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Biomedical subjects

P Tandon

Publications and source records attributed to P Tandon.

At least 19 recordsLinked to original sources

Age-dependent effects of glutamate toxicity in the hippocampus.

While prolonged seizures can cause brain damage at any age, the extent of brain damage following prolonged seizures is highly age-dependent. Seizures in the immature brain are followed by far less histological damage than seizures of similar duration and intensity in mature animals. The reasons for this age-related phenomenon are unclear. Seizure-induced cell death may be due to the neurotoxic effects of excessive glutamate release, we tested the hypothesis that the immature brain is less vulnerable to glutamate-induced neurotoxicity than the mature brain. We administered equal amounts of glutamate (0.5 mumol in 1.0 microliter) unilaterally into the CA1 subfield of the hippocampus of rats at postnatal (P) days 10, 20, 30, and 60. Equal volumes of saline were injected in the contralateral hippocampus. Rats were killed 7 days later and their brains were examined for hippocampal cell loss. The size of the resultant hippocampal lesion was highly age-dependent. Minimal cell loss was noted in the P10 rats, lesions in the P20 rats were smaller than those at P30 and P60, which were similar in extent. This study demonstrates that the extent of glutamate neurotoxicity in the hippocampus is highly age-dependent, with immature hippocampi relatively resistant to glutamate-induced cell death.

Aging

Long-term effects of excitatory amino acid antagonists NBQX and MK-801 on the developing brain.

Because of the critical role of excitatory amino acids (EAAs) in epileptogenesis and seizure-induced brain damage, EAA antagonists are now being considered as a possible therapy for seizures. However, during development EAAs play a pivotal role in learning, memory, and brain plasticity. To evaluate the long-term effects of a short course of EAA antagonists on the developing brain, a non-NMDA antagonist, NBQX, or a NMDA antagonist, MK-801, were administered over 7 days by osmotic pumps stereotaxically implanted into the lateral ventricles of normal 10 day old rats. Alternatively, 10 and 20 day old rats received a 7 day course of intraperitoneal (i.p.) NBQX. One month later, the NBQX-, MK-801-treated rats, and controls underwent a series of behavioral studies: handling test, open field, and Morris water maze. Flurothyl inhalation was used to test seizure susceptibility in all groups. Although all of the rats treated with NBQX via osmotic pumps has spontaneous seizure, rats surviving infusion of EAAs had no deficits in learning, memory, or behavior and did not differ from controls in seizure susceptibility with flurothyl. In the developing animal, a short-term course of EAA antagonists leads to no long-term adverse effects on behavior or seizure susceptibility.

Animals

Recurrent seizures in immature rats: effect on auditory and visual discrimination.

The effect of recurrent seizures in developing rats on subsequent long-term behavior was studied. Fifteen day old rats received a convulsant dosage of flurothyl three times daily for five consecutive days. When the rats were fully mature, they underwent behavioral testing using the water maze and auditory quality or location discrimination. With serial flurothyl administration seizure duration increased progressively but latency to seizure onset did not change. Compared to controls, flurothyl-treated rats had impaired performance in the water maze and on auditory location, but not on quality discrimination. Histological examination showed no gross cell loss in the hippocampus. This study demonstrates that serial seizures in the developing brain cause detrimental effects on visual and auditory spatial learning.

Animals

Fenthion produces a persistent decrease in muscarinic receptor function in the adult rat retina.

Several reports have suggested that exposure to organophosphate pesticides damages the visual system. The prolonged effects of an acute dose of fenthion (dimethyl 3-methyl-4-methylthiophenyl phosphorothionate) were studied on the cholinergic system of the rat retina. Fenthion was administered in a single dose of 0 or 100 mg/kg (sc, in corn oil) to adult, male, Long-Evans rats. The animals were killed 4, 14, or 56 days after treatment and cholinesterase (ChE) activity as well as muscarinic receptor (mChR) function measured in the retina and frontal cortex. Fenthion produced 89% inhibition of ChE activity in both tissues at 4 days, and, although there was recovery, slight (15%) inhibition of the enzyme activity was still observed at 56 days in both tissues. A long-lasting decrease in carbachol-stimulated inositolphosphate (IP) release was observed following fenthion treatment in the retina: IP release was depressed at 4 days and this depression persisted up to 56 days after dosing. The density of mChR in the retina as well as in the cortex was decreased by 14-20% at 4 days and returned to control levels by 56 days. Fenthion had no effect on the metabolism of phospholipids in the retina following intraocular injections of labeled precursors [3H]myo-inositol, [methyl-14C]choline, or [2-3H]glycerol 4 days after fenthion treatment. These prolonged effects of fenthion on mChR function (signal transduction) appear to be specific to the retina as the cortex showed no change in receptor-stimulated IP release even in the presence of significant mChR down-regulation and ChE inhibition. This dose of fenthion did not produce overt morphological changes in the retina or in the cortex, as observed with light microscopy, although an increase in glial fibrillary acidic protein immunoreactivity (GFAP IR) extending from the internal limiting membrane to the external limiting membrane of the retina was noted. This increase in GFAP IR was observed at 14 days and persisted as long as 56 days post-treatment in the retina, but was not noted in the cortex at any of the time points studied. Thus, this long-lasting perturbation in the retinal cholinergic second messenger system induced by fenthion may occur independently of depressed ChE activity and down-regulation of mChR.

Animals

Compensatory changes in the hippocampus following intradentate infusion of colchicine.

Direct infusion of colchicine into the dentate gyrus of the hippocampus kills granule cells and elicits behavioral, neurochemical and neuroanatomical changes. Colchicine-treated rats are less sensitive to the behavioral effects of cholinergic muscarinic receptor antagonists and more sensitive to cholinergic agonists. These behavioral changes are associated with time- and dose-dependent alterations in the cholinergic signal transduction mechanism. Carbachol-stimulated turnover of phosphoinositides is increased in the hippocampus of colchicine-treated rats; similar changes are not observed in the cortex or striatum of colchicine-treated animals. Intradentate colchicine produces a significant increase in choline- acetyltransferase activity and staining for acetylcholinesterase activity in the hippocampus, suggesting reactive synaptogenesis of cholinergic fibers. Other studies have shown that the integrity of the septohippocampal pathway is necessary for these colchicine-induced compensatory changes to occur. It is suggested that the mechanism for these neurochemical changes in colchicine-treated animals may be occurring via alterations in negative feedback control of receptor-G-protein-mediated phosphoinositide hydrolysis.

Animals

Dynamics of Met5- and Leu5-enkephalin and their receptor binding activity in relation to morphine.

A complete normal coordinate analysis of Met5- and Leu5-enkephalins using Wilson's GF matrix method and Urey Bradley force field has been carried out to understand the dynamical behaviour of enkephalins. In addition, the charge distributions on different atoms of the two enkephalins and morphine using CNDO/2 method are also reported. The similarity in the charge distribution on the part of these two molecules is indicative of the possible interactions at the same receptor site as that of morphine and its derivatives. Apart from the topographical features and charge distribution, binding onto receptor site is not a static but a dynamic process and low frequency modes must play an important role in the recognition process. The significance of the out-of-plane amide VII band and other skeletal modes as characteristic of conformational states of Met5- and Leu5-enkephalins are discussed.

Enkephalin, Leucine

Operations on gliomas involving speech centres.

One hundred patients with gliomas of the dominant hemisphere, who survived for more than one year after operation, have been analysed. In all of them radical tumour removal had been attempted. Already preoperatively 58 of them had signs of speech deficit. Postoperatively 65% improved and only 15% deteriorated with regard to their speech function. Therefore it seems not to be justified to deny operative tumour removal to patients with gliomas located within or near the speech areas.

Adult

Locally synthesized phosphatidylcholine, but not protein, undergoes rapid retrograde axonal transport in the rat sciatic nerve.

Retrograde axonal transport of phosphatidylcholine in the sciatic nerve has been demonstrated only after injection of lipid precursors into the cell body region. We now report, however, that after microinjection (1 microliter) of [methyl-3H]choline chloride into the rat sciatic nerve (35-40 mm distal to the L4 and L5 dorsal root ganglia), time-dependent accumulation of 3H-labeled material occurred in dorsal root ganglia ipsilateral, but not contralateral, to the injection site. The level of radioactivity in the ipsilateral dorsal root ganglia was minimal at 2 h after isotope injection but was significantly increased at 7, 24, 48, and 72 h after intraneural isotope injection (n = 3-8 per time point); at these time points, all of the radiolabel in the chloroform/methanol extract of the ipsilateral dorsal root ganglia was present in phosphatidylcholine. The radioactivity in the water-soluble fraction did not show a time-dependent accumulation in the ipsilateral dorsal root ganglia as compared with the contralateral DRGs, ruling out transport or diffusion of precursor molecules. In addition, colchicine injection into the sciatic nerve proximal to the isotope injection site prevented the accumulation of radiolabel in the ipsilateral dorsal root ganglia. Therefore, this time-dependent accumulation of radiolabeled phosphatidylcholine in the ipsilateral dorsal root ganglia is most likely due to retrograde axonal transport of locally synthesized phospholipid material. Moreover, 24 h after injection of both [3H]choline and [35S]-methionine into the sciatic nerve, the ipsilateral/contralateral ratio of radiolabel was 11.7 for 3H but only 1.1 for 35S, indicating that only locally synthesized choline phospholipids, but not protein, were retrogradely transported.

Animals

Developmental changes in carbachol-stimulated inositolphosphate release in pigmented rat retina.

Carbachol-stimulated release of inositolphosphates (IP) was studied in the whole retina from Long-Evans rats of different ages (day 5, 10, 15, 20, adult) following in vitro incorporation of [3H]myo-inositol. Unlike the albino rat retina, the pigmented retina was highly light-sensitive, making it necessary to dark adapt the animals and perform retinal dissections under low illumination to prevent light-induced IP release. Retinae from postnatal day 10 rats showed the highest amount of carbachol-stimulated IP released. This response to carbachol decreased with age until postnatal day 20 when it reached adult levels. The pigmented rat retina showed a sharp fall in the degree of carbachol (1 mM)-stimulated IP released at the time of eye-opening (450% above basal in retinae from 10 day old animals, as compared to 230% above basal in 15 day old retinae). Basal release of IP was not altered in the retina during development. Muscarinic cholinergic receptor density was, however, found to increase 5 fold with age, reaching adult levels by PND 20. Retinal weight and protein per retina also increased (four fold) from day 5 to adult; however, the in vitro incorporation of [3H]myo-inositol into phosphoinositides (calculated as per mg protein) did not change during development. Thus, in animals prior to eye opening, a much higher proportion of phosphoinositides appears to be hydrolyzed upon muscarinic receptor stimulation. During retinal development a change in sensitivity to the agonist-sensitive pool(s) of phosphoinositides may occur and/or there may be alterations in the efficacy of receptor coupling to the second messenger system resulting in the disassociation observed between the drastic increase in receptor number and the apparent decrease in receptor-stimulated release of IP.

Aging

Invasive thymoma: cytomorphological features on fine needle aspiration cytology.

Although thymomas are the commonest neoplasms of the anterior mediastinum, distinction between benign and malignant thymomas is controversial on Fine needle aspiration biopsy. We present cytomorphological features of a case of invasive thymoma on computed tomographic guided fine needle aspiration cytology and its basis is discussed in light of current concepts of thymic tumours.

Biopsy, Needle

Acute renal failure in lymphoma of the kidney.

Involvement of kidney by lymphomatous process occurs in 30-40% of cases of lymphoma, if the disease is left untreated. Incidence of renal involvement at initial presentation is 2.7%-6%. Mostly it is in the form of insidious renal failure. Acute renal failure as initial manifestation of the disease is very rare. A case of lymphomatous involvement of the kidney, with initial presenting manifestation of ARF is discussed, and the mechanisms responsible for rarity of this is analysed.

Acute Kidney Injury

The role of the septohippocampal pathway in the mediation of colchicine-induced compensatory changes in the rat hippocampus.

To study the involvement of the septohippocampal pathway in colchicine-induced changes in the hippocampus, colchicine was used to lesion the septum and/or hippocampus of male, Fischer-344 rats. Rats were killed 12 weeks post-lesion and histochemical and biochemical measurements were performed. [3H]-QNB binding, choline acetyltransferase (ChAT) activity and agonist-stimulated release of inositol phosphates (IPs) were measured in hippocampal slices. AChE histochemistry was also performed to visualize AChE positive fibers in the hippocampus. Increases in ChAT activity, AChE staining and carbachol-stimulated IP release observed in hippocampal-lesioned animals were attenuated in animals receiving both septal and hippocampal lesions. However, the decrease observed in [3H]-QNB binding sites after intradentate colchicine was not affected by septal lesions. Subsequent studies also found enhanced sensitivity to excitatory amino acid (EAA)-stimulated IP release in hippocampal-lesioned animals. Similar to the changes observed in carbachol-stimulated PI hydrolysis, this increase was also long-lasting. However, the hyperstimulation of EAA-induced IP release was not attenuated by the septal lesion. Thus, it appears that the neurochemical and morphological changes observed in the hippocampus following intradentate colchicine are dependent upon more than one afferent projection to the hippocampus.

Animals

Intestinal lymphangiectasia: evaluation by CT and scintigraphy.

Intestinal lymphangiectasia caused severe diarrhea and generalized edema in a 40-year-old man. The diagnosis was established by clinical, laboratory, and duodenal biopsy findings. The abnormalities detected on computed tomography (CT) and scintigraphy using 99mTc human serum albumin are herein described and pertinent literature is briefly reviewed.

Adult

The neurobiological effects of colchicine: modulation by nerve growth factor.

To study the effects of exogenously applied nerve growth factor (NGF) on colchicine-induced neurodegeneration in the dentate gyrus of the rat hippocampal formation, colchicine (COLCH) or artificial cerebrospinal fluid (ACSF) was infused into the dorsal hippocampus (HPC) followed by unilateral infusion of either purified beta-NGF (in ACSF) or cytochrome C. One week later, animals were tested in activity chambers when NGF treatment was found to reduce the COLCH-induced hyperactivity. Animals were sacrificed 3 or 12 weeks postlesion for neurochemical or morphological analysis. Carbachol-stimulated phosphatidyl inositol (PI) turnover performed in hippocampal slices was not affected by any treatment at 3 weeks. However, 12 weeks after the lesion, CARB stimulation of PI hydrolysis was increased in the COLCH/ACSF group. NGF treatment significantly reduced the hyperstimulation in COLCH-treated rats. Morphological analysis showed that COLCH treatment increased AChE staining in the hippocampus, whereas NGF treatment had no effect on AChE staining. There was no difference in the number of septal ChAT immunoreactive cell bodies of controls or colchicine-treated rats at either time point examined. However, NGF treatment resulted in a significant increase in the number of ChAT immunoreactive cell bodies 3 weeks postlesion. Results from this study indicate that NGF can modify colchicine-induced compensatory changes in hippocampal signal transduction and has transitory influences on cholinergic cells in the medial septum.

Acetylcholinesterase

Conformational transitions and specific heat anomaly in poly(dG-dC) and its methylated analogue.

The Zimm and Bragg theory of the helix<-->coil transition has been modified to explain order<-->order transitions in polynucleotides, in particular B<-->Z<-->psi(-)<-->coil transitions in poly(dG-dC) and poly(dG-me5dC). Lambda anomalies in specific heat measurements around the transition point have also been explained by a further modification of the same theory. Theoretical results are found to be in good agreement with the experimental data. The nucleation parameter is consistent with the stabilization/destabilization of the ordered states (Z helix) under various environmental conditions, e.g. methylation of cytosine residue at C5 position or change in the cationic concentration of the solvent.

Calorimetry