Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine whether some constitutional symptoms of influenza, such as headache, myalgia and nausea, could represent a viral infection of brain, muscle, and liver, we inoculated juvenile Balb/c mice intranasally with 103 plaque forming units of influenza B/Lee virus. Blood, brain, liver, skeletal muscle, and lung tissues were removed aseptically and assayed for infectivity by a plaque assay, viral RNA by reverse transcriptase-polymerase chain reaction (RT - PCR), viral antigen by immunoperoxidase staining, and histologic changes by light microscopy. Mice became ill 2 - 3 days post inoculation (PI). A productive viral infection of the lungs developed from days 1 - 8 with maxima of virus titers, pneumonia, and the number of immunoperoxidase staining lung cells occurring on days 2 - 6 PI. Virus isolation from blood was rare and viral RNA was detected intermittently in blood by RT - PCR. In many animals, a non-permissive or abortive infection of brain occurred from days 1 - 8 and peaked on days 3 - 4 PI. Viral RNA was detected in brain tissue and viral antigen was seen in cerebral endothelial cells but infectious virus was rarely isolated from brain. In liver, viral RNA was detected and viral antigen was seen occasionally in hepatocytes. In skeletal muscle, viral RNA was detected but neither infectious virus nor viral antigen was seen. A correlation existed between the severity of the illness, pneumonia, lung virus titer, viral antigen in lung cells, and extent of a non-permissive viral infection of brain and liver but not muscle. These studies demonstrate that following intranasal infection of influenza virus in mice, a viral pneumonia develops with subsequent intermittent viremia and non-permissive or abortive infection of brain, liver and muscle.
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PMID:Experimental influenza causes a non-permissive viral infection of brain, liver and muscle. 1117 25

Patients treated with nucleoside analogue reverse transcriptase inhibitors (NRTIs) develop a varying degree of myopathy or neuropathy after long-term therapy. Zidovudine (AZT) causes myopathy; zalcitabine (ddC), didanosine (ddl) and lamuvidine (3TC) cause neuropathy; stavudine (d4T) and fialuridine (FIAU) cause neuropathy or myopathy and lactic acidosis. The tissue distribution of phosphorylases responsible for phosphorylation of NRTIs relates to their selective tissue toxicity. The myopathy is characterized by muscle wasting, myalgia, fatigue, weakness and elevation of CK. The neuropathy is painful, sensory and axonal. In vitro, NRTIs inhibit the gamma-DNA polymerase, responsible for replication of mtDNA, and cause mtDNA dysfunction. In vivo, patients treated with AZT, the best studied NRTI, develop a mitochondrial myopathy with mtDNA depletion, deficiency of COX (complex IV), intracellular fat accumulation, high lactate production and marked phosphocreatine depletion, as determined with in vivo MRS spectroscopy, due to impaired oxidative phosphorylation. Animals or cultured cells treated with NRTIs develop neuropathy, myopathy, or cell destruction with similar changes in the mitochondria. There is evidence that the NRTI-related neuropathy is also due to mitochondrial toxicity. The NRTIs (AZT, ddC, ddl, d4T, 3TC) contain azido groups that compete with natural thymidine triphosphate as substrates of DNA pol-gamma and terminate mtDNA synthesis. In contrast, FIAU that contains 3'-OH groups serves as an alternate substrate for thymidine triphosphate with DNA pol-gamma and is incorporated into the DNA causing permanent mtDNA dysfunction. The NRTI-induced mitochondrial dysfunction has an influence on the clinical application of these agents, especially at high doses and when combined. They have produced in humans a new category of acquired mitochondrial toxins that cause clinical manifestations resembling the genetic mitochondrial disorders.
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PMID:Peripheral neuropathy and antiretroviral drugs. 1129 2

A 48-year-old-man returned to the Netherlands from Sierra Leone and was admitted with nausea, crampy abdominal pain, myalgia, arthralgia, headache and watery diarrhoea. This was the first case of Lassa fever diagnosed in the Netherlands since 1980. Despite treatment with ribavirin, the patient died on the 16th day of illness. Prompt diagnosis of Lassa fever is critical for the timely administration of ribavirin which improves diagnosis considerably, and for the timely implementation of isolation measures. Recently, a reverse transcriptase polymerase chain reaction (RT-PCR) has become available for the rapid diagnosis of acute Lassa fever, which was implemented to diagnose this patient.
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PMID:[A man with fatal Lassa fever following a stay in Sierra Leone]. 1246 60

Severe acute respiratory syndrome (SARS) is a newly emerged infectious disease with a significant morbidity and mortality. The major clinical features include persistent fever, chills/rigor, myalgia, malaise, dry cough, headache, and dyspnoea. Older subjects may present without the typical febrile response. Common laboratory features include lymphopenia, thrombocytopenia, raised alanine transaminases, lactate dehydrogenase, and creatine kinase. The constellation of compatible clinical and laboratory findings, together with certain characteristic radiological features and lack of clinical response to broad spectrum antibiotics, should arouse suspicion of SARS. Measurement of serum RNA by real time reverse transcriptase-polymerase chain reaction technique has a detection rate of 75%-80% in the first week of the illness.
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PMID:Severe acute respiratory syndrome (SARS): epidemiology and clinical features. 1525

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.
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PMID:[Intolerance to and/or drug interactions of anti-HIV and anti-HVC therapy]. 1591 Nov 83

Crimean-Congo haemorrhagic fever (CCHF) is an often fatal viral infection described in about 30 countries, and it has the most extensive geographic distribution of the medically important tickborne viral diseases, closely approximating the known global distribution of Hyalomma spp ticks. Human beings become infected through tick bites, by crushing infected ticks, after contact with a patient with CCHF during the acute phase of infection, or by contact with blood or tissues from viraemic livestock. Clinical features commonly show a dramatic progression characterised by haemorrhage, myalgia, and fever. The levels of liver enzymes, creatinine phosphokinase, and lactate dehydrogenase are raised, and bleeding markers are prolonged. Infection of the endothelium has a major pathogenic role. Besides direct infection of the endothelium, indirect damage by viral factors or virus-mediated host-derived soluble factors that cause endothelial activations and dysfunction are thought to occur. In diagnosis, enzyme-linked immunoassay and real-time reverse transcriptase PCR are used. Early diagnosis is critical for patient therapy and prevention of potential nosocomial infections. Supportive therapy is the most essential part of case management. Recent studies suggest that ribavirin is effective against CCHF, although definitive studies are not available. Health-care workers have a serious risk of infection, particularly during care of patients with haemorrhages from the nose, mouth, gums, vagina, and injection sites. Simple barrier precautions have been reported to be effective.
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PMID:Crimean-Congo haemorrhagic fever. 1655 45

In late March 2009, an outbreak of influenza A virus infection was detected in Mexico with subsequent cases observed in many other countries. The pandemic was caused by an H1N1 virus that represents a quadruple reassortment of 2 swine strains, 1 human strain, and 1 avian strain of influenza. Until February 1, 2010, a total of 47 cases of influenza A (Inf A) were recorded by the Spanish Society of Nephrology in kidney transplant recipients. Herein we have reported our 3 cases (6.4%) in this registry. A 17-year-old girl with hepatorenal polycystosis received a liver and kidney transplant at 37 months previously. She displayed high fever and mild respiratory symptoms that resolved without treatment. A 38-year-old woman with chronic renal failure (CRF) of undetermined etiology received a kidney transplant 9 months previously. She was admitted with a 5-day history of febrile syndrome and respiratory symptoms, with extensive bilateral pneumonia and acute severe respiratory failure that required admission to the intensive care unit. Her evolution was satisfactory. A 38-year-old woman with CRF of undetermined etiology received a kidney transplant 2.5 months previously. She was admitted in November 2009 with a 2-week history of fever, myalgia, general malaise, cough, and expectoration. Her course was satisfactory. In these cases we determined H1N1 Inf A pandemic variant by detection of Inf A Matrix Protein 2 gene M2 and the specific H1 gene for influenza pandemic H1N1 2009 with reverse transcriptase polymerase chain reaction Inf A/H1N1 (Roche). The 3 cases of Inf A in kidney transplant recipients recorded in the province of Almeria occurred in young women shortly after kidney transplantation, and with no other risk factors apart from those associated with the transplantation itself. From the consideration of respiratory and renal situations, their courses were satisfactory.
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PMID:Cases of swine flu in kidney transplant recipients in our hospital. 2097 Jun 30

A 58-year-old man presented to a local physician with cough, fever, myalgia and dyspnea. His chest X-ray film showed abnormal shadows and therefore he was admitted to our hospital. Chest computed tomography showed bilateral ground-glass opacities and bilateral consolidation. We suspected influenza pneumonia, but the results of both an influenza rapid antigen test and reverse transcriptase-polymerase chain reaction test for novel influenza (H1N1 2009) were negative. Transbronchial lung biopsy showed diffuse alveolar damage patterns. We diagnosed acute interstitial pneumonia and initiated corticosteroid therapy. Moreover, because influenza pneumonia could not be excluded according to his clinical picture, oseltamivir was administered. His condition improved and he was discharged. After discharge, the levels of antibody titers for influenza A virus significantly increased. We therefore re-evaluated his transbronchial lung biopsy specimen and found that immunohistochemical staining was positive for influenza A antigen in his bronchial and bronchiolar cells. We re-diagnosed his condition as influenza pneumonia. The possibility that influenza pneumonia may present in cases originally diagnosed as acute interstitial pneumonia must be considered.
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PMID:[Type A influenza pneumonia with diffuse alveolar damage diagnosed by increased antibody titers and immunohistochemical staining]. 2235 57

The HMG-CoA reductase inhibitors are a class of drugs also known as statins. These drugs are effective and widely prescribed for the treatment of hypercholesterolemia and prevention of cardiovascular morbidity and mortality. Seven statins are currently available: atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin. Although these drugs are generally well tolerated, skeletal muscle abnormalities from myalgia to severe lethal rhabdomyolysis can occur. Factors that increase statin concentrations such as drug-drug interactions can increase the risk of these adverse events. Drug-drug interactions are dependent on statins' pharmacokinetic profile: simvastatin, lovastatin and atorvastatin are metabolized through cytochrome P450 (CYP) 3A, while the metabolism of the other statins is independent of this CYP. All statins are substrate of organic anion transporter polypeptide 1B1, an uptake transporter expressed in hepatocyte membrane that may also explain some drug-drug interactions. Many HIV-infected patients have dyslipidemia and comorbidities that may require statin treatment. HIV-protease inhibitors (HIV PIs) are part of recommended antiretroviral treatment in combination with two reverse transcriptase inhibitors. All HIV PIs except nelfinavir are coadministered with a low dose of ritonavir, a potent CYP3A inhibitor to improve their pharmacokinetic properties. Cobicistat is a new potent CYP3A inhibitor that is combined with elvitegravir and will be combined with HIV-PIs in the future. The HCV-PIs boceprevir and telaprevir are both, to different extents, inhibitors of CYP3A. This review summarizes the pharmacokinetic properties of statins and PIs with emphasis on their metabolic pathways explaining clinically important drug-drug interactions. Simvastatin and lovastatin metabolized through CYP3A have the highest potency for drug-drug interaction with potent CYP3A inhibitors such as ritonavir- or cobicistat-boosted HIV-PI or the hepatitis C virus (HCV) PI, telaprevir or boceprevir, and therefore their coadministration is contraindicated. Atorvastatin is also a CYP3A substrate, but less potent drug-drug interactions have been reported with CYP3A inhibitors. Non-CYP3A-dependent statin concentrations are also affected although to a lesser extent when coadministered with HIV or HCV PIs, mainly through interaction with OATP1B1, and treatment should start with the lowest available statin dose. Effectiveness and occurrence of adverse effects should be monitored at regular time intervals.
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PMID:Drug-drug interactions between HMG-CoA reductase inhibitors (statins) and antiviral protease inhibitors. 2370 78

Sandfly fever is an infectious disease transmitted to people through sandfly bites. It usually takes three days and causes chills, high fever, headache, nausea-vomiting and myalgia. The causative agent, namely sandfly fever virus (SFV), is a member of the Bunyaviridae family, Phlebovirus genus. Toscana virus (TOSV) is a serotype of SFV, as so Sicilian and Naples viruses. Seroprevalence studies have demonstrated that SFV infections which have mild symptoms or asymptomatic, can be overcome. Studies concerning TOSV infections in Turkey are limited to a small number of regional seroprevalence surveys, blood-donor screening studies and detection of viral RNA in previously collected cerebrospinal fluid samples of suspected meningoencephalitis patients in whom no causative agents were identified. In this report from Turkey, the first acute case of TOSV infection diagnosed in a patient with HIV seropositivity, was presented. A 42-year-old male patient was admitted to Numune Research and Training Hospital Adana, Turkey with high fever, headache and malaise. The patient who lived in an area near to a forest in Istanbul, had no contact history with ticks, mosquitoes and other animals. He stated that he had had the symptoms before arriving to Adana. The patient was hospitalized due to leucopenia, anemia, and thrombocytopenia accompanying high fever. Serum samples were sent to National Arbovirus and Viral Zoonotic Diseases Unit of the Turkish Public Health Institute, for the detection of Crimean-Congo haemorrhagic fever (CCHF) virus and SFV. Western Blot test was run to confirm the presence of anti-HIV antibodies detected twice with ELISA. In the following days, the patient's fever and symptoms decreased, and thrombocyte levels increased. Although CCHF virus PCR and ELISA IgM tests as well as SFV IgM and IgG immunofluorescence antibody (IFA) tests were negative, real time reverse transcriptase PCR test yielded a positive result for TOSV. SFV IgG antibodies against Toscana and Naples viruses were found to be positive in the serum sample collected at the end of a three-week follow-up. Even though TOSV infection is usually known to have an asymptomatic clinical course, it may rarely lead to serious manifestations like meningoencephalitis. In our country where SFV is endemic, TOSV should be considered in the differential diagnosis of patients presenting with high fever and meningoencephalitis symptoms.
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PMID:[Acute Toscana virus infection in an anti-HIV positive patient]. 2450 28


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