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)

This review describes the transmission, clinical picture and immunological abnormalities of HIV infection in children in general, and the special problems of AIDS in African children. The review begins with a thorough introduction to the epidemiology of AIDS. Transmission to children generally involves vertical transmission by placental transfer or transmission of HIV via transfusion of blood and blood products, or by contaminated needles. Casual transfer is unknown, and only a few cases of transmission via breast milk are known. The clinical picture of HIV infection in infants and children differs from that in adults in 3 important aspects: earlier onset, different clinical presentation and existence of AIDS embryopathy. The average onset was 5 months of age. The most common symptoms in young children are chronic interstitial pneumonitis without demonstrable etiology, hepatomegaly, failure to thrive, adenopathy, diarrhea, oral or perineal thrush, eczema and thrombocytopenia. The common opportunistic infections are pneumocystis carinii pneumonia, cytomegalovirus, Epstein-Barr virus, Cryptosporidium diarrhea, pyogenic infections of the middle ear and gram-negative septicemia. Several infections seen in adult AIDS cases are rare in children: mycobacterium avium-intracellulare, toxoplasma gondii, hepatitis B, as well as Kaposi's sarcoma, malignant lymphoma and cardiac abnormalities. The AIDS embryopathy or HIV dysmorphic syndrome is characterized by immunological abnormalities, growth failure, and craniofacial dysmorphism, particularly microcephaly, prominent box-like forehead, hypertelorism, flattened nasal bridge, obliquity of the eyes, blue sclerae and patulous lips. AIDS in African children is extremely difficult to diagnose because of similarities between the presenting symptoms and those commonly seen in sick children there, many of whom are also immune compromised. Where serotesting is available, the picture is complicated by cross reaction between the test agents and some factor found in sera from malaria patients. Seropositivity in some areas is high, increased by the prevalence of transfusion and injection treatments. Diagnosis is made more difficult by lack of laboratory facilities and difficulties in follow-up for pediatric patients. The CDC definitions of AIDS and ARC, and the WHO/CDC definitions of AIDS are appended.
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PMID:Human immunodeficiency virus infection in childhood. 245 15

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. 804 85

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

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