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Biomedical subjects

H S Sharma

Publications and source records attributed to H S Sharma.

At least 109 records · Page 6Linked to original sources
PubMed1997

Acute heat stress induces edema and nitric oxide synthase upregulation and down-regulates mRNA levels of the NMDAR1, NMDAR2A and NMDAR2B subunits in the rat hippocampus.

The influence of heat stress on constitutive isoform of neuronal nitric oxide synthase (cNOS) and NMDA receptor gene expression in hippocampus was examined in a rat model. Subjection of animals to 4 h heat stress at 38 degrees C resulted in a marked upregulation of cNOS in the hippocampus accompanied with a marked general expansion and edematous cell changes. On the other hand NMDA receptor messenger RNA encoding NMDAR1, NMDAR2A and NMDAR2B subunits showed a marked downregulation in the hippocampus of heat stressed rats compared to the controls. Our results show that upregulation of cNOS is instrumental in heat stress associated edema and cell injury. Furthermore, an increased production of NO as evident with upregulation of cNOS appears to be a key factor in the downregulation of NMDA receptor gene expression in heat stress.

Acute Disease↗
PubMed1997

Pulmonary expression of vascular endothelial growth factor and myosin isoforms in rats with congenital diaphragmatic hernia.

Abnormalities of the pulmonary vasculature are well documented in cases of congenital diaphragmatic hernia (CDH). Vascular endothelial growth factor (VEGF), an angiogenic factor, is a recently described endothelial cell-specific growth factor. Myosin heavy chain (MHC) isoforms such as SMemb, SM1 and SM2 are important molecular markers used to study vascular smooth muscle cell differentiation. SMemb is predominantly expressed in immature smooth muscle cells (SMC), and SM2 is expressed in mature SMCs. The authors investigated the expression of VEGF and SMC differentiation in pulmonary vessels in CDH rat lungs and in controls. The lungs of nitrofen-induced CDH rat fetuses (n = 16, gestational age 16, 18, 20, and 22 days) were stained immunohistochemically using antibodies against VEGF, SMemb and SM2, while alpha-actin was used as a general marker of vascular smooth muscle cells. In the CDH group VEGF expression was negative in pulmonary vessels before birth, and in the control group VEGF was positive in smooth muscle cells in vessel walls from 20 days both in vessels at the hilum and in pulmonary parenchyma. In both control and CDH groups, SMemb expression was positive from 16 days' gestation. SM2 expression was negative in vessel walls during the prenatal period in both groups. Alpha-actin was localized in both lungs obtained from control and CDH groups in the lung hilum from 16 days and around peripheral vessels from 18 days. Differences in vascular smooth muscle cell differentiation were not observed between control and CDH lung. These findings suggest that differences in pulmonary vascular development exist between control and CDH rats for VEGF expression, and maturational differences in smooth muscle cell differentiation are not present. This role of altered endothelial cell growth might be related to the different pulmonary vascular reactivity present in CDH lungs.

Animals↗
PubMed1997

Increased expression of angiogenic growth factors in age-related maculopathy.

AIMS/BACKGROUND: The late stages of age-related maculopathy (ARM), especially neovascular macular degeneration (ARMD), can severely affect central vision and are the main cause of blindness in the elderly in the Western world. It has been shown that angiogenic growth factors are present in neovascular membranes in ARMD. However, it is not known if angiogenic growth factors play a role in the onset of neovascularisation. METHODS: In order to elucidate the involvement of angiogenic growth factors in the initiation of neovascularisation in early stages of ARM, the expression patterns of VEGF, TGF-beta, b-FGF, and PDGF-AA on 18 human maculae with ARM, and on 11 control specimens were investigated immunohistochemically. RESULTS: A significantly increased expression of VEGF (p = 0.00001) and TGF-beta (p = 0.019) was found in the retinal pigment epithelium (RPE) of maculae with ARM compared with control maculae. Furthermore, an increased expression of VEGF and PDGF was found in the outer nuclear layer of maculae with ARM. CONCLUSION: These results demonstrate an increased expression of VEGF in the RPE, and in the outer nuclear layer in maculae with ARM, that could be involved in the pathogenesis of neovascular macular degeneration. Furthermore, enhanced TGF-beta expression in the RPE cells of maculae with early stages of ARM was shown.

Adult↗
PubMed1996

Fourth branchial pouch cyst: an unusual cause of neonatal stridor.

Fourth branchial pouch anomalies are extremely rare and only a few such cases showing sinuses and cystic masses have been reported in the literature. We describe a patient who presented on the third day of life with cystic neck swelling of fourth branchial pouch origin giving rise to respiratory obstruction and stridor. Despite repeated aspiration of the cystic mass to relieve respiratory obstruction, rapid recurrence of the mass continued to cause stridor and ultimately required surgical excision. The clinical, radiological, and histopathological findings of this unusual condition are discussed with a review of the literature.

Airway Obstruction↗
PubMed1996

Induction of the haem oxygenase gene expression during the reperfusion of ischemic rat myocardium.

A variety of stress including oxidative stress, hyperthermia and heavy metals can induce the expression of haem oxygenase in mammalian tissue. In this study we examined whether an ischemic stress could induce haem oxygenase in heart. Isolated perfused rat hearts were subjected to either 5 or 20 min of ischemia followed by 15, 30, 45 and 60 min of reperfusion in each case. The results of our study indicate that haem oxygenase is not induced by ischemia, but can be induced by reperfusion. The induction of haem oxygenase is a function of the duration of reperfusion. This induction can be blocked by pre-perfusing the hearts with oxygen free radical scavengers, superoxide dismutase (SOD) and catalase. Haem oxygenase was also induced in the hearts by perfusing them with oxygen free radical generating system. This induction was also blocked by SOD and catalase. Immunohistochemical localization revealed that haem oxygenase-1 is primarily accumulated in the perivascular region and in the cardiomyocytes. This suggests that it is oxygen free radicals that is produced during the reperfusion is the stimulus for the expression of haem oxygenase in the ischemic/reperfused myocardium.

Animals↗
PubMed1996

Involvement of nitric oxide in acute spinal cord injury: an immunocytochemical study using light and electron microscopy in the rat.

The possibility that nitric oxide participates in the pathophysiology of spinal cord injury was examined using a constitutive isoform of neuronal nitric oxide synthase immunoreactivity in a rat model. Spinal cord trauma was produced by making an incision into the right dorsal horn of the T10-11 segments. Five h after trauma, a marked upregulation of NOS-immunostained neurons was seen in the perifocal T9 and T12 segments of the cord. The immunolabelling was most pronounced in the dorsal horn of the ipsilateral side. Topical application of an antiserum to nitric oxide synthase (NOS) 2 min after injury prevented the trauma-induced upregulation of NOS-immunoreactivity. In contrast, application of preabsorbed serum or L-NAME, an inhibitor to NOS, was ineffective in reducing the induction of NOS-immunoreactivity. Trauma caused a marked expansion of the cord and resulted in marked cell changes. This expansion and cell reaction was significantly reduced following application of NOS antiserum but it was not seen after application of preabsorbed antiserum or L-NAME. Our results for the first time show that a focal trauma to the spinal cord has the capacity to upregulate neuronal NOS immunoreactivity and that application of NOS antiserum has a neuro protective effect. This indicates that nitric oxide is somehow involved in the pathogenesis of secondary injuries after spinal cord trauma.

Amino Acid Sequence↗
PubMed1996

Metastatic osteosarcoma of the ethmoid: an unusual cause of recurrent epistaxis and proptosis.

Osteosarcoma is the most common primary malignant tumour of bone and it usually metastasises to the lung. In the nasal cavity metastatic disease is extremely rare. We describe a case of osteosarcoma presenting with recurrent epistaxis, and proptosis due to secondaries in the nasal cavity. To our knowledge such a case has not been reported previously in the available English literature.

Adolescent↗
PubMed1995

Probable involvement of serotonin in the increased permeability of the blood-brain barrier by forced swimming. An experimental study using Evans blue and 131I-sodium tracers in the rat.

The possibility that endogenous serotonin (5-hydroxytryptamine, 5-HT) participates in alteration of the blood-brain barrier (BBB) following short-term forced swimming (FS) exercise was examined in a rat model. Subjection of conscious young (age 8-9 weeks, 80-90 g) animals to continuous FS (at a water temperature of 30 +/- 1 degrees C) for 30 min, increased the permeability of the BBB to Evans blue albumin (EBA) and 131I-sodium in six and nine brain regions, respectively. The EBA staining was noted in posterior cingulate cortex, parietal, occipital cortices, cerebellar vermis, medial lateral cerebellar cortices and dorsal surface of hippocampus. In addition to these brain regions, the BBB permeability to 131I-sodium was further extended to caudate nucleus, thalamus and hypothalamus. This effect of FS on the BBB permeability was absent in adult (age 24-30 weeks, 300-400 g) animals. Measurement of 5-HT showed a profound increase of plasma and brain in young rats by 180% and 250%, respectively, from the control group. Adult animals showed only a minor increase in brain and plasma 5-HT levels. In young animals, pretreatment with p-CPA (a 5-HT synthesis inhibitor) and indomethacin (a prostaglandin synthesis inhibitor) prevented the FS induced increase in BBB permeability and 5-HT levels. Destruction of serotonergic neurons with 5,7-dihydroxytryptamine (5,7-DHT) reduced the breakdown of the BBB and attenuated the brain 5-HT level without affecting the plasma 5-HT. Cyproheptadine, ketanserin (5-HT2 receptor antagonists) and vinblastine (a vesicular transport inhibitor) prevented the increased permeability of the BBB alone. The plasma and brain 5-HT continued to remain high. These observations suggest that (i) 5-HT plays an important role in the breakdown of BBB permeability in FS, (ii) this effect of 5-HT on BBB permeability is mediated by 5-HT2 receptors, and (iii) FS induced increase in BBB permeability is age dependent.

5,7-Dihydroxytryptamine↗
PubMed1995

Nucleotide sequence and expression of the porcine vascular endothelial growth factor.

We cloned and sequenced two cDNAs encoding the angiogenic, vascular endothelial growth factor (VEGF) from the porcine heart. Deduced amino acid sequence of the clone pPVE-18 and pPVE-5 predicted 164 (VEGF164), and 120 (VEGF120) residues of VEGF, respectively, with a putative N-terminal signal sequence of 26 amino acids. The porcine VEGF is shorter by one amino acid as compared to human VEGF, but a potential glycosylation site is present at Asn-74. PCR detection, and verification of the identity of the PCR products by Southern hybridization, confirmed wide expression of VEGF in different porcine tissues. Northern blot analysis with a radiolabeled porcine specific VEGF probe, showed one major (3.9 kb) and one minor (1.7 kb) mRNA species expressed in all four chambers of the heart.

Amino Acid Sequence↗
PubMed1995

A serotonin synthesis inhibitor, p-chlorophenylalanine reduces the heat shock protein response following trauma to the spinal cord: an immunohistochemical and ultrastructural study in the rat.

The influence of the serotonin synthesis inhibitor, p-CPA on the expression of the heat shock protein (70 kDa), which occurs around an injury to the rat spinal cord, was examined by immunohistochemistry. A longitudinal incision was made into the right dorsal horn at the T10-11 level. Five hours later samples were removed from the T9 and T12 segments. Samples from untreated traumatised animals showed signs of edema and many distorted neurons, particularly in the ipsilateral grey matter. Neurons of the same regions showed a profound increase in HSP-70 immunostaining compared with intact controls. At ultrastructural level, the immunoreactivity was detected in neuronal cytoplasm attached to the surface of organelles including endoplasmic reticulum, in the nucleus and in dendrites. Other groups of rats were given p-CPA before injury to reduce the synthesis of serotonin and to minimise its stores in the cord. The HSP-immunostaining in neurons of the T9 and T12 segments of the spinal cord was virtually lacking in the drug treated animals. The signs of edema and the structural changes of these segments were markedly reduced. The results show that inhibition of serotonin synthesis prior to the traumatic insult has an inhibitory influence on HSP response occurring in neurons around the site of injury to the spinal cord, not reported earlier.

Animals↗
PubMed1995

Vascular permeability to growth hormone in the rat central nervous system after focal spinal cord injury. Influence of a new anti-oxidant H 290/51 and age.

Vascular permeability to the growth hormone (GH) across the blood-brain barrier (BBB) is unknown. This investigation was undertaken to examine vascular permeability to 125I-labelled rat growth hormone (rGH) in the central nervous system (CNS) of normal animals. Since age and spinal cord injury influences the metabolism of GH, these factors were also included. No statistically significant difference was seen regarding rGH permeability between young (aged 19-21 weeks) and old (age 38-42 weeks) animals. A focal trauma to the cord, produced by an incision into the right dorsal horn of the T10-11 segments in young animals, increased rGH permeability in several spinal cord segments at 0.5-5.0 h after injury. This permeability increase progressed over time. Similar trauma to old rats resulted in a significantly less increase in rGH permeability in the spinal cord 5 h after the trauma. This indicates that trauma-induced increased permeability of rGH is age-dependent. Pretreatment of normal young animals with a new antioxidant (H 290/51) did not influence the rGH permeability. However the drug prevented the trauma-induced increase of rGH permeability at 5 h after injury. This indicates that inhibition of lipid peroxidation has some protective effect on trauma-induced increase in rGH permeability.

Aging↗
PubMed1995

Expression of vascular permeability factor/vascular endothelial growth factor in pig cerebral microvascular endothelial cells and its upregulation by adenosine.

Porcine brain-derived microvascular endothelial cells (BMEC) express the mRNA of the polypeptide mitogen vascular permeability factor/vascular endothelial growth factor (VPF/VEGF). The VEGF mRNA expression in BMEC could be upregulated 2.5 fold after 6 h of treatment with 5 microM adenosine and adenosine agonists. Adenosine A1 and A2 receptor antagonists completely abolished the upregulation of the VEGF mRNA caused by adenosine. Agents like forskolin and cAMP phosphodiesterase inhibitors which are known to increase the cAMP level decreased the VEGF mRNA expression slightly whereas agents like phorbolester which activate the proteinkinase C (PKC) pathway enhanced the VEGF mRNA expression 3.2 fold. The specific inhibitor of the PKC bisindolymaleimide (BIM) abolished the upregulation of the VEGF mRNA by adenosine completely. The BMEC conditioned medium stimulated the proliferation of BMEC itself and Western blot analysis of the BMEC conditioned medium using a polyclonal antibody to human VEGF showed one band at 18 kDa which was slightly upregulated after treatment with adenosine. Results suggest that the effect of adenosine on the VEGF mRNA expression is mediated via the A1 receptor and that an activation of the PKC may be involved in the observed effects of adenosine on the VEGF mRNA expression. VEGF produced by BMEC and which is inducible by adenosine may function via the autocrine pathway and may be involved in repair reactions of brain blood vessels and/or the maintenance of these cells.

Adenosine↗
PubMed1995

Impairment of blood-brain barrier function by serotonin induces desynchronization of spontaneous cerebral cortical activity: experimental observations in the anaesthetized rat.

The possibility that elevation of serotonin in the circulation, which is found in various pathological states, influences the spontaneous cerebral cortical activity was examined in a rat model. The electroencephalogram was recorded using bipolar epidural electrodes placed over the frontal and parietal cerebral cortex. Intravenous infusion of serotonin (10 micrograms/kg per min for 10 min) decreased the electroencephalogram amplitude in both frontal and parietal recordings within 4 min of infusion. This decrease in amplitude was reversible, Pretreatment with cyproheptadine (a potent serotonin2 receptor antagonist) prevented the serotonin-induced decrease of the electroencephalogram amplitude. The blood-brain barrier permeability to Evans Blue and [131I]sodium was increased in frontal and parietal cortex. This increase in blood-brain barrier permeability was absent in animals pretreated with cyproheptadine. These results provide direct evidence that an elevated level of serotonin in blood has the capacity to influence spontaneous cortical electrical activity. This effect of serotonin on electroencephalogram appears to be due to its ability to enter into the brain parenchyma by inducing a short-term breakdown of the blood-brain barrier, probably via serotonin2 receptors.

Anesthesia↗