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)

7,12-Dimethylbenz[a]anthracene (7,12-DMBA) exerts adrenocorticolytic effects which set it apart from all other polynuclear aromatic hydrocarbons and aromatic amines which have been investigated. Adrenal damage by this compound appears to be due to its steric and electronic properties together with its unusually high solubility in lipides. Many compounds given prior to 7,12-DMBA induced protection of adrenal. The most efficient inducers of protection are flat condensed aromatics possessing 4 or 5 rings; very small doses of these compounds were required to induce protection. Other compounds devoid of these properties induced protection but large or repeated doses were necessary. All inducers of protection had to be given prior to 7,12-DMBA to prevent adrenal necrosis; when given simultaneously with, or later than, this compound adrenal apoplexy resulted. Protective aromatics and 7,12-DMBA as well induced synthesis of menadione reductase in liver. 3-Methylcholanthrene (3-MC) induced this enzyme in many normal organs including liver, lung, adrenal, and in mammary cancer as well. dl-Ethionine under appropriate conditions of time and dosage eliminated the adrenal protection induced by aromatics and also delayed the induction of menadione reductase while depressing the amount of this enzyme which was synthesized. 7,12-DMBA caused a greatly reduced incorporation of tritium from thymidine-H(3) into washed acid-insoluble residue of adrenal. 3-MC given in advance mitigated the drastic effect of 7,12-DMBA on DNA synthesis and increased considerably the amount of tritium which was incorporated. The specific damage to adrenal by 7,12-DMBA is a direct effect on cells. Protection of adrenal is a secondary effect which requires induction of protein synthesis and it results in improvement in synthesis of DNA.
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PMID:INDUCED PROTECTION OF ADRENAL CORTEX AGAINST 7,12-DIMETHYLBENZ(ALPHA)ANTHRACENE. INFLUENCE OF ETHIONINE. INDUCTION OF MENADIONE REDUCTASE. INCORPORATION OF THYMIDINE-H3. 1417 66

In healthy humans, ganglionic blockade unmasks a clear age-related decrease in cardiac responses to isoproterenol but not to epinephrine. We postulated that an age-related decrease in neuronal uptake (which affects epinephrine but not isoproterenol) may offset a parallel decrease in beta-receptor-mediated responses. To test this concept, nine young (mean 29 +/- 2 yr) and eight older (mean 61 +/- 2 yr) healthy subjects were infused on three different study mornings with epinephrine at increasing rates either alone or combined with desipramine to eliminate differences in neuronal uptake or with desipramine and trimetaphan to induce ganglionic blockade and thereby also eliminate differences in arterial baroreflex activity. Epinephrine caused the expected rate-related increases in systolic blood pressure, heart rate, stroke volume, ejection fraction, and cardiac index. Except for the systolic blood pressure, the extent of the changes was similar in young and older subjects. After desipramine, cardiac responsiveness to epinephrine was markedly enhanced, although more (P < 0.01) in young vs. older subjects for heart rate and cardiac index (+14 vs. 7 beats/min and +1.6 vs. 1.1 l.min(-1).m(-2), respectively, at 20 ng.kg(-1).min(-1)). Combined with desipramine and trimetaphan, cardiac responses to epinephrine were further enhanced, again more (P < 0.01) in young subjects, resulting in large differences in heart rate and ejection fraction increases (+29 vs. 17 beats/min and +14 vs. 7%, respectively, at 20 ng.kg(-1).min(-1)). Here, we show that "healthy aging" in humans is associated with decreased cardiac responsiveness to the beta-agonist epinephrine; however, this decrease can be balanced by concomitant decreases in buffering of these responses by neuronal uptake and the arterial baroreflex.
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PMID:Aging and cardiac responses to epinephrine in humans: role of neuronal uptake. 1562 90

The effects of adrenergic stimulation on mean circulatory filling pressure (MCFP), central venous pressure (P(CV)) and stroke volume (Vs), as well as the effects of altered MCFP through changes of blood volume were investigated in rattlesnakes (Crotalus durissus). MCFP is an estimate of the upstream pressure driving blood towards the heart and is determined by blood volume and the activity of the smooth muscle cells in the veins (venous tone). MCFP can be determined as the plateau in P(CV) during a total occlusion of blood flow from the heart. Vs decreased significantly when MCFP was lowered by reducing blood volume in anaesthetised snakes, whereas increased MCFP through infusion of blood (up to 3 ml kg(-1)) only led to a small rise in Vs. Thus, it seems that end-diastolic volume is not affected by an elevated MCFP in rattlesnakes. To investigate adrenergic regulation on venous tone, adrenaline as well as phenylephrine and isoproterenol (alpha- and beta-adrenergic agonists, respectively) were infused as bolus injections (2 and 10 microg kg(-1)). Adrenaline and phenylephrine caused large increases in MCFP and P(CV), whereas isoproterenol decreased both parameters. This was also the case in fully recovered snakes. Therefore, adrenaline affects venous tone through both alpha- and beta-adrenergic receptors, but the alpha-adrenergic receptor dominates at the dosages used in the present study. Injection of the nitric oxide donor SNP caused a significant decrease in P(CV) and MCFP. Thus, nitric oxide seems to affect venous tone.
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PMID:Venous tone and cardiac function in the South American rattlesnake Crotalus durissus: mean circulatory filling pressure during adrenergic stimulation in anaesthetised and fully recovered animals. 1616 52

Aldosterone synthase (CYP11B2) and 11beta-hydroxylase (CYP11B1) catalyze the production of aldosterone and corticosterone, respectively, in the rat adrenal cortex. Recently, there has been some debate as to whether these corticosteroids are also produced in the hearts of rodents and humans, possibly contributing to the development of hypertrophy and myocardial fibrosis. To investigate this, we have used our established, highly sensitive real-time quantitative RT-PCR method to measure CYP11B1 and CYP11B2 mRNA levels in adrenal and cardiac tissue from several rat models of cardiovascular pathology. We have also studied isolated adult rat ventricular myocytes treated with angiotensin II and ACTH. Total RNA was isolated from the adrenal and cardiac tissue of 1) male Wistar rats with heart failure induced by coronary artery ligation and sham-operated controls; 2) stroke-prone spontaneously hypertensive rats and Wistar Kyoto rats as controls; 3) cyp1a1Ren-2 transgenic rats and Fischer controls; 4) isolated adult Sprague-Dawley ventricular myocytes incubated with 11-deoxycorticosterone (DOC), DOC plus angiotensin II, or DOC plus ACTH. Adrenal CYP11B2 expression was significantly increased in transgenic rats compared with Fischer controls (1.3 x 10(9)+/- 1.2 x 10(9) vs. 2.1 x 10(7) +/- 7.0 x 10(6) copies/microg RNA; P < 0.05). There were no other significant differences in adrenal CYP11B2 or CYP11B1 expression between the model animals and their respective controls. Cardiac CYP11B1 and CYP11B2 mRNA transcript levels from all in vivo and in vitro groups were never greater than 100 copies per microgram total RNA and therefore too low to be detected reproducibly. This suggests that cardiac corticosteroid production is unlikely to be of any physiological or pathological significance.
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PMID:The aldosterone synthase (CYP11B2) and 11beta-hydroxylase (CYP11B1) genes are not expressed in the rat heart. 1617 17

Although neuroprotective strategies and pharmaceutical agents have been initiated in the treatment of numerous disorders of the central and peripheral nervous systems, including trauma, epilepsy, stroke, Huntington disease, amyotrophic lateral sclerosis,and AIDS dementia, none have yet been applied to the treatment of glaucoma. A prospective, placebo-controlled, multi-institutional trial of memantine is underway. One would not expect the treatment modalities that form the bases of nonpharmaceutical, traditional medical systems to be used to lower IOP. Glaucoma was unknown when these medicinal treatments were developed over the centuries. Their primary use is in improving the cardiovascular and immune systems and in what is now called neuro-protection. Rather than single compounds that target a specific receptor and have demarcated side effects in other systems, plant products are a blend of many compounds and, according to those most versed in them, they achieve a balanced therapy, helping in specific symptomatic complexes while reducing side effects through ameliorating effects in other areas. It is not insignificant that, now that the rain forests are rapidly dwindling, together with their inhabitants and the knowledge of medicinal plants (especially in South America), the pharmaceutical companies are spending large amounts of money in a sudden, almost frantic attempt to gather the knowledge about rainforest plants before all has been completely lost. Proof of effects clinically in a chronic disease such as glaucoma remains largely lacking, and controlled trials are unlikely to be initiated, except perhaps through the National Institutes of Health, because these compounds have been in the public domain for many years. Perhaps those as yet unknown or un-recorded are patentable and perhaps these include drugs known only to small surviving communities of hunter-gatherers, which explains the pharmaceutical interest in these areas. When more accurate and rapid means of assessment of progression of glaucomatous damage than perimetry and optic nerve head photography are eventually developed and trials can be reduced in time, number of subjects, or even the use of nonhuman subjects for the bulk of studies, studies could be done for verification of effect of various compounds and also comparative studies. At the present time, GBE is the best documented of all the complementary medicinal agents and seems to have the greatest potential value. Ginkgo biloba extract has numerous properties that theoretically should be beneficial in treating non-IOP-dependent mechanisms in glaucoma. Its multi-ple beneficial actions, including increased ocular blood flow, antioxidant activity, platelet activating factor inhibitory activity, nitric oxide inhibition, and neuroprotective activity, combine to suggest that GBE could prove to be of major therapeutic value in the treatment of glaucoma.
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PMID:Complementary therapy for the treatment of glaucoma: a perspective. 1631 22

A new hypothesis is presented on the function of factor XII, which is postulated to be a "missing link" between acute stress and transient hypercoagulability. The implications of this idea are developed to show how chronic stress, which involves activation of hypertension and migraine as well as hypercoagulability, can cause of cerebrovascular disease. "Acute stress" is defined as "the normal short-term physiological response to the perception of major threats or demands". "Chronic stress" is "the abnormal ongoing physiological response to the continuing perception of unresolvable major threats or demands". The factor XII hypothesis is as follows: Acute stress includes release of epinephrine by the adrenal medulla. Epinephrine activates platelets by binding to alpha-2A adrenergic receptors. Activated platelets convert pre-bound factor XII to its active form, which then initiates the intrinsic coagulation cascade. This can be called the "activated platelet initiation pathway" for coagulation. Neither tissue factor nor pre-formed thrombin is required. Thrombosis proceeds to completion, but only a minute amount of thrombin is formed, and the process normally stops at this point. In people who lapse into a state of chronic stress, essential hypertension, which is also a manifestation of stress, synergizes with hypercoagulability: there is both a baseline rise in blood pressure and systemic platelet activation as well as superimposed labile rises of both. Upregulation of these two stress parameters is atherogenic: epinephrine-activated platelets stimulating thrombin formation interact with endothelial cells activated by angiotensin II to cause, first, smooth muscle cell proliferation, which is a histological hallmark of atherosclerosis, and, lastly, a symptomatic thrombotic occlusion-the stroke. The migraine symptoms which often accompany this process are a marker of chronic stress and ongoing pathophysiologic damage. Therapeutic predictions are made regarding novel ways of blocking stress-induced hypercoagulability and hypertension. Hypercoagulability could be targeted by monoclonal antibodies directed against the platelet-specific alpha-2 adrenergic receptor or the (putative) platelet receptor for Factor XII; hypertension could be treated with monoclonal antibodies directed against the beta-adrenergic receptor in the juxtaglomerular apparatus or by surgical denervation of the kidneys, either of which would decrease the renin release which helps drive the hypertension.
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PMID:Factor XII (Hageman factor) is a missing link between stress and hypercoagulability and plays an important role in the pathophysiology of ischemic stroke. 1675 26

The new CPR guidelines are based on a scientific consensus which was reached by 281 international experts. Chest compressions (100/min, 4-5 cm deep) should be performed in a ratio of 30:2 with ventilation (tidal volume 500 ml, Ti 1 s, FIO2 if possible 1.0). After a single defibrillation attempt (initially biphasic 150-200 J, monophasic 360 J, subsequently with the respective highest energy), chest compressions are initiated again immediately for 2 min. Endotracheal intubation is the gold standard; other airway devices may be employed as well depending on individual skills. Drug administration routes for adults and children: first choice IV, second choice intraosseous, third choice endobronchial [epinephrine dose 2-3x (adults) or 10x (pediatric patients) higher than IV]. Vasopressors: 1 mg epinephrine every 3-5 min IV. After the third unsuccessful defibrillation attempt amiodarone IV (300 mg); repetition (150 mg) possible. Sodium bicarbonate (1 ml/kg 8.4%) only in excessive hyperkalemia, metabolic acidosis, or intoxication with tricyclic antidepressants. Consider atropine (3 mg) and aminophylline (5 mg/kg). Thrombolysis during spontaneous circulation only in myocardial infarction or massive pulmonary embolism; during CPR only during massive pulmonary embolism. Cardiopulmonary bypass only after cardiac surgery, hypothermia or intoxication. Pediatrics: best improvement in outcome by preventing cardiocirculatory collapse. Alternate chest thumps and chest compression (infants), or abdominal compressions (>1-year-old) in foreign body airway obstruction. Initially five breaths, followed by chest compressions (100/min; approximately 1/3 of chest diameter): ventilation ratio 15:2. Treatment of potentially reversible causes (4 "Hs", "HITS": hypoxia, hypovolemia, hypo- and hyperkaliemia, hypothermia, cardiac tamponade, intoxication, thrombo-embolism, tension pneumothorax). Epinephrine 10 microg/kg IV or intraosseously, or 100 microg (endobronchially) every 3-5 min. Defibrillation (4 J/kg; monophasic oder biphasic) followed by 2 min CPR, then ECG and pulse check. Newborns: inflate the lungs with bag-valve mask ventilation. If heart rate<60/min chest compressions:ventilation ratio 3:1 (120 chest compressions/min). Postresuscitation phase: initiate mild hypothermia [32-34 degrees C for 12-24 h; slow rewarming (<0.5 degrees C/h)]. Prediction of CPR outcome is not possible at the scene; determining neurological outcome within 72 h after cardiac arrest with evoked potentials, biochemical tests and physical examination. Even during low suspicion for an acute coronary syndrome, record a prehospital 12-lead ECG. In parallel to pain therapy, aspirin (160-325 mg PO or IV) and in addition clopidogrel (300 mg PO). As antithrombin, heparin (60 IU/kg, max. 4000 IU) or enoxaparine. In ST-segment elevation myocardial infarction, define reperfusion strategy depending on duration of symptoms until PCI (prevent delay>90 min until PCI). Stroke is an emergency and needs to be treated in a stroke unit. A CT scan is the most important evaluation, MRT may replace a CT scan. After hemorrhage exclusion, thrombolysis within 3 h of symptom onset (0.9 mg/kg rt-PA IV; max 90 mg within 60 min, 10% of the entire dosage as initial bolus, no aspirin, no heparin within the first 24 h). In severe hemorrhagic shock, definite control of bleeding is the most important goal. For successful CPR of trauma patients, a minimal intravascular volume status and management of hypoxia are essential. Aggressive fluid resuscitation, hyperventilation, and excessive ventilation pressure may impair outcome in severe hemorrhagic shock. Despite bad prognosis, CPR in trauma patients may be successful in select cases. Any CPR training is better than nothing; simplification of contents and processes remains important.
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PMID:[The new 2005 resuscitation guidelines of the European Resuscitation Council: comments and supplements]. 1691 4

Synbranchus marmoratus is a facultative air-breathing fish, which uses its buccal cavity as well as its gills for air-breathing. S. marmoratus shows a very pronounced tachycardia when it surfaces to air-breathe. An elevation of heart rate decreases cardiac filling time and therefore may cause a decline in stroke volume (V(S)), but this can be compensated for by an increase in venous tone to maintain stroke volume. Thus, the study on S. marmoratus was undertaken to investigate how stroke volume and venous function are affected during air-breathing. To this end we measured cardiac output (Q), heart rate (f(H)), central venous blood pressure (P(CV)), mean circulatory filling pressure (MCFP), and dorsal aortic blood pressures (P(DA)) in S. marmoratus. Measurements were performed in aerated water (P(O2)>130 mmHg), when the fish alternated between gill ventilation and prolonged periods of apnoeas, as well as during hypoxia (P(O2)<or=50 mmHg), when the fish changed from gill ventilation to air-breathing. Q increased significantly during gill ventilation compared to apnoea in aerated water through a significant increase in both f(H) and V(S). P(CV) and MCFP also increased significantly. During hypoxia, when the animals surface to ventilate air, we found a marked rise in f(H), P(CV), MCFP, Q and V(S), whereas P(DA) decreased significantly. Simultaneous increases in P(CV) and MCFP in aerated, as well as in hypoxic water, suggests that the venous system plays an important regulatory role for cardiac filling and V(S) in this species. In addition, we investigated adrenergic regulation of the venous system through bolus infusions of adrenergic agonists (adrenaline, phenylephrine and isoproterenol; 2 microg kg(-1)). Adrenaline and phenylephrine caused a marked rise in P(CV) and MCFP, whereas isoproterenol led to a marked decrease in P(CV), and tended to decrease MCFP. Thus, it is evident that stimulation of both alpha- and beta-adrenoreceptors affects venous tone in S. marmoratus.
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PMID:Cardiovascular changes under normoxic and hypoxic conditions in the air-breathing teleost Synbranchus marmoratus: importance of the venous system. 1702 9

Cardiac arrest and sudden cardiac death remain major causes of mortality. Early intervention has been facilitated by emergency medical response systems and the development of training programs in basic life support and advanced cardiac life support (ACLS). Despite the implementation of these programs, the likelihood of a meaningful outcome in many life-threatening situations remains poor. Pharmacotherapy plays a role in the management of patients with cardiac arrest, with new guidelines for ACLS available in 2005 providing recommendations for the role of specific drug therapies. Epinephrine continues as a recommended means to facilitate defibrillation in patients with pulseless ventricular tachycardia or ventricular fibrillation; vasopressin is an alternative. Amiodarone is the primary antiarrhythmic drug that has been shown to be effective for facilitation of defibrillation in patients with pulseless ventricular tachycardia or fibrillation and is also used for the management of atrial fibrillation and hemodynamically stable ventricular tachycardia. Epinephrine and atropine are the primary agents used for the management of asystole and pulseless electrical activity. Treatment of electrolyte abnormalities, severe hypotension, pulmonary embolism, acute ischemic stroke, and toxicologic emergencies are important components of ACLS management. Selection of the appropriate drug, dose, and timing and route of administration are among the many challenges faced in this setting. Pharmacists who are properly educated and trained regarding the use of pharmacotherapy for patients requiring ACLS can help maximize the likelihood of positive patient outcomes.
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PMID:Pharmacotherapy considerations in advanced cardiac life support. 1712 34

Cardiac beta-receptor responsiveness is diminished by both aging and hypertension. However, concomitant decreases in the activity of counterregulatory mechanisms, such as the arterial baroreflex and neuronal catecholamine uptake, influence the ultimate cardiac responses to adrenergic agents in vivo. In the present study, we evaluated by echocardiography cardiac responses to intravenous infusion of epinephrine in 14 young and 18 older normotensive men and women and in 10 young and 17 older hypertensive men and women. To assess the relative contribution of intrinsic cardiac and counterregulatory components to the overall response, infusions were repeated combined with a ganglionic blocker in the young groups. Epinephrine-induced increases in heart rate were similar in the four groups. Increases in stroke volume, ejection fraction, and cardiac index were similar in the two hypertensive and two young normotensive groups. In contrast, they were attenuated in the older normotensive group, resulting in higher left ventricular responses in older hypertensive than in normotensive subjects. Heart rate and left ventricular responses to epinephrine in the presence of ganglionic blockade did not differ between the two young groups. Increases in plasma norepinephrine due to epinephrine infusion were larger in hypertensive than in normotensive subjects. One may conclude that compared with young normotensive subjects, in hypertensive subjects mechanisms increasing versus decreasing cardiac responses to epinephrine may remain in balance, and, compared with older normotensive subjects, older hypertensive subjects exhibit enhanced cardiac responses to sympathetic stimulation.
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PMID:Effects of hypertension on cardiovascular responses to epinephrine in humans. 1730 99


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