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Thromboxane inhibitors attenuate pathological changes in alcoholic liver disease in the rat. | Thromboxane levels correlate with severity of liver injury in rats given alcohol. The aim of this study was to evaluate the effect of thromboxane inhibitors on pathological changes in experimental alcoholic liver disease.Male Wistar rats were given a liquid diet and ethanol intragastrically for 1 month. The thromboxane inhibitors tested were a thromboxane receptor antagonist (TXRA) and a thromboxane synthase inhibitor (TXSI). Pathological changes; liver and plasma thromboxane levels; 6-ketoprostaglandin F1 | 8978360 | [
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Thromboxane inhibitors attenuate pathological changes in alcoholic liver disease in the rat. | alpha levels; lipid peroxidation; and messenger RNA levels for tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF) beta were evaluated.Treatment with thromboxane inhibitors prevented necrosis and inflammation. In the TXSI-treated group; fatty liver was also decreased. Ethanol administration led to a 3-4-fold increase in liver thromboxane levels; a reduction in thromboxane levels and lipid peroxidation was seen in the TXSI group. In all treatment groups; TNF-alpha and TGF-beta messenger RN | 8978360 | [
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Thromboxane inhibitors attenuate pathological changes in alcoholic liver disease in the rat. | A levels were decreased.The prevention of necroinflammatory changes in thromboxane-treated groups is related to a decrease in TNF-alpha levels. Inhibition of TGF-beta expression may also prevent fibrosis in ethanol-treated rats. | 8978360 | [
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8-Isoprostaglandin F2 alpha, a product of lipid peroxidation, increases portal pressure in normal and cirrhotic rats. | The F2-isoprostanes are a recently described class of prostaglandins formed by free radical-mediated lipid peroxidation. 8-Isoprostaglandin F2 alpha (8-iso-PGF2 alpha); an F2-isoprostane; has previously been shown to be a potent renal vasoconstrictor acting via a thromboxane-like receptor. The aim of this study was to investigate whether 8-iso-PGF2 alpha increases portal pressure.Livers from normal and bile duct-ligated cirrhotic rats were perfused; and portal pressure response to infused agonist was monito | 8978361 | [
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8-Isoprostaglandin F2 alpha, a product of lipid peroxidation, increases portal pressure in normal and cirrhotic rats. | red continuously.Infusion of 8-iso-PGF2 alpha increased portal pressure in both groups; with a significantly greater response in cirrhotic rats. At a dose of 2.5 nmol/min; the mean portal pressure increased from a baseline of 8.2 +/- 0.6 to 9.8 +/- 1.3 mm Hg; whereas in cirrhotic animals; the increase was from 12.0 +/- 0.9 to 18.6 +/- 1.8 mm Hg. This response was completely blocked by SQ29548; a thromboxane receptor antagonist. A similar response pattern was observed with the thromboxane receptor agonist U4 | 8978361 | [
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8-Isoprostaglandin F2 alpha, a product of lipid peroxidation, increases portal pressure in normal and cirrhotic rats. | 6619.8-iso-PGF2 alpha can increase portal pressure in cirrhotic rats. If extrapolated to patients with cirrhosis; lipid peroxidation secondary to alcoholic liver injury; sepsis; or other liver pathology may cause an acute increase in portal pressure such as that observed in acute liver injury. | 8978361 | [
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Bile acid concentrations in human and rat liver tissue and in hepatocyte nuclei. | Bile acids exert cellular and molecular effects in the liver; but little is known about tissue concentrations. The aim of this study was to characterize bile acid composition in human and rat liver tissue and hepatocyte nuclei and examine the effects of experimental cholestasis and bile acid administration.Bile acids were measured by gas chromatography-mass spectrometry.Liver tissue concentrations of sham-operated rats were 130.8 +/- 21.3 nmol/g; representing 2%-4% of the bile acid pool; cholic and delta 22 | 8978363 | [
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Bile acid concentrations in human and rat liver tissue and in hepatocyte nuclei. | -beta-muricholic acids were the major bile acids identified. Concentrations increased 7-8-fold with bile duct ligation; deoxycholate and hyodeoxycholate disappeared. Lithocholate concentrations were higher in ligated rats (6.4 +/- 0.4 vs. 3.9 +/- 0.5 nmol/g for sham-operated). Total bile acid concentrations in human liver tissue were 61.6 +/- 29.7 nmol/g and comprised mainly chenodeoxycholic and cholic acids. Concentrations were higher during ursodeoxycholate or tauroursodeoxycholate administration (157.2 + | 8978363 | [
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Bile acid concentrations in human and rat liver tissue and in hepatocyte nuclei. | /- 45.6 and 161.6 +/- 43.4 nmol/g; respectively); and liver tissue was enriched 30% in ursodeoxycholate at the expense of hydrophobic bile acids. Bile acids were identified in rat hepatic nuclei (50-110 pmol/4 x 10(7) nuclei); accounting for < 0.1% of liver tissue levels.Human and rat liver tissue bile acid concentrations are low; increase with bile acid administration or bile duct ligation; and account for only a small fraction of the bile acid pool. | 8978363 | [
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Hepatocyte transport of bile acids and organic anions in endotoxemic rats: impaired uptake and secretion. | In sepsis; intrahepatic cholestasis occurs frequently; suggesting impaired hepatocyte transport of bile acids and organic anions. The aim of the study was to define the magnitude; time course; and the site of impaired biliary secretion in a rat sepsis model.Maximal transport for two bile acids (cholyltaurine and chenodeoxycholyltaurine) and two organic anions (sulfobromophthalein and sulfolithocholyltaurine) was measured in isolated perfused livers at various times after lipopolysaccharide injection. Basola | 8978362 | [
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Hepatocyte transport of bile acids and organic anions in endotoxemic rats: impaired uptake and secretion. | teral and canalicular liver plasma membrane vesicles were used to characterize the impairment in hepatocyte transport.Maximal hepatocyte transport was reduced for all compounds by 60%-81% compared with controls. Bile acid-independent bile flow was reduced by 51%. Impairment was maximal 12 hours after endotoxin injection and recovered thereafter. In basolateral plasma membrane vesicles; sodium-dependent transport for bile acids was reduced by 36%-47%. Sodium-independent transport of organic anions was reduce | 8978362 | [
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Hepatocyte transport of bile acids and organic anions in endotoxemic rats: impaired uptake and secretion. | d by 40%-55%. Adenosine triphosphate-stimulated transport was greatly decreased in canalicular vesicles prepared from endotoxemic animals for all four compounds probably because of a reduced number of transport molecules; based on kinetic studies.Basolateral and canalicular bile acid and organic anion transport are markedly impaired in endotoxemia. These mechanisms may contribute to the cholestasis of sepsis. | 8978362 | [
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Fatal hyperammonemia following orthotopic lung transplantation. | There have been anecdotes of unexplained coma and death in patients after otherwise successful orthotopic lung transplantation. A patient with primary pulmonary hypertension who underwent a technically uncomplicated single orthotopic lung transplantation is described. The patient developed intractable status epilepticus 4 days after surgery in association with the presence of a markedly elevated plasma ammonium level. Despite multiple therapeutic interventions; the hyperammonemia ultimately resulted in the | 8978364 | [
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Fatal hyperammonemia following orthotopic lung transplantation. | patient's death. Both metabolic and enzymatic studies showed that the unique physiological disturbance in this disorder results at least in part from defective in vivo conversion of waste nitrogen to urea and increased production of waste nitrogen. Although the rate of hepatic ureagenesis was therefore insufficient to prevent accumulation of ammonium; the cause was not severe liver disease. Liver histology showed widespread; microvesicular steatosis on light-microscopic examination; but only electron-micros | 8978364 | [
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Fatal hyperammonemia following orthotopic lung transplantation. | copic examination showed severe microvesicular steatosis with severe mitochondrial injury. As in Reye's syndrome; it was unclear whether the hepatic mitochondrial injury played a role in development or if it was the result of hyperammonemia. We recommended that any patient with an unexplained alteration of mental status after solid organ transplantation be evaluated for hyperammonemia. | 8978364 | [
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Basidiobolomycosis: an unusual fungal infection mimicking inflammatory bowel disease. | Basidiobolus ranarum is a fungus belonging to the Entomophthoraceae family and is mainly associated with subcutaneous soft tissue infection. The disease is usually characterized by an insidious onset of massive induration of the subcutaneous tissue involving the limbs; trunk; or buttocks. Most cases of basidiobolomycosis have been reported from Africa; South America; and tropical Asia. Visceral involvement is extremely rare. Only 4 cases with involvement of the gastrointestinal tract; including 1 fatal case | 8978366 | [
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Basidiobolomycosis: an unusual fungal infection mimicking inflammatory bowel disease. | originating in the United States; have been well documented in the English-language literature. This case report describes the first successfully treated patient residing in the United States who had B. ranarum infection involving the gastrointestinal tract. | 8978366 | [
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A new syndrome of Crohn's disease and pachydermoperiostosis in a family. | Few syndromic associations with Crohn's disease are described. The aim of this study was to characterize a new syndrome of Crohn's disease associated with pachydermoperiostosis in 3 brothers. Three probands; 6 siblings; both parents; 20 of 21 third-generation relatives; and 9 spousal controls were evaluated. Serological evaluation for antineutrophil cytoplasmic antibodies and human leukocyte antigens as well as genetic testing for tumor necrosis factor microsatellites; intercellular adhesion molecule 1 poly | 8978365 | [
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A new syndrome of Crohn's disease and pachydermoperiostosis in a family. | morphisms; the interleukin 1 receptor antagonist gene; and the interleukin 1 beta gene were performed. Only the 3 probands were affected and developed pachydermoperiostosis between ages 14 and 17 years. Pachydermoperiostosis preceded Crohn's ileocolitis by 6 and 20 years in two probands; excluding secondary hypertrophic osteoarthropathy. Two probands were antineutrophil cytoplasmic antibody positive vs. 1 of 27 unaffected relatives (P < 0.001; chi 2). Haplotypes for human leukocyte antigen and tumor necrosi | 8978365 | [
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A new syndrome of Crohn's disease and pachydermoperiostosis in a family. | s factor microsatellites were discordant. The probands' generation was homozygous for the common allele 1 of the interleukin 1 receptor antagonist and interleukin 1 beta genes. Two probands carried a rare polymorphism of the intercellular adhesion molecule 1 gene. A new syndrome of Crohn's disease and pachydermoperiostosis associated with antineutrophil cytoplasmic antibodies is described. Inheritance is most likely autosomal recessive by pedigree. No clear association was found between this syndrome and th | 8978365 | [
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A new syndrome of Crohn's disease and pachydermoperiostosis in a family. | e gene regions evaluated. | 8978365 | [
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The pathobiology of biliary epithelia. | Our understanding of the pathobiology of biliary epithelia is rapidly growing because of a surge of investigative activity. This became possible after suitable experimental models and techniques were developed with which to study cholangiocyte biology. Although the molecular mechanisms of bile formation by cholangiocytes and the role of these cells as a major cellular target in a variety of severe hepatobiliary diseases are currently being investigated; many questions remain unanswered; particularly regardi | 8978368 | [
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The pathobiology of biliary epithelia. | ng cholangiocellular functions; both in normal and abnormal conditions. As current experimental models become more refined; scientists with interests as diverse as cell biology and physiology; morphology; pharmacology; immunology; genetics; and oncology can be expected to further clarify the pathobiology of biliary epithelia. | 8978368 | [
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Abnormal gastric histology and decreased acid production in cholecystokinin-B/gastrin receptor-deficient mice. | The cholecystokinin (CCK)-B/gastrin receptor is one of several regulators of gastric acid secretion and mucosal growth. To elucidate the contribution of this receptor relative to other trophic and secretory factors; mice that lack the CCK-B/gastrin receptor have been generated and studied.Both alleles of the CCK-B/gastrin receptor were inactivated by targeted gene disruption. Analysis of the mice included measurement of basal gastric pH and plasma gastrin levels. In addition; multiple gastric mucosal cell t | 8978369 | [
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Abnormal gastric histology and decreased acid production in cholecystokinin-B/gastrin receptor-deficient mice. | ypes were identified by immunostaining and quantified.Homozygous mutant mice were viable; fertile; and appeared grossly normal into adulthood. The receptor-deficient mice exhibited a marked increase in basal gastric pH (from 3.2 to 5.2) and an approximately 10-fold elevation in plasma gastrin concentration compared with wild-type controls. In the stomach of mutant animals; parietal and enterochromaffin-like cells were decreased; providing a likely explanation for the reduction in acid output. In the antrum; | 8978369 | [
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Abnormal gastric histology and decreased acid production in cholecystokinin-B/gastrin receptor-deficient mice. | a decrease in somatostatin cell density and an increase in the gastrin cell number were observed; consistent with the concomitant elevation in circulating gastrin.Together; these findings demonstrate the importance of the CCK-B/gastrin receptor in maintaining the normal cellular composition and function of the gastric mucosa. | 8978369 | [
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What is a gold standard for colon polyps? | nan | 8978372 | [
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Colonoscopy and barium enema: radiologist's response. | nan | 8978373 | [
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Do pANCA define a clinical subgroup in patients with Crohn's disease? | nan | 8978380 | [
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Apoptosis repressor genes Bcl-2 and Bcl-x-long are expressed in the rat brain following global ischemia. | The proto-oncogenes bcl-2 and bcl-x-long have been shown to suppress apoptotic cell death in a variety of in vitro systems and cell lines; including neurons. An alternatively spliced from of bcl-x; bcl-x-short; is a promoter of apoptotic death. Whether these genes are induced after ischemia or play any role in determining the fate of ischemic neurons is unknown. To begin to address this issue; we studied the expression of bcl-2; and bcl-x mRNA and protein after global ischemia in the rat. Ischemia was induc | 8978381 | [
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Apoptosis repressor genes Bcl-2 and Bcl-x-long are expressed in the rat brain following global ischemia. | ed in isoflurane-anesthetized rats by the four-vessel occlusion method. mRNA expression was studied by Northern blot analysis at 24 h after ischemia and by in situ hybridization at 2; 4; 8; 24; and 72 h after 15 min of global ischemia. Protein expression was studied using both immunocytochemistry at 4; 8; 16; 24; and 72 h after ischemia and Western blot analysis from tissue harvested at 16; 24; and 72 h after ischemia. Western blots showed that bcl-x-long is the predominant form of bcl-x protein expressed i | 8978381 | [
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Apoptosis repressor genes Bcl-2 and Bcl-x-long are expressed in the rat brain following global ischemia. | n both normal and ischemic brain. Both bcl-2 and bcl-x-long mRNA were expressed in CA1; CA3; and the molecular layer of the dentate after ischemia. However; bcl-2 and bcl-x protein were expressed only in CA3 and dentate. Thus; while bcl-2 and bcl-x-long mRNA were expressed in both surviving and dying neurons; their proteins were expressed in neurons destined to survive. These results support potential roles for these two apoptosis suppressor proteins in promoting survival after cerebral ischemia. | 8978381 | [
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Expression of interleukin-1 beta converting enzyme gene family and bcl-2 gene family in the rat brain following permanent occlusion of the middle cerebral artery. | Recent investigations have been suggesting that some neuronal subpopulations may die via programmed cell death after focal ischemic injury. To clarify the possible roles of the genes involved in the cell-death program; this study examined the expression of three members of the interleukin-1 beta converting enzyme (Ice) gene family (Ice; Nedd2; and Yama/CPP32) and two members of the bcl-2 gene family (bcl-2 and bcl-x) in the rat brain after permanent occlusion of the middle cerebral artery. Northern blot ana | 8978382 | [
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Expression of interleukin-1 beta converting enzyme gene family and bcl-2 gene family in the rat brain following permanent occlusion of the middle cerebral artery. | lysis revealed a transient induction of Nedd2 mRNA 8 h after the ischemic insult (3.8-fold) and an increase in Yama/CPP32 mRNA 16 to 24 h after the insult (5.8-fold at 24 h); whereas the expression of Ice remained constant. The expression of bcl-2 and bcl-x remained constant after the ischemic insult. Taking into account the key role of the Ice gene family in the execution of programmed cell death; the induction of Ice gene family might play a causative role in apoptotic cell death. | 8978382 | [
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Intravenous infusion of adrenomedullin and increase in regional cerebral blood flow and prevention of ischemic brain injury after middle cerebral artery occlusion in rats. | The intravenous infusion of rat adrenomedullin; at concentrations ranging from 0.1 to 1.0 microgram/kg/min; for 60 min increased the regional cerebral blood flow (rCBF) in a dose-dependent manner in rats. rCBF was measured using a laser Doppler flowmetry device placed on the surface of the parietal cortex. The increase in rCBF induced by 1.0 microgram/kg/min of adrenomedullin was up to 145 +/- 10.8% of controls at 60 min (n = 5; p < 0.001). These concentrations of adrenomedullin did not affect systemic bloo | 8978383 | [
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Intravenous infusion of adrenomedullin and increase in regional cerebral blood flow and prevention of ischemic brain injury after middle cerebral artery occlusion in rats. | d pressure or other physiologic parameters; including pH; PaCO2; PaO2; hemoglobin; and blood glucose. Repeated infusion of 1.0 microgram/kg/min of adrenomedullin at 2-h intervals caused tachyphylaxis (n = 5; p < 0.01). Rat adrenomedullin (1.0 microgram/kg/min) demonstrated a more potent effect than the same dose of human adrenomedullin. The C-terminal fragment of human adrenomedullin (0.5 and 5.0 micrograms/kg/min); adrenomedullin22-52; which did not affect rCBF alone; inhibited the effect of rat adrenomedu | 8978383 | [
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Intravenous infusion of adrenomedullin and increase in regional cerebral blood flow and prevention of ischemic brain injury after middle cerebral artery occlusion in rats. | llin (0.5 microgram/kg/min) as a receptor antagonist in a dose-dependent manner. In a model of middle cerebral artery (MCA) occlusion in spontaneously hypertensive rats; pre- and postinfusion of 1.0 microgram/kg/min of adrenomedullin suppressed the reduction in rCBF following MCA occlusion (control; 29 +/- 15.1%; adrenomedullin group; 45 +/- 14.4%; not significant) and decreased the volume of ischemic brain injury (control; 288 +/- 35 mm3; adrenomedullin group; 232 +/- 35 mm3; p < 0.05). These results sugge | 8978383 | [
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Intravenous infusion of adrenomedullin and increase in regional cerebral blood flow and prevention of ischemic brain injury after middle cerebral artery occlusion in rats. | st that adrenomedullin increases rCBF and prevents ischemic brain injury; partly by increasing the collateral circulation. | 8978383 | [
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Methionine sulfoximine, a glutamine synthetase inhibitor, attenuates increased extracellular potassium activity during acute hyperammonemia. | Hyperammonemia causes glutamine accumulation and astrocyte swelling. Inhibition of glutamine synthesis reduces ammonia-induced edema formation and watery swelling in astrocyte processes. Ordinarily; astrocytes tightly control extracellular K+ activity [K+]e. We tested the hypothesis that acute hyperammonemia interferes with this tight regulation such that [K+]e increases and that inhibition of glutamine synthetase reduces this increase in [K+]e. Ion-sensitive microelectrodes were used to measure [K+]e in pa | 8978385 | [
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Methionine sulfoximine, a glutamine synthetase inhibitor, attenuates increased extracellular potassium activity during acute hyperammonemia. | rietal cortex continuously over a 6-h period in anesthetized rats. After i.v. sodium acetate infusion in eight control rats; plasma ammonia concentration was 33 +/- 26 mumol/L (+/- SD) and [K+]e remained stable at 4.3 +/- 1.6 mmol/L. During ammonium acetate infusion in nine rats; plasma ammonia increased to 594 +/- 124 mumol/L at 2 h and to 628 +/- 135 mumol/L at 6 h. There was a gradual increase in [K+]e from 3.9 +/- 0.7 to 6.8 +/- 2.7 mmol/L at 2 h and 11.8 +/- 6.7 mmol/L at 6 h. In eight rats; L-methioni | 8978385 | [
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Methionine sulfoximine, a glutamine synthetase inhibitor, attenuates increased extracellular potassium activity during acute hyperammonemia. | ne-D;L-sulfoximine (150 mg/kg) was infused 3 h before ammonium acetate infusion to inhibit glutamine synthetase. At 2 and 6 h of ammonium acetate infusion; plasma ammonia concentration was 727 +/- 228 and 845 +/- 326 mumol/L; and [K+]e was 4.5 +/- 1.9 and 6.1 +/- 3.8 mmol/L; respectively. The [K+]e value at 6 h was significantly less than that obtained with ammonium acetate infusion alone but was not different from that obtained with sodium acetate infusion. We conclude that acute hyperammonemia impairs ast | 8978385 | [
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Methionine sulfoximine, a glutamine synthetase inhibitor, attenuates increased extracellular potassium activity during acute hyperammonemia. | rocytic control of [K+]e and that this impairment is linked to glutamine accumulation rather than ammonium ions per se. | 8978385 | [
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Blood glucose concentration does not affect outcome in brain trauma: A 31P MRS study. | Effects of blood glucose concentration on biochemical and neurologic outcome following lateral fluid percussion-induced traumatic injury of moderate severity (2.8 atm) in rats were studied using radioactive phosphorus (31P) magnetic resonance spectroscopy (MRS) and a battery of tests designed to evaluate posttraumatic neurologic motor function. Prior to injury; male Sprague-Dawley rats (n = 18) were randomly assigned to receive either dextrose; 2 ml 50% (wt/vol); zinc insulin (10 IU/kg) or no treatment; thu | 8978386 | [
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Blood glucose concentration does not affect outcome in brain trauma: A 31P MRS study. | s dividing the animals into hyperglycemic; hypoglycemic; and normoglycemic groups; respectively. Animals were then injured; monitored for 4 h by 31P MRS before being allowed to recover; and assessed for posttraumatic motor function. Following brain injury; there was no difference in brain intracellular pH between groups over the 4-h posttraumatic MRS monitoring period. Similarly; intracellular free magnesium; cytosolic phosphorylation potential; and neurologic outcome posttrauma were not significantly diffe | 8978386 | [
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Blood glucose concentration does not affect outcome in brain trauma: A 31P MRS study. | rent between groups. We conclude that; unlike models of ischemia; blood glucose concentration may not be a significant factor affecting outcome in traumatic brain injury. | 8978386 | [
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Reactive astrocytosis from excitotoxic injury in hippocampal organ culture parallels that seen in vivo. | Reactive astrocytes influence not only the severity of brain injury; but also the capacity of brain to reshape itself with learning. Mechanisms responsible for astrogliosis remain unknown but might be best studied in vitro; where improved access and visualization permit application of modern molecular and cellular techniques. We have begun to explore whether gliosis might be studied in hippocampal organotypic cultures (HOTCs); where potential cell-to-cell interactions are preserved and the advantages of an | 8978384 | [
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Reactive astrocytosis from excitotoxic injury in hippocampal organ culture parallels that seen in vivo. | in vitro preparation are still realized. Following HOTC exposure to N-methyl-D-aspartate (NMDA); dose-dependent changes occurred in the optical density (OD) values for the astrocytic immunohistochemical [immunostaining (IS)] markers glial fibrillary acidic protein (GFAP) and vimentin. Exposure of HOTCs to NMDA (10 microM) caused selective death in the CA1 hippocampal region and the dentate gyrus. It also significantly increased GFAP IS and vimentin IS OD values in these regions. Increased GFAP IS and viment | 8978384 | [
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Reactive astrocytosis from excitotoxic injury in hippocampal organ culture parallels that seen in vivo. | in IS OD values were also seen in CA3; a hippocampal region that displayed no cell death. Light microscopic examination revealed hypertrophied GFAP and vimentin IS cells; characteristic of reactive astrocytes. Cellular proliferation; as assessed by proliferating cell nuclear antigen IS; was also significantly increased in all three of these hippocampal regions. In contrast; exposure of HOTCs to a noninjurious level of NMDA (1 microM) caused only minor changes in GFAP IS and vimentin IS OD values but a signi | 8978384 | [
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Reactive astrocytosis from excitotoxic injury in hippocampal organ culture parallels that seen in vivo. | ficantly reduced cellular proliferation in all HOTC regions. These results show that reactive astrocytosis from excitotoxic injury of HOTC parallels changes seen in vivo after global ischemia. Furthermore; since resting astroglia within HOTCs are also similar to their counterparts in vivo; HOTCs may be used to examine mechanisms by which these cells are transformed into reactive species within tissue that resembles intact brain. | 8978384 | [
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Examination of potential mechanisms in the enhancement of cerebral blood flow by hypoglycemia and pharmacological doses of deoxyglucose. | Cerebral blood flow (CBF) rises when the glucose supply to the brain is limited by hypoglycemia or glucose metabolism is inhibited by pharmacological doses of 2-deoxyglucose (DG). The present studies in unanesthetized rats with insulin-induced hypoglycemia show that the increases in CBF; measured with the [14C]iodoantipyrine method; are relatively small until arterial plasma glucose levels fall to 2.5 to 3.0 mM; at which point CBF rises sharply. A direct effect of insulin on CBF was excluded; insulin admini | 8978387 | [
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Examination of potential mechanisms in the enhancement of cerebral blood flow by hypoglycemia and pharmacological doses of deoxyglucose. | stered under euglycemic conditions maintained by glucose injections had no effects on CBF. Insulin administration raised plasma lactate levels and decreased plasma K+ and HCO3- concentrations and arterial pH. These could not; however; be related to the increased CBF because insulin under euglycemic conditions had similar effects without affecting CBF; furthermore; the inhibition of brain glucose metabolism with pharmacological doses (200 mg/kg intravenously) of DG increased CBF; just like insulin hypoglycem | 8978387 | [
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Examination of potential mechanisms in the enhancement of cerebral blood flow by hypoglycemia and pharmacological doses of deoxyglucose. | ia; without altering plasma lactate and K+ levels and arterial blood gas tensions and pH. Nitric oxide also does not appear to mediate the increases in CBF. Chronic blockade of nitric oxide synthase activity by twice daily i.p. injections of NG-nitro-L-arginine methyl ester for 4 days or acutely by a single i.v. injection raised arterial blood pressure and lowered CBF in normoglycemic; hypoglycemic; and DG-treated rats but did not significantly reduce the increases in CBF due to insulin-induced hypoglycemia | 8978387 | [
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Examination of potential mechanisms in the enhancement of cerebral blood flow by hypoglycemia and pharmacological doses of deoxyglucose. | (arterial plasma glucose levels; 2.5-3 mM) or pharmacological doses of deoxyglucose. | 8978387 | [
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A model for the coupling between cerebral blood flow and oxygen metabolism during neural stimulation. | A general mathematical model for the delivery of O2 to the brain is presented; based on the assumptions that all of the brain capillaries are perfused at rest and that all of the oxygen extracted from the capillaries is metabolized. The model predicts that disproportionately large changes in blood flow are required in order to support small changes in the O2 metabolic rate. Interpreted in terms of this model; previous positron emission tomography (PET) studies of the human brain during neural stimulation de | 8978388 | [
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A model for the coupling between cerebral blood flow and oxygen metabolism during neural stimulation. | monstrating that cerebral blood flow (CBF) increases much more than the oxygen metabolic rate are consistent with tight coupling of flow and oxidative metabolism. The model provides a basis for the quantitative interpretation of functional magnetic resonance imaging (fMRI) studies in terms of changes in local CBF. | 8978388 | [
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] |
Cerebral [15O] water clearance in humans determined by positron emission tomography: II. Vascular responses to vibrotactile stimulation. | When used to measure blood flow; water leaves a residue in the vascular bed; which may contribute to the calculation of increased blood flow during functional activation of brain tissue. To assess the magnitude of this contribution with the two-compartment positron emission tomography (PET) method; we mapped the water clearance (K1) of the brain as an index of cerebral blood flow (CBF) and the apparent vascular distribution of nonextracted H2 15O (Vo). The latter map represented mainly the cerebral arterial | 8978389 | [
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Cerebral [15O] water clearance in humans determined by positron emission tomography: II. Vascular responses to vibrotactile stimulation. | and arteriolar volume. We also prepared subtraction maps (delta K1; delta Vo) of the response to vibrotactile stimulation of the fingertips of the right hand of six normal volunteers. Using magnetic resonance (MR) images of all subjects; the data were rendered into Talairach's stereotaxic coordinates and the averaged subtraction images (activation minus baseline) merged with the corresponding averaged MRI image. The delta K1 map revealed the expected response in the primary sensory hand area; the delta Vo | 8978389 | [
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Cerebral [15O] water clearance in humans determined by positron emission tomography: II. Vascular responses to vibrotactile stimulation. | response was located about 13 mm more anteriorly; close to the central fissure; most likely reflecting changes of the arteries feeding the primary sensory hand area. We conclude that cerebral perfusion and cerebrovascular responses to vibrotactile stimulation may occur in disparate locations that can be identified separately by using the two-compartment method. | 8978389 | [
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Analysis of dynamic radioligand displacement or "activation" studies. | We present a simple way of assessing dynamic or time-dependent changes in displacement during single-subject radioligand positron emission tomography (PET) activation studies. The approach is designed to facilitate dynamic activation studies using selective radioligands. These studies are; in principle; capable of characterising functional neurochemistry by analogy with the study of functional neuroanatomy using rCBF activation studies. The proposed approach combines time-dependent compartmental models of t | 8978390 | [
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Analysis of dynamic radioligand displacement or "activation" studies. | racer kinetics and the general linear model used in statistical parametric mapping. This provides for a comprehensive; voxel-based and data-led assessment of regionally specific effects. The statistical model proposed in this paper is predicated on a single-compartment model extended to allow for time-dependent changes in kinetics. We have addressed the sensitivity and specificity of the analysis; as it would be used operationally; by applying the analysis to 11C-Flumazenil dynamic displacement studies. The | 8978390 | [
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Analysis of dynamic radioligand displacement or "activation" studies. | activation used in this demonstration study was a pharmacological (i.v. midazolam) challenge; 30 min after administration of the tracer. We were able to demonstrate; and make statistical inferences about; regional increases in k2 (or decreases in the volume of distribution) in prefrontal and other cortical areas. | 8978390 | [
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Nitric oxide of neuronal origin is involved in cerebral blood flow increase during seizures induced by kainate. | In a previous study; we reported that the sustained increase in CBF concomitant with seizures induced by kainate is mainly due to the potent vasodilator nitric oxide (NO). However; the production site of NO acting at cerebral vessels was undetermined. In the present study; we investigated whether NO responsible for the cerebral vasodilation is of either neuronal or endothelial origin. We used a putative selective inhibitor of neuronal NO synthase; 7-nitro indazole (7-NI). CBF was measured continuously in pa | 8978391 | [
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Nitric oxide of neuronal origin is involved in cerebral blood flow increase during seizures induced by kainate. | rietal cortex by means of laser Doppler flowmetry in awake rats. Systemic variables and electroencephalograms were monitored. Kainate (10 mg/kg i.p.) was given to rats previously treated with saline (n = 8) or 7-NI (25 mg/kg i.p.; n = 8) or L-arginine (300 mg/kg i.p.; n = 8) followed 30 min later by 7-NI (25 mg/kg i.p.). Under basal conditions; 7-NI decreased CBF by 27% without modifying the mean arterial blood pressure. Under kainate; 7-NI prevented significant increases in CBF throughout the seizures desp | 8978391 | [
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Nitric oxide of neuronal origin is involved in cerebral blood flow increase during seizures induced by kainate. | ite sustained paroxysmal electrical activity. L-arginine; the substrate in the production of NO; prevented any decrease in CBF under 7-NI in basal conditions and partially; but nonsignificantly; reversed the cerebrovascular influence of 7-NI during seizures. In a separate group of rats (n = 6); inhibition of cortical NO synthase activity by 7-NI was assayed at 73%. The present results show that neurons are the source of NO responsible for the cerebrovascular response to seizure activity after kainate system | 8978391 | [
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Nitric oxide of neuronal origin is involved in cerebral blood flow increase during seizures induced by kainate. | ic injection. | 8978391 | [
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Role of nitric oxide, cyclic nucleotides, and the activation of ATP-sensitive K+ channels in the contribution of adenosine to hypoxia-induced pial artery dilation. | Previously; it had been observed that nitric oxide (NO) contributes to hypoxia-induced pial artery dilation in the newborn pig. Additionally; it was also noted that activation of ATP-sensitive K+ channels (KATP) contribute to cGMP-mediated as well as to hypoxia-induced pial dilation. Although somewhat controversial; adenosine is also thought to contribute to hypoxic cerebrovasodilation. The present study was designed to investigate the role of NO; cyclic nucleotides; and activation of KATP channels in the e | 8978392 | [
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Role of nitric oxide, cyclic nucleotides, and the activation of ATP-sensitive K+ channels in the contribution of adenosine to hypoxia-induced pial artery dilation. | licitation of adenosine's vascular response and relate these mechanisms to the contribution of adenosine to hypoxia-induced pial artery dilation. The closed cranial window technique was used to measure pial diameter in newborn pigs. Hypoxia-induced artery dilation was attenuated during moderate (PaO2 approximately 35 mm Hg) and severe hypoxia (PaO2 approximately 25 mm Hg) by the adenosine receptor antagonist 8-phenyltheophylline (8-PT) (10(-5) M) (26 +/- 2 vs. 19 +/- 2 and 34 +/- 2 vs. 22 +/- 2% for moderat | 8978392 | [
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Role of nitric oxide, cyclic nucleotides, and the activation of ATP-sensitive K+ channels in the contribution of adenosine to hypoxia-induced pial artery dilation. | e and severe hypoxia in the absence vs. presence of 8-PT; respectively). This concentration of 8-PT blocked pial dilation in response to adenosine (8 +/- 2; 16 +/- 2; and 23 +/- 2 vs. 2 +/- 2; 4 +/- 2; and 6 +/- 2% for 10(-8); 10(-6); and 10(-4) M adenosine before and after 8-PT; respectively). Similar data were also obtained using adenosine deaminase as a probe for the role of adenosine in hypoxic pial dilation. Adenosine-induced dilation was associated with increased CSF cGMP concentration (390 +/- 11 and | 8978392 | [
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Role of nitric oxide, cyclic nucleotides, and the activation of ATP-sensitive K+ channels in the contribution of adenosine to hypoxia-induced pial artery dilation. | 811 +/- 119 fmol/ml for control and 10(-4) M adenosine; respectively). The NO synthase inhibitor; L-NNA; and the cGMP antagonist; Rp 8-bromo cGMPs; blunted adenosine-induced pial dilation (8 +/- 1; 14 +/- 1; and 20 +/- 3 vs. 3 +/- 1; 5 +/- 1; and 8 +/- 3% for 10(-8); 10(-6); and 10(-4) M adenosine before and after L-NNA; respectively). Adenosine dilation was also blunted by glibenclamide; a KATP antagonist (9 +/- 2; 14 +/- 3; 21 +/- 4 vs. 4 +/- 1; 8 +/- 2; and 11 +/- 2% for 10(-8); 10(-6); and 10(-4) M ade | 8978392 | [
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Role of nitric oxide, cyclic nucleotides, and the activation of ATP-sensitive K+ channels in the contribution of adenosine to hypoxia-induced pial artery dilation. | nosine before and after glibenclamide; respectively). Finally; it was also observed that adenosine-induced dilation was associated with increased CSF cAMP concentration and the cAMP antagonist; Rp 8-bromo cAMPs; blunted adenosine pial dilation. These data show that adenosine contributes to hypoxic pial dilation. These data also show that NO; cGMP; cAMP; and activation of KATP channels all contribute to adenosine induced pial dilation. Finally; these data suggest that adenosine contributes to hypoxia-induced | 8978392 | [
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Developmental and regional differences in nitric oxide synthase activity and blood flow in the sheep brain. | Nitric oxide synthase (NOS) participates in the regulation of cerebral blood flow and neurotransmitter release and as a second messenger of glutamatergic and cholinergic systems. Developmental differences in NOS activity have been described in the rat; but not in a species with longer gestation and a larger; lobulated brain at birth. We assayed NOS activity by conversion of [14C]L-arginine to [14C]L-citrulline in 50-mg tissue samples from eight brain regions in sheep at 70; 92; 110; and 135 days gestation ( | 8978393 | [
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Developmental and regional differences in nitric oxide synthase activity and blood flow in the sheep brain. | term = 145 days); newborns (< 7 days); and adults to test the hypothesis that NOS activity in the brain is developmentally regulated from midgestation through adulthood and matures along the neuroaxis in parallel with the known development of cerebral blood flow and neuronal activity. Three patterns of maturation of NOS activity were evident: increasing to or exceeding adult levels before 70 days gestation in the thalamus; cerebellum; and medulla; increasing to adult levels between 70 and 92 days in the hip | 8978393 | [
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Developmental and regional differences in nitric oxide synthase activity and blood flow in the sheep brain. | pocampus; and increasing to adult levels after 92 days in the cortex and caudate. Additionally; there were regional differences in cortical NOS activity: at 70 and 92 days of gestation; frontal cortex NOS activity was greater than parietal or occipital activity; and at 135 days gestation and in the newborn and adult; cortical and caudate activity exceeded that in most of the more caudal regions. The up to fourfold increase in regional cortical NOS activity between 92 and 135 days gestation was associated wi | 8978393 | [
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Developmental and regional differences in nitric oxide synthase activity and blood flow in the sheep brain. | th twofold increases in cerebral blood flow and oxygen consumption during this period. Inhibition of NOS activity with administration of 60 mg/kg of NG-nitro-L-arginine methylester (L-NAME) resulted in 27% and 25% reductions in cerebral blood flow at 93 and 133 days gestation. While the associated increases in NOS activity with increases in CBF and CMRO2 do not appear causative; at various points in gestation the development of NOS activity may participate in the development of mature patterns of cerebral b | 8978393 | [
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Positron emission tomography for quantitative determination of glucose metabolism in normal and ischemic brains in rats: an insoluble problem by the Harderian glands. | To examine the reliability of quantitative positron emission tomography studies in the rat (Rat-PET); we assessed the influence of radioactivity accumulated in the Harderian glands on PET CMRglc determination. We measured CMRglc by PET and ex vivo dissection methods by using 2-[18F]fluoro-2-deoxy-D-glucose in rats with and without focal brain ischemia. The CMRglc values obtained by PET; after correcting with recovery coefficients; were higher than those measured by the ex vivo method at rostral slices; and | 8978394 | [
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Positron emission tomography for quantitative determination of glucose metabolism in normal and ischemic brains in rats: an insoluble problem by the Harderian glands. | reduction of the CMRglc in the ischemic brain was not demonstrated by PET in the frontal cortex. The radioactivity accumulated in the Harderian glands prevents the quantitative determination of CMRglc using Rat-PET. | 8978394 | [
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Society for the Study of Fertility and Dutch-Flemish Fertility Society joint winter meeting. Ghent, 1996. abstracts. | nan | 8978395 | [
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Androgen-induced redox changes in prostate cancer cells: what are causes and effects? | nan | 8978396 | [
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Indoor radon exposure and lung cancer: risky or not?--all over again. | nan | 8978397 | [
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Ashkenazim not alone: other ethnic groups have breast cancer gene mutations, too. | nan | 8978398 | [
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Chronic care crisis: escalating cost and incidence. | nan | 8978403 | [
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Gene therapy for cancer: what have we done and where are we going? | Gene-based therapies for cancer in clinical trials include strategies that involve augmentation of immunotherapeutic and chemotherapeutic approaches. These strategies include ex vivo and in vivo cytokine gene transfer; drug sensitization with genes for prodrug delivery; and the use of drug-resistance genes for bone marrow protection from high-dose chemotherapy. Inactivation of oncogene expression and gene replacement for tumor suppressor genes are among the strategies for targeting the underlying genetic le | 8978404 | [
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Gene therapy for cancer: what have we done and where are we going? | sions in the cancer cell. A review of clinical trial results to date; primarily in patients with very advanced cancers refractory to conventional treatments; indicates that these treatments can mediate tumor regression with acceptably low toxicity. Vector development remains a critical area for future research. Important areas for future research include modifying viral vectors to reduce toxicity and immunogenicity; increasing the transduction efficiency of nonviral vectors; enhancing vector targeting and s | 8978404 | [
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Gene therapy for cancer: what have we done and where are we going? | pecificity; regulating gene expression; and identifying synergies between gene-based agents and other cancer therapeutics. | 8978404 | [
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Prooxidant-antioxidant shift induced by androgen treatment of human prostate carcinoma cells. | Prostate cancer is a disease associated with aging. Also commonly associated with increasing age is a shift in the prooxidant-antioxidant balance of many tissues toward a more oxidative state; i.e.; increased oxidative stress. We hypothesize that androgen exposure; which has long been associated with the development of prostate cancer; may be a means by which the prooxidant-antioxidant balance of prostate cells is altered.Using established prostate carcinoma cell lines; we studied the effect of androgens on | 8978405 | [
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