Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pharmacological activity of N-[2-(2,6-dimethoxyphenoxy) ethyl]-2-(2-methoxyphenoxy) ethanaminium chloride (ACC-7513) was determined in isolated smooth and cardiac muscle and its effect on blood pressure and heart rate assessed in the spontaneously hypertensive rat (SHR). ACC-7513 was found to be a potent alpha-adrenoceptor blocking agent (pA2:8.33) and a 5-hydroxytryptamine (5-HT) antagonist (pA2:7.01), both in rabbit aortic strips. The affinity for alpha-adrenoceptors was about 20 times greater than that for 5-HT-receptors. High concentrations of ACC-7513 did not block histamine in rabbit aortic strips, or beta 1- or beta 2-adrenoceptor responses induced by isoprenaline in guinea-pig right atria and trachea, respectively, but did block cholinoceptor responses induced by carbachol in rat uterus, non-competitively. High concentrations of ACC-7513 also produced sino-atrial depression in guinea-pig right atria and direct relaxation of depolarized rabbit aortic strips. ACC-7513 depressed blood pressure of conscious SHRs and produced a reflex increase in heart rate. The reductions in pressure were modest and of short duration. It is concluded that: (a) ACC-7513 is a potent, selective alpha-adrenoceptor and 5-HT receptor antagonist; and (b) ACC-7513 is not likely to be useful in the treatment of hypertension.
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PMID:Pharmacological activity of ACC-7513, a selective alpha-adrenoceptor and 5-hydroxytryptamine receptor blocking agent. 286 Sep 40

The beta-adrenergic receptor blocking properties of ACC-9089 were studied in isolated cardiac and tracheal tissues from guinea pigs and in anesthetized dogs. The compound was a potent, nonselective beta-blocker in isolated tissues (atrial pA2 8.01; tracheal pA2 8.16). ACC-9089 was without intrinsic sympathomimetic action and caused direct cardiac depression only at concentrations that were four orders of magnitude higher than its pA2. In anesthetized dogs, ACC-9089 produced steady-state beta-blockade within 20 min of initiation of 3-h intravenous infusions. Recovery from beta-blockade occurred rapidly following termination of infusion (80% recovery in 17 +/- 2 min after 1.2 microgram/kg/min). Intravenous infusion of ACC-9089 caused dose-dependent inhibition of heart rate responses to sympathetic nerve stimulation and inhibition of isoproterenol-induced decreases in perfusion pressure in a perfused hindlimb preparation. The compound (a) did not produce alpha-blockade; (b) had no direct effect on hindlimb vascular resistance; and (c) did not alter hemodynamic variables in catecholamine-depleted dogs. The results indicate that ACC-9089 is a novel, ultra-short-acting beta-blocker that does not possess direct cardiovascular effects beyond those expected as a result of beta-blockade.
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PMID:Cardiovascular pharmacology of ACC-9089--a novel, ultra-short-acting, beta-adrenergic receptor antagonist. 620 7

The recent document of the ESC/ACC Committee for the redefinition of myocardial infarction (MI) has introduced the measurement of cardiac troponin as the biochemical standard for the diagnosis of MI. This change has been mainly driven by the demonstration that any amount of myocardial damage, as detected by cardiac troponins, implies a worse long-term outcome of the patient. The results of several studies consistently show that there is a continuous relationship between the degree of troponin elevation and the patient's prognosis. The new definition has important consequences on the diagnostic and therapeutic approaches to patients with acute coronary syndromes; in fact, patients with increased troponins, i.e. patients with MI, necessitate more aggressive treatment than those without troponin elevations, i.e. patients with unstable angina. The application of the new definition is expected to increase the number of cases of MI by about 30% and to decrease mortality. We believe that several aspects of the new definition need to be discussed before the new criteria for MI are used in clinical practice in Italy. The most relevant issues are the following: 1) the definition of troponin elevation should meet the analytical performance of the available assays, the diagnostic cutoff of which is frequently too imprecise. We propose that troponin elevations be defined as values exceeding the concentration corresponding to a total analytical imprecision of 10%. We disclose such a concentration for the currently available assays and suggest its use in clinical practice to mitigate the possibility of false-positive values; 2) the number of samples required for the diagnosis should be sufficient for the assessment of the changes in concentration over time. When only one sample is available, or when the temporal pattern of the changes in marker concentration is not consistent with the time elapsed from the onset of symptoms, we suggest that objective evidence that myocardial ischemia is the likely cause of myocardial damage should be obtained; 3) the diagnosis of MI after a percutaneous coronary intervention represents a unique situation. In contrast with myocardial damage occurring during spontaneous ischemia, available data do not support the concept that any troponin elevation is associated with an adverse prognosis. In the absence of conclusive studies, we suggest that the diagnosis of MI after a percutaneous coronary intervention be based on conventional criteria. Finally, we propose this summary with the aim of overcoming some of the more controversial aspects of the ESC/ACC redefinition of MI: Criteria for acute, evolving or recent MI. Either one of the following criteria satisfies the diagnosis for an acute, evolving or recent MI: 1) elevation of biochemical markers of myocardial necrosis (preferably troponin) with at least one of the following: a) ischemic symptoms; b) development of pathologic Q waves on the ECG; c) ECG changes indicative of ischemia (ST segment elevation or depression); d) coronary artery intervention (e.g., coronary angioplasty). Marker elevations should be accompanied by objective evidence that myocardial ischemia is the likely cause of myocardial damage when: a) only one blood sample is available; b) marker changes over time are not consistent with the onset of symptoms; 2) pathologic findings of an acute MI. Criteria for established MI. Anyone of the following criteria satisfies the diagnosis for established MI: 1) development of new pathologic Q waves on serial ECGs. The patient may or may not remember previous symptoms. Biochemical markers of myocardial necrosis may have normalized, depending on the length of time that has passed since the infarct developed; 2) pathologic findings of a healed or healing MI.
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PMID:The new definition of myocardial infarction: analysis of the ESC/ACC Consensus Document and reflections on its applicability to the Italian Health System. 1240 56

The recent document of the ESC/ACC Committee for the redefinition of myocardial infarction (MI) has introduced the measurement of cardiac troponin as the biochemical standard for the diagnosis of MI. This change has been mainly driven by the demonstration that any amount of myocardial damage, as detected by cardiac troponins, implies a worse long-term outcome of the patient. The results of several studies consistently show that there is a continuous relationship between the degree of troponin elevation and the patient's prognosis. The new definition has important consequences on the diagnostic and therapeutic approaches to patients with acute coronary syndromes; in fact, patients with increased troponins, i.e. patients with MI, necessitate more aggressive treatment than those without troponin elevations, i.e. patients with unstable angina. The application of the new definition is expected to increase the number of cases of MI by about 30% and to decrease mortality. We believe that several aspects of the new definition need to be discussed before the new criteria for MI are used in clinical practice in Italy. The most relevant issues are the following: 1) the definition of troponin elevation should meet the analytical performance of the available assays, the diagnostic cut-off of which is frequently too imprecise. We propose that troponin elevations be defined as values exceeding the concentration corresponding to a total analytical imprecision of 10%. We disclose such a concentration for the currently available assays and suggest its use in clinical practice to mitigate the possibility of false-positive values; 2) the number of samples required for the diagnosis should be sufficient for the assessment of the changes in concentration over time. When only one sample is available, or when the temporal pattern of the changes in marker concentration is not consistent with the time elapsed from the onset of symptoms, we suggest that objective evidence that myocardial ischemia is the likely cause of myocardial damage should be obtained; 3) the diagnosis of MI after a percutaneous coronary intervention represents a unique situation. In contrast with myocardial damage occurring during spontaneous ischemia, available data do not support the concept that any troponin elevation is associated with an adverse prognosis. In the absence of conclusive studies, we suggest that the diagnosis of MI after a percutaneous coronary intervention be based on conventional criteria. Finally, we propose this summary with the aim of overcoming some of the more controversial aspects of the ESC/ACC redefinition of MI: Criteria for acute, evolving or recent MI. Either one of the following criteria satisfies the diagnosis for an acute, evolving or recent MI: 1) elevation of biochemical markers of myocardial necrosis (preferably troponin) with at least one of the following: a) ischemic symptoms; b) development of pathologic Q waves on the ECG; c) ECG changes indicative of ischemia (ST segment elevation or depression); d) coronary artery intervention (e.g., coronary angioplasty). Marker elevations should be accompanied by objective evidence that myocardial ischemia is the likely cause of myocardial damage when: a) only one blood sample is available; b) marker changes over time are not consistent with the onset of symptoms; 2) pathologic findings of an acute MI. Criteria for established MI. Anyone of the following criteria satisfies the diagnosis for established MI: 1) development of new pathologic Q waves on serial ECGs. The patient may or may not remember previous symptoms. Biochemical markers of myocardial necrosis may have normalized, depending on the length of time that has passed since the infarct developed; 2) pathologic findings of a healed or healing MI.
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PMID:[New definition of myocardial infarction: analysis of the consensus document ESC/ACC and thoughts about applicability to the Italian health situation]. 1240 66

The early use of glycoprotein (GP) IIb/IIIa-receptor inhibitors in patients with non-ST-segment-elevation (NSTE) acute coronary syndromes (ACSs) is discussed. Unstable angina and NSTE myocardial infarction, collectively known as NSTE ACSs, are among the leading causes of morbidity and mortality in the United States. Updated guidelines from the American College of Cardiology and the American Heart Association for the management of NSTE ACSs strongly recommend that patients with intermediate- to high-risk features (e.g., ST-segment depression, elevated cardiac markers, and recurrent ischemia) be managed with an early invasive or other aggressive strategy (diagnostic angiography within 48 hours and, if warranted, percutaneous or surgical revascularization) and immediate treatment with a GP IIb/IIIa-receptor inhibitor. In low-risk patients, either an early invasive or an early conservative strategy (diagnostic angiography only for recurrent or refractory ischemia or a positive stress test result) is appropriate. For patients managed with an early conservative approach, the guidelines recommend GP IIb/IIIa-receptor inhibitor therapy with eptifibatide or tirofiban hydrochloride, especially in high-risk patients. Abciximab should not be used in patients in whom percutaneous coronary intervention is not planned. Greater implementation of the recommendations concerning the early use of GP IIb/IIIa-receptor inhibitors may result in reduced mortality rates. A large body of clinical evidence supports the updated ACC and AHA recommendations for managing patients with NSTE ACSs.
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PMID:Early use of glycoprotein IIb/IIIa-receptor inhibitors in non-ST-segment-elevation acute coronary syndromes. 1243 11

Pain catastrophizing, or characterizations of pain as awful, horrible and unbearable, is increasingly being recognized as an important factor in the experience of pain. The purpose of this investigation was to examine the association between catastrophizing, as measured by the Coping Strategies Questionnaire Catastrophizing Subscale, and brain responses to blunt pressure assessed by functional MRI among 29 subjects with fibromyalgia. Since catastrophizing has been suggested to augment pain perception through enhanced attention to painful stimuli, and heightened emotional responses to pain, we hypothesized that catastrophizing would be positively associated with activation in structures believed to be involved in these aspects of pain processing. As catastrophizing is also strongly associated with depression, the influence of depressive symptomatology was statistically removed. Residual scores of catastrophizing controlling for depressive symptomatology were significantly associated with increased activity in the ipsilateral claustrum (r = 0.51, P < 0.05), cerebellum (r = 0.43, P < 0.05), dorsolateral prefrontal cortex (r = 0.47, P < 0.05), and parietal cortex (r = 0.41, P < 0.05), and in the contralateral dorsal anterior cingulate gyrus (ACC; r = 0.43, P < 0.05), dorsolateral prefrontal cortex (r = 0.41, P < 0.05), medial frontal cortex (r = 0.40, P < 0.05) and lentiform nuclei (r = 0.40, P < 0.05). Analysis of subjects classified as high or low catastrophizers, based on a median split of residual catastrophizing scores, showed that both groups displayed significant increases in ipsilateral secondary somatosensory cortex (SII), although the magnitude of activation was twice as large among high catastrophizers. Both groups also had significant activations in contralateral insula, SII, primary somatosensory cortex (SI), inferior parietal lobule and thalamus. High catastrophizers displayed unique activation in the contralateral anterior ACC, and the contralateral and ipsilateral lentiform. Both groups also displayed significant ipsilateral activation in SI, anterior and posterior cerebellum, posterior cingulate gyrus, and superior and inferior frontal gyrus. These findings suggest that pain catastrophizing, independent of the influence of depression, is significantly associated with increased activity in brain areas related to anticipation of pain (medial frontal cortex, cerebellum), attention to pain (dorsal ACC, dorsolateral prefrontal cortex), emotional aspects of pain (claustrum, closely connected to amygdala) and motor control. These results support the hypothesis that catastrophizing influences pain perception through altering attention and anticipation, and heightening emotional responses to pain. Activation associated with catastrophizing in motor areas of the brain may reflect expressive responses to pain that are associated with greater pain catastrophizing.
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PMID:Pain catastrophizing and neural responses to pain among persons with fibromyalgia. 1496 Apr 99

Allelic variants in the promoter region of the serotonin transporter (5-HTT) gene have been implicated in several psychiatric disorders and personality traits. In particular, two common alleles in a variable repeat sequence of the promoter region (SLC6A4) have been differentially associated with a display of abnormal levels of anxiety and affective illness in individuals carrying the "s" allele. The aim of this study was to compare the basal cerebral metabolic activity of non-psychiatric subjects in fronto-limbic structures to determine whether differences exist in basal metabolic activity within this functional polymorphism. PET scans with fluorine-18 fluorodeoxyglucose as radiotracer were performed in 71 non-psychiatric subjects previously screened for psychopathology and subsequently genotyped for SLC6A4; PET images were compared with SPM2 according to s/s (n = 27), s/l (n = 25), and l/l (n = 19) groups considering a significance threshold in a priori selected areas of P < 0.001 and an extent threshold > or =5 voxels. The analysis showed an effect of interest among the three genotype groups in right anterior cingulate gyrus (ACC), left middle frontal gyrus, and left posterior cingulate gyrus (PCC). Comparison between l/l vs. s/s showed increased metabolism for l/l in left middle frontal gyrus and an increase for s/s in right ACC and left PCC. Comparison between s/s vs. s/l showed an increase for s/s in left PCC and right ACC. Increased basal metabolism in fronto-limbic structures for the s/s group may be conceived as an "overactive metabolic state" of these structures, possibly related to an increased susceptibility for developing an anxiety-depression spectrum disorder.
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PMID:Frontal and limbic metabolic differences in subjects selected according to genetic variation of the SLC6A4 gene polymorphism. 1585 Jul 37

Activity-dependent synaptic plasticity is known to be important in learning and memory, persistent pain and drug addiction. Glutamate NMDA receptor activation stimulates several protein kinases, which then trigger biochemical cascades that lead to modifications in synaptic efficacy. Genetic and pharmacological techniques have been used to show a role for Ca2+/calmodulin-dependent kinase II (CaMKII) in synaptic plasticity and memory formation. However, it is not known if increasing CaMKII activity in forebrain areas affects behavioral responses to tissue injury. Using genetic and pharmacological techniques, we were able to temporally and spatially restrict the over expression of CaMKII in forebrain areas. Here we show that genetic overexpression of CaMKII in the mouse forebrain selectively inhibits tissue injury-induced behavioral sensitization, including allodynia and hyperalgesia, while behavioral responses to acute noxious stimuli remain intact. CaMKII overexpression also inhibited synaptic depression induced by a prolonged repetitive stimulation in the ACC, suggesting an important role for CaMKII in the regulation of cingulate neurons. Our results suggest that neuronal CaMKII activity in the forebrain plays a role in persistent pain.
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PMID:Forebrain overexpression of CaMKII abolishes cingulate long term depression and reduces mechanical allodynia and thermal hyperalgesia. 1677 32

Gastric cancer was detected in a 71-year-old man with severe aortic stenosis. According to ACC/AHA guidelines, aortic stenosis in the patient was so severe that noncardiac surgery was considered appropriate only after aortic valve replacement. However, due to uncontrollable hemorrhage from gastric cancer, total gastrectomy was urgently required. Surgery was performed under epidural and general anesthesia. Blood pressure and heart rate were stable during anesthetic induction, tracheal intubation and skin incision. Just after peritoneal incision, however, ST decreased significantly following hypertension and sinus tachycardia, which were controllable by deepening of the anesthetic level. This ST depression was dependent on heart rate but not blood pressure. Therefore, in order to control the heart rate and prevent myocardial ischemia, low dose landiolol was infused prophylactically. This agent regulated the heart rate below 85 beats per minute without inducing hypotension and prevented myocardial ischemia during the remaining anesthetic course including extubation and recovery from anesthesia. Although beta blocker is not generally recommended in patients with aortic stenosis, present case suggests that landiolol is effective and useful to prevent cardiac ischemia even in a patient with severe aortic stenosis.
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PMID:[Landiolol prevented myocardial ischemia in a patient with severe aortic stenosis undergoing total gastrectomy]. 1751

Early life adversities are risk factors for later mood and emotional disorders. Repeated separation of infant marmosets from their parents provides a validated primate model of depression vulnerability, producing in-vivo biochemical and behavioural effects indicative of persistently altered stress reactivity and mild anhedonia. Here we report the long-term effect (in adolescence) of this intervention on the expression of synaptophysin, GAP-43, VGluT1, VGAT, MAP-2, spinophilin, and 5-HT1A and 5-HT2A receptors, in the anterior cingulate cortex (ACC; supragenual and subgenual areas) and amygdala (lateral, basal and central nuclei). These genes and regions are implicated in the response to stress or in mood disorder. The profile of 5-HT1A receptor binding in ACC was affected by early deprivation, notably in the subgenual region, with a decrease in deep laminae but an increase in superficial laminae. Following early deprivation, spinophilin mRNA was reduced in subgenual ACC. In the amygdala, no significant effects of the manipulation were seen, but expression of several transcripts was sexually dimorphic. There were correlations between expression of some transcripts and in-vivo measurements. The results show that early deprivation in a non-human primate has a selective long-term effect on expression of genes in the ACC, particularly the subgenual area. The results differ from those reported in the hippocampus of the same animals, indicating the presence of limbic region-specific long-term molecular responses to early life stress.
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PMID:Gene expression in the anterior cingulate cortex and amygdala of adolescent marmoset monkeys following parental separations in infancy. 1910 16


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