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

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Query: UMLS:C0019163 (hepatitis B)
38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human hepatitis B virus (HBV) carriers run an increased risk of hepatocellular carcinoma (HCC), where the expression of HBV genes play the most important role in the initial stage of hepatocarcinogenesis. As the integration of HBV DNA into the cellular DNA of HCC as well as chronic hepatitis was demonstrated very frequently, the virus-cell fusion gene was considered to be most essential for hepatocarcinogenesis. Among the virus-cell fusion genes, the X gene is known to function as a transactivator for viral and cellular genes at the time of chronic infection. One mechanism for hepatocarcinogenesis that appears particularly reasonable is transactivation of cellular oncogenes by the X-cell fusion protein. In 1990, we found a part of the amino acid sequences in the X protein to be highly homologous to functionally essential sequences in the Kunitz domain, characteristic of Kunitz-type serine protease inhibitors. It has been recently demonstrated that X protein expressed in E. coli or from the in vitro translation system binds to a specific serine protease from the liver cells. These results indicate that transactivation function of X protein may be exerted by acting as a protease inhibitor analogue to control the proteolytic pathway of cellular transcription factor(s). On the other hand, viral hepatitis resulting from viruses other than hepatitis A virus and HBV has been referred to as non-A, non-B hepatitis. In 1989, the viral genome was molecularly cloned as a positive-strand RNA having about 10 kb in size and named as hepatitis C virus (HCV). Details of genetic structure and mechanism of expression are currently under investigation at molecular level.
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PMID:[Gene expression of hepatitis viruses in the liver and hepatocarcinogenesis]. 132 91

The emphysema associated with the inherited serum deficiency of alpha 1-antitrypsin appears to result from an imbalance between neutrophil elastase and its major inhibitor within the alveolar structures. In the present study we assessed the feasibility of reversing this biochemical defect within the lung via parenteral replacement therapy with an alpha 1-antitrypsin concentrate of normal plasma. A 20--40% polyethylene glycol precipitate of pooled human donor plasma was used to obtain an enriched alpha 1-antitrypsin concentrate devoid of hepatitis B antigen and immunoglobulins. Using this material, five individuals with severe serum alpha 1-antitrypsin deficiency (PiZ phenotype) and advanced emphysema received 4 g of alpha 1-antitrypsin intravenously at weekly intervals for four doses. During this period of weekly replacement therapy alpha 1-antitrypsin serum levels were maintained at greater than or equal to 70 mg/dl, the level likely required for effective antielastase protection of the lung. In addition, assessment of lower respiratory tract antielastase activity by bronchoalveolar lavage demonstrated that parenteral replacement of alpha 1-antitrypsin resulted in establishment of effective antielastase activity within the alveolar structures. There were no untoward side effects consequent to this approach to the replacement therapy of alpha 1-antitrypsin. These results demonstrate that the parenteral replacement of alpha 1-antitrypsin provides a means of obtaining elastase-antielastase balance within the lung of individuals with this serum protease inhibitor deficiency.
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PMID:Replacement therapy of alpha 1-antitrypsin deficiency. Reversal of protease-antiprotease imbalance within the alveolar structures of PiZ subjects. 702 85

In the last few years, plasma fractionation has been subjected to major technological changes which have contributed to improve the viral safety and overall purity of plasma derivatives. New viral inactivation treatments, primarily solvent-detergent and pasteurization, have been introduced in the manufacturing processes of plasma derivatives to ensure the inactivation of major plasma-borne viruses, including HIV and hepatitis B and C viruses. Concurrently, new highly purified products obtained by chromatographic methods (mainly ion exchange and/or immunopurification) have been developed in the last five years and have replaced former preparations, providing a significantly higher safety level in terms of purity and viral risks. For an example, the new generation of Factor VIII and Factor IX concentrates (to treat hemophilia A and hemophilia B, respectively), which have been introduced in the last five years, are purified over 10,000- to 20,000-fold from plasma, as compared to only 50- to 100-fold for the former products. Similarly, new, standardized, clotting factor or protease inhibitor concentrates have been made available, thus permitting to carry out selective hemotherapy of specific diseases. Examples include the development of von Willebrand factor, factor XI, protein C, or alpha 1-antitrypsin concentrates for the substitutive therapy of congenital or acquired deficiencies. In addition, the concept of good manufacturing practices has been implemented, whereas carefully controlled, validated processes are contributing to the consistency in the quality of those products. Current major problems in plasma fractionation relate to the potential occurrence of new pathogenic agents that could resist present viral inactivation treatments and to the potential effect of given purification technologies on the development of immunogenic properties of proteins. Current trends indicate that significant progress in viral safety of plasma derivatives (for example through the introduction of new concept such as viral filtration) are to be expected very soon. Further research in this very important field is mandatory as plasma should remain the starting material of important therapeutic products in the coming years.
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PMID:[Plasma fractionation. Progress, problems and perspectives]. 799 59

Early prophylaxis after exposure to human immunodeficiency virus (HIV) can reduce the risk of HIV infection 10-fold and should be recommended or offered after all parenteral exposures. The current recommendations from the Centers for Disease Control and Prevention call for the use of two nucleoside antiretroviral drugs (zidovudine and lamivudine) with or without a protease inhibitor. The use of interferon alfa-2b has not been extensive but may be of benefit in cases of massive exposure. Both the HIV-source patient and the person exposed to HIV should be tested for hepatitis B and C and syphilis, as well as HIV antibody.
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PMID:New recommendations for prophylaxis after HIV exposure. 935 25

Hepatitis B virus (HBV) resistance to lamivudine has not been extensively documented in human immunodeficiency virus (HIV)-infected patients. We studied the long-term incidence of HBV resistance to lamivudine in HIV-positive patients. Sixty-six HIV-HBV-coinfected patients were studied while receiving lamivudine (150 mg twice daily) as a part of antiretroviral therapy. All these patients had a detectable serum HBV DNA at the beginning of lamivudine therapy. Serum HBV DNA was quantified by molecular hybridization. Sequence analysis of the HBV polymerase was performed in patients who became resistant to lamivudine. After 2 months of lamivudine, HBV DNA became undetectable in 57 patients (86.4%, 95% CI: 75.7%-93.6%). After 2 years of lamivudine, 47% +/- 18.6% of the patients, had sustained HBV-DNA suppression. All the 22 tested patients with HBV resistance developed mutation at position 550 in the YMDD motif of the DNA polymerase. None of the following variables were associated with an increased risk of lamivudine resistance: age, associated protease inhibitor therapy, Center for Disease Control (CDC) stage C, known HIV-infection duration, serum HBV-DNA level at baseline, CD4 cell count and serum alanine transaminase levels at baseline and at HBV-replication suppression (2 months of lamivudine). Lamivudine (300 mg/d) is effective for the inhibition of HBV replication in HIV-infected patients. However, emergence of lamivudine-resistant HBV may occur in 20% of patients per year.
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PMID:Long-term incidence of hepatitis B virus resistance to lamivudine in human immunodeficiency virus-infected patients. 1077 55

Since many new anti-HIV drugs are variations of currently available drugs, they may be more effective for people who are beginning treatment. One study shows favorable results when using efavirenz in triple combination therapy; however, it is recommended that this therapy be reserved for people who are treatment-naive and symptom-free. It is still unclear if all non-nucleoside RT inhibitors (NNRTIs) are as potent as efavirenz and whether the long-term potential for them is as promising as standard combinations. Researchers caution against pairing an NNRTI with a protease inhibitor in the event that resistance to the combination develops. That resistance may eliminate the option of using any other protease inhibitor or NNRTI in future therapies. Conversely, abacavir, an NARTI, has been effective in combination with many protease inhibitors. Amprenavir shows good antiviral activity; although studies show that it may not be successful as a salvage therapy with protease inhibitors. Nucleotide analogue reverse transcriptase inhibitors, such as adefovir and bis-poc PMPA, showed moderate anti-HIV potency. A study evaluating FTC alone showed a good reduction in viral load. FTC also fights hepatitis B and requires only one dose daily. Information is included about expanded access programs for abacavir, adefovir, and efavirenz.
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PMID:New drugs on the horizon. 1136 12

In collaboration with the Dutch Institute for Health Care Improvement (CBO) and on the basis of recent developments, new guidelines have been developed for the diagnosis and treatment of HIV-infected patients. The most important recommendations are: Treatment of adult patients is indicated if HIV load > 30,000 RNA copies/ml, or when CD4+ cell count is < 350 x 10(6) cells/l. Treatment of children is indicated if HIV load > 5,000 copies/ml, even when CD4+ cell count is > 500 x 10(6) cells/l. Optimal antiretroviral treatment consists of a combination of two nucleoside reverse transcriptase inhibitors (NRTIs) and one protease inhibitor, or a combination of two NRTIs and one non-nucleoside reverse transcriptase inhibitor. Patients on antiretroviral treatment should be monitored every 3 months. Undetectable HIV load should be the target of first- or second-line antiretroviral treatment. In order to prevent HIV transmission from mother to child, prescription of antiretroviral drugs after the first three months of pregnancy is indicated in pregnant women with a detectable HIV load. Prophylaxis of opportunistic infections can be discontinued if CD4+ cell count recovers above 200 x 10(6)/l. In case of exposure to HIV due to a needle or other occupational accident or unsafe sexual contact, post-exposure prophylaxis should be offered after careful risk evaluation. Preferably, vaccination to prevent pneumococci infections, influenza, hepatitis A or hepatitis B should be given when CD4+ cell count is > 200 x 10(6)/l.
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PMID:[CBO guidelines 'Antiretroviral therapy in the Netherlands']. 1153 75

Risk factors associated with the occurrence of protease inhibitor (PI)-related severe and serious adverse drug reactions (SADRs) were analyzed in a prospective cohort of 1155 patients who initiated PI-containing therapy. During a total follow-up of 2037 patient-years, 169 SADRs were reported, yielding a rate of 8 incidents per 100 patient-years (95% confidence interval [CI], 6.8-8.6). The most frequent SADRs were elevated transaminase levels (in 49 events); renal colic (27); abnormal hematological findings (23); and metabolic (18), neuromuscular (7), pancreatic (6), cutaneous (6), cardiovascular (5), and psychiatric disorders (5). Among baseline characteristics, plasma human immunodeficiency virus RNA levels of >or=5 log(10) copies/mL (hazard ratio [HR], 1.5; 95% CI, 1.1-2.2), elevated aspartate aminotransferase levels (HR, 1.1 for each 20 IU of elevation; 95% CI, 1.1-1.2), creatinine clearance levels of <70 mL/min (HR, 2.1; 95% CI, 1.2-3.7), test results positive for hepatitis C virus antibodies or hepatitis B surface antigenemia (HR, 2.6; 95% CI, 1.8-3.7), and receipt of indinavir (HR, 1.7; 95% CI, 1.2-2.4) were independently predictive of a SADR. SADRs were frequent in the first 4 months after initiation of highly active antiretroviral therapy but continued to occur after that time period.
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PMID:Incidence of and risk factors for adverse drug reactions in a prospective cohort of HIV-infected adults initiating protease inhibitor-containing therapy. 1530 35

Emtricitabine is a once-daily nucleoside reverse transcriptase inhibitor (NRTI) that selectively and potently inhibits human immunodeficiency virus type 1 (HIV-1) replication. Emtricitabine is used in combination with other antiviral agents for the treatment of HIV-1 and is currently under investigation for the treatment of hepatitis B virus (HBV) infection. Like other NRTIs, emtricitabine is activated to a triphosphate derivative, which mediates the antiviral effect. Emtricitabine triphosphate is incorporated into a primer DNA strand resulting in chain termination and blockade of DNA- or RNA-directed DNA synthesis. One key benefit of emtricitabine over other NRTIs is its favorable pharmacokinetic profile that permits once-daily dosing; it has a long mean plasma elimination half-life of 8-10 hours, and the intracellular half-life of emtricitabine triphosphate is 39 hours after multiple doses of 200 mg daily. In adult patients infected with HIV-1, emtricitabine has a convenient and simple dosing schedule of one 200-mg capsule once daily, and is as effective as lamivudine 150 mg twice daily and more effective than stavudine twice daily at suppressing plasma HIV-1 RNA when administered as part of a triple-drug regimen. Also, triple therapy including emtricitabine is as effective as a protease inhibitor- based regimen in maintaining durable suppression of plasma HIV-1 RNA levels in adults. Early clinical results show that triple therapy including emtricitabine is also effective in decreasing or maintaining durable suppression of HIV-1 RNA levels in children and adolescents with HIV-1 infection. It is also effective against HBV in patients co-infected with HIV-1 and in patients monoinfected with HBV. In clinical practice, emtricitabine is generally very well tolerated, with most adverse events being mild to moderate in severity. The now available combination of emtricitabine with tenofovir in the same pill makes it a very attractive backbone combination to use in conjunction with other antiretroviral drugs.
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PMID:Emtricitabine: a novel nucleoside reverse transcriptase inhibitor. 1603 88

Atazanavir is a novel and potent protease inhibitor that differs from other protease inhibitors because of its good gastrointestinal tolerability, once-daily dosing, low pill burden and it does not seem to cause insulin resistance or lipid elevations in short-term use. Atazanavir produces an increase in indirect bilirubin levels, which is not related to hepatotoxicity. The incidence of atazanavir-related hyperbilirubinaemia does not seem to be increased in hepatitis B or C coinfection. I50L is atazanavir's signature mutation. It has been shown in previously treated patients that resistance is likely when three or more protease inhibitor resistance-related primary mutations are present.
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PMID:Review of atazanavir: a novel HIV protease inhibitor. 1608 44


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