Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The immune maladaptation hypothesis of preeclampsia is concordant with cytokine-mediated oxidative stress, chronology of endothelial activation, lipid changes, adverse effect of changing partners, and the protective effect of sperm exposure. Genetic factors may involve underlying hereditary thrombophilic disorders and hyperhomocysteinemia, essential hypertension and/or obesity, or control of the Th1/Th2 balance and thus affect the maternal response against fetal antigens. Placental ischemia and increased syncytiotrophoblast deportation are probably end-stage disease phenomena.
 ...
PMID:The immunology of preeclampsia. 1010 68

Internists are frequently asked to do preoperative consultations and to manage perioperative complications. Realistic goals are to identify patient factors that increase the risk of surgery, to quantify this risk in order to make decisions about the appropriateness of and timing of the surgery, to provide recommendations on how to minimize the risk, to identify and manage coexisting medical conditions and their associated medication requirements, to monitor the patient for perioperative problems, and to make recommendations to deal with these problems when they occur. With few exceptions, nonselective imaging and laboratory screening tests have repeatedly been shown to be of little value when the history and physical do not suggest a problem. The risk associated with the planned surgery can be estimated, with the most common serious complications being cardiac events. Updated versions of Goldman's risk indices are particularly helpful for this. Clinical variables are optimally combined with selective stress testing to discern which patients will benefit from preoperative revascularization. This has been studied best in the setting of vascular surgery. A critical guiding principle is that the value of revascularization must be judged in terms of long term gains rather than just immediate perioperative benefit. Other interventions include the selective use of beta blockers, adequate analgesia for all, control of hypertension, and appropriate volume management, especially in the settings of preexisting CHF or valvular disease. It must also be recognized that perioperative ischemia and CHF often present atypically. An approach that combines aspects of both the ACC/AHA and the ACP guidelines seems optimal. A variety of noncardiac issues must also be addressed. Postoperative pulmonary complications are common, especially with preexisting pulmonary disease, thoracic and upper abdominal surgery, and obesity. PFTs and ABGs are indicated in selected patients. Stopping smoking, incentive spirometry, and selective use of bronchodilators and antibiotics are helpful. Patients with rheumatologic diseases have specific concerns based on systemic manifestations of disease including anemia, thrombocytopenia, pulmonary fibrosis, pericarditis, and hypercoagulability; medication effects particularly from steroids and nonsteroidal anti-inflammatory drugs; and specific joint problems including contractures and atlantoaxial joint instability. Diabetes increases the risk of infection and cardiac complications. Prevention of ketoacidosis and glucose control are necessary and can be achieved through a variety of approaches, depending on whether the patient suffers from Type 1 or Type 2 diabetes. The threshold for transfusion has increased in recent years, as has the use of erythropoietin and autologous blood donation. There is no longer an absolute hemoglobin that requires transfusion, although most require transfusion for hemoglobins less than 8 mg/dL, especially in the setting of cardiac disease and bloody surgery. The elderly require surgery at an increased rate and often do not do as well as younger patients. The primary issues are, however, not their age but their increased frequency of underlying disease and diminished reserve. The latter makes them prone to postoperative delirium, sensitivity to medications, and cardiac and pulmonary problems. Despite the many diseases that patients often have and the stresses of surgery itself, modern anesthetic and surgical techniques allow almost all patients to undergo necessary procedures at acceptable risk. The internist plays a critical role in minimizing this risk even further.
 ...
PMID:Recognition and management of preoperative risk. 1046 30

Fasting and postglucose hyperinsulinemia are recognized risk factors for acute coronary events. The insulin reactivity of patients with acute coronary syndromes, however, has not been carefully compared with that of patients with chronic stable angina. We used Bergman's minimal model to analyze the insulin response to intravenous glucose in 21 subjects: 8 patients with previous (>3 months) acute coronary syndrome but no effort-related angina; 6 patients with stable effort angina but no prior acute event; and 7 healthy controls. Diabetes mellitus, systemic hypertension, dyslipidemias, and obesity were excluded. All patients underwent coronary angiography. Insulin sensitivity, glucose effectiveness, and glucose tolerance were determined from insulin and glucose concentrations measured frequently up to 3 hours after a 0.33 g/kg intravenous glucose bolus. Patients with previous unstable angina or acute myocardial infarction had less extensive disease at angiography than patients with stable angina (p = 0.007). Both patient groups had higher basal and 180-minute insulinemia than controls (p <0.0007). However, patients with stable angina did not differ significantly from controls with regard to early and late insulinemic response to glucose. In contrast, patients with previous acute onset of ischemia had significantly greater 180-minute integrated insulinemia (p = 0.04) and reduced insulin sensitivity (p = 0.05) after the glucose challenge than did the stable angina group. These data suggest that patients with acute presentation of coronary artery disease, compared with patients with uncomplicated chronic stable angina, have an impaired insulin response to glucose despite less extensive coronary disease at angiography.
 ...
PMID:Comparison of insulin response to intravenous glucose in healed myocardial infarction, in "cooled-off" unstable and stable angina pectoris, and in healthy subjects. 1053 2

Silicone gastric banding procedures for severe obesity have been done on 303 patients; 214 as primary operations and 89 as revisions of different types of gastric restriction operations. Twenty-five bands were removed, and in 16 of these cases full thickness gastric wall biopsies were done at the banding site. The pathologic changes at the banding site in these 16 patients consisted of variable local tissue responses consistent with constriction due to the banding process. The most significant finding, seen in only one patient, was full thickness fibrous replacement of the muscular wall. Ten patients had only serosal fibrosis at the banding site and four had both serosal fibrosis and patchy fibrous replacement of the muscularis propria. One biopsy specimen showed no pathologic changes. Notably absent in all cases were evidence of ischemia and evidence of penetration of the gastric wall by the band.
 ...
PMID:Pathologic Changes in the Stomach at the Site of Silicone Gastric Banding. 1071 63

The opening of potassium (K+) channels, causing hyperpolarization of the cell membrane, is a physiological means of decreasing cell excitability. Thus, drugs with this property will demonstrate a broad clinical potential. The identification of synthetic molecules that evoke physiological responses (for example smooth muscle relaxation) by the opening of K+ channels led to a new direction in the pharmacology of ion channels. The term "potassium channel openers" was initially associated with a group of chemically diverse agents (for example, cromakalim, pinacidil, nicorandil) that evoke K+ efflux through adenosine 5'-triphosphate (ATP)-sensitive K+ channels (KATP). This finding initiated a search to identify molecules that specifically open other K+ channel subtypes (for example large conductance calcium-activated K+ channels [BKCa]). K+ channel opening properties have been demonstrated in a diverse range of synthetic chemical structures and endogenous substances. Second generation KATP channel openers (KATPCOs) demonstrate heterogeneous pharmacology indicative of independent sites of action for the different agents. Successful cloning of the KATP channel has shed light on the heterogeneity of the structure targeted by KATPCOs. Expression of the actions of KATPCOs involves three isoforms of the sulfonylurea (SUR) receptor (which forms the beta subunit of the KATP channel). The distribution of the SUR isoforms (and potential of identifying new isoforms) provides unique targets for the development of selective KATPCOs giving focused therapeutic approaches to clinical conditions for example cardiac ischemia, urinary incontinence, neurodegeneration, obesity and autoimmune diseases. BKCa channels are found in a diverse array of tissues and due to voltage and Ca sensitivity may work as a negative feedback process. A variety of small synthetic molecules (for example, NS004, fenamates) and natural product-derived compounds (DHS-I, maxikdiol) have been identified as selective BKCa channel openers which should have a profound impact in controlling diseases. The discovery of numerous variants of the alpha subunit (ion conductance pore) and beta subunit (contributes biophysical and pharmacological properties) complex of the BKCa channel gives potential to target specific tissues with selective openers. Little is known, however, about the site(s) of interaction of openers of these channels. The discovery of K+ channel subtype-specific openers and their evaluation in different diseases will determine the degree to which these channels (KATP, BKCa), or their isoforms, represent realistic therapeutic targets. Drugs already marketed that open K+ channels were discovered empirically, and most have serious safety and efficacy problems. New scientific methods, utilizing molecular insight, are implicating K+ channel dysfunction in numerous disease states and are identifying new targets for the future generation of K+ channel opening drugs.
 ...
PMID:Potassium channel openers as potential therapeutic weapons in ion channel disease. 1072 Sep 37

The treatment of non-traumatic ischaemic osteonecrosis of the femoral head (ONFH) remains problematical and there is evidently scope to seek for a medical treatment of this disease which often leads to a surgical procedure for hip prosthesis. If we exclude the context of hemoglobin disorders, necrosis appears mainly in adults, when their limb bones contain a fatty marrow. Investigations such as intramedullary pressure measurement and transosseous phlebography suggest a disorder of the intraosseous blood circulation. Various studies in animals and man have provided arguments indicating that a kind of intraosseous 'obesity' due to hyperplasia and/or hypertrophy of the fatty tissue of the femoral marrow play a role in the development of necrosis. In this respect, the blood flow of the yellow marrow is close to ischemia, whereas red marrow flow can be very high. In various conditions, mainly hemolytic anemias, the femoral yellow marrow can convert to red marrow, which has also been described in anemias induced by blood loss. If it is not thought unreasonable to consider ONFH an 'ischemic' disease, these observations are an encouragement to attempt treatment by repeated phlebotomies. This procedure may locally restore red marrow, and then an adequate blood flow which could stabilize or even reverse the lesions if they are diagnosed early.
 ...
PMID:Phlebotomy: a treatment of ischaemic necrosis of the femoral head? Analysis of a hypothesis. 1087 13

Diabetic patients have a higher prevalence of hypertension, dyslipidemia and obesity. However, diabetes is by itself a major independent risk factor for cardiovascular disease. About two-thirds of total mortality are due to diabetic macroangiopathy. It is characterised by accelerated atherosclerosis, with more severe, more extensive and more diffuse lesions, as compared with nondiabetic patients. Patients with diabetes present more frequently acute pulmonary oedema despite similar infarct sizes than do nondiabetic patients. They are more frequently at risk for ventricular dysfunction, for ventricular aneurysm and for congestive heart failure. At the time of diagnosis of type 2 diabetes, more than 50% of patients have pre-existing coronary heart disease, probably related to painless ischemia, caused by an autonomic denervation of the heart in diabetic patients. International recommendations suggest that all diabetic patients should be evaluated at least annually for the development or progression of risk factors that would prompt cardiac testing. The standard bicycle exercise test should be chosen in an asymptomatic patient with only one other risk factor and with a normal resting ECG. For all other diabetic patients, stress echocardiography or stress myocardial perfusion imaging should be preferably chosen.
 ...
PMID:[Cardiac complications of type 2 diabetes]. 1092 96

Genetically obese male Zucker rats have an impaired secretion of GH, coupled to hyperinsulinemia, hyperlipidemia and glucose intolerance. The aim of this study was to evaluate whether a chronic treatment with hexarelin, a synthetic enkephalin-derived hexapeptide with a potent GH-releasing activity, might be able to ameliorate the somatotropic function and reverse some metabolic alterations associated with obesity in male obese Zucker rats. Furthermore, as decreased GH secretion and insulin resistance are associated with increased cardiovascular risk, we also tested the capacity of hexarelin to prevent postischemic ventricular dysfunction in hearts of male obese Zucker rats. Obese and lean male rats of the Zucker strain were treated with hexarelin (80 microgram/kg, b.i.d., s.c.) or saline (1 ml/kg, b.i.d., s.c.) for 30 days. An acute hexarelin injection (80 microgram, s.c.) at the 28th day of treatment elicited a rise in plasma GH levels in ! lean but not in obese rats (pretreated or not with hexarelin); lean rats chronically treated with hexarelin showed a greater increase in plasma GH as compared with control counterparts. At the end of the experiment, pituitary GH mRNA levels were significantly reduced in obese rats and hexarelin administration failed to increase pituitary GH mRNA and IGF-I concentrations in plasma and heart. Chronic treatment with hexarelin increased insulinemia and blood glucose levels in obese but not in lean rats, left unaltered the high triglyceride levels but significantly decreased plasma cholesterol concentrations in obese rats. Heart preparations from lean and obese Zucker rats treated with saline, subjected to low flow ischemia and reperfusion, showed at reperfusion: a) a low recovery of postischemic left ventricular developed pressure (LVDP), coupled to a substantial increase in coronary perfusion pressure, and b) a marked increase in creatine kinase released in the perfusates. Hexare! lin administration for 30 days counteracted the heart ischemic damage both in lean and obese Zucker rats. In fact, the recovery of LVDP at reperfusion was significantly higher than in controls and the increase in coronary resistance was minimal. Collectively, these data indicate that a 30-day treatment with hexarelin was unable to improve somatotropic function in male obese Zucker rats but was successful in decreasing plasma cholesterol concentrations. Hexarelin exerted a cardioprotective effect in both lean and obese rats. The heart-protective activity afforded by the peptide was divorced from any stimulation of the GH axis and is probably exerted through activation of specific cardiac receptors.
 ...
PMID:Endocrine, metabolic and cardioprotective effects of hexarelin in obese Zucker rats. 1097 47

L-Arginine (Arg) is the substrate for the synthesis of nitric oxide (NO), the endothelium-derived relaxing factor essential for regulating vascular tone and hemodynamics. NO stimulates angiogenesis, but inhibits endothelin-1 release, leukocyte adhesion, platelet aggregation, superoxide generation, the expression of vascular cell adhesion molecules and monocyte chemotactic peptides, and smooth muscle cell proliferation. Arg exerts its vascular actions also through NO-independent effects, including membrane depolarization, syntheses of creatine, proline and polyamines, secretion of insulin, growth hormone, glucagon and prolactin, plasmin generation and fibrinogenolysis, superoxide scavenging and inhibition of leukocyte adhesion to nonendothelial matrix. Compelling evidence shows that enteral or parenteral administration of Arg reverses endothelial dysfunction associated with major cardiovascular risk factors (hypercholesterolemia, smoking, hypertension, diabetes, obesity/insulin resistance and aging) and ameliorates many common cardiovascular disorders (coronary and peripheral arterial disease, ischemia/reperfusion injury, and heart failure). Dietary Arg supplementation may represent a potentially novel nutritional strategy for preventing and treating cardiovascular disease.
 ...
PMID:Arginine nutrition and cardiovascular function. 1105 97

Choroid plexus (CP) is an important target organ for polypeptides. The fenestrated phenotype of choroidal endothelium facilitates the penetration of blood-borne polypeptides across the capillary walls. Thus, both circulating and cerebrospinal fluid (CSF)-borne polypeptides can reach their receptors on choroidal epithelium. Several polypeptides have been demonstrated to regulate CSF formation by controlling blood flow to choroid plexus and/or the activity of ion transport in choroidal epithelium. However, many ligand-receptor interactions occurring in the CP are not involved in the regulation of fluid secretion. Increasing evidence suggests that the choroidal epithelium plays an important role in hormonal signaling via a receptor-mediated transport into the brain (e.g., leptin) and helps to clear certain CSF-borne polypeptides (e.g., soluble amyloid beta-protein). Thus, impaired choroidal transport or insufficient clearance of polypeptides may contribute to pathogenesis of systemic or central nervous system (CNS) disorders, such as obesity or Alzheimer's disease. CP epithelium is not only a target but is also a source of neuropeptides, growth factors, and cytokines in the CNS. These polypeptides following their release into the CSF may exert distal, endocrine-like effects on target cells in the brain due to bulk flow of this fluid. Distinct temporal patterns of choroidal expression of several polypeptides are observed during brain development and in various CNS disorders, including traumatic brain injury and ischemia. Therefore, it is proposed that the CP plays an integral role not only in normal brain functioning, but also in the recovery from the injury. This review attempts to critically analyze the available data to support the above hypothesis.
 ...
PMID:Choroid plexus: target for polypeptides and site of their synthesis. 1113 50


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>