal for enterococci. Chequerboard titration of a combination of trospectomycin with ampicillin revealed an FIC index of 1.0 for all the isolates tested. Time-kill curves also did not show any enhancement of bactericidal activity of ampicillin when combined with trospectomycin. A combination of ampicillin and gentamicin was synergistic for enterococci under similar experimental conditions. Trospectomycin can be used as a safe alternative to aminoglycosides or beta-lactam antibiotics in enterococcal infection where bactericidal activity is not required, or in the event of serious side effects from these two classes of antibiotics.
The net transport of glucose from blood to the cerebrospinal fluid compartment of cats was measured by ventriculocisternal perfusion to determine over a large range of serum glucose concentrations the influence of serum glucose levels and their changes on the net transport rate. Changes in serum glucose levels were followed within minutes by corresponding changes in cerebroventricular effluent fluid glucose concentration. At mean values of serum glucose concentration of 6.2 mM and cerebrospinal fluid formation rate of 24.3 microliter/min, the net glucose influx rate was 1.6 mmol/min. The effluent fluid-to-serum glucose concentration ratio was 0.25 and decreased when serum glucose was greater than 11.1 mM. The rate of glucose transport from blood to effluent fluid during ventricular perfusion was saturable, and approached a maximum of 3.5 mumol/min at serum glucose levels above 22 mM. From the cerebrospinal fluid formation and net glucose influx rates the calculated glucose concentration of nascent cerebrospinal fluid was 6.5 mM and higher than the corresponding serum glucose of 5.6 mM. It is concluded that during perfusion over a wide range of serum glucose concentrations, a saturable mediated glucose transport mechanism can be demonstrated. Changes in serum glucose are rapidly reflected in corresponding effluent fluid glucose levels. From effluent fluid-to-serum glucose concentration ratios and calculations of the glucose in newly formed cerebrospinal fluid, the technique, however, overestimates the glucose influx rates at normal serum glucose levels.
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The net contribution of vasogenic brain edema to cerebrospinal fluid (CSF) formation was studied by ventriculocisternal perfusion. Individual cats were perfused both before and 2 1/2 hours after a severe cold-induced injury to the cerebral cortex, and the results were compared. Although the edema had occupied the larger part of the hemispheric white matter and bordered the lateral ventricle, a decrease rather than an increase in CSF formation rate was observed. This decrease was related to a decrease in the cerebral perfusion pressure by a regression equation that was not affected by the cold injury.
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This report examines the effect of decreasing serum osmolality on movement into the ventricular system of fluid and of test material injected into the brain. Trace quantities of 22NaCl and 125I-labeled cat serum albumin (CSA) were injected into cerebral white matter of cats. The rates of cerebrospinal fluid volume flow, and appearance of 22Na and 125I-CSA were measured in the effluent fluid using ventriculocisternal perfusion before and while serum osmolality was acutely decreased by the intravenous infusion of a 60 mOsm sucrose solution. As compared to the control period, at the end of the infusion serum osmolality decreased from 321 +/- 4.2 mOsm to 283 +/- 4.0 mOsm and CSF volume flow increased from 21.8 +/- 2.3 microliter/min to 54.9 +/- 4.1 microliter/min (means +/- S.E.). The slope of the regression line describing 22Na influx went from 1.04 to 1.79, while for 125I the slope went from 0 to 1.38. These results suggest that a common pathway may exist for the movement, through the brain and into the ventricular system, of water, ions and large molecules.
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The seed oil of Azadirachta indica (neem oil) is well known for its medicinal properties in the indigenous Indian system of medicine. Its acute toxicity was documented in rats and rabbits by the oral route. Dose-related pharmacotoxic symptoms were noted along with a number of biochemical and histopathological indices of toxicity. The 24-h LD50 was established as 14 ml/kg in rats and 24 ml/kg in rabbits. Prior to death, animals of both species exhibited comparable pharmacotoxic symptoms in order and severity, with lungs and central nervous system as the target organs of toxicity. Edible mustard seed oil (80 ml/kg) was tested in the same manner to document the degree to which the physical characteristics of an oil could contribute to the oral toxicity of neem oil.
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