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Biomedical subjects

A Prasad

Publications and source records attributed to A Prasad.

At least 19 recordsLinked to original sources

Ethanol modulation of GABA receptor-activated Cl- currents in neurons of the chick, rat and mouse central nervous system.

Modulation of gamma-aminobutyric acidA (GABAA) receptor function by drugs such as ethanol may depend on the genetic heterogeneity of GABAA receptor subunits, which vary across species and cell types. For this reason, the effects of ethanol on gamma-aminobutyric acid receptor-activated chloride currents (IGABA) were examined using whole-cell voltage-clamp recordings in primary cultures of neurons obtained from different species (chick, mouse and rat) and from different brain regions (cerebral cortex, hippocampus, cerebellum and spinal cord), and in acutely dissociated neurons from rat neocortical slices. Low concentrations (1-50 mM) of ethanol produced an enhancement of IGABA in some cells from each brain region examined. In cells obtained from the rat and chick cerebral cortex, 40-58% of cells exhibited an ethanol-sensitive IGABA. Moreover, a statistically significant variation in the response to ethanol was found in rat cortical neurons obtained from different litters. In mouse hippocampal neurons, potentiation of IGABA was obtained with ethanol concentrations (1-10 mM) well below those needed to inhibit neuronal responses to N-methyl-D-aspartic acid (30-50 mM), suggesting a differential sensitivity of these two receptor mechanisms to ethanol. Potentiation of IGABA by ethanol was reversed by the benzodiazepine receptor partial inverse agonist RO15-4513 (ethyl 8-azido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine - 3-carboxylate), but was not affected by chelation of intracellular calcium. Furthermore, high concentrations of GABA attenuated the ability of ethanol to enhance IGABA. These results are consistent with the hypothesis that ethanol facilitates coupling between receptor binding and chloride channel activation.

Animals

Uncoupling of GABA-benzodiazepine receptors in chick cerebral cortical neurons requires co-activation of both receptor sites.

Primary cultures of chick cerebral cortical neurons were exposed to 1 microM flurazepam in vitro, and the effect of flurazepam on GABA-activated membrane current (IGABA) was examined using whole-cell voltage-clamp recording. Exposure of chick cerebral cortical neurons to flurazepam alone for 3-10 days resulted in a significant decrease in the degree of potentiation of IGABA elicited by 0.5 microM flurazepam. When GABA or nipecotic acid (a GABA uptake blocker) were added with flurazepam during chronic drug exposure, neuronal responses to GABA were significantly less sensitive to modulation by 0.5 microM flurazepam compared to flurazepam treatment alone. Furthermore, this effect was significantly reduced by co-administration of the GABAA receptor antagonist bicuculline. These results suggest that tolerance to benzodiazepines in vitro requires activation of both the GABA and the benzodiazepine binding sites on the GABAA receptor-channel complex.

Animals

Cryptogenic osteomyelitis of the skull and intracerebral abscess.

The authors report a rare case of cryptogenic osteomyelitis of the skull with an intracerebral and a subgaleal abscess. Total excision of the abscess extending from the cortical surface to the lateral ventricle led to ventriculitis and subgaleal cerebrospinal fluid collection. These complications could have been avoided by aspirating the abscess after removing the infected portion of the skull and the epidural granulation tissue. Neurosurgeons preferring to excise such an abscess should leave a small area of capsule at the base in order to avoid having to open the ventricle.

Brain Abscess

Resistance to insulin-induced hyperphagia in fat-preferring rats.

Outbred male Sprague-Dawley rats were screened for their macronutrient (fat, carbohydrate and protein) preference profile and divided into two groups, the low- and high fat-preferring groups each deriving 23% and 72% of its total caloric intake from fat respectively. Subcutaneous administration of bovine insulin (6U/kg) resulted in an increase in total caloric intake in the low, but not the high fat-preferring group. Furthermore, the increased caloric intake in the low fat-preferring group was entirely due to increased carbohydrate consumption. These data suggest a defect in the action of insulin in fat-preferring rats.

Animals

Solitary spinal osteochondroma causing neural syndromes.

Three cases of solitary osteochondroma of the spine are reported. Two presented with cervical myelopathy and one with radiculopathy. Plain radiography or tomography is adequate for the diagnosis in the majority of cases; nevertheless, a CT scan or MRI is of immense help in planning surgical treatment. The radiological features of spinal exostoses are reviewed.

Adolescent

Ethanol enhances GABAA receptor-activated chloride currents in chick cerebral cortical neurons.

Primary cultures of cerebral cortical neurons were prepared from 7- to 8-day-old chick embryos. The effect of ethanol on GABA-activated membrane current was examined using whole-cell voltage-clamp recording in cells maintained for 3-25 days in vitro. In approximately 60% of neurons examined ethanol caused a potentiation of the membrane current elicited by GABA. The threshold concentration of ethanol was 1 mM, and the potentiating effect of ethanol on GABA-activated currents was maximal at 10 mM. In many cells higher concentration (40-50 mM) of ethanol inhibited GABA-activated currents. These effects of ethanol were all reversible.

Animals

Development and migration of avian sympathetic preganglionic neurons.

Modern neuronanatomical techniques were used to investigate the development of the avian sympathetic preganglionic cell column in the spinal cord of the chick embryo. [3H]thymidine autoradiography indicated that the majority of these preganglionic, or "Terni column" neurons are generated between stages 18 and 24 (days 2-4). This coincides with the genesis of the somatic motoneurons in the thoracic levels of the cord, and therefore differences in the time of origin cannot explain the divergent fates of these two neuronal populations. Data obtained from short-survival autoradiographic experiments indicated that many early born cells remain close to the ventral region of the ventricular epithelium until day 5 of incubation. Ventral root injections used to label retrogradely neurons projecting an axon into the ventral root (Terni cells and somatic motoneurons) have labeled neurons next to the ventricular epithelium at the same early stages. Thus, it seems likely that some Terni cells, if not all, maintain medial positions and do not migrate laterally to join a common motor column before initiating a dorsal migration. Analysis of a closely staged series of embryos, whose Terni column neurons were retrogradely labeled with wheat germ agglutinin-horseradish peroxidase (WGA-HRP), revealed that between days 5 and 8 of incubation, Terni column neurons migrated dorsally to attain their adult position adjacent to the central canal. These changes in position were reflected in the changing morphology of the Terni column neurons, visualized by the Golgi-like HRP labeling. The positions of the migrating Terni cells differed from those of commissural cells, indicating that these fibers are not the substrate for the dorsal migration. The dorsal migration of Terni column cells was not disrupted by the surgical removal of the sympathetic ganglia, the synaptic targets of these neurons, nor by disruption of spinal afferents. Taken together, these results suggest that the migratory behavior of Terni cells in distinctive when compared to that of somatic motoneurons, and that local and/or intrinsic cues within the spinal cord guide the dorsal migration of Terni column cells.

Animals

Medulloblastoma with extensive calcification.

Calcification in cases of medulloblastoma has been described with varying frequency (10%-15.4%) on computed tomographic (CT) scan. Usually these calcifications are small in size and speckled. The authors report a case of medulloblastoma with extensive calcification in the lateral hemisphere of the cerebellum in an 18-year-old boy.

Adolescent

Acute ataxic neuropathy: a clinical, electrophysiological and morphological study.

Sensory ataxia as the chief manifestation of acute neuropathy is rather rare. Of the 224 cases of acute polyneuropathy seen over 6 years (1984-1990) only 10 patients (M:F 3:7) had disabling ataxia as the presenting feature. Their ages ranged from 14-61 years. Antecedent febrile illness was present in 6 patients and the peak deficit evolved over 2-25 days. Severe ataxia, paresthesia, distal areflexia and predominant joint sense loss were common to all, motor weakness was either absent or insignificant. CSF was acellular and revealed elevated protein in 3 subjects. All patients had electrophysiological evidence of severe sensory neuropathy with mild or no motor neuropathy. Sural nerve biopsy in one patient showed loss of large, as well as small, diameter myelinated fibres, secondary demyelination, but no evidence of inflammation. At follow up marginal to moderate improvement in ataxia was noted in only 5 patients. Absence of ophthalmoplegia and motor weakness, poor prognosis and characteristic electrophysiological and histopathological observations suggest that acute ataxic neuropathy may be a distinct entity.

Adolescent

Lymphocytic hypophysitis: can open exploration of the sella be avoided?

A case of lymphocytic hypophysitis (LYHY) in a menopausal woman is presented. A review of the literature suggests that conservative treatment may be tried in suspected cases of LYHY, if the vision of the patient is not threatened. A transphenoidal stereotactic biopsy of the mass may be performed if the patient fails to improve or deteriorates, thus avoiding open exploration of the sella in selected cases.

Adult

The role of the perforated segment of the ventricular catheter in cerebrospinal fluid leakage into the brain.

Two cases of gross post-operative cerebrospinal fluid (CSF) leakage along an indwelling ventricular catheter are reported. The CSF appeared to leak through the perforations of the ventricular catheter, as well as at the site of penetration of the ventricular wall. A small or slit ventricle with high intraventricular pressure may thus be a predisposing factor for this localized CSF collection.

Catheters, Indwelling

Cystatins in human tear fluid.

The activities of cysteine proteinases which include several lysosomal cathepsins are controlled by naturally occurring inhibitory proteins termed cystatins. Cystatins occur both intracellularly and extracellularly in various tissue fluids including tears. Tears were collected by the Schirmer paper strip method from healthy volunteers who had no history or signs of external ocular disease. The tear components were extracted from the filter papers, and used to determine the apparent free cystatin activity and cystatin levels of tears, and for immunoblots. Tears were also collected using capillary tubes for the measurements of cystatins. By titrating papain, a cysteine proteinase, of known specific activity with tear fluid, relatively high levels of apparent free cystatin activity were demonstrated in tears: 28.8 +/- 3.47 (S.E.M.) pmols papain inhibited per mg tear protein (n = 9). The concentrations of cystatins in tear samples were measured by an indirect enzyme-linked immunosorbent assay (ELISA) using antibodies against human salivary cystatin S and purified cystatin S as standard. The ELISAS revealed that tears contain high levels of cystatin-like immunoreactive material, amounting to about 10% of tear proteins. In microgram cystatin S/mg protein the values were: right eye: 94.7 +/- 9.9; left eye: 115.5 +/- 14.8; n = 12. Cystatin levels of tears collected using capillary tubes were comparable: 120.7 +/- 19 micrograms/mg protein (n = 10). Immunoblots of tear fluids revealed a protein of about 14,000 molecular weight which reacted with antihuman cystatin SN monoclonal antibodies. Protein(s) of similar molecular weight were visualized using antibodies against human cystatins S and C. Less abundant additional cystatin-like immuno-reactive proteins were detected by using the two latter antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult