Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Soluble CD54 levels in sera were quantitated in asymptomatic intravenous drug users, homosexuals, and patients with lymphadenopathy, AIDS-related complex, or acquired immunodeficiency syndrome. Soluble CD54 levels were elevated in human immunodeficiency virus (HIV)-seronegative asymptomatic intravenous drug users, reflecting infections like cytomegalovirus, Epstein-Barr virus, and hepatitis B virus. The sera of human immunodeficiency virus-seropositive groups of patients also had elevated levels of soluble CD54, reflecting infections like cytomegalovirus and human immunodeficiency virus infection.
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PMID:Elevated levels of soluble CD54 (ICAM-1) in human immunodeficiency virus infection. 810 44

The compound 9-(2-phosphonylmethoxyethyl)adenine (PMEA) is a potent inhibitor of a number of viruses in vitro such as human immunodeficiency virus types 1 and 2, herpes simplex virus types 1 and 2, hepatitis B virus, cytomegalovirus, and Epstein-Barr virus. PMEA also proved to be effective in vivo against feline immunodeficiency virus in cats and simian immunodeficiency virus in rhesus monkeys. In an open, non-placebo-controlled trial, the safety of weekly doses of PMEA in 10 patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex was studied for a period of 11 weeks. CD4+ T-cell counts at baseline were between 10 and 450/mm(3). The drug was administered intravenously at a dose of 1000 mg. No serious side-effects were seen. On one occasion one patient showed alanine aminotransferase and aspartate aminotransferase levels 5 times higher than the upper limit of normal and another patient showed on one occasion aspartate aminotransferase levels 5 times higher than the upper limit of normal. In another patient serum amalyse levels increased, on one occasion 1.5 times above the upper limit of normal. An improvement in general well-being was reported by all patients. For patients with a CD4+ T-cell count > 100/mm(3) at baseline, the CD4+ T-cell count increased from a mean of 283/mm(3) at baseline to a mean of 448/mm(3) at the end of the study. Repeat infusions of PMEA at a dose of 1000 mg were safe and well tolerated. Our results suggest that PMEA, administrated according to this treatment schedule, may be effective in treating patients with human immunodeficiency virus infection.
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PMID:Safety of 9-(2-phosphonylmethoxyethyl)adenine (PMEA) in patients with human immunodeficiency virus infection: a pilot study. 886 29

Three different groups of asymptomatic children, aged from 12 to 24 months (30 subjects per each group), i.e. controls, only HIV, or HIV/hepatitis B virus (HBV) double infected, were studied, as concerned the following systemic immune parameters: immunoglobulin (IgG, IgM, IgA, IgD) levels; absolute numbers of blood CD+4, CD+8, CD+16 and CD+19 cells; phytohaemagglutinin (PHA)-blast responsiveness of T lymphocytes; natural killer (NK) cell activity--as tested by means of cytotoxicity assays; per cent suppression of PHA-dependent T cell blastogenesis in the presence of concanavalin A (Con A) selected T suppressor (Ts) cells. On the other hand, in 15 ARC-shifting cases belonging to HIV, and HIV/HBV groups, respectively, a second serum sample was collected and searched comparatively with the corresponding first serum sample, as regarded: presence of total and anti-p24 HIV antibodies, patterns of Western Blot (WB), as well as amounts of free p24-HIV antigen. In asymptomatic double HIV/HBV infected subjects, some immune disorders occurred, at a more significant degree, as compared to only HIV-infected. Once the shift toward ARC being installed, in both infected groups a decrease of anti-p24 HIV antibody presence, disappearance of corresponding band in WB confirmation test, as well as presence of free p24 antigen in serum, were noticed. However, greater amounts of p24 antigen in HIV/HBV infected, as compared to only HIV infected patients, were found. Some considerations about diagnostic and predictive value of presented data are discussed.
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PMID:Comparative study on some systemic humoral and cellular immune markers in only HIV or HIV and hepatitis B infected children. 970 55

This article, based on information from specialists at Johns Hopkins, poses and then answers 3 broad questions about the acquired immunodeficiency syndrome (AIDS). 1st, it is asked, "What is AIDS and how serious is it?" It is noted that AIDS is only 1 of several forms taken by infection with the human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). The earliest form of infection is believed to occur within a few weeks of exposure to the virus, and some patients develop an acute syndrome that resembles infectious mononucleosis. These symptoms disappear after 4-6 weeks, by which time the patient has developed antibodies to the virus. About 2-4%/year of asymptomatic carriers go on to develop AIDS-related complex (ARC), and 15-30% of ARC patients develop AIDS within 5 years. The 2nd question posed is, "How do you catch AIDS?" To cause infection, the virus must go directly into the blood, although the virus alone may not be enough to cause sickness. Previous viral infections such as hepatitis B, herpes, cytomegalovirus, and intestinal parasites have been suggested as co-factors of AIDS. Promiscuity increases the chances of contracting AIDS. Observations of the families of AIDS patients and health care personnel who work with AIDS patients suggest that AIDS cannot be caught by casual contact. Finally, it is asked, "What is being done about AIDS?" 4 strategies are outlined: 1) as a result of donor screening for antibodies to HTLV-III/LAV, AIDS has been completely removed from the blood banks; 2) virologists are attempting to understand the virus so that it can be attacked, and understanding has been advanced by the theory that HTLV-III might be what is called a "slow virus;" 3) education about AIDS is changing the sexual practices that transmit AIDS; and 4) epidemiologists are carefully following those who are at risk, have been exposed, or are already sick.
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PMID:AIDS: just the facts from specialists at Johns Hopkins. 1231 1

Current therapies for chronic hepatitis B virus infection (CHB) - nucleos(t)ide analogue reverse transcriptase inhibitors and interferons - result in low rates of functional cure defined as sustained off-therapy seroclearance of hepatitis B surface antigen (HBsAg). One likely reason is the inability of these therapies to consistently and substantially reduce the levels of viral antigen production. Accumulated evidence suggests that high serum levels of HBsAg result in exhaustion of the host immune system, rendering it unable to mount the effective antiviral response required for HBsAg clearance. New mechanistic approaches are required to produce high rates of HBsAg seroclearance in order to greatly reduce off-treatment disease progression. Already shown to be a clinically viable means of reducing gene expression in a number of other diseases, therapies based on RNA interference (RNAi) can directly target hepatitis B virus transcripts with high specificity, profoundly reducing the production of viral proteins. The fact that the viral RNA transcripts contain overlapping sequences means that a single RNAi trigger can result in the degradation of all viral transcripts, including all messenger RNAs and pregenomic RNA. Advances in the design of RNAi triggers have increased resistance to degradation and reduced nonspecific innate immune stimulation. Additionally, new methods to effectively deliver the trigger to liver hepatocytes, and specifically to the cytoplasmic compartment, have resulted in increased efficacy and tolerability. An RNAi-based drug currently in clinical trials is ARC-520, a dynamic polyconjugate in which the RNAi trigger is conjugated to cholesterol, which is coinjected with a hepatocyte-targeted, membrane-active peptide. Phase 2a clinical trial results indicate that ARC-520 was well tolerated and resulted in significant, dose-dependent reduction in HBsAg for up to 57days in CHB patients. RNAi-based therapies may play an important role in future therapeutic regimes aimed at improving HBsAg seroclearance and eliminating the need for lifelong therapy. This paper forms part of a symposium in Antiviral Research on "An unfinished story: from the discovery of the Australia antigen to the development of new curative therapies for hepatitis B."
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PMID:Synthetic RNAi triggers and their use in chronic hepatitis B therapies with curative intent. 2612 70

ARC-520 Injection, an RNA interference drug for the treatment of hepatitis B that targets cccDNA-derived viral mRNA transcripts with high specificity, effectively reduces the production of viral proteins and HBV DNA. In this phase 1 randomized, double-blind, placebo-controlled study, 54 healthy volunteers (half male, half female) received a single, intravenous dose of 0.01-4.0 mg/kg ARC-520 Injection (n = 36) or placebo (n = 18). Assessments included safety, tolerability, pharmacokinetics, and pharmacodynamics (cytokines and complement). Pharmacokinetics of the siRNA and peptide excipient components contained in ARC-520 Injection showed a relatively short half-life of 3-5 and 8-10 hours, respectively. Dose exposure linearity was demonstrated within the dose range. ARC-520 Injection was well tolerated, with adverse-event frequency the same as placebo and no serious adverse events. ARC-520 Injection was initially found to induce histamine release through mast cell degranulation, resulting in 2 moderate hypersensitivity reactions. However, after initiation of pretreatment with oral antihistamine, no further hypersensitivity reactions occurred. Low-level, transient complement induction and sporadic, mild, and transient elevations of several cytokines were observed but not associated with any symptoms. ARC-520 Injection showed a favorable tolerability profile in this single-dose study in healthy volunteers. Oral antihistamine pretreatment is recommended in the future to offset mast cell degranulation stimulation.
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PMID:Safety, Tolerability, and Pharmacokinetics of ARC-520 Injection, an RNA Interference-Based Therapeutic for the Treatment of Chronic Hepatitis B Virus Infection, in Healthy Volunteers. 2773 30


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