Biomedical subjects

P K Mishra

Publications and source records attributed to P K Mishra.

At least 19 recordsLinked to original sources

PubMed2005

An electrographic analysis of the synchronous discharge patterns of GEPR-9s generalized seizures.

Previous results from our Laboratory have shown a synchronous discharge pattern (less than 1 ms apart) in monopolar recordings from electrodes placed in the cortex, inferior colliculus, and medulla of seizing GEPR-9s. However, the wave morphology of the ictal EEG is quite different for electrodes placed in different anatomical structures. These results lead us to hypothesize that wave morphology was indicative of neural circuitry involved in the GEPR9 seizure and that volume conduction was accounting for synchronous epileptiform EEG pattern. We decided to approach the problem by using a set of two experiments. Experiment 1: Perform a complete precollicular transection in GEPR-9s before inducing seizure in order to observe changes in EEG morphology after forebrain circuitry removal. Experiment 2: A novel methodological approach using a three-dimensional bipolar array enabled the reconstruction of a vector indicative of to which direction is voltage increasing. Such time-varying vector is indicative of the source direction of the high-amplitude epileptiform EEG signal. By placing such an array of electrodes, used to record the 3 bipolar EEGs, in the forebrain, midbrain, and hindbrain, we were able to use a simple intersection method to infer source localization. Our results suggest that the slow wave component of the GEPR9 epileptiform ictal EEG pattern is associated with a midbrain-forebrain circuit while the spike component is associated with a midbrain-hindbrain substrate. These results are supported by experiment 1 in which only the spike component of EEG remained after the precollicular transection.

Action Potentials↗

PubMed2005

A comprehensive electrographic and behavioral analysis of generalized tonic-clonic seizures of GEPR-9s.

This study records noise-free intracerebral EEG of the genetically epilepsy prone rat (GEPR-9), along with behavioral correlates, during a seizure on unanesthetized freely behaving unrestrained animals. The GEPR-9 exhibits acoustically triggered generalized tonic-clonic seizures, and often times the EEG, recorded with conventional techniques, has resulted in data with imbedded movement artifact. For noise-free video-EEG recordings, we used a previously developed system that consists of a head connector with a FET preamplifier and battery, signal conditioning device (5000x gain, 1 Hz-100 Hz filters), A/D converter and video/PC-PC/video computer boards for recording image data. Each animal was implanted with three monopolar/referential electrodes chosen among the following areas: cortex, inferior colliculus, reticular formation and caudal medulla. The video-EEG data were quite similar for all recorded animals: (1) basal desynchronized EEG before sound stimulus; (2) increase in EEG frequency after stimulus and before seizure onset; (3) high-amplitude polyspikes during massive myoclonic thrusts with or without a very fast running episode; (4) an electrodecremental response during tonic extension; (5) wave and spike complex during forelimb and hindlimb tonic rigidity and posttonic clonus; (6) low-amplitude EEG during postictal depression. Time sequenced spectral analysis also highlights the epileptiform EEG pattern during seizure with high reproducibility between animals. While testing seizure naive GEPR-9s, there was a clear evolution from modest epileptiform EEG activity on the first acoustic stimulation to progressively higher amplitude, duration and frequency epileptiform EEG activity throughout seizure repetition.

Acoustic Stimulation↗

PubMed2004

Effect of confinement on coil-globule transition.

The equilibrium thermodynamic properties of a linear polymer chain confined to a space between two impenetrable walls (lines) at a distance D under various solvent conditions have been studied using series analysis and exact enumeration technique. We have calculated the end-to-end distance of polymer chain, which shows a nonmonotonic behavior with inter wall separation D. The density distribution profile shows a maxima at a particular value of (D=)D*. Around this D*, our results show that the collapse transition occurs at higher temperature as compared to its bulk value of 2d and 3d. The variation of theta-temperature with D shows a re-entrance behavior. We also calculate the force of compression exerted by the walls (lines) on the polymer.

Journal Article↗

PubMed2004

Ultrastructural changes in the testis and epididymis of rats following treatment with the benzene chromatographic fraction of the chloroform extract of the seeds of Carica papaya.

The benzene chromatographic fraction of the chloroform extract of the seeds of Carica papaya at a dose of 10 mg/rat/day for 150 days, which has shown a total inhibition of motility, reduced sperm count and infertility, was tested to de fi ne the mode of action at the subcellular level in the testis and epididymis. The ultrastructure of the testis of the treated animals revealed no appreciable changes in the subcellular characteristics. The mechanism of protein synthesis as well as steroidogenesis were evident in the Sertoli cells while the spermatogonia, spermatocytes and spermatids, both round and elongated, depicted a prominent nucleus, distinct nuclear membrane and cytoplasmic characteristics indicating normal germ cell differentiation. The principal cells of the cauda epididymis were characterized by the presence of well-de fi ned rough endoplasmic reticulum, mitochondria, Golgi bodies and secretary granules, suggesting active secretory functions. The absorptive function of the cauda epididymis was evidenced by the presence of numerous vesicles and multivesicular bodies adjacent to stereocilia. It is concluded that the inhibition of sperm motility by the drug could be due to other epididymal factors rather than the subcellular characteristics of testis and epididymis.

Animals↗

PubMed2004

An efficient parallel algorithm for shortest paths in planar layered digraphs.

This paper presents an efficient parallel algorithm for the shortest path problem in planar layered digraphs that runs in O(log3n) time with n processors. The algorithms uses a divide and conquer approach and is based on the novel idea of a one-way separator, which has the property that any directed path can be crossed only once.

Journal Article↗

PubMed2004

Optimal parallel algorithm for shortest paths problem on interval graphs.

This paper presents an efficient parallel algorithm for the shortest-path problem in interval graph for computing shortest-paths in a weighted interval graph that runs in O(n) time with n intervals in a graph. A linear processor CRCW algorithm for determining the shortest-paths in an interval graphs is given.

Algorithms↗

PubMed2003

Resuscitation of asphyxiated newborns with room air or 100% oxygen at birth: a multicentric clinical trial.

OBJECTIVE: To compare the short-term efficacy of room air versus 100% oxygen for resuscitation of asphyxic newborns at birth. DESIGN: Multicentric quasi randomized controlled trial. SETTING: Teaching hospitals. INCLUSION CRITERIA: Asphyxiated babies weighing greater than 1000 grams, with heart rate less than 100 per min and/or apnea, unresponsive to nasopharyngeal suction and tactile stimuli and having no lethal abnormalities. INTERVENTION: Asphyxiated neonates born on odd dates were given oxygen and those on even dates room air for resuscitation. OUTCOME MEASURES: Primary: Apgar score at 5 minutes; Secondary: Mortality and Hypoxic ischaemic encephalopathy (HIE) during first 7 days of life. RESULTS: A total of 431 asphyxiated babies, 210 in the room air and 221 in 100% oxygen group were enrolled for the study. Both the groups were comparable for maternal, intrapartum and neonatal characteristics. The heart rates in room air and 100% oxygen groups were comparable at 1 minute (94 bpm and 88 bpm), 5 minutes (131 bpm and 131 bpm) and 10 minutes (135 bpm and 136 bpm). Median apgar scores at 5 min [7 versus 7] and 10 minutes [8 versus 8 ], in the room air and oxygen groups respectively, were found to be comparable. Median time to first breath (1.5 versus 1.5 minutes) was similar in the room air and oxygen group. Median time to first cry (2.0 versus 3.0 minutes) and median duration of resuscitation (2.0 versus 3 minutes) were significantly shorter in the room air group. The number of babies with HIE during first seven days of life in the two treatment groups (35.7% babies in room air and 37.1% in the 100% oxygen group) were similar. There was also no statistically significant difference in the overall and asphyxia related mortality in the two treatment groups (12.4% and 10.0% in room air versus 18.1% and 13.6% in oxygen group). CONCLUSION: Room air appears as good as 100% oxygen for resuscitation of asphyxic newborn babies at birth.

Air↗

PubMed2002

Chloroform extract of Carica papaya seeds induces long-term reversible azoospermia in langur monkey.

AIM: To evaluate the antifertility activity of the chloroform extract of Carica papaya seeds by oral administration in langur monkey, Presbytis entellus entellus. METHODS: The chloroform extract of Carica papaya seeds, 50 mg/kg/day, was administered orally for 360 days to adult male langur monkeys. The sperm characteristics by light and electron microscopy, the sperm functional tests, the semen biochemistry, the serum testosterone level, the Leydig cell function, and the histology and ultrastructure of testis were determined to evaluate the antifertility activity and the blood biochemistry and hematology, to evaluate the toxicology. RESULTS: The extract gradually decreased the sperm concentration since days 30-60 of treatment with a total inhibition of sperm motility, a decrease in sperm viability and increase in sperm abnormality. Azoospermia was observed after day 90 of treatment and continued during the whole treatment period. Treatment withdrawal resulted in a gradual recovery in these parameters and 150 days later they reverted to nearly the pretreatment values. Morphological observation of the ejaculated sperm by light and scanning electron microscopy showed deleterious changes, particularly on the mid-piece. Sperm functional tests, viz., sperm mitochondrial activity index, acrosome intactness test and hypo-osmotic swelling test scored in the infertile range during treatment and returned to the fertile values 150 days after drug withdrawal. Histology of the testis revealed shrunken tubules, germ cell atrophy and normal Leydig cells. Ultrastructure of the testis showed vacuolization in the cytoplasm of Sertoli cells and germ cells. Loss of cytoplasmic organelles were evident in the spermatocytes and spermatids. Round spermatids showed loss of Golgi bodies, peripheral mitochondria and vacuolated cytoplasm, indicating maturational arrest. Leydig cell functional test indicated a mild inhibition of steroidogenic function. Haematology and serum biochemistry study disclosed no significant toxicological effect and the serum testosterone level was not affected. CONCLUSION: Carica papaya seed extract may selectively act on the developing germ cells, possibly mediated via Sertoli cells, leading to azoospermia.

Animals↗

PubMed2001

Penetrance and expressivity of genes involved in the development of epilepsy in the genetically epilepsy-prone rat (GEPR).

In order to understand the level of complexity of the epileptic phenotype in the two strains of Genetically Epilepsy-Prone Rats (GEPRs), we determined two important measures of genetic complexity, penetrance and expressivity. Penetrance is the percentage of animals of a specific genotype who express the phenotype associated with that underlying genotype. Expressivity refers to the degree that a particular genotype is expressed as a phenotype within an individual. Incomplete penetrance and variable expressivity are caused by genetic and environmental variation. In this paper we have studied the epileptic phenotype for 20,373 rats. Animals were tested on three occasions for audiogenic seizure and given an audiogenic response score (on a scale of 0-9, 0 being no seizure and 9 being the most severe). The GEPR-3 and GEPR-9 animals both show incomplete penetrance and variable expressivity of the underlying genetic predisposition. The GEPR-9 strain has more animals that have variable levels of seizure predisposition (as measured by a scoring system that denotes the severity of generalized tonic/clonic seizures) and a greater percentage of animals that exhibit no susceptibility to such seizures induced by sound. Both strains have a number of animals that are not susceptible to sound-induced GTCSs and that exhibit some variability in seizure severity. The GEPR-9 males show greater differences in expressivity and penetrance compared to GEPR-9 females. The GEPR-3 animals also show sex-associated variable penetrance and expressivity of the epileptic phenotype, although the differences are much smaller. These findings are the first step toward the mapping of the underlying quantitative trait loci (QTL) for seizure in these animals.

Animals↗

PubMed2001

Vas deferens, a site of male contraception: an overview.

The vas deferens is a site which can be exploited for male contraception without undue side effects. The only effective technique available for male contraception is vasectomy, being practiced world wide, despite that it is a permanent surgical procedure and its successful reversal is not assured. Although no-scalpel vasectomy minimizes surgical procedures, the fate of its reversal is akin to that of vasectomy. Several occlusive and non-occlusive vasal procedures which claim to be reversible without surgical intervention, possess more disadvantages than advantages. Vas occlusion with plug, 'Shug' or medical grade silicone rubber, although claimed to produce reversible azoospermia without affecting spermatogenesis, requires skilled microsurgery for their implantation and later removal. RISUG, a non-sclerotic polymer styrene maleic anhydride (SMA), could be more advantageous than vasectomy and other vas occlusive procedures in that it could be a totally non-invasive procedure by "no-scalpel injection" and "non-invasive reversal". It is claimed to offer long-term contraception without adverse side effects and also to be possible as a male spacing method by repeated vas occlusion and non-invasive reversal. The drug is currently under multicentre Phase III clinical trial.

Animals↗

PubMed2000

Antifungal activity of venenatine, an indole alkaloid isolated from Alstonia venenata.

The indole alkaloid venenatine exhibited antifungal activity against some plant pathogenic and saprophytic fungi. Venenatine in an aqueous acetic acid solution inhibited spore germination of all the 10 tested fungi, Fusarium udum, Alternaria brassicicola, Ustilago cynodontis and Aspergillus flavus showed an especially high sensitivity towards this compound, exhibiting germination levels below 10%. The spore germination and colony development of the parasitic fungus Erysiphe pisi, which causes powdery mildew in pea (Pisum sativum), on excised leaves of pea was also significantly affected. Pre-inoculation rather than post inoculation treatment of the leaves was more inhibitory against spore germination and colony development.

Alkaloids↗

PubMed2000

Contraceptive evaluation and toxicological study of aqueous extract of the seeds of Carica papaya in male rabbits.

The contraceptive evaluation and toxicological effects of the aqueous extract of the seeds of Carica papaya in adult male rabbits have been reported. Thirty adult male rabbits were divided into five groups of six animals each; Group I, control; Groups II-V were administered orally with aqueous extract of the seeds of C. papaya at doses of 20, 50, 75 and 100 mg/kg per day for 150 days, respectively. The body weight, reproductive organs weight, semen analysis, semen biochemistry, toxicological profiles and the fertility status have been recorded. The aqueous extract failed to exhibit contraceptive effects at any of the dose regimens tested, contrary to the observations made in the previous studies. Unaltered toxicological profiles indicated that the drug was free of side effects. The results suggest that the failure of contraceptive effects may be due to species specificity, relative resistance of the animals to the drug or lack of potency of the extract due to factors generally affect biological activity of the plant preparations.

Animals↗

PubMed2000

Sterility due to inhibition of sperm motility by oral administration of benzene chromatographic fraction of the chloroform extract of the seeds of Carica papaya in rats.

The contraceptive effects of benzene chromatographic fraction of the chloroform extract of the seeds of Carica papaya have been reported in male albino rats at the dose regimens 5 and 10 mg/animal/day; oral for 150 days. The body weight, weight of testis, epididymis, seminal vesicle and ventral prostate remained unaltered during the entire course of the investigation. Total suppression of cauda epididymal sperm motility coincided with a decrease in sperm count, viability and an increase in per cent abnormal spermatozoa during 60-150 days observation period. Minor changes in the germ cell proliferations in the testis and vacuolization and pyknotic nuclei in the few epithelial cells of the cauda epididymis were observed. Histology and biochemical composition of testis and accessory sex organs, haematology and serum clinical biochemistry and serum testosterone levels remained unchanged throughout the course of the investigation. Test for estrogenicity indicated mild estrogenicity. Monthly fertility test showed negative fertility. All the altered parameters returned to normal level following 60 days withdrawal of the treatment. The results suggest that the benzene chromatographic fraction of the chloroform extract of the seeds of Carica papaya exerts antifertility effects in rats without adverse toxicity and that the effects may be directly rendered on the spermatozoa.

Administration, Oral↗

PubMed2000

Investigating the role of the geminal dimethyl groups of coenzyme A: synthesis and studies of a didemethyl analogue.

An analogue 2 of coenzyme A (CoA) has been prepared in which the geminal methyl groups are replaced with hydrogens. An NMR titration study was conducted and shifts in frequency of protons in the pantetheine portion of the molecule upon titration of the adenine base were observed as has been previously reported with CoA. These studies indicate that the geminal dimethyl groups are not essential for adoption of a partially folded conformation in solution. Based on 1H-1H coupling constants, the distribution of conformations about the carbon-carbon bonds in the region of the methyl deletion were estimated. The results suggest that the conformer distribution is similar to that of CoA, but with small increases in population of the anti conformers. A simple model compound containing the didemethyl pantoamide moiety was prepared and subjected to similar conformational analysis. The coupling constants and predicted conformer distribution were almost identical to that of the CoA analogue, indicating that the conformer distribution is controlled by local interactions and not influenced by interactions between distant parts of the CoA molecule. The acetyl derivative of 2 was a fairly good substrate for the acetyl-CoA utilizing enzymes carnitine acetyltransferase, chloramphenicol acetyltransferase, and citrate synthase, with 1.3- to 10-fold increased Km values and 2.5- to 11-fold decreases in Vmax. The combined results indicate that the geminal dimethyl groups of CoA have modest effects on function and minimal effects on conformation.

Carnitine O-Acetyltransferase↗

PubMed2000

Repeated vas occlusion and non-invasive reversal with styrene maleic anhydride for male contraception in langur monkeys.

The feasibility of a spacing method for contraception, using Styrene Maleic Anhydride (SMA) as a vas occlusive agent, has been assessed in male langur monkeys. The vas deferens of 6 animals were occluded with 60 mg SMA in 120 microL DMSO. After 150 days, the occlusion was reversed by a technique which involved palpation, percutaneous electrical stimulation, forced vibratory movement, suprapubic percussion and per-rectal digital massage of the vas segments. The vas deferens were then re-occluded with SMA and reversed by the non-invasive method after three consecutive azoospermic samples. The second vas occlusion resulted in uniform azoospermia after the third ejaculation and reversal caused the reappearance of spermatozoa in the semen to severe oligozoospermic levels in the first two ejaculations and rising to normospermia in the subsequent ejaculations. Ultrastructure of the spermatozoa by SEM and TEM and sperm function tests revealed that the spermatozoa had recovered normal morphology. Vas morphology also regained a normal pseudostratified columnar epithelium containing basal and principal cells. The results suggest that the SMA-based spacing technique for male contraception could be extrapolated to the human by use of no-scalpel injection and non-invasive reversal.

Animals↗

PubMed2000

Human sperm immobilization effect of Carica papaya seed extracts: an in vitro study.

AIM: To examine if the seed extracts of Carica papaya, which showed antispermatogenic/sperm immobilization properties in animal models, could cause human sperm immobilization in vitro. METHODS: Chloroform extract, benzene chromatographic fraction of the chloroform extract, its methanol and ethyl acetate sub-fractions and the isolated compounds from the sub-fractions i.e., ECP 1 & 2 and MCP 1 &2, of the seeds of Carica papaya were used at concentrations of 0.1%, 0.5%, 1% and 2%. Sperm motility was assessed immediately after addition of extracts and every 5 minutes thereafter for 30 minutes. RESULTS: There were dose-dependent spermicidal effects showing an instant fall in the sperm motility to less than 20% at 2% concentration. Isolated compounds ECP 1 & 2 were more effective inducing a motility of less than 10%. Many of the spermatozoa became vibratory on the spot. Total inhibition of motility was observed within 20-25 min at all concentrations of all products. Scanning and transmission electron microscopy revealed deleterious changes in the plasma membrane of the head and mid-piece of spermatozoa. Sperm viability test and the number of abnormal spermatozoa after completion of incubation suggested that the spermatozoa were infertile. The effects were spermicidal but not spermiostatic as revealed by the sperm revival test. CONCLUSION: The results reveal spermicidal activity in vitro of the seed extracts of Carica papaya.

Fruit↗

PubMed1999

Morphological deficits in noradrenergic neurons in GEPR-9s stem from abnormalities in both the locus coeruleus and its target tissues.

The epileptic condition of the genetically epilepsy-prone rat (GEPR) appears to be caused partially by deficiencies in the locus coeruleus (LC) innervation of the superior colliculus (SC). Previous studies provide quantitative documentation of noradrenergic morphological deficits in the moderately epileptic GEPR-3. The present findings extend these studies by applying cell culture methodology to assessments of the severely epileptic GEPR-9. Our data show that total neurite length, the number of neurite branch points per cell, the cross-sectional area of cell bodies, and the cell perimeter are deficient in noradrenergic neurons in LC + SC cocultures derived exclusively from GEPR-9s compared to analogous cocultures obtained solely from nonepileptic control rats. Partial restoration of LC neuron morphology toward normal occurs when the GEPR-9 SC component of the coculture is replaced with nonepileptic control SC. Finally, when the GEPR-9 SC is cocultured with the control LC, a partial morphological deficit occurs in the otherwise normal noradrenergic neurons. However, the magnitude of this deficit is less than that observed in noradrenergic neurons of the GEPR-9 LC cocultured with the control SC. These data support the hypothesis that the developmental deficiencies of noradrenergic neurons of the GEPR-9 are derived from two sources, the LC and its target tissue, in this case, the SC. Also, intrinsic abnormalities of the LC appear to make a more pronounced contribution to the noradrenergic deficits than do those which reside in the SC.

Animals↗

PubMed1999

Ultrastructural changes in the vas deferens of langur monkeys Presbytis entellus entellus after vas occlusion with styrene maleic anhydride and after its reversal.

Ultrastructural changes in the vas deferens of langur monkeys after 150 days of vas occlusion with styrene maleic anhydride (SMA) and after 150 days of noninvasive reversal are reported. The vas deferens of the sham-operated control animals revealed active secretory and absorptive functions. The basal cells showed prominent nucleus and sparse cytoplasmic organelles, and the principal cells characterized by oval or irregular nucleus, well developed mitochondria, Golgi bodies, rough endoplasmic reticulum, secretory granules in the Golgi area, free ribosomes, and glycogen granules in the supranuclear region suggesting secretory function. Vesicles and stereocilia in the apex region suggested absorptive functions of the vas deferens. Vas occlusion by SMA resulted in exfoliation of epithelial cells, pyknotic nuclei, and vacuolated cytoplasm virtually devoid of cytoplasmic organelles and stereocilia. After noninvasive reversal, the vas epithelium regained a state of normalcy as evidenced by prominent plasma membrane, nucleus, cytoplasmic organelles, and stereocilia. The results suggest that the exfoliation of the epithelium due to vas occlusion by SMA regains normalcy after 150 days of noninvasive reversal.

Animals↗