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Biomedical subjects

H S Sharma

Publications and source records attributed to H S Sharma.

At least 163 records · Page 9Linked to original sources
PubMed1990

Changes in blood-brain barrier and cerebral blood flow following elevation of circulating serotonin level in anesthetized rats.

Plasma serotonin (5-HT) was elevated by an intravenous infusion of this amine into urethane-anaesthetized rats and the concentration approximated that present in various neurological diseases and mental abnormalities. An infusion of 10 micrograms per kg body weight for 10 min significantly increased blood-brain barrier (BBB) permeability to Evans blue and 131I-sodium measured in whole brain. Regional BBB determinations with labelled 131I-sodium showed that the permeability to this compound was increased in the cerebral cortex, hippocampus, caudate nucleus, hypothalamus, colliculus and the cerebellum but not in the pons and the medulla oblongata. Regional blood flow was reduced in the same parts which showed BBB abnormality tested with 125I-labeled microspheres. Pretreatment with cyproheptadine, a 5-HT2 receptor antagonist, prevented the BBB increase and the regional blood flow was near normal values. Similar effects were obtained with indomethacin, a prostaglandin synthesis inhibitor. Vinblastine, known to influence vesicular transport, eliminated extravasation of the tracers but the regional blood flow remained depressed. A hypothesis is put forward that serotonin after binding to its receptor in the cerebral vessels stimulates prostaglandin which either directly or by means of cyclic adenosine monophosphate causes an increased vesicular transport across the endothelial cells and thus an extravasation of tracer substances in the brain. Obviously, this form of exudation can be influenced by pharmacological means.

Animals↗
PubMed1990

Molecular biologic concepts of coronary anastomoses.

The discovery that collateral development after progressive coronary stenosis proceeds by means of DNA synthesis, mitosis and proliferation of endothelial and smooth muscle cells in preformed small interconnecting arterioles (canine heart) and capillaries (porcine heart) has stimulated research into the molecular mechanisms of vascular growth. Growth is tightly controlled under physiologic conditions, and several factors must act in concert to overcome control. Because the result of growth is a much larger orderly structure of complex design, we expect the existence of a genetic blueprint for its construction. Peptide growth factors have recently been isolated from a variety of organs, including the heart. We have provided experimental evidence that the heparin-binding growth factor beta-ECGF shows an increased transcription in growing pig collateral vessels. Because the chain of events probably originates in the ischemic cardiac myocyte, it appears logical to search there for the initiating factor. In addition to local production, growth factors can also be transported into ischemic myocardium by blood-borne cells. Monocytes adhere to altered endothelium in a potentially ischemic region and start to produce growth factors in situ. Platelets are rich sources of transforming growth factor-beta (TGF-beta), platelet-derived endothelial cell growth factor (PDECGF) and platelet-derived growth factor (PDGF), all of which are known angiogenic factors or mitogens.

Adaptation, Physiological↗
PubMed1990

Maternal vitamin A restriction alters biochemical development of the brain in rats.

The biochemical development of the fetal brain in relation to maternal vitamin A restriction was studied in rats. The vitamin A status of pregnant rats was varied by supplying low, medium and adequate amounts (6, 40, and 100 micrograms retinol/day/kg body weight, respectively) of vitamin A during pregnancy and suckling. The maternal vitamin A restriction caused an altered brain development in terms of tissue weight, DNA, RNA and protein levels, and biosynthesis of DNA and protein from [3H]-thymidine and [3H]-leucine, respectively. A dose-dependent effect of maternal vitamin A restriction on the metabolism of DNA, RNA and protein was noticed in the developing fetal brain of rats.

Animals↗
PubMed1990

Dynamics of tracer distribution in radiation induced brain oedema in rats.

The dynamic behaviour of the distribution of Evans blue (EB), sodium fluorescein (SF), Lucifer yellow (LY) and horseradish peroxidase (HRP) was studied using standard light- and fluorescence microscopy following ultraviolet radiation induced brain oedema in the rat model. The cerebral cortex was irradiated after craniotomy (2 x 2 mm) under anaesthesia. The tracers were injected (iv) 30 min prior to radiation. Animals were perfused with glutaraldehyde through the heart at different survival periods ranging from 30 min to 24 h post irradiation. The results showed a remarkable difference in distribution and spread of these tracers in the oedematous brain following radiation. The extravasation of EB was evident in ipsilateral cortex 6 h after radiation which extended to the contralateral side at the end of the 24 h survival period. The HRP reaction product was seen in the necrotic area 3 h after radiation which further extended to the underlying white matter at 24 h survival. The LY stained the ipsilateral micronecrotic area 6 h after radiation, whereas a non-specific diffuse fluorescence of SF was noted at this time period. These results point out a specific selectivity of tracer distribution in oedematous brain following ultraviolet radiation.

Animals↗
PubMed1990

Brain oedema and cellular changes induced by acute heat stress in young rats.

Exposure of young animals (70-80 g, Age 6-7 weeks) to heat stress (HS) at 38 degrees C for 4 h in a B.O.D. incubator (rel humid 50-55%, wind vel 28.6 cm/sec) resulted in a 4.41% increased brain water content from the control value. Morphological studies in parietal cerebral cortex at light microscopical level revealed chromatolysis and appearance of dark neurons. Electron microscopy of similar regions showed perivascular oedema, vacuolation and collapsed microvessels. The swelling of astrocytes and of postsynaptic membranes was frequent. A diffuse infiltration of lanthanum (La[NO3]3) in endothelial cell cytoplasm and in the vesicles was very common. Occasionally, the lanthanum was seen in the basement membrane but the tight junctions were mainly intact. At this time period, a significant increase in blood-brain barrier (BBB) permeability as well as 5-HT levels in brain and plasma were observed. Pretreatment with p-CPA (a 5-HT synthesis inhibitor) prevented the increase of brain water content. BBB permeability and 5-HT levels in brain and plasma. Cyproheptadine (a 5-HT2 receptor antagonist) treatment significantly reduced the occurrence of increased brain water content and the BBB permeability. The 5-HT level continued to remain high. These results point out a probable role of 5-HT in pathophysiology of HS via 5-HT2 receptors.

Acute Disease↗
PubMed1990

Increased 5-hydroxytryptamine immunoreactivity in traumatized spinal cord. An experimental study in the rat.

The possibility that serotonin (5-hydroxytryptamine, 5-HT) is involved in the early tissue reactions occurring in spinal cord trauma was examined in a rat model using an immunocytochemical technique. The injury was made in the form of a 5-mm long and 2.5-mm wide lesion of the right dorsal horn at the level of T10-11. Injured rats, pretreated with the 5-HT synthesis blocking agent, p-chlorophenyl alanine (p-CPA) were compared with untreated injured controls and the animals were allowed to survive for 5 h. The distribution of 5-HT was examined in proximal and distal cross- sections of the cord, located 2 and 5 mm away from the injury. Normal rats showed immunoreactive material in nerve cell processes and in a few nerve cell bodies of the ventral horns. The trauma to the spinal cord caused a marked increase in 5-HT immunoreactivity in the segments located 2 mm proximal and distal to the injury, particularly in the ipsilateral ventral horn. The segment located 5 mm distal to the lesion showed a similar increase in immunoreactivity but it was apparently less pronounced in the corresponding proximal segment. Treatment with p-CPA markedly reduced the trauma-induced increase in 5-HT immunoreactivity in all the segments. These immunohistochemical findings were in line with the changes in the contents of 5-HT measured biochemically in corresponding spinal cord segments. At the onset of the trauma to the spinal cord 5-HT is thus present in the tissue, mainly in the form of 5-HT-containing nerve cell processes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effects of p-chlorophenylalanine on microvascular permeability changes in spinal cord trauma. An experimental study in the rat using 131I-sodium and lanthanum tracers.

The possibility that serotonin can take part in the initiation of the increased microvascular permeability occurring in a spinal cord trauma was investigated in a rat model with 131I-sodium and lanthanum as tracers. We influenced the serotonin content in the tissue pharmacologically by treating animals with a serotonin synthesis inhibitor, p-chlorophenylalanine (p-CPA), before the production of the injury and compared the results with injured, untreated controls. A small incision was made in the dorsal horn of the lower thoracic cord. It caused a progressive extravasation of 131I-sodium in the damaged segment, measured after 1, 2 and 5 h. Rostral and caudal segments also showed a significant but lower accumulation of 131I-sodium. Lanthanum added to the fixative was used as an ionic tracer detectable by electron microscopy. The endothelial cells of microvessels removed from the perifocal region after 5 h showed a marked increase in the number of lanthanum-filled vesicles. Many endothelial cells had a diffuse penetration of the tracer into the cytoplasm and the basement membrane. However, the tight junctions usually remained closed to lanthanum. Pretreatment with p-CPA markedly reduced the extravasation of 131I-sodium measured at 5 h in the traumatized cord. At the cellular level, the endothelial vesicles filled with lanthanum approached the condition of uninjured animals. The diffuse infiltration of lanthanum into endothelial cells and its spread into the basement membrane of the vascular wall were usually absent. Our results indicate that serotonin plays a role in the initiation of the increased microvascular permeability which occurs in spinal cord injuries.

Animals↗
PubMed1990

Edema formation and cellular alterations following spinal cord injury in the rat and their modification with p-chlorophenylalanine.

The possibility that serotonin can modify the early pathological sequences occurring in spinal cord trauma was investigated in a rat model. To that end we took advantage of the possibility of influencing serotonin pharmacologically by treating animals with a serotonin synthesis inhibitor, p-chlorophenylalanine (p-CPA) before the production of the injury and compared the results with injured, untreated controls. A unilateral incision was made into the dorsal horn of the lower thoracic cord (about 2.5 mm deep, 4.5 mm long) and the rats were allowed to survive up to 5 h after the trauma. The injured region from untreated animals showed macroscopically at that time a pronounced swelling and the water content had increased by 3.5% as compared to intact controls. The segments rostral and caudal to the lesion also exhibited a profound increase in water content. Light microscopy revealed a significant expansion of the spinal cord as compared to controls. The swelling was most pronounced in the gray matter on the injured side. Electron microscopy showed distorted neurons, swollen astrocytes and extracellular edema in the gray matter in and around the primary lesion. There was also a sponginess in the surrounding white matter with disruption of myelin, collapsed axons and widened periaxonal spaces. Pretreatment of the rats with p-CPA significantly reduced the swelling of the injured spinal cord and there was no visible expansion. The ipsilateral edema in the central gray matter was considerable less pronounced as compared to that in untreated animals. The increase in water content was less than 1% in these animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Vascular permeability of spinal nerve roots. A study in the rat with Evans blue and lanthanum as tracers.

The permeability of blood vessels in rat spinal nerve roots was investigated with Evans blue-albumin as an in vivo macromolecular tracer and lanthanum nitrate as an electron microscopic ionic marker added to a fixative. Rats injected intravenously with Evans blue, showed macroscopic distinct staining of dorsal root ganglia, whereas spinal nerve roots remained unstained. Fluorescence microscopy, however, revealed clear extravascular fluorescence both in ventral and dorsal roots 2 or 18 h after tracer administration. Two different types of blood vessels exists in spinal nerve roots; large extrinsic (radicular) in the root sheath and minute intrinsic vessels in the parenchyma. Lanthanum added to a fixative, perfused through the vessels was detected in the lumen of both types of vessels, usually adhering to the luminal plasma membrane and in many invaginations from that membrane. Lanthanum also entered the clefts between endothelial cells but was always stopped at the junctions which are, thus, of the tight type. Diffuse penetration of the compound into the cytoplasm was seen in one endothelial cell, but no fenestrations were detected. Junctions between the endothelial cells of vessels in rat spinal nerve roots are impermeable to lanthanum and most likely also to other large molecular substances like albumin. Thus, probable routes for serum albumin to enter the nerve roots, where it normally is present, must be either by centripetal extracellular diffusion from the ganglia and the peripheral nerve or by vascular leakage in the roots, caused by for instance pinocytosis across endothelial cells.

Animals↗
PubMed1990

Early accumulation of serotonin in rat spinal cord subjected to traumatic injury. Relation to edema and blood flow changes.

Changes in the concentration of serotonin (5-hydroxytryptamine) in the early period after a focal traumatic injury to rat spinal cord were determined and related to the formation of edema and alterations in blood flow. A unilateral, 5-mm-long and 3-mm-deep traumatic injury located 2 mm from the midline was created in the T10-11 segment of the cord. Five hours after the injury the serotonin concentration in the traumatized segment had increased more than 100% compared with controls. There was also a progressive increase in water content of the traumatized segment measured 1-5 h after the injury. On the other hand, the spinal cord blood flow showed a progressive decrease to about 35% of its initial value at 5 h. Pretreatment with p-chlorophenylalanine, a serotonin synthesis inhibitor, impeded the elevation in water content measured 5 h after the trauma. The spinal cord blood flow remained close to normal values and the increase in serotonin was absent. Our results show that trauma to the rat spinal cord will induce changes in the serotonin concentration of the tissue and that the associated formation of edema and blood flow alterations can be alleviated in serotonin depleted rats. Obviously, serotonin plays a significant role in the pathophysiology of traumatic injury of rat spinal cord.

Animals↗
PubMed1990

Alteration of substance P after trauma to the spinal cord: an experimental study in the rat.

The distribution of substance P was determined in the rat spinal cord and brain after a focal traumatic injury to the thoracic region (T10-11) of the spinal cord. There was at 1 and 2 h after the injury a statistically significant increase of the substance P content not only in the injured segment but also in samples removed 5 mm proximal (T9) and distal (T12) to the lesion. At 5 h the substance P content of the injured segment of the cord was reduced by 30% compared with controls. However, there was a significant increase in the concentration of this peptide in segments located 5 mm cranial and caudal to the injury (65% and 22%, respectively). Interestingly, the whole brain content of substance P showed a statistically significant 22% increase from control values at 5 h after the injury. At 1 and 2 h after the spinal cord injury there was a significant decrease in whole brain substance P concentration by 25% and 65%, respectively. Pretreatment with p-chlorophenylalanine (a serotonin synthesis inhibitor) markedly reduced the endogenous content of substance P in whole brain of normal animals. In these animals, the spinal cord content of the peptide was elevated by 83-123% as compared to untreated control animals. Spinal cord trauma inflicted on p-chlorophenylalanine-treated animals did not affect the brain peptide level at all. However, a profound decrease was noted in all the spinal cord segments at 5 h as compared to the untreated traumatized group. The decrease in this peptide was more pronounced in the cranial and the injured segments as compared to the caudal one.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Isolation of heparin-binding growth factors from bovine, porcine and canine hearts.

Fresh bovine, porcine and canine hearts were homogenized and mitogens for mesoderm-derived cells were purified in three different steps. Extraction by two different ammonium sulfate precipitations was followed by cation-exchange chromatography and by heparin-Sepharose affinity chromatography. A heparin-Sepharose fraction from heart (eluted at 1.1 M NaCl) increased mitotic activity in serum-deprived cultures of porcine aortic endothelial and smooth muscle cells, and in human fibroblasts. This mitogenic activity is potentiated by heparin and inhibited by gamma-interferon. The heart mitogenic fraction showed one double peak on HPLC at A215 and one polypeptide band on SDS/PAGE. These peaks and bands were identical to those obtained from bovine brain. The heart acidic fibroblast growth factor (aFGF) showed a positive signal in Western blots using antibodies raised against brain aFGF. Gas-phase amino acid sequencing established that the mitogens were identical to aFGF and the N-terminally truncated aFGF. Extraction in the presence of a protease inhibitor (pepstatin A) produced a higher-molecular mass form of aFGF with a blocked amino terminus. Another mitogen, eluted at 1.6 M NaCl from heparin-Sepharose, reacted with polyclonal antiserum against human recombinant basic fibroblast growth factor (bFGF) and showed a 66% (12 from 18 amino acids determined by gas-phase sequencing) similarity with bFGF. This polypeptide increased the mitotic activity of the same cell lines but was more potent than aFGF.

Amino Acid Sequence↗
PubMed1989

Secretion pattern of retinol-binding protein in blood of goats: effect of vitamin A, provitamin A and their dosing schedule.

Studies were conducted on the secretion of retinol-binding protein (RBP) in blood of goats given different treatments of preformed vitamin A, beta-carotene and plant carotenoids. Administration of these sources either in a single massive dose or massive dose split into four equal doses, markedly increased the secretion of RBP in blood. The secretion of RBP in blood occurred at least in two phases, one at early periods and the other at later periods.

Animals↗
PubMed1989

Role of histamine in traumatic brain edema. An experimental study in the rat.

The possibility that histamine plays a role in the formation of traumatic brain edema was investigated in the rat. A 3 mm deep and 3 mm long stab injury was performed in the right parietal cortex under urethane anaesthesia. The brain water content and histamine levels in plasma and brain were measured at the end of 1, 2 and 5 h periods after trauma. There was a 3.46% increase in brain water content in the traumatized hemisphere from the value in the control group at 5 h. The histamine content was increased by 107% in plasma and 51% in the traumatized brain hemisphere from the control value at this time period. The increased brain water content as well as the elevated plasma and brain histamine levels were prevented by prior treatment with the histamine H2-receptor antagonist cimetidine. Mepyramine (a histamine H1-receptor antagonist) failed to reduce the increased brain water content and the histamine levels in plasma and brain remained high. The results strongly indicate that histamine has a role in the formation of early traumatic brain edema and that this reaction can be influenced by pharmacological procedures.

Animals↗
PubMed1988

Vitamin A supply and biochemical development of the rat heart: studies on cellular DNA, RNA and protein.

The effect of restricted vitamin A supply to the mother on the biochemical development of the heart in rats has been studied. The vitamin A status of female rats was varied by supplying low, medium and adequate amounts (6, 40, 100 micrograms retinol/day/kg body weight respectively) of vitamin A during pregnancy and suckling. The vitamin A status of the mother caused an alteration in the developmental pattern of fetal heart in parameters of tissue weight, DNA, RNA and protein contents and the biosynthesis of DNA and protein from [3H]-thymidine and [3H]-leucine respectively. A dose-dependent effect of vitamin A on the metabolism of DNA, RNA and protein was observed in the developing rat hearts. Hence, emphasis should be given to the adequate availability of vitamin A to dams for the normal growth and development of fetal organs.

Aging↗
PubMed1988

EEG changes following increased blood-brain barrier permeability under long-term immobilization stress in young rats.

A continuous 8 h of immobilization stress in conscious young rats increased the blood-brain barrier (BBB) permeability to 131I-sodium in 12 out of 14 brain regions studied. A flattening of electroencephalographic (EEG) activity was noted during this time period. The mean cerebral blood flow (CBF) was reduced by 17% (during this time period) but the regional flow reduction was not related to the regional increase in BBB permeability. On the other hand, a correlation was observed between increased plasma and brain 5-HT levels and increased BBB permeability. p-Chloro-phenylalanine (p-CPA) pretreatment has prevented the occurrence of increased BBB permeability, and the flattening of EEG activity as well as 5-HT levels in plasma and brain. These results suggest that the long-term immobilization stress induces causally related sequential events in rats: enhancement of circulating 5-HT, impairment of BBB, free access of 5-HT into the brain, and eventually flattening of EEG.

Animals↗
PubMed1987

Influence of long-term acute heat exposure on regional blood-brain barrier permeability, cerebral blood flow and 5-HT level in conscious normotensive young rats.

Exposure of conscious young rats to 4 h heat stress at 38 degrees C in B.O.D. incubator was associated with increased blood-brain barrier (BBB) permeability in 14 brain regions studied. In the same regions cerebral flow (CBF) diminished by 4-65%, but the magnitude of flow reduction was not correlated with the degree of increased BBB permeability. On the other hand, a correlation was observed with increased plasma and brain 5-hydroxytryptamine (5-HT) levels. p-Chlorophenylalanine (p-CPA), indomethacin and diazepam pretreatment prevented both the increased BBB permeability and 5-HT levels following heat exposure. Whereas cyproheptadine and vinblastine pretreatment prevented the increased BBB permeability alone. The probable mechanism(s) underlying the BBB permeability is discussed.

Animals↗