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Biomedical subjects

M R Jain

Publications and source records attributed to M R Jain.

At least 19 recordsLinked to original sources
PubMed2004

2,4,6-trinitrotoluene transformation by a tropical marine yeast, Yarrowia lipolytica NCIM 3589.

Yarrowia lipolytica NCIM 3589, a tropical marine degrader of hydrocarbons and triglycerides transformed 2,4,6-trinitrotoluene (TNT) very efficiently. Though this yeast could not utilize TNT as the sole carbon or nitrogen source, it was capable of reducing the nitro groups in TNT to aminodinitrotoluene (ADNT). In a complete medium containing glucose and ammonium sulphate as the available carbon and nitrogen sources respectively, the culture was able to completely transform 1 mM (227 ppm) of TNT under such conditions. A dual pathway was found to be functional, one of which resulted in the formation of the hydride-Meisenheimer complex (H(-)TNT) as a transiently accumulating metabolite that was subsequently denitrated to 2,4-dinitrotoluene (2,4-DNT), whereas the other pathway resulted in the formation of amino derivatives. The presence of increasing amounts of reducing equivalents in the form of glucose promoted better growth and the nitroreductases of this yeast to reduce the aromatic ring to 2,4-DNT although, the reduction of the nitro groups to amino groups was the major functional pathway. The ability of this tropical marine yeast to transform TNT into products such as 2,4-DNT which in turn could be metabolized by other microbes has implications in the use of this yeast for bioremediation of TNT polluted marine environments.

Biodegradation, Environmental↗
PubMed2000

Evidence that NPY Y1 receptors are involved in stimulation of feeding by orexins (hypocretins) in sated rats.

Neuropeptide Y (NPY) produced in the arcuate nucleus (ARC) of the hypothalamus stimulates feeding both directly by activating NPY receptors and indirectly through release of the orexigenic peptides, galanin and beta-endorphin (beta-END), in the paraventricular nucleus (PVN) and surrounding neural sites. Orexin A and orexin B, produced outside the ARC in the lateral hypothalamic area (LH), have recently been shown to stimulate feeding. In the present studies we tested the hypothesis that NPYergic signaling may mediate feeding stimulated by orexins. In adult male rats injected intracerebroventricularly (i.c.v.) with orexin A (3, 10, 15 nmol) or orexin B (3, 10, 30 nmol) feeding was stimulated in a dose-dependent manner; maximal feeding was seen after 15 nmol orexin A and 30 nmol orexin B. To determine whether NPY may mediate this orexin stimulated feeding, we used 1229U91, a selective NPY Y1 receptor antagonist (NPY-A). Whereas NPY-A on its own was ineffective, it suppressed NPY-induced feeding. Furthermore, NPY-A completely blocked the feeding evoked by either orexin A (15 nmol) or orexin B (30 nmol). These results show that orexin A and B stimulate feeding and further suggest that these excitatory effects may be mediated by NPYergic signaling through Y1 receptors. These findings are in accord with the view that the orexin-NPY pathway may comprise a functional link upstream from NPY within the hypothalamic appetite regulating network.

Animals↗
PubMed2000

Subcommissural organ-Reissner's fiber complex of the teleost Clarias batrachus responds to GABA treatment.

Subcommissural organ (SCO) is a highly specialized ependymal gland located in the roof of the third ventricle. The secretory products of the SCO, which condense to form Reissner's fiber (RF), were recently found to cross-react with the anti-calcitonin antibody. To understand the mechanisms regulating the formation of the RF and the possible function of these discrete structures, we studied the response of the SCO-RF complex to intracranially administered GABA, using immunocytochemical labeling with anti-calcitonin antibody. Although the SCO-RF complex of control fish was intensely immunostained, 1 h after GABA treatment, the ependymal cells revealed partial loss of immunoreactivity; the RF showed occasional loss of immunoreactivity with its diameter increased by about 56% of the control value. Following 2 h of GABA treatment, the SCO revealed dramatic loss of calcitonin-like immunoreactivity from the ependymal cells. The RF showed a dual response in this group, while in some segments the RF appeared conspicuously thick, elsewhere it appeared thin. The mean diameter was, however, not significantly different from the normal. Following 4 h of GABA treatment, while calcitonin-like immunoreactive material made its reappearance in the SCO, the RF diameter was uniformly reduced to about 35% of the control value. The responses by the RF as well as the SCO to intracranially administered GABA were blocked by pretreatment with bicuculline, a GABA(A) receptor antagonist. The results suggest that GABA, acting via GABA(A) receptors, may trigger the release of secretory material from the SCO and induce histomorphological changes in the RF indicative of discharge of stored material.

Animals↗
PubMed1999

Evidence that stimulation of two modalities of pituitary luteinizing hormone release in ovarian steroid-primed ovariectomized rats may involve neuropeptide Y Y1 and Y4 receptors.

A large body of evidence indicates that neuropeptide Y (NPY) is involved in stimulation of basal and cyclic release of hypothalamic LHRH and pituitary LH. To identify the NPY receptor subtypes that mediate the excitatory effects of NPY in these two modalities of LH release, we studied the effects of 1229U91, a selective Y1 receptor antagonist and Y4 receptor agonist, in two experimental paradigms that reproduce the two modalities of LH secretion in steroid-primed ovariectomized (OVX) rats. Rats were ovariectomized and implanted with a permanent cannula into the lateral cerebroventricle. In the first experiment, rats received estradiol benzoate (EB, 30 microg/rat) on day 5, followed 2 days later with progesterone (2 mg/rat) at 1000 h to induce an afternoon LH surge. 1229U91 (30 microg/3 microl) or vehicle (control) was injected intracerebroventricularly into these rats either once at 1300 h or twice (15 microg/injection) at 1100 and 1200 h. Blood samples were collected before progesterone injection at 1000 h and at hourly intervals from 1300 -1800 h via an intrajugular cannula implanted on the previous day. In control rats, serum LH levels rose significantly at 1400 h, and these high levels were maintained until 1700 h. After two injections of 1229U91, LH levels displayed a tendency to rise at 1300-1400 h, as in controls, but thereafter, decreased rapidly below the control range. In the second experiment, the acute effect of 1229U91 on LH release was evaluated in OVX rats pretreated with EB alone. Saline alone or saline containing 1, 3, 10, or 30 microg 1229U91 was injected intracerebroventricularly at 1000 h, and the effects on LH release were analyzed at 10, 20, 30, and 60 min. 1229U91 elicited a dose-dependent stimulation of LH release, with maximal response (950% of basal levels) occurring at 10 min after the 30-microg dose; elevated levels were maintained for 1 h. Because 1229U91 is a potent Y4 agonist with some affinity for Y5 receptors, these results raised the possibility that activation of Y4/Y5 receptors by 1229U91 may augment LH release. Therefore, we examined the effects of icv administration of rat pancreatic polypeptide, a Y4-selective agonist, and [D-Trp32]-NPY, a Y5 agonist on LH release in EB-primed rats. Rat pancreatic polypeptide (0.5-2 microg/rat) stimulated LH release in a dose-related manner, and peak levels (280% of basal levels) were seen at 10-20 min; the response evoked by a higher dose (10 microg) was smaller than that induced by 0.5 or 2 microg. [D-Trp32]-NPY was relatively less effective, because only the highest (10-microg) dose elicited a modest stimulation (244% of basal levels). These results demonstrate that 1229U91, a Y1 antagonist and Y4 agonist, evokes two types of responses; it suppresses the protracted ovarian steroid-induced LH surge, and acutely, it also stimulates LH. These results imply that normally two different types of NPY receptors may mediate the stimulation of LH release. Because 1229U91 is a Y1 receptor antagonist, inhibition of the steroid-induced LH surge by 1229U91 suggests that Y1 receptors may mediate the cyclic release of LH. On the other hand, acute stimulation of LH by 1229U91 implies that the Y4 agonist-like activity of 1229U91 may mediate the basal release of LH and that either NPY or a yet-to-be-identified endogenous Y4 receptor agonist may activate Y4 receptors in the hypothalamus to stimulate LH release.

Amino Acid Sequence↗
PubMed1999

Interactions between neuropeptide Y and gamma-aminobutyric acid in stimulation of feeding: a morphological and pharmacological analysis.

Neuropeptide Y (NPY) produced in neurons in the arcuate nucleus and brain stem and released in the paraventricular nucleus (PVN) and surrounding areas is involved in stimulation of feeding in rats. We recently reported that gamma-aminobutyric acid (GABA) is coexpressed in a subpopulation of NPY neurons in the arcuate nucleus. To determine whether GABA is colocalized in NPY terminals in the PVN, the site of NPY action, light and electron microscopic double staining for NPY and GABA using pre- and postembedding immunolabeling was performed on rat brain sections. GABA was detected in NPY-immunopositive axons and axon terminals within both the parvocellular and magnocellular divisions of the PVN. These morphological findings suggested a NPY-GABA interaction in the hypothalamic control of feeding. Therefore, the effects of muscimol (MUS), a GABA(A) receptor agonist, on NPY-induced food intake were examined in sated rats. When injected intracerebroventricularly, both NPY and MUS elicited dose-dependent feeding responses that were blocked by the administration of 1229U91 (a putative Y1 receptor antagonist) or bicuculline (a GABA(A) receptor antagonist), respectively. Coadministration of NPY and MUS intracerebroventricularly amplified the feeding response over that evoked by NPY or MUS alone. Similarly, microinjection of either NPY or MUS into the PVN stimulated food intake in a dose-related fashion, and coinjection elicited a significantly higher response than that evoked by either individual treatment. These results suggest that GABA and NPY may coact through distinct receptors and second messenger systems in the PVN to augment food intake.

Animals↗
PubMed1998

Orexins, a novel family of hypothalamic neuropeptides, modulate pituitary luteinizing hormone secretion in an ovarian steroid-dependent manner.

Orexin A and orexin B are a newly described family of orexigenic hypothalamic neuropeptides. The distribution of orexin immunoreactive fibers overlaps with the luteinizing hormone-releasing hormone (LHRH) neuronal system in the septo-preoptic area and the arcuate nucleus-median eminence region. To test the hypothesis that orexins may be involved in the regulation of pituitary LH secretion by influencing LHRH release, the effects of orexin A and orexin B on LH secretion were evaluated in ovariectomized (ovx) and ovarian steroid-treated ovx rats. Intracerebroventricular injection of orexin A or orexin B rapidly stimulated LH secretion in a dose- (0.3 and 3.0 nmol) and time-related fashion in estradiol benzoate- (EB) and progesterone (P)-pretreated ovx rats. Peak plasma LH concentration at 10 min were significantly higher in orexin A- than in orexin B-injected rats. On the other hand, both orexins (3 nmol) inhibited LH release in unprimed ovx rats. This ovarian steroid-dependent bimodal LH response is reminiscent of that of other orexigenic neuropeptides, such as neuropeptide Y. These findings show that orexins belong to a group of hypothalamic messengers that neurochemically bridge the regulatory networks that controls reproduction and energy balance.

Animals↗
PubMed1998

Neuropeptide Y release in the paraventricular nucleus is decreased during transient hyperphagia induced by microinjection of colchicine into the ventromedial nucleus of rats.

Disruption of neural signaling in the ventromedial nucleus (VMN) of rats by microinjection of the neurotoxin colchicine (COL) results in transient hyperphagia accompanied by enhanced weight gain. We tested the hypothesis that release of neuropeptide Y (NPY), a potent orexigenic signal is augmented within the paraventricular nucleus (PVN) of COL-treated hyperphagic rats. Adult male rats were microinjected bilaterally with either COL (4 microg/0.5 microl in saline) or saline in the VMN and a push-pull guide cannula aimed at the PVN was implanted for analysis of extra-cellular NPY. COL-injected rats gained 37.8+/-6.1 g while the saline-injected rats lost 9.3+/-3.4 g during the 4 days following surgery. On day 4, post-injection, the PVN of these rats was perfused with artificial cerebrospinal fluid via the push-pull cannula. NPY levels in perfusates collected at 10 min intervals from hyperphagic, COL-injected rats were markedly diminished. Cumulative NPY efflux over the 180 min sampling period was significantly less in COL-treated (27.7+/-6.0 pg) versus saline-injected control rats (110.6+/-32.2 pg; P < 0.05). These results show that impairment of neural signaling in the VMN by COL suppressed NPY release in the PVN. These observations taken together with previous studies showing diminution in preproNPY mRNA in the arcuate nucleus (ARC) and NPY levels in the PVN are in accordance with the thesis that the VMN normally exerts a facilitatory influence on NPYergic signaling in the ARC-PVN axis.

Animals↗
PubMed1998

FMRFamide-like immunoreactivity in the olfactory system responds to morphine treatment in the teleost Clarias batrachus: involvement of opiate receptors.

In view of the close relationship between the FMRF-related peptides and the central opiate-sensitive system, we investigated the effects of morphine, alone and in combination with naloxone, on the FMRFamide-like immunoreactivity in the olfactory system of the teleost, Clarias batrachus. In the olfactory system of normal and untreated fish, FMRFamide-like immunoreactivity was confined to the ganglion cells and fibers of the terminal nerve; the cells in the olfactory epithelium per se or the olfactory nerve were not immunoreactive. Intensely immunoreactive cells appeared in the olfactory epithelium following 2 h of intracranial morphine administration. FMRFamide-like immunoreactivity also appeared in the olfactory nerve fibers as they ran caudally and arborized in the glomerular layer of the bulb. However, immunoreactivity in the ganglion cells of the terminal nerve and the ensuing fibers was abolished, suggesting the transport/release of the immunoreactive material. Pretreatment with naloxone, a potent opiate receptor antagonist, reversed the effects of morphine, suggesting the involvement of opiate receptors in the regulation of the ganglion cells of the terminal nerve. The results provide initial immunocytochemical evidence in favor of a relationship between the opiates and FMRFamide-containing systems within the framework of the olfactory system.

Amino Acid Sequence↗
PubMed1997

Calcitonin-like immunoreactivity in the subcommissural organ and Reissner's fiber in the teleost Clarias batrachus, frog Rana tigrina and lizard Calotes versicolor.

In the CNS of vertebrates, although the subcommissural organ (SCO) has been identified as an ependymal brain gland and Reissner's fiber (RF) as a condensed product of its secretion, the exact nature of the secretory substances has remained elusive. In the present study, immunocytochemical application of polyclonal antibodies against calcitonin revealed intense immunoreactivity in the cells, cell processes and cerebrospinal spinal fluid (CSF)-contacting apical terminals of the columnar ependymal cells of the SCO in the teleost, Clarias batrachus. Intense immunoreactivity was also seen throughout the length of the RF as it extended along the Sylvian aqueduct, fourth ventricle and central canal of the spinal cord. Control procedures were employed to confirm the specificity of the immunoreaction. The results for the first time suggest that calcitonin-like substance may be the synthetic and secretory product of the SCO that may be released into the CSF or stored in the RF. Presence of calcitonin-like immunoreactivity in the SCO-RF complex of the frog Rana tigrina and the lizard Calotes versicolor underscores wider significance of the phenomenon. In view of the potentials of these findings, it is felt that investigations aimed at establishing the precise nature of calcitonin-like immunoreactive material in the SCO-RF complex may be rewarding.

Animals↗
PubMed1996

Involvement of corticosteroid-like neurosteroids in pentobarbital-induced sleep.

Recent reports have confirmed the involvement of neurosteroids in a number of neurophysiological processes, including sleep, and that these compounds interact with the gamma-aminobutyric acid receptor A complex. As many of the behavioural effects of pentobarbital are as a result of the activity at this complex, we investigated the role of corticosteroid-like neurosteroids in regulation of sleep, using metyrapone as a tool. Metyrapone, a blocker of the enzyme 11 beta-hydroxylase, which is essential for the biosynthesis of corticosteroids, when administered intracerebroventricularly (i.c.v.) at low doses (50-5000 ng) caused a dose-dependent reduction in sleep time induced by pentobarbital. This effect was, however, antagonized by concomitant administration of anti-corticotropin-releasing factor antisera. The present study reveals for the first time that corticosteroid-like neurosteroids might be involved in the regulation of CNS excitability.

Adrenal Cortex Hormones↗
PubMed1996

Activation of hypothalamic neurons by intraovarian pressure signals in a teleost fish, Clarias batrachus: role of mechanosensitive channels.

Application of intraovarian pressure is known to trigger profound cytomorphological changes in the neurosecretory cells of nucleus preopticus in the teleost Clarias batrachus. These findings indicate the presence of stretch receptors in the ovaries, perhaps equipped with mechanosensitive channels that transduce the stretch signals to be transmitted to the brain. To test the occurrence of the mechanosensitive channels in the ovaries, we administered a range of pharmacological agents (lignocaine, quinidine, tetraethylammonium chloride, ethylene-diaminetetraacetic acid and gadolinium) known to block the mechanosensitive ion channels, in the ovarian lumen prior to the administration of the intraovarian pressure. Pretreatment with the above agents inhibited the response by the nucleus preopticus neurosecretory cells to intraovarian pressure. The results suggest the occurrence of the mechanosensitive channels in the ovaries of teleostean fishes. In terms of function we speculate that the stretch sensory system and the ensuing pathway connecting the ovaries with the hypothalamus might play a role in apprising the brain of the status of ovarian maturity and in the initiation of the spawning reflex.

Animals↗
PubMed1994

Intracranial metyrapone stimulates CRF-ACTH axis in the teleost, Clarias batrachus: possible role of neurosteroids.

Intracranial administration of metyrapone, a blocker of the enzyme 11-beta-hydroxylase, which is essential for the biosynthesis of corticosteroids, resulted in profound stimulation of the nucleus preopticus and the CRF-ACTH axis in the teleost, Clarias batrachus. It is suggested that the putative blockade of the neurosteroid biosynthesis following metyrapone might be responsible for this action. The present study for the first time uncovers the possibility of inhibitory regulation of the CRF-ACTH axis by metyrapone sensitive neurosteroids.

Adrenocorticotropic Hormone↗
PubMed1993

Direct action of metyrapone on brain: implication in feeding.

While the inhibitory effect of metyrapone on the biosynthesis of adrenal corticosteroid hormones is well known, the drug has not been tested for central actions. The present study is aimed at finding out the direct central action of metyrapone, if any, employing feeding behaviour as a test parameter. Low doses of metyrapone (10-1000 ng) administered via an i.c.v. route reduced the food intake in a dose dependent manner; the effect was functionally antagonized by concomitant administration of anti-CRF antisera. The results reveal for the first time, that metyrapone might be capable of exerting a direct action on the adrenal cortex.

Analysis of Variance↗
PubMed1993

Increase in number of LHRH neurones in septal-preoptic area of rats following chronic amitriptyline treatment: implication in antidepressant effect.

Recent studies have implicated the peptide LHRH in a variety of actions including a role in modulation of affective behavior. The present study has been undertaken to determine its involvement in the action of antidepressants, if any, using amitriptyline (AMT) as the model antidepressant drug. The repeated administration of AMT (10 mg/kg/day) in rats increased the number of LHRH neurones in the septal-preoptic area. While 1 week of AMT treatment slightly augmented the number of LHRH neurones, the rise was not statistically significant, however, following 2 weeks of AMT treatment, a significant (P < 0.05) increase (41.05%) was observed. Three and four weeks of AMT treatment further increased the number of neurones by 60.84% and 72.96% respectively; a remarkable rise in the LHRH immunoreactivity around organum vasculosum of lamina terminalis (OVLT) was also noticed. Acute AMT treatment had no effect on the number of neurons; however, the intensity of immunoreaction in the OVLT was slightly decreased. In the behavior despair test, a single dose of AMT displayed an immobility reducing effect which was also shown by a single dose of LHRH (1 mg/kg). The combination of LHRH (1 mg/kg) and AMT also reduced the immobility; the effect was the same as one produced by each drug given separately. The results suggest that chronic AMT treatment may induce transcription and translation in LHRH cells and that the peptide LHRH may be involved in the mediation of the antidepressant effect, characteristic of AMT.

Amitriptyline↗
PubMed1988

Drug delivery through soft contact lenses.

Clinical studies were conducted on 466 patients waiting for senile cataract surgery and receiving chloromycetin, gentamicin, or carbenicillin subconjunctivally and through New Sauflon 70 and New Sauflon 85 lenses. The aqueous drug levels were biologically estimated at various time intervals. Soft contact lenses provided significantly higher drug penetration than subconjunctival therapy. Both modes of treatment provided therapeutically effective levels against most of the common ocular pathogens for varying intervals of 2 to 12 hours.

Anti-Bacterial Agents↗
PubMed1988

Ocular penetration of subconjunctivally injected gentamicin, sisomicin and cephaloridine.

The intraocular penetration of three current bactericidal broad-spectrum antibiotics, namely, gentamicin sulphate, sisomicin sulphate (Ensamycin) and cephaloridine, following subconjunctival injection was studied in 95 patients undergoing elective cataract surgery. Rapid and high penetration of all three drugs was evidenced by the fact that the first samples assayed by modified disc diffusion technique 15 minutes after injection showed drug levels effective against all susceptible pathogens. Peak levels of gentamicin, sisomicin and cephaloridine attained one hour after injection were 14.913 +/- 0.310, 19.000 +/- 0.408 and 30.830 +/- 1.195 micrograms/ml, respectively. Such high drug titres would provide drug concentrations 6 to 8 times the minimum inhibitory concentration necessary against susceptible organisms. The duration of the effective bioavailability of the drugs studied varied from 12 to 18 hours. We believe our study is the first to document the excellent penetration of sisomicin and the little-studied drug cephaloridine, and hope our results will open an avenue for in vivo studies to evaluate their clinical use.

Aged↗