Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Much of the research related to cardiopulmonary bypass in recent years has been directed toward defining the changes in plasma and blood cells during bypass. In this review, recent information is reexamined for six areas of current interest. These areas are complement activation, immune response, anaphylactic reactions, coagulation, and cerebral dysfunction. Complement may be activated by either the classical or alternate pathway during cardiopulmonary bypass and protamine administration. Membrane oxygenators appear to diminish the degree of complement activation. Complement is a major factor in the whole body inflammatory response; which often accompanies cardiopulmonary bypass. A product of complement activation, C5a- desArg, causes activation and aggregation of granulocytes. Other products of complement activation lead to lysis of blood cells including granulocytes and red cells. Bubble oxygenators appear to have a distinct disadvantage compared to membrane oxygenators regarding infection. Airborne microorganisms are more likely to be entrained into circulating blood with bubble oxygenators than with membrane oxygenators. Bubble oxygenators cause a greater decrease in leukocyte number and function than membrane oxygenators. Anaphylactic reactions have been associated with use of antibiotics, blood products, protamine, and volume expanders during cardiopulmonary bypass. Protamine reactions may be on an immunological basis or due to direct toxicity of the drug. Free radicals including superoxide, hydrogen peroxide, and the hydroxyl radical may be generated during cardiopulmonary bypass and reperfusion. Free radical scavengers including; vitamin E, coenzyme Q, vitamin C, mannitol, and glutathione have been studied. The avoidance of blood transfusion because of risk of transmitted infection including AIDS has become a major goal in cardiac surgery. Factors that correlate with increased transfusion requirement include low hematocrit, female gender, increased age, small body size, low ejection fraction, reoperation, and emergency operation. Heparin resistance due to antithrombin III deficiency is being recognized more commonly. Antithrombin III deficiency may be corrected with fresh frozen plasma. Patients with heparin induced thrombocytopenia may be difficult to manage. Several management protocols are suggested. The most straightforward appears to be the use of aspirin preoperatively and platelet transfusions postoperatively. The incidence of cerebral dysfunction after cardiopulmonary bypass depends on the sensitivity of the test or indicator used. Perioperative stroke is associated with intrinsic cerebrovascular disease and atherosclerosis of the ascending aorta. Retinal angiograms during cardiopulmonary bypass show that microemboli are very common. Cerebroplegia has been shown to extend the period of safe circulatory arrest in animals. Much of the new knowledge concerning cardiopulmonary bypass is the result of close collaboration between cardiac surgeons and nonsurgical scientists.
 ...
PMID:Pathophysiology of cardiopulmonary bypass: current issues. 213 41

A series of 12 patients with cerebellar infarcts diagnosed by computerized tomography are reviewed. The clinical features of cerebellar infarctions cover a wide spectrum, mimicking symptoms and signs from an acute labyrinthitis to a rapidly expanding posterior fossa mass lesion with brain stem and cerebral dysfunction. Two patients were asymptomatic and three showed signs of cerebellar dysfunction only. Three patients had evidence of brain stem dysfunction with cranial nerve palsies accompanying the cerebellar deficit. Two presented a pseudovestibular form with sudden onset of nausea, vomiting, rotary dizziness and ataxia. A pseudotumoral form with intracranial hypertension was found in two cases, in which softening tissue acts as a rapidly expanding posterior foss mass lesion. It is difficult to identify the exact artery involved in a cerebellar infarct because of the collateral circulation and connections between the three major arteries. Atherosclerosis and general decrease in blood flow can be regarded as the most likely factors precipitating focal cerebellar infarction. Surveillance is necessary during the first days with anti-edematous therapy. Rapid deterioration of consciousness should be considered a sign of increasing intracranial pressure progressing with the development of hydrocephalus. If necessary, surgical decompression by external drainage or by direct access to the posterior fossa can be carried out.
 ...
PMID:[Cerebellar infarct. Clinical presentation and x-ray computed tomography of the brain]. 394 88

We studied the relationship between postoperative brain dysfunction and the state of atherosclerosis in the patients of open heart surgery, by analyzing the intraoperative cerebral oxygen saturation (rSO2) and the CO2 reaction. The subjects were 143 patients with average age of 64 years. The patients with low postoperative Hasegawa's Dementia Score were categorized as brain dysfunction group. rSO2 was utilized to monitor cerebral blood flow, and AI and stiffness parameter beta were used for evaluation of systemic atherosclerosis. Postoperative brain dysfunction was confirmed in 12%. There were significantly high values of AI and beta as well as low rSO2, in elder age with low cardiac index and no correlation was observed between rSO2 and PaCO2 in the brain dysfunction group. The results suggested that a higher level of atherosclerosis is associated with the postoperative brain dysfunction with resultant decreased cerebral blood flow and disturbed reaction to CO2 of cerebral blood vessels.
 ...
PMID:[Association of postoperative brain dysfunction and atherosclerosis, intraoperative rSO2 and CO2 reaction in open heart surgery]. 872 Nov 25

The various mechanisms that may explain the association between brain dysfunction and the pathogenesis of metabolic syndrome (MS) leading to cardiovascular disease and type 2 diabetes have been reviewed. A Medline search was conducted until September 2003, and articles published in various national and international journals were reviewed. Experts working in the field were also consulted. Compelling evidence was found that saturated and total fat and low dietary n-3 fatty acids and other long-chain polyunsaturated fatty acids (PUFAs) in conjunction with sedentary behavior and mental stress combined with various personality traits can enhance sympathetic activity and increase the secretion of catecholamine, cortisol and serotonin, all of which appear to be underlying mechanisms involved in MS. Excess secretion of these neurotransmitters in conjunction with underlying long-chain PUFA deficiency may damage the neurons in the ventromedial hypothalamus and insulin receptors in the brain, in particular during fetal life, infancy and childhood, and lead to their dysfunction. Since 30-50% of the fatty acids in the brain are long-chain PUFAs, especially omega-3 fatty acids which are incorporated in the cell membrane phospholipids, it is possible that their supplementation may have a protective effect. Omega-3 fatty acids are also known to enhance parasympathetic activity and to increase the secretion of anti-inflammatory cytokines as well as acetylecholine in the hippocampus. It is possible that a marginal deficiency of long-chain PUFAs, especially n-3 fatty acids, due to poor dietary intake during the critical period of brain growth and development in the fetus, and later in the infant and also possibly in the child, adolescent and adult may enhance the release of tumor necrosis factor-alpha (TNF-alpha) interleukin (IL)-1, 2 and 6 and cause neuronal dysfunction. Experimental studies indicate that ventromedial hypothalamic lesions in rats induce hyperphagia, resulting in glucose intolerance and insulin resistance. Treatment with neuropeptide Y abolished hyperphagia and ob mRNA (leptin mRNA) in this animal model. Long-term infusion of norepinephrine and serotonin into the ventromedial hypothalamus impaired pancreatic islet function inasmuch as ventromedial hypothalamic norepinephrine and serotonin levels were elevated in hyperinsulinemic and insulin-resistant animals. Treatment with insulin was associated with restoration of hypothalamic neurotransmitter abnormalities, indicating that ventromedial hypothalamus dysfunction can impair pancreatic beta cells resulting in metabolic abnormalities consistent with MS. Treatment with omega-3 fatty acids, beta blockers, ACE inhibitors, estrogen, and meditation may have a beneficial effect on insulin receptors and ventromedial hypothalamic dysfunction. However, no definite or precise insight into the pathophysiological link between MS, brain function and nutrition is available. Despite this, epidemiological studies and intervention trials indicate that treatment with n-3 fatty acids may be adopted in clinical practice and used to direct therapy for prevention of type 2 diabetes, hypertension, coronary artery disease (CAD), and atherosclerosis, thereby indicating that MS may also respond to this treatment.
 ...
PMID:Can brain dysfunction be a predisposing factor for metabolic syndrome? 1575 41

We have evaluated the effect of diabetes-mimicking conditions on the inhibition of kynurenic acid (KYNA) production exerted by mitochondrial toxins: 3-nitropropionic acid (3-NPA) and aminooxyacetic acid (AOAA), by endogenous agonists of glutamate receptors: L-glutamate and L-cysteine sulfinate, and by a risk factor of atherosclerosis, D,L-homocysteine. Hyperglycemia (30 mM; 2 h) itself did not influence KYNA synthesis in brain cortical slices. However, it significantly enhanced the inhibitory effects of 3-NPA, AOAA and D,L-homocysteine, but not of L-glutamate and L-cysteine sulfinate, on KYNA production. Their IC(50) values were lowered from 5.8 (4.5-7.4) to 3.7 (3.1-4.5) mM (p < 0.01), from 11.6 (8.6-15.5) to 7.1 (4.9-10.3) microM (p < 0.05), and from 4.5 (3.5-5.8) to 2.4 (1.8-3.2) mM (p < 0.01), respectively. The obtained data suggest that during hyperglycemia, the mitochondrial impairment and high levels of D,L-homocysteine evoke stronger inhibition of KYNAsynthesis what may further exacerbate brain dysfunction and play a role in central complications of diabetes.
 ...
PMID:Hyperglycemia enhances the inhibitory effect of mitochondrial toxins and D,L-homocysteine on the brain production of kynurenic acid. 1765 26

Polyphenols have an important protective role against a number of diseases, such as atherosclerosis, brain dysfunction, stroke, cardiovascular diseases, and cancer. Cardiovascular diseases are the number one cause of death worldwide: more people die annually from cardiovascular diseases than from any other cause. The most important behavioural risk factors of heart disease and stroke are unhealthy diet, physical inactivity, tobacco use, and excess alcohol intake. The dietary consumption of polyphenols has shown to be inversely associated with morbidity and mortality by cardio- and cerebrovascular diseases. It is well-known that the protective effects of polyphenols in vivo depend on the grade how they are extracted from food and on their intestinal absorption, metabolism, and biological action with target tissues. The aim of this review was to summarise the relation between polyphenols of different plant sources and stroke in human intervention studies, animal models, and in vitro studies.
 ...
PMID:Dietary Polyphenols in the Prevention of Stroke. 2920 49