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Biomedical subjects

H S Sharma

Publications and source records attributed to H S Sharma.

At least 55 records · Page 3Linked to original sources
PubMed2000

p-Chlorophenylalanine, an inhibitor of serotonin synthesis reduces blood-brain barrier permeability, cerebral blood flow, edema formation and cell injury following trauma to the rat brain.

The role of serotonin in trauma induced alterations in blood-brain barrier (BBB) permeability, cerebral blood flow (CBF), brain edema and cell changes were examined in a new model of cortical injury in the rat using a pharmacological approach. A longitudinal incision into the right parietal cerebral cortex (about 3 mm deep and 5 mm long) was associated with a profound increase in the BBB permeability to Evans blue and [131]I-sodium, brain water content, and a reduction in the CBF in both the ipsilateral and contralateral hemispheres 5 h after trauma. Nissl staining showed a profound nerve cell reaction in the parietal cerebral cortex of both hemispheres. The intensity of these pathological changes was most pronounced in the traumatised hemisphere. Pretreatment with p-CPA, a serotonin synthesis inhibitor, significantly attenuated breakdown of the BBB permeability, brain edema and the CBF disturbances. Damaged and distorted nerve cells were markedly less frequent in p-CPA treated rats. This effect of the drug was most pronounced in the contralateral hemisphere. The observations strongly suggest that serotonin is one of the important neurochemical mediators of BBB permeability disturbances and brain edema formation in the trauma induced brain damage.

Animals↗
PubMed2000

A new antioxidant compound H-290/51 attenuates upregulation of constitutive isoform of heme oxygenase (HO-2) following trauma to the rat spinal cord.

Influence of a new antioxidant compound H-290/51 on carbon monoxide (CO) production following spinal cord injury was examined using immunohistochemistry of the constitutive isoform of heme oxygenase-2 (HO-2) in a rat model. Subjection of rats to 5 h spinal cord injury by making an incision into the right dorsal horn of the T10-11 segments resulted in upregulation of HO-2 in the injured and adjacent T9 and T12 segments. At this time, disruption of the blood-spinal cord barrier (BSCB) permeability, edema formation and cell injury were more pronounced. Pretreatment with H-290/51 (50 mg/kg, p.o., 30 min before trauma) significantly attenuated the HO-2 immunoreactivity along with breakdown of the BSCB permeability, edema and cell injury. These results for the first time demonstrate that the antioxidant compound H-290/51 is capable of attenuating HO-2 expression and thereby influencing CO production. Furthermore, our observations indicate that oxidative stress is involved in CO production, as reflected by HO-2 expression, which is injurious to the cord and H-290/51 exerts powerful neuroprotective effects in spinal cord injury.

Animals↗
PubMed2000

A bradykinin BK2 receptor antagonist HOE-140 attenuates blood-spinal cord barrier permeability following a focal trauma to the rat spinal cord. An experimental study using Evans blue, [131]I-sodium and lanthanum tracers.

The role of bradykinin in breakdown of the blood-spinal cord barrier (BSCB) permeability following a focal lesion to the cord was examined using a potent bradykinin BK2 receptor antagonist, HOE-140 in a rat model. Spinal cord injury was produced by an incision into the right dorsal horn of the T10-11 segment. In a separate group of rats HOE-140 (1 mg/kg) was administered intravenously 30 min before injury. A focal trauma to the cord markedly increased the extravasation of Evans blue and [131]I-sodium tracers in the cord at 5 h. Pretreatment with HOE-140 significantly attenuated the extravasation of these tracers in the spinal cord. At ultrastructural level, lanthanum was seen within the endothelial cell cytoplasm, in vesicular profiles as well as in the basal lamina in the untreated traumatised rats. In HOE-140 treated rats, the lanthanum was mainly confined within the lumen. These observations strongly suggest that bradykinin is involved in the breakdown of the BSCB permeability probably via bradykinin BK2 receptors, not reported earlier.

Animals↗
PubMed2000

Neurotrophic factors attenuate alterations in spinal cord evoked potentials and edema formation following trauma to the rat spinal cord.

Influence of brain derived neurotrophic factor (BDNF) and insulin like growth factor-1 (IGF-1) on spinal cord injury induced disturbances in spinal cord conduction, edema formation and cellular stress response was examined in a rat model. Pretreatment with BDNF or IGF-1 significantly attenuated the loss of SCEP negative amplitude seen immediately after spinal cord injury. In these neurotrophins treated rats, upregulation of heat shock protein (HSP 72 kD) immunoreactivity, a measure of cellular stress response and spinal cord edema formation were considerably reduced 5 h after injury. These results suggest that neurotrophic factors improve spinal cord conduction after trauma and this beneficial effect of growth factors may be related with their ability to attenuate trauma induced cellular stress response, not reported earlier.

Animals↗
PubMed2000

Spinal cord injury induced c-fos expression is reduced by p-CPA, a serotonin synthesis inhibitor. An experimental study using immunohistochemistry in the rat.

Influence of serotonin on upregulation of cellular-fos (c-fos) following a focal spinal cord injury was examined using immunohistochemistry in a rat model. Spinal cord injury was produced by making a unilateral longitudinal incision of the dorsal horn of the T10-11 segments. A focal lesion to the cord markedly upregulated c-fos immunohistochemistry at 5 h which was mainly located in the edematous regions of the cord in the injured as well as in the perifocal T9 and T12 segments. Pretreatment with p-CPA, a serotonin synthesis inhibitor, significantly attenuated the c-fos upregulation along with the edematous expansion of the cord. These results for the first time suggest that trauma induced release of serotonin and edema formation are important biological signals inducing c-fos expression.

Animals↗
PubMed2000

Topical application of brain derived neurotrophic factor influences upregulation of constitutive isoform of heme oxygenase in the spinal cord following trauma an experimental study using immunohistochemistry in the rat.

Influence of brain derived neurotrophic factor (BDNF) on carbon monoxide (CO) production following spinal cord injury was examined using expression of the constitutive isoform of the enzyme hemeoxygenase-2 (HO-2) in a rat model. A longitudinal incision of the right dorsal horn on the T10-11 segment markedly increased the HO-2 immunostaining in the cord at 5 h. At this time period, breakdown of the blood-spinal cord barrier (BSCB) and edema formation were quite prominent. Repeated topical application of BDNF (20 microliters of a 1 microgram/ml solution) over the exposed surface of the cord significantly attenuated the edematous expansion of the cord and the disturbances in the BSCB permeability. In BDNF-treated rats, expression of HO-2 immunoreactivity was considerably reduced. These results strongly suggest that BDNF is neuroprotective in spinal trauma and this growth factor has the capacity to attenuate CO production by downregulating HO-2 expression.

Animals↗
PubMed2000

Antioxidant compounds EGB-761 and BN-520 21 attenuate heat shock protein (HSP 72 kD) response, edema and cell changes following hyperthermic brain injury. An experimental study using immunohistochemistry in the rat.

Influence of the extract of Gingko biloba (EGB-761) and one of its constituent Gingkolide B (BN-52021) on hyperthermia induced cellular damage and heat shock protein (HSP 72kD) response was examined in a rat model. Rats subjected to 4h heat stress at 38 degrees C in a biological oxygen demand (BOD) incubator (relative humidity 50-55%, wind velocity 20-25cm/sec) resulted in profound edema and cell injury in many parts of the cerebral cortex, hippocampus, cerebellum, thalamus, hypothalamus and brain stem. Immunostaining of HSP 72 kD showed marked upregulation in the damaged and distorted neurons located within the edematous area. Pretreatment with EGB-761 (50mg/kg/day, p.o.) and BN-520 21 (2mg/kg, p.o.) per day for 5 days significantly reduced HSP expression and attenuated cell damage. Our results show that EGB-761 and its component Gingkolide B (BN-52021) has the capacity to reduce edema and cell injury following hyperthermia and this effect of the compound is somehow associated with a reduction in cellular stress response as evidenced with a reduction in HSP expression.

Animals↗
PubMed2000

Growth hormone attenuates alterations in spinal cord evoked potentials and cell injury following trauma to the rat spinal cord. An experimental study using topical application of rat growth hormone.

The influence of exogenous rat growth hormone on spinal cord injury induced alterations in spinal cord evoked potentials (SCEP) and edema formation was examined in a rat model. Repeated topical application of rat growth hormone (20microl of 1microg/ml solution) applied 30min before injury and at 0min (at the time of injury), 10min, 30min, 60min, 120min, 180min, and 240min, resulted in a marked preservation of SCEP amplitude after injury. In addition, the treated traumatised cord showed significantly less edema and cell changes. These observations suggest that growth hormone has the capacity to improve spinal cord conduction and attenuate edema formation and cell injury in the cord indicating a potential therapeutic implication of this peptide in spinal cord injuries.

Animals↗
PubMed2000

Spinal nerve lesion induces upregulation of constitutive isoform of heme oxygenase in the spinal cord. An immunohistochemical investigation in the rat.

The influence of carbon monoxide (CO) on chronic spinal nerve lesion induced spinal cord neurodegeneration was examined using immunohistochemical expression of the constitutive isoform of its synthesising enzyme, hemeoxygenase-2 (HO-2) in a rat model. Spinal nerve lesion at L-5 and L-6 level was produced according to the Chung model of neuropathic pain and rats were allowed to survive for 8 weeks. Sham operated rats, in which the spinal nerves were exposed but not ligated, served as controls. Ligation of spinal nerves in rats resulted in an upregulation of HO-2 expression which was most pronounced in the ipsilateral gray matter of the spinal cord compared to the contralateral side. In these rats, morphological investigations showed distorted neurons, membrane disruption, synaptic damage and myelin vesiculation. Sham operated rats did not show an upregulation of HO-2 expression and the structural changes in the spinal cord were absent. These observations strongly suggest that spinal nerve lesion is associated with an increased production of CO which is somehow contributing to the neurodegenerative changes in the spinal cord, not reported earlier.

Animals↗
PubMed2000

A new antioxidant compound H-290/51 attenuates nitric oxide synthase and heme oxygenase expression following hyperthermic brain injury. An experimental study using immunohistochemistry in the rat.

Influence of a new anti-oxidant compound H-290/51 on expression of nitric oxide synthase (NOS) and heme oxygenase (HO) enzymes responsible for nitric oxide (NO) and carbon monoxide (CO) production, respectively was examined in the CNS following heat stress in relation to cell injury. Exposure of rats to 4h heat stress at 38 degrees C in a biological oxygen demand (BOD) incubator (relative humidity 50-55%, wind velocity 20-25cm/sec) resulted in profound edema and cell injury in many parts of the cerebral cortex, hippocampus, cerebellum, thalamus, hypothalamus and brain stem. Immunostaining of constitutive isoforms of neuronal NOS (nNOS) and HO-2 revealed marked upregulation in damaged and distorted neurons located within the edematous brain regions. Pretreatment with H-290/51 (50 mg/kg, p.o., 30 min before heat stress) significantly reduced the edematous swelling and cell injury and resulted in a marked attenuation of nNOS and HO-2 expression. These observations suggest that upregulation of NOS and HO is associated with cell injury, and the antioxidant compound H-290/51 is neuroprotective in heat stress.

Animals↗
PubMed2000

Remodeling of pulmonary arteries in human congenital diaphragmatic hernia with or without extracorporeal membrane oxygenation.

PURPOSE: The aim of this study was to describe in detail the perinatal developmental profile of the pulmonary vasculature in congenital diaphragmatic hernia (CDH) and to examine the potential beneficial effects of extracorporeal membrane oxygenation (ECMO) on the vascular morphology. Additionally the authors aimed to identify the differences in pulmonary vascular morphology among CDH cases according to the primary cause of death: either extreme lung hypoplasia (LH) or persistent pulmonary hypertension (PPH). METHODS: The authors studied autopsy sections from 30 high-risk CDH cases with respect to the pulmonary arteries in relation to gestational age (GA) and ECMO treatment. They were grouped into CDH-I: 20 cases with GA greater than 34 weeks who were not subjected to ECMO and CDH-II: 10 cases with GA greater than 34 weeks, who were subjected to ECMO for an average time of 237 hours. Five age-matched neonates who died from placental insufficiency or birth asphyxia without evidence of lung hypoplasia served as controls (CON). Medial and adventitial thicknesses of pulmonary arteries were measured in lung sections stained with Elastic van Gieson by 2 investigators blinded for the clinical data. Immunohistological staining with anti-alpha-smooth muscle actin (alpha-SMA) was performed to confirm the precise location of the arterial media before morphometry. CDH cases were subgrouped and compared according to the primary cause of death. Unpaired Student t test was used for statistics, with significant P value < or =.05. RESULTS: In CDH newborns, a significant increase in medial, adventitial, and total wall thickness was found in pulmonary arteries with an external diameter of less than 200 microm as compared with age-matched controls (P<.004, .0001, and .0009, respectively). ECMO-treated CDH newborns showed a significantly thinner arterial adventitia than CDH patients who did not receive this treatment (P<.0001), approaching normal values. However, the medial thickness remained increased. Morphometrically, no significant differences in CDH cases between patients dying of PPH or severe LH could be determined. CONCLUSIONS: (1) In CDH, there is failure of the normal arterial remodeling processes occurring in the perinatal period. (2) Pulmonary vascular morphology in CDH does not differ between the groups with lung hypoplasia or persistent pulmonary hypertension as primary cause of death. (3) Adventitial thinning of these arteries might be one of the mechanisms by which ECMO alters PPH in CDH cases.

Extracorporeal Membrane Oxygenation↗
PubMed2000

Molecular cloning, sequence analysis and pharmacological properties of the porcine 5-HT(1D) receptor.

A cDNA encoding the full-length 5-HT(1D) receptor derived from porcine cerebral cortex was amplified, cloned and sequenced, using guinea-pig 5-HT(1D) receptor coding sequence oligonucleotide primers in reverse transcription-polymerase chain reaction (RT - PCR). The 5' and 3' ends of the porcine 5-HT(1D) receptor cDNA were verified by inverse PCR. Sequence analysis of porcine 5-HT(1D) receptor cDNA revealed an open reading frame of 1134 nucleotides encoding a polypeptide of 377 amino acids having 92% homology with the human 5-HT(1D) receptor and 88 - 90% homology with other species homologues. The porcine 5-HT(1D) receptor cDNA was further subcloned into a mammalian expression vector pcDNA3 and expressed in monkey Cos-7 cells. Radioligand binding assays using either [(3)H]-5-CT or [(3)H]-GR125743 on Cos-7 cell membranes showed that pK(i) values of 14 serotonin ligands were highly correlated with those obtained with the human 5-HT(1D) receptor. Nonetheless, a selective antagonist at the human 5-HT(1D) receptor, BRL15572, only poorly recognized the porcine homologue. Using membranes from cells co-expressing the porcine 5-HT(1D) receptor and rat G(alphail)Cys(351) Ile protein, it was shown that 5-HT and zolmitriptan increased, while ketanserin decreased basal [(35)S]-GTPgammaS binding. The potency of zolmitriptan in the [(35)S]-GTPgammaS binding assay (pEC(50): 8. 46+/-0.08) agreed with its affinity in displacing the radioligands [(3)H]-5-CT and [(3)H]-GR125743 (pK(i): 8.38+/-0.15 and 8.67+/-0.08, respectively). In conclusion, we have established the cDNA sequence and pharmacology of the cloned porcine 5-HT(1D) receptor. This information would be useful in exploring the role of divergent amino acid residues in the receptor-ligand interaction as well as the role of 5-HT(1D) receptor in pathophysiological processes relevant for novel drug discovery in diseases such as migraine.

Amino Acid Sequence↗
PubMed2000

Mushroom (Agaricus bisporus) compost quality factors for predicting potential yield of fruiting bodies.

A quality model has been developed from parameters determining the interactions of physical, chemical, and biological factors during the preparation of mushroom compost for growing Agaricus bisporus. Our results show that a partial least square model based on the combination of pH, dry matter, ammonia, carbon, hydrogen, ash, Cu, Fe, and Na could explain nearly 90% of the variation in mushroom yield obtained from four compost comparative trials. The yields in the data base for generating the model ranged from 138 to 305 kg per ton of compost. The validity of the yield model has been confirmed in a trial carried out in collaboration with experienced commercial growers. This has significant implications for compost producers, as production efficiencies can be maintained by targeting the important parameters.

Agaricus↗
PubMed2000

Physical degradation of wheat straw by the in-vessel and windrow methods of mushroom compost production.

Mushroom compost manufacturers in Ireland are moving away from the traditional outdoor phase I windrow method, favouring in-vessel production. Composters and growers have reported better quality compost with faster spawn run and higher yields produced by this process. In the present study, physical examination of samples highlighted differences when comparing the windrow and in-vessel methods of compost production. Observations using scanning electron microscopy suggest that the cuticle of wheat straw from in-vessel production is damaged during phase I, peeling away from the surface in fragments, and exposing the epidermis. Changes in silicon levels on the straw surface acted as a marker for cuticle damage when comparing both composting systems. Cuticle damage may be important during composting and afterwards, as substrate colonisation is faster, and consequently spawn run is shorter. The phase I compost microbial community is altered by the in-vessel technique, producing a predominantly thermophilic bacterial flora in contrast to the mesophilic and thermophilic bacteria and fungi found in windrow phase I compost. These differences may be significant in mushroom compost production.

Agaricus↗
PubMed2000

Tumor necrosis factor-alpha enhances mRNA expression and secretion of interleukin-6 in cultured human airway smooth muscle cells.

Airway smooth muscle (ASM) is considered to be an end-target cell for the effects of mediators released during airway wall inflammation. Several reports suggest that activated ASM may be capable of generating various proinflammatory cytokines. We investigated the effects of tumor necrosis factor (TNF)-alpha, a potent proinflammatory cytokine, on cultured human ASM cells by examining the expression and release of the cytokine interleukin (IL)-6, cell proliferation, and the expression pattern of c-fos and c-jun, two nuclear proto-oncogenes constituting the activator protein-1 transcription factor. Growth-arrested cell monolayers were stimulated with human recombinant TNF-alpha in a concentration- and time-dependent manner. TNF-alpha stimulated the expression of IL-6 messenger RNA (mRNA), which was detected after 15 min, reaching a maximum at 1 h. IL-6 protein was readily detected in ASM cell-conditioned medium after 2 h of TNF-alpha stimulation. Protein levels increased in a time- and concentration-dependent manner. Release of IL-6 elicited by TNF-alpha was significantly inhibited by dexamethasone, cycloheximide, and nordihydroguaiaretic acid (NDGA). TNF-alpha did not alter DNA biosynthesis up to 48 h or cell numbers up to 120 h. Northern blot analysis of proto-oncogene expression revealed that c-fos and c-jun mRNA levels were elevated after 30 min of TNF-alpha incubation with maximum levels at 1 h and 45 min, respectively. Expression of c-fos mRNA was downregulated by NDGA. Four hours of TNF-alpha treatment resulted in translocation of c-jun immunofluorescence from the cytoplasm to the nucleus in human ASM cells. Our results suggest that despite the lack of a mitogenic response to TNF-alpha, upregulation of primary response genes in human ASM cells may account for the induction of proinflammatory cytokines, such as IL-6, in human airways.

Bronchi↗
PubMed2000

Neurotrophic factors influence upregulation of constitutive isoform of heme oxygenase and cellular stress response in the spinal cord following trauma. An experimental study using immunohistochemistry in the rat.

The influence of brain derived neurotrophic factor (BDNF) or insulin like growth factor-1 (IGF-1) on spinal cord trauma induced carbon monoxide (CO) production and cellular stress response was examined using immunostaining of the constitutive isoform of the hemeoxygenase (HO-2) enzyme and the heat shock protein (HSP 72kD) expression in a rat model. Subjection of rats to a 5 h spinal trauma inflicted by an incision into the right dorsal horn at T10-11 segment markedly upregulated the HO-2 and HSP expression in the adjacent spinal cord segments (T9 and T12). Pretreatment with BDNF or IGF-1 significantly attenuated the trauma induced HSP expression. The upregulation of HO-2 was also considerably reduced. These results show that BDNF and IGF-1 attenuate cellular stress response and production of CO following spinal cord injury which seems to be the key factors in neurotrophins induced neuroprotection.

Animals↗