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

To develop a new concept of central acting drugs, the modulation of brain Ca2+ flux must be considered as one of the important factors. This is because excessive Ca2+ influx to neuronal cells damages or kills these cells, and also because abnormal intracellular Ca2+ concentrations induce several types of mental disorders. Recently, both pre-clinical and clinical studies indicated that some Ca2+ channel blockers (Ca antagonists) will be useful for the treatment of grand mal, manic depressive insanity, panic disorder and anxiety. Furthermore, it has been estimated by animal studies and clinical pharmacology that ischemia-induced neuronal death can be prevented by the treatment with a Ca antagonist. However, the latter data, especially, has been mainly explained by pharmacological effects on the cerebrovascular system, not because of possible direct central actions. To invoke the notion of direct central action, it must be assumed that Ca antagonists might pass the blood-brain barrier (BBB). This potentiality that some Ca antagonists (i.e., flunarizine, nicardipine, nimodipine, etc.) can pass the BBB has been initially explored. If substantiated, such direct central effects of Ca antagonists may explain both the psychotropic effects and neuronal protection by these agents. To investigate the actual therapeutic effects of Ca2+ antagonists on psychotropic disorders and neuronal death, a suitable animal model and reasonable methods and criteria must be established. Then, both preclinical and clinical studies can be expected to relate to atypical central acting drugs modulating the brain Ca2+ channels, and also to the development of new pharmacological properties of Ca2+ antagonists.
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PMID:[Central effect of Ca2+ channel blockers: multiple sites of action]. 139 35

Panic disorder serves as a clinical model for testing whether mental stress can cause heart disease. Our own cardiologic management of panic disorder provides case material of recurrent emergency room attendances with angina and electrocardiogram ischemia, triggered arrhythmias (atrial fibrillation, ventricular fibrillation), and documented coronary artery spasm, in some cases with coronary spasm being complicated by coronary thrombosis. Application of radiotracer catecholamine kinetics and clinical microneurography methodology suggests there is a genetic predisposition to panic disorder that involves faulty neuronal norepinephrine uptake, possibly sensitizing the heart to symptom generation. During panic attacks there are large sympathetic bursts, recorded by clinical microneurography in the muscle sympathetic nerve neurogram, and large increases in cardiac norepinephrine spillover, accompanied by surges of adrenal medullary epinephrine secretion. In other conditions such as heart failure and presumably here also, a high level of sympathetic nervous activation can mediate increased cardiac risk. The sympathetic nerve cotransmitter, neuropeptide Y (NPY), is released from the cardiac sympathetics during panic attacks, an intriguing finding given that NPY can cause coronary artery spasm. There is ongoing, continuous release of epinephrine from the heart in panic sufferers, perhaps attributable to epinephrine loading of cardiac sympathetic nerves by uptake from plasma during panic attacks, or possibly to in situ synthesis of epinephrine through the action of intracardiac phenylethanolamine-N-methytransferase (PNMT) activated by repeated cortisol responses. We have used internal jugular venous sampling and measurement of overflowing lipophilic brain monoamine metabolites to quantify brain norepinephrine and serotonin turnover in untreated patients with panic disorder. We find normal norepinephrine turnover but a marked increase in brain serotonin turnover in patients with panic disorder, in the absence of a panic attack, which presumably represents an underlying neurotransmitter substrate for the condition.
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PMID:Cardiac sympathetic nerve biology and brain monoamine turnover in panic disorder. 1524 Apr 8

Panic disorder (PD) and panic-like anxiety have been associated with an increased risk of cardiovascular death. No study has specifically examined the association between panic attacks and ischemia in patients who have coronary artery disease (CAD). We hypothesized that panic attacks would induce myocardial perfusion defects in patients who have CAD and PD. Sixty-five patients who had CAD and positive results with nuclear exercise stress testing (35 with PD and 30 without PD served as controls) underwent a well-established panic challenge test (1 vital capacity inhalation of a gas mixture containing 35% carbon dioxide and 65% oxygen) and were injected with technetium-99m sestamibi at inhalation. Single-photon emission computed tomography was used to assess per-panic challenge perfusion defects, and heart rate, blood pressure, and 12-lead electrocardiogram were continuously measured during the procedure. Patients were not withdrawn from their cardiac medications. Patients who had PD were significantly younger than the controls; otherwise groups did not differ with respect to gender, cardiac medications, nuclear exercise test results, and baseline heart rate and blood pressure. Seventy-four percent of patients (26 of 35) who had PD had a panic attack at inhalation versus 6.7% of controls (2 of 30, p <0.001). As hypothesized, patients who had PD and demonstrated a panic attack were more likely to develop a reversible myocardial perfusion defect than were controls who did not have an attack (80.9% vs 46.4% p = 0.009). Thus, despite being on their cardiac medications, panic attacks preferentially induced significant perfusion defects in patients who had CAD and PD. In conclusion, panic attacks in patients who have CAD appear to be bad for the heart.
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PMID:Myocardial perfusion study of panic attacks in patients with coronary artery disease. 1621 39

The T cell death-associated gene 8 (TDAG8) is a pH-sensing GPCR with a reported immune-specific expression profile. Here, we demonstrate pH-induced activation of TDAG8 receptor cloned from rodent brain (rTDAG8). Cloned rTDAG8 transcript showed 88-95% homology with human and mouse transcripts of lymphoid origin. RT-PCR revealed high expression of TDAG8 in forebrain limbic regions. Extracellular acidification induced significantly elevated intracellular cyclic AMP, and phosphorylated CREB in TDAG8 expressing cells. Acidification-induced LDH release was significantly attenuated in cells expressing TDAG8, suggesting neuroprotective potential against acidosis-related cell injury. Our results open up new areas of investigation into the relevance of TDAG8 in pH homeostasis and pathological states associated with acid-base dys-regulation in the brain such as ischemia and panic disorder.
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PMID:Acid-sensing by the T cell death-associated gene 8 (TDAG8) receptor cloned from rat brain. 1950 Oct 50

Adenosine is a naturally occurring nucleoside present ubiquitously throughout the body as a metabolic intermediate. Besides its metabolic role within the cells, adenosine is released into the extracellular space either by neurons or astrocytes acting as a neuromodulator. Extracellular adenosine exerts its action by activating multiple G-protein coupled receptors (subtypes A(1), A(2A), A(2B) and A(3)) having a wide range of physiological effects in the brain. Adenosine levels rise markedly in response to ischemia, hypoxia, excitotoxicity or inflammation being a neuroprotectant under these conditions. However, adenosine may also contribute to neuronal damage and cell death in other circumstances. These actions are firmly established using multiple animal models. Therefore, increasing attention is now given to the role of adenosine in human brain function and its potential benefit for clinical applications. This review covers recent studies undertaken mostly in humans revealing the actions of adenosine and related drugs in cognition and memory as well as in various pathological situations such as psychiatric disorders, drug addiction and neurodegenerative disorders. The actual use of adenosine or adenosine receptor ligands in ongoing clinical trials for the treatment of schizophrenia, panic disorder and anxiety, cocaine dependence and Parkinson's disease is discussed. The evidence herein reviewed highlights the promising potential of adenosine or adenosine receptor ligands as therapeutic agents in several brain disorders.
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PMID:Adenosine and related drugs in brain diseases: present and future in clinical trials. 2140 93

Approximately 1 percent of primary care office visits are for chest pain, and 1.5 percent of these patients will have unstable angina or acute myocardial infarction. The initial goal in patients presenting with chest pain is to determine if the patient needs to be referred for further testing to rule in or out acute coronary syndrome and myocardial infarction. The physician should consider patient characteristics and risk factors to help determine initial risk. Twelve-lead electrocardiography is typically the test of choice when looking for ST segment changes, new-onset left bundle branch block, presence of Q waves, and new-onset T wave inversions. For persons in whom the suspicion for ischemia is lower, other diagnoses to consider include chest wall pain/costochondritis (localized pain reproducible by palpation), gastroesophageal reflux disease (burning retrosternal pain, acid regurgitation, and a sour or bitter taste in the mouth), and panic disorder/anxiety state. Other less common but important diagnostic considerations include pneumonia (fever, egophony, and dullness to percussion), heart failure, pulmonary embolism (consider using the Wells criteria), acute pericarditis, and acute thoracic aortic dissection (acute chest or back pain with a pulse differential in the upper extremities). Persons with a higher likelihood of acute coronary syndrome should be referred to the emergency department or hospital.
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PMID:Outpatient diagnosis of acute chest pain in adults. 2341 61

Chest pain is often seen alongside with panic attacks. Moreover, panic disorder has been suggested as a risk factor for cardiovascular disease and even a trigger for acute coronary syndrome. Patients with coronary artery disease may have myocardial ischemia in response to mental stress, in which panic attack is a strong component, by an increase in coronary vasomotor tone or sympathetic hyperactivity setting off an increase in myocardial oxygen consumption. Indeed, coronary artery spasm was presumed to be present in cases of cardiac ischemia linked to panic disorder. These findings correlating panic disorder with coronary artery disease lead us to raise questions about the favorable prognosis of chest pain in panic attack. To investigate whether myocardial ischemia is the genesis of chest pain in panic attacks, we developed a myocardial perfusion study through research by myocardial scintigraphy in patients with panic attacks induced in the laboratory by inhalation of 35% carbon dioxide. In conclusion, from the data obtained, some hypotheses are discussed from the viewpoint of endothelial dysfunction and microvascular disease present in mental stress response.
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PMID:Myocardial perfusion imaging study of CO(2)-induced panic attack. 2418 91