Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During the late 1980s and early 1990s, much research effort in the pharmaceutical industry was focused on the development of novel systems for sustained delivery of effective, but intrinsically short-acting, antihypertensive agents. This advance was motivated by a desire both to improve trough/peak ratios (as suggested by the US Food and Drug Administration [FDA]) and also to protect the proprietary patient life for older agents that would otherwise be susceptible to generic substitution. Additional benefits of such sustained-release systems include: improved side-effect profiles, shorter time from development to regulatory approval (because of the already established safety record of the immediate-release compound), improved compliance with medication, and reduced administrative cost. The latter two are presumably related to the fact that patients generally have to use fewer doses of sustained-release than immediate-release preparations. Disadvantages include: generally higher per-dose cost (which includes a licensing fee for the patented delivery system), altered efficacy and potential problems in patients with abnormal absorptive surfaces (gut or skin), and altgered first-pass metabolism rates (compared with immediate-release preparations). Some of the novel drug delivery systems that have already received FDA approval include: alginate matrix, Geomatrix, several formulations of pellet-based systems, several transdermal systems, and the Gastrointestinal therapeutic system (GITS), which releases the pharmacologically active agent at a predictable rate. A novel variant of this last system has been developed, based on the idea that the peak serum concentration of antihypertensive medication will occur just before or at the time of the greatest change in blood pressure (ie, the few hours around awakening). Data are now being gathered to convince authorities that this theoretically advantageous delivery system will be as effective in reducing rates of cardiovascular death, nonfatal stroke, or myocardial infarction as diuretics or beta blockers.
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PMID:Drug delivery systems for antihypertensive agents. 1023 92

Total gut lavage is a widely recommended method in preparation for colonoscopy and there are almost no reports of severe complications in the literature. Application of orthograde lavage by a nasogastric tube may be necessary in disorientated patients, assisted by slight medical sedation, if necessary. Despite absolutely correct appliance of the method, a case of severe aspiration with subsequent hypoxemia and stroke in a senile female patient, suffering from a common hiatal hernia, is described.
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PMID:Aspiration: a possible severe complication in colonoscopy preparation of elderly people by orthograde intestine lavage. 1034 44

A 69 year old man is described with a 12 year history of intermittent syncope associated with ingesting solid food, mainly after having fasted. He was taking enalapril, propranolol, bendrofluazide (bendroflumethiazide), omeprazole, finasteride, and aspirin. Detailed investigations, including gastrointestinal evaluation, measurement of various gut hormones, and autonomic testing, indicated no abnormality. A liquid meal, performed before fasting, failed to elicit an episode. However, a solid meal after an overnight fast provoked near-syncope. Continuous non-invasive haemodynamic monitoring (with a Portapres II) indicated a short lived rise in blood pressure and heart rate, followed by severe hypotension, a fall in stroke volume and cardiac output, and then bradycardia. This favoured an initial increase in sympathetic activity, followed by vasodepression due to sympathetic withdrawal or activation of humoral vasodilatatory mechanisms, with bradycardia secondary to impaired cardiac filling. Withdrawal of enalapril abolished the episodes. The unusual nature of this case, in which haemodynamic recordings continuously were made during and after swallow syncope, induced soon after food ingestion, is discussed.
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PMID:Continuous haemodynamic monitoring in an unusual case of swallow induced syncope. 1040 95

The passage of a barium meal (15 % by mass) was followed through the digestive system of the blue crab Callinectes sapidus by flash-freezing crabs at set intervals, followed by radiography of specimens. Food moved from the oesophagus into the stomach region within 15 min. After 1-2 h, food was visible in the midgut, at 6 h it had reached the hindgut, and material was still present in the stomach at this time. The stomach was emptied between 8 and 10 h after feeding, and the entire digestive system was cleared of material after 18 h. A pulsed-Doppler flowmeter was used to monitor cardiac variables and arterial haemolymph flows during a 4 h control and 24 h postprandial period. Heart rate increased immediately upon food detection and remained elevated for 16-18 h after food ingestion. There was no significant change in stroke volume of the heart, and total cardiac output increased significantly and remained elevated above pre-feeding levels for 24 h after feeding. There was no change in haemolymph flow through the anterior or posterior aorta, but flow increased in the sternal, anterolateral and hepatic arteries. These changes in haemolymph flow reflected the use of the chelae and mouthparts in feeding, contraction of the visceral muscle surrounding the gut system and mobilisation of enzymes from the hepatopancreas. There was also a postprandial increase in the rate of oxygen uptake (apparent specific dynamic action). The rate of oxygen consumption (M(dot)(O2)) reached maximal levels 4 h after feeding and decreased slowly thereafter, reflecting the increased use of oxygen in digestion and absorption.
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PMID:Integrated physiological responses to feeding in the blue crab Callinectes sapidus. 1060 45

Obesity is one of the pathologies with ever-increasing prevalence in modern societies. Its occurrence is strongly associated with increased risk of developing diabetes mellitus, atherosclerosis, hypertension, stroke, heart and respiratory failure, breast, prostate and gut cancer, gall stones, arthropathy. Obesity is common in Polish population. Obesity treatment is difficult and frustrating. It consists of several parts like diet, increased physical activity, lifestyle changes, drug therapy and surgery. However, obesity treatment is very often a failure, mostly because of discouraging long-term results and the necessity of intensive patient's involvement in the therapy. For many patients and doctors weight-decreasing agents look promising. The groups of anti-obesity drugs are presented in the article, with special reference to serotoninergic agents and intestinal lipase inhibitors. The prospects for new anti-obesity agents are discussed. Nevertheless, despite intensive research on obesity, we are still waiting for the development of an effective and safe drugs helping lose weight.
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PMID:[The role of pharmacotherapy for treatment of obesity in adults]. 1120 19

We explored the effects of the nucleoside transport inhibitor draflazine on regional blood flow, O2 extraction capabilities, and tumor necrosis factor (TNF) release in acute endotoxic shock. Fourteen anesthetized and mechanically ventilated dogs received 2 mg/kg of Escherichia coli endotoxin and were divided into two groups. Seven dogs received 0.1 mg/kg of draflazine 30 min before endotoxin, and 7 dogs served as a control group. Draflazine decreased arterial pressure without influencing cardiac index. Mesenteric and portal blood flow and ileum mucosal perfusion increased, but renal blood flow dramatically decreased. After endotoxemia, the draflazine-treated dogs had a lesser fall in cardiac index, filling pressures, and left ventricular stroke work index, and a lesser increase in pulmonary vascular resistance. After fluid resuscitation, they had a consistently lower renal blood flow and ileum mucosal perfusion, but a higher mixed venous and hepatic oxygen saturation and arterial pH than the control group. When cardiac index was reduced by tamponade to study the O2 extraction capabilities, renal blood flow and ileum mucosal perfusion remained lower in the draflazine group. Draflazine did not influence whole-body O2 extraction capabilities, but it delayed the occurrence of liver O2 supply dependency as indicated by a significantly lower liver DO2crit (27.7 +/- 3.9 vs. 43.3 +/- 10.8 mL/min) and a higher O2ERcrit (62.7 +/- 9.5 vs. 42.5 +/- 7.1%) than controls (both P< 0.05). On the other hand, draflazine increased intestinal DO2crit (42.4 +/- 15.4 vs. 27.7 +/- 6.5 mL/min, P < 0.05) compared to the control group. TNF levels remained higher in the draflazine group than in the control group, particularly 3 and 4 h after endotoxin administration. We conclude that nucleoside transport inhibition with draflazine does not alter global and hepatosplanchnic hemodynamics but may decrease gut mucosal perfusion and renal blood flow. However, this intervention can improve liver O2 extraction capabilities in acute endotoxic shock.
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PMID:Effects of nucleoside transport inhibition on hepatosplanchnic perfusion, oxygen extraction capabilities, and TNF release during acute endotoxic shock. 1133 98

Pathologic data from the gastrointestinal tract in heat-stroke victims, although documented, are confusing. The object of this study was to document the gastrointestinal changes observed during induced total body hyperthermia (42 degrees C) followed by cooling. An established heat-stroke model was used in a university animal laboratory. Group A underwent immersion hyperthermia for 1 hour, followed by cooling to normothermia. Group B underwent hyperthermia to cardiac arrest, followed by resuscitation plus cooling to normothermia. The postmortem findings in the gastrointestinal tract were evaluated. In group A, several hours after return to normothermia and stable vital signs, delayed secondary deterioration with massive gastrointestinal bleeding occurred. The postmortem findings revealed bleeding into the whole intestine and serosanguineous fluid in the peritoneal cavity. In group B, an adynamic gut was observed after 165 +/- 21 minutes (range 125-174) of heating when mean arterial pressure (MAP) decreased to 38 +/- 21 mm Hg (range 30-70). Cardiac arrest occurred at 178 +/- 26 minutes (range 140-208) of immersion. Eight monkeys could be resuscitated to spontaneous circulation with return of normal gut motility, then they rearrested at 158 +/- 68 minutes (range 45-228). The postmortem findings resembled those in group A. The Postmortem findings in the four monkeys in which restoration of spontaneous circulation failed, revealed only some intestinal wall edema and occasional petechial hemorrhages. It is concluded that after a hyperthermic event, tissue injury continues to develop. The pathologic findings are related to the time lapse between hyperthermia, cooling, and death. The similarity to the descriptions of septic shock, multiple organ failure, and the gut reperfusion syndrome is striking. An immunologic response as a mechanism for all these syndromes is discussed.
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PMID:The role of the gut in the pathogenesis of death due to hyperthermia. 1144 54

Adrenomedullin (AM), a potent vasodilatory peptide, has recently been reported to be involved in the altered cardiovascular responses under various pathophysiological conditions. Although the increase in plasma AM levels is associated with upregulation of AM gene expression in various tissues, it remains unknown whether the gut is an important source of AM release under such conditions. To determine this, adult male rats were subjected to sepsis by cecal ligation and puncture (CLP) followed by fluid resuscitation. Systemic and portal blood samples were collected simultaneously at 10 and 20 h after CLP or sham operation. A portion of the jejunum was also harvested. Plasma and tissue levels of AM were then determined by RIA. The localization of AM in the intestinal tissue was examined using immunohistochemistry. In an additional group of normal rats, synthetic rat AM (8.5 microg/kg body wt) was infused for 15 min at a constant rate via the portal vein (which produces a similar level of AM as observed during sepsis). Cardiac output, stroke volume, total peripheral resistance, and microvascular blood flow in various organs were determined before and 30 min after AM administration. The results indicate that AM levels in portal blood were significantly higher than in systemic blood at 10 and 20 h after CLP. Intestinal AM was also markedly elevated. Immunohistochemical visualization shows that AM immunostainings were localized in the mucosa, submucosa, and intestinal nerve fibers, and they were increased at 10-20 h post-CLP. Because AM-immunopositive nerve fibers increase in the gut during sepsis, a nerve pathway may be involved in the regulation of vascular reactivity by this peptide. Moreover, intraportal administration of AM increased cardiac output, stroke volume, and microvascular blood flow in the liver, kidney, small intestine, and spleen. In contrast, total peripheral resistance was significantly reduced. Thus the gut plays an important role in increasing the levels of circulating AM during the progression of sepsis. Gut-derived AM appears to be a major factor in initiating the hyperdynamic response after the onset of sepsis.
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PMID:The small intestine is an important source of adrenomedullin release during polymicrobial sepsis. 1144 71

Oral tolerance is a long recognized method to induce peripheral immune tolerance. Oral tolerance has been used successfully to treat animal models of autoimmune diseases and is being tested in human diseases. Low doses of oral antigen induce active suppression, whereas high doses induce clonal anergy and deletion. Oral antigen preferentially generates a Th2(IL-4/IL-10)- or a Th3(TGF-beta)-type response. Th3-type cells are a unique T-cell subset which primarily secrete TGF-beta, provide help for IgA and have suppressive properties for Th1 and other immune cells. Th3-type cells appear distinct from the Th2 cells as CD4(+) TGF-beta-secreting cells with suppressive properties in the gut have been generated from IL-4-deficient animals. In vitro differentiation of Th3-type cells from Th0 precursors from TCR transgenic mice is enhanced by culture with TGF-beta, IL-4, IL-10 and anti-IL-12. Because regulatory T cells generated by oral antigen are triggered in an antigen-specific fashion but suppress in an antigen-nonspecific fashion, they mediate bystander suppression when they encounter the fed autoantigen at the target organ. Thus, mucosal tolerance can be used to treat inflammatory processes that are not autoimmune in nature. Mucosal antigen has also been used to treat animal models of stroke and of Alzheimer's disease. Induction of low-dose oral tolerance is enhanced by oral administration of IL-4 and IL-10. Coupling antigen to CTB or administration of Flt-3 ligand enhances oral tolerance. Anti-B7.2 but not anti-B7.1 blocks low-dose, but not high-dose oral tolerance. High-dose oral tolerance is blocked by anti-CTLA-4. CD25(+) CD4(+) regulatory T-cell function also appears to be related to TFG-beta.
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PMID:Oral tolerance: immune mechanisms and the generation of Th3-type TGF-beta-secreting regulatory cells. 1156 43

Changes of circulatory parameters in splanchnic territory lead to gut ischemia in an acute or chronic form (postprandial abdominal stroke). The implicated factors in intestinal ischemia are the timing and kind of onset, countercurrent vascularization and the eventuality of anastomotic subsystems for becoming hypertrophic. Superior mesenteric artery (SMA) is the "key" blood vessel implicated in the production of chronic intestinal ischemia, the atherosclerotic lesion being localized more frequent near SMA's ostium or even at ostium itself. Nonoclusif ischemia is induced by another stimulus that provokes mesenteric vasoconstriction, status that affects more the antimesenteric intestinal border, with a larger expansion at mucosa level. The most reseed diagnostic methods are selective angiographies and ultrasound examination. Usually chronic intestinal ischemia is clinically asymptomatic and becomes clinical evident just in the presence of an acute superposed factor or when at least two digestive arteries are affected. Revascularization methods are different, based on the type, mechanism and site of obstruction, each with its advantages and disadvantages. The most used method is retrograde aortomesenteric by-pass, at infrarenal aortic level (that is more accessible than the supraceliac aorta) and SMA reimplantation.
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PMID:[Anatomic and physiopathologic basis for the diagnosis and treatment of intestinal ischemia]. 1209 26


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