Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Telomerase is a specialized RNA-directed DNA polymerase that extends telomeres of eukaryotic chromosomes. Telomerase gene expression is active in germinal, stem and tumoral cells and repressed in normal human somatic cells. Activation of telomerase involves immortalization, while repression of this enzyme involves the shortening of telomeres in each round of chromosomal replication. Telomere shortening constitutes a mechanism for cells to control cell division and the entrance in the replicative senescence state. If the expression of this enzyme is forced, senescent human cells will extend their life span reaching the immortalization and malignization of the cells. Activation or depression of telomerase activity has important implications in aging and cancer therapy. Telomerase regulation is a multifactorial process in which telomerase expression, post-translational protein-protein interactions and protein phosphorylation are involved.
...
PMID:[Physiopathologic implications of telomerase]. 1120 52

Cortical spreading depression (CSD) is characterized by reversible neuronal dysfunction in the absence of cell death. Preconditioning by CSD induces tolerance against subsequent lethal ischemia. In this study, we used quantitative reverse transcriptase-polymerase chain reaction and immunocytochemistry to analyze proinflammatory cytokine expression after CSD induced by topical application of potassium chloride (KCl) to the cortical surface of rat brains. Relative to control cortex, we found an increase of tumor necrosis factor-alpha (mean 62-fold, P < 0.001) and interleukin (IL)-1beta (mean 24-fold, P < 0.001) mRNA levels within 4 hours ipsilateral to the site of KCl application. At 16 hours cytokine expression was decreasing toward baseline levels. Ipsilateral cytokine induction was abolished by pretreatment with the noncompetitive N-methyl-d-aspartate antagonist, MK-801. In contrast to focal cortical infarction, cytokine induction in CSD was not accompanied by the expression of inducible nitric oxide synthase mRNA. In immunocytochemical studies, expression of IL-1beta protein was localized to ramified microglia in cortical layers I to III of the ipsilateral hemisphere. Our finding that NMDA receptor signaling without subsequent neuronal cell death is sufficient to induce inflammatory cytokine expression in the brain has basic implications for central nervous system immunoregulation. We postulate that cytokine expression in CSD forms part of a physiologic stress response that contributes to the development of ischemic tolerance in this and other preconditioning paradigms.
...
PMID:Cortical spreading depression induces proinflammatory cytokine gene expression in the rat brain. 1129 76

St. John's wort, an herbal treatment for depression, should not be combined with certain drugs, including some antiretrovirals. St. John's wort can speed up the body's elimination of some drugs. When HIV medications are used, blood levels could drop low enough to allow resistance to occur. So far, St. John's wort has been tested only with the protease inhibitor indinavir (Crixivan), but it is likely to affect other drugs in that class and possibly non-nucleoside reverse transcriptase inhibitors. This warning follows a study by the National Institutes of Health (NIH) on dosing and blood levels of indinavir in HIV-negative test subjects. More information on the study is available on The Lancet's Web site. The text of the FDA's advisory letter is included.
...
PMID:St. John's wort warning: do not combine with protease inhibitors, NNRTIs. 1136 7

The treatment of HIV infection has changed dramatically in recent years as a result of the development of new drugs which allows a variety of multitherapy combinations more adapted to patients' needs and thereby improving compliance. Efavirenz is a non-nucleoside reverse transcriptase inhibitor. In addition to a potent antiretroviral activity, efavirenz is an easy-to-take drug with once-daily dosing and is usually well tolerated. Efavirenz, however, may induce psychic alterations which are variable and atypical in both their clinical presentation and severity. As early as the first days of treatment, efavirenz may provoke surprising phenomena such as nightmares, vivid dreams, hallucinations or illusions, and twilight states. Depersonalization and derealization episodes, personality alterations, stream of thought troubles and unusual thought contents, atypical depression and cognitive disorders have also been observed. These phenomena may occur either early or later on treatment. The prevalence of severe psychic disorders is less than 5%, but they are often responsible for harmful treatment discontinuations. Psychiatric side effects are heterogeneous and probably not related to pre-existing psychologic weakness. We do not have enough data to evaluate these side effects and their etiopathogeny. The drug could act directly on the central nervous system since it crosses the blood-brain barrier, on the serotoninergic and dopaminergic systems. Some authors have compared efavirenz-induced psychic effects to those associated with LSD and found structural similarities between the two molecules. However, the heterogeneity and low prevalence of the psychiatric side effects of efavirenz suggest and individual sensitivity. In order to improve patient care, a better clinical approach, neuropsychological evaluation, and functional brain imagery should be used to progress in the analysis and comprehension of these disorders. We discuss in this paper the case of Mister H. This HIV-infected person presented with two severe melancholic episodes associated with marked cognitive disorders which resisted two successive antidepressant treatments (viloxazine and citalopram, respectively) prescribed at effective doses and for sufficient time duration. Mister H. had no personal or family psychiatric antecedent. His psychic condition improved only when efavirenz was discontinued. However, drug discontinuation may not be an obligatory step to improve the patient's condition since antidepressant treatment has been found effective in some similar situations. Actually, each case should be discussed with the clinicians taking care of the patient.
...
PMID:[Apropos of atypical melancholia with Sustiva (efavirenz)]. 1148 60

Cortical spreading depression (CSD) may be the underlying mechanism of migraine aura. The role of CSD in initiating a migraine headache remains to be determined, but it might involve specific changes in gene expression in the brain. To examine these changes, four episodes of CSD at 5-minute intervals were induced in the mouse brain by application of 300mM KCl, and gene expression was examined 2 hours later using cDNA array and reverse transcriptase-polymerase chain reaction. Controls consisted of groups that received anesthesia only, attachment of recording electrodes only, and application of 0.9% NaCl. Of the over 1,180 genes examined in our experiments, those consistently regulated by CSD included vasoactive peptides; the vasodilator atrial natriuretic peptide was induced by CSD, while the vasoconstrictor neuropeptide Y was downregulated. Other genes specifically regulated by CSD were involved in oxidative stress responses (major prion protein, glutathione-S-transferase-5, and apolipoprotein E). L-type calcium channel mRNA was upregulated. In summary, CSD regulates genes that are intrinsic to its propagation, that identify accompanying vascular responses as a potential source of pain, and that protect against its potential pathological consequences. We believe these observations have strong relevance to the mechanisms of migraine and its outcomes.
...
PMID:Cortical spreading depression and gene regulation: relevance to migraine. 1192 Oct 56

Efavirenz is a nonnucleoside reverse transcriptase inhibitor that can be given with other antiretroviral agents for the treatment of human immunodeficiency virus infection. A 47-year-old man with acquired immunodeficiency syndrome developed severe depression and suicidal ideation necessitating psychiatric hospitalization and antidepressant therapy. The symptoms occurred in temporal relation to the introduction of efavirenz into his highly active antiretroviral therapy regimen. Similar serious psychiatric adverse effects have been associated with this agent. Clinicians should monitor for central nervous system adverse effects in all patients taking efavirenz.
...
PMID:Central nervous system adverse effects with efavirenz: case report and review. 1212 26

Resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) increases with the wider use of this class of antiretroviral therapy. The association between adherence and resistance to NNRTI-based regimens is poorly understood. Predictors of virologic failure and resistance according to a baseline evaluation of nonadherence risk factors were determined in a cohort of 71 human immunodeficiency virus (HIV)-infected patients with early virologic response who received an NNRTI-based regimen. During the median follow-up of 29 months, 20 (28%) of 71 patients experienced virologic failure with an NNRTI-based regimen. Virologic failure was associated with repeated drug holidays (> or =48 h of unplanned drug cessation), depression, younger age, and low adherence to therapy during baseline evaluation. Moreover, repeated drug holidays was the only risk factor for developing a major mutation conferring cross-resistance to the NNRTI class (hazard ratio, 22.5; 95% confidence interval, 2.8-180.3; P<.0001). Patients' previous adherence to therapy and drugs genetic barriers, not only the number of pills or doses involved, should be taken into consideration in the decision to simplify highly active antiretroviral therapy.
...
PMID:Predictors of virologic failure and resistance in HIV-infected patients treated with nevirapine- or efavirenz-based antiretroviral therapy. 1512 46

Cushing's syndrome secondary to ectopic adrenocorticotropic hormone (ACTH) secretion is rarely observed in breast carcinoma and only four cases have been previously published. We report here the case of a 50-year-old woman who presented with a history of diffuse bone pain associated with multiple hepatic, pulmonary, and bone metastases. A core needle biopsy specimen revealed an invasive ductal carcinoma in the right breast. The patient subsequently developed an ACTH-dependent paraneoplastic Cushing's syndrome and she died of arrhythmia and heart failure, despite treatment. At autopsy, immunohistochemical staining showed chromogranin A and ACTH positivity in the breast tumor and a lung metastasis. The mRNA expression of the pro-opiomelanocortin (POMC) gene was detected in tumoral cells by reverse transcriptase polymerase chain reaction (RT-PCR). This is the first case of Cushing's syndrome secondary to ectopic ACTH secretion where the presence of ACTH by immunohistochemistry and the expression of the POMC gene by RT-PCR have both been demonstrated in a breast carcinoma with metastases. The clinical history and the pathologic findings are presented with the methods and results of the molecular analysis. This case illustrates an example of ectopic ACTH syndrome in a breast carcinoma with neuroendocrine (NE) differentiation. This NE phenotype is directly related to the synthesis of ACTH by the tumoral cells. It should be kept in mind that an ectopic ACTH syndrome may be produced not only by small cell carcinoma or endocrine tumors but also by breast cancer. No relationship has been established between NE features and prognostic factors or patient outcome for this peculiar type of breast carcinoma. The demonstration of mRNA POMC in breast carcinoma with NE features suggests a depression and/or an activation of the POMC gene linked to the NE differentiation.
...
PMID:Pro-opiomelanocortin expression in a metastatic breast carcinoma with ectopic ACTH secretion. 1523 95

We investigated the antagonistic effect of 1-piperidinecarboxamide, N-[2-[[5amino-l-[[4-(4-pyridinyl)-l-piperazinyl]carbonyl]pentyl]amino]-1-[(3,5-dibromo-4-hydroxyphenyl)methyl]-2-oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl) (BIBN4096BS) on the calcitonin gene-related peptide (CGRP)-induced responses by using isometric myograph and FURA-2 technique in human subcutaneous arteries removed in association with abdominal surgery. BIBN4096BS, at the concentration of 1 pm, had no significant effect on the CGRP-induced relaxation in these vessels. At the concentration of 10 pM, BIBN4096BS had a competitive antagonistic-like behaviour characterized by parallel rightward shift in the log CGRP concentration-tension curve with no depression of the E(max). At the higher concentrations (0.1 and 1 nM), BIBN4096BS had a concentration-dependent noncompetitive antagonistic effect on the CGRP-induced responses. The efficacy and potency of CGRP was significantly greater in the smaller (lumen diameter approximately 200 microM) human subcutaneous arteries compared to the larger ones. The apparent agonist equilibrium dissociation constant, K(A), for CGRP(1) receptors in the human subcutaneous arteries was approximately 1 nM. Analysis of the relationship between receptor occupancy and response to CGRP indicates that the receptor reserve is relatively small. Using reverse transcriptase-polymerase chain reaction (RT-PCR), the presence of mRNA sequences encoding the calcitonin receptor-like receptor, receptor activity modifying protein (RAMP1, RAMP2, RAMP3) and receptor component protein were demonstrated in human subcutaneous arteries, indicating the presence of CGRP(1)-like receptor and the necessary component for the receptor activation. In conclusion, the inhibitory action of BIBN4096BS at the low concentration (10 pM) on the CGRP-tension curve (but not intracellular calcium concentration ([Ca(2+)](i)) resembles what is seen with a reversible competitive antagonist. However, at the higher concentrations (0.1 and 1 nM), BIBN4096BS acts as a selective noncompetitive inhibitor at CGRP(1) receptors in human subcutaneous arteries.
...
PMID:Noncompetitive antagonism of BIBN4096BS on CGRP-induced responses in human subcutaneous arteries. 1547 23

Treating Hepatitis C among HIV patients under antiretroviral drug therapy requires a high degree of vigilance and continuous monitoring because of frequent problems with intolerance and/or drug interactions. Recent studies, including three therapeutic trials, on Ribavic, APRICOT, and ACTG A5671, have given some insights on following these patients up. The adverse effects are relatively similar in HCV-HIV-co-infected patients and patients infected by HCV only. Their frequency is, on the other hand, higher among HCV-HIV-Co-infected patients. The adverse-effects are consistent, in a non-exhaustive way, with pseudo influenza-like symptoms, fever, myalgia, cephalgia, with psychiatric disorders (irritability, depression, etc.); endocrine disorders (thyroid dysfunction, diabetes...); and with hematological anomalies especially anemia and leucopenia. But the percentage of lymphocyte T CD4 is not modified, therefore there is no risk of opportunistic infection. Pharmacokinetic interactions between antiretroviral drugs and treatment for HCV infection including ribavirin plus interferon alpha (IFN-alpha) or pegylated IFN are described. They are almost exclusively due to the combination of ribavirin and of nucleoside analogue reverse transcriptase inhibitors. One of the principal consequences is the emergence of mitochondrial toxicity defined by the occurrence of hyperlactatemia, or acute pancreatitis). Thus, some combinations should be avoided such as ddI+ribavirin and ddI+d4T+ribavirin. The d4T+ribavirin combination must also be used with caution.
...
PMID:[Intolerance to and/or drug interactions of anti-HIV and anti-HVC therapy]. 1591 Nov 83


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

---