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)

We used colloidal Au to enhance the amount of antibody immobilized on a gold electrode and ultimately monitored the interaction of antigen-antibody by impedance measurement. Self-assembly of 6 nm (diameter) colloidal Au onto the self-assembled monolayers (SAMs) of 4-aminothiophenol modified gold electrode resulted in an easier attachment of antibody. The redox reactions of [Fe(CN)6](4-)/[Fe(CN)6](3-) on the gold surface were blocked due to the procedures of self-assembly of 4-aminothiophenol and antibody immobilization, which were investigated by cyclic voltammetry and impedance spectroscopy. The interaction of antigen with grafted antibody recognition layers was carried out by soaking the modified electrode into a phosphate buffer at pH 7.4 with various concentrations of antigen at 37 degrees C for 30 min. The antibody recognition layers and their interactions with various concentrations of antigen could be detected by measurements of the impedance change. The results show that this method has good correlation for detection of Hepatitis B virus surface antigen in the range of 0.5-200 microg/l and a detection limit of about 50 ng/l.
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PMID:Application of impedance spectroscopy for monitoring colloid Au-enhanced antibody immobilization and antibody-antigen reactions. 1468 41

For the simultaneously visual detection of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus type-1 (HIV-1), a qualitative DNA chip method, combining multiplex and nested polymerase chain reaction (PCR) with arrayed anchored primer PCR and a biotin-avidin alkaline phosphatase (Av-AP) indicator system, was developed. After pretreatment of infected blood samples and reverse transcription of the RNA virus genome, PCR was performed in a single tube by using the outer primer pairs. Second round nested multiplex PCR was performed on the DNA chip, on which the primers array had already been prepared. During the arrayed anchored multiplex PCR, 5[N-(N-biotinylaminocaproyl)-epsilon-3-aminoallyl]-2-deoxy-uridine-5-triphosphate (biotin-11-dUTP) was incorporated into the extended DNA chains in order to bind avidin alkaline phosphatase via avidin and biotin. To produce purple precipitates on the chips, the enzyme substrate 5-bromo-4-chloro-3-indolyl phosphate (BCIP) was used in conjunction with the enhancer, nitro blue tetrazolium (NBT). Blood samples containing the three viruses were tested using this DNA chip and about 1 pg of specific viral DNA fragments were detected on the chip wells after nested PCR.
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PMID:A visual DNA chip for simultaneous detection of hepatitis B virus, hepatitis C virus and human immunodeficiency virus type-1. 1470 86

Immunoassays for the detection of hepatitis B virus (HBV) in biological samples were developed. Using recombinant HBV antigens (Ags) and HBV-specific antibodies (Abs), we designed and evaluated a panel of enzyme-linked immunosorbent assays (ELISAs) detecting the main hepatitis B-related viral markers, namely HBV surface Ag (HBsAg), HBV e Ag (HBeAg), Abs to HBsAg (anti-HBs), Abs to HBV core Ag (anti-HBc) and Abs to HBeAg (anti-HBe), in blood serum. The ELISAs were validated using a panel of prescreened, by commercial tests, serum samples. In principle, HBV Ags or anti-HBV monoclonal antibodies (mAbs) were immobilised on microplate wells. Horseradish peroxidase (HRP) or biotin were used to prepare labeled Abs. Specifically for the determination of HBsAg and HBeAg, two-site sandwich immunoenzymometric assays were developed. The useful range was estimated at 20-500 ng/ml and human serum samples assayed were diluted 10- and 4-fold for HBsAg and HBeAg, respectively, with phosphate buffered saline (PBS) containing Tween 20 and gelatin. For the detection of Abs to HBs an indirect ELISA was formulated. Sera were similarly 4-fold diluted in the same buffer. Finally, competitive ELISAs were used for detecting anti-HBc and anti-HBe and sera tested were diluted 20- and 5-fold, respectively. All selected dilutions resulted in the accurate and reliable determination of HBV Ags and anti-HBV Abs. Taken altogether, these ELISAs are highly specific and equally sensitive to the circulating tests. However, their design could be very useful for research and/or preclinical studies of selected HBV-infected individuals.
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PMID:Serological detection of hepatitis B viral infection by a panel of solid-phase enzyme-linked immunosorbent assays (ELISA). 1501 59

Hepatitis B surface antigen (HBsAg) differs from many antigens because of its associated lipid bilayer that is largely composed of phospholipids. In general, phosphate groups adsorb strongly to hydroxylated mineral surfaces by ligand exchange. The purpose of this study was to investigate the mechanism of adsorption of hepatitis B surface antigen to aluminum hydroxide adjuvant with emphasis on the role of phospholipids in this adsorption. The adsorption of HBsAg by aluminum hydroxide adjuvant exhibits a high affinity adsorption isotherm. The Langmuir equation was used to calculate the adsorptive capacity (1.7 microg/microg Al), which is the amount of HBsAg adsorbed at monolayer coverage and the adsorptive coefficient (6.0 ml/microg), which is a measure of the strength of the adsorption force. The relatively high value of the adsorptive coefficient indicates that adsorption is due to a strong attractive force. Ligand exchange between a phosphate of the antigen and a surface hydroxyl of the adjuvant provides the strongest adsorption mechanism. The adsorption capacity of HBsAg was not affected by increased ionic strength indicating that electrostatic attraction is not the predominant adsorption force. Adsorption was also not affected by the addition of ethylene glycol indicating that hydrophobic interactions were not the predominant adsorption force. The strength of the adsorption force was indicated by the resistance of HBsAg to elution when exposed to interstitial fluid. Less than 5% of the HBsAg adsorbed to aluminum hydroxide adjuvant in a model vaccine was eluted during a 12 h in vitro exposure to interstitial fluid at 37 degrees C. Less than 1% of the adsorbed HBsAg in two commercial vaccines was eluted by in vitro exposure to interstitial fluid for 48 h at 37 degrees C. Thus, it was concluded that adsorption of HBsAg by aluminum hydroxide adjuvant is predominantly due to ligand exchange between the phospholipids in HBsAg and surface hydroxyls in aluminum hydroxide adjuvant.
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PMID:Mechanism of adsorption of hepatitis B surface antigen by aluminum hydroxide adjuvant. 1506 71

Targeting drugs to specific organs, tissues, or cells is an attractive strategy for enhancing drug efficacy and reducing side effects. Drug carriers such as antibodies, natural and manmade polymers, and labeled liposomes are capable of targeting drugs to blood vessels of individual tissues but often fail to deliver drugs to extravascular sites. An alternative strategy is to use low molecular weight prodrugs that distribute throughout the body but cleave intracellularly to the active drug by an organ-specific enzyme. Here we show that a series of phosphate and phosphonate prodrugs, called HepDirect prodrugs, results in liver-targeted drug delivery following a cytochrome P450-catalyzed oxidative cleavage reaction inside hepatocytes. Liver targeting was demonstrated in rodents for MB06866 [(2R,4S)-9-[2-[4-(3-chlorophenyl)-2-oxo-1,3,2-dioxaphosphorinan-2-yl]methoxyethyl]adenine (remofovir)], a Hep-Direct prodrug of the nucleotide analog adefovir (PMEA), and MB07133 [(2R,4S)-4-amino-1-[5-O-[2-oxo-4-(4-pyridyl)-1,3,2-dioxaphosphorinan-2-yl]-beta-d-arabinofuranosyl]-2(1H)-pyrimidinone], a HepDirect prodrug of cytarabine (araC) 5'-monophosphate. Liver targeting led to higher levels of the biologically active form of PMEA and araC in the liver and to lower levels in the most toxicologically sensitive organs. Liver targeting also confined production of the prodrug byproduct, an aryl vinyl ketone, to hepatocytes. Glutathione within the hepatocytes rapidly reacted with the byproduct to form a glutathione conjugate. No byproduct-related toxicity was observed in hepatocytes or animals treated with HepDirect prodrugs. A 5-day safety study in mice demonstrated the toxicological benefits of liver targeting. These findings suggest that HepDirect prodrugs represent a potential strategy for targeting drugs to the liver and achieving more effective therapies against chronic liver diseases such as hepatitis B, hepatitis C, and hepatocellular carcinoma.
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PMID:Liver-targeted drug delivery using HepDirect prodrugs. 1534 17

The purpose of this study was to develop a stable single-dose vaccine based on recombinant hepatitis B surface antigen (HBsAg) in poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres, in which HBsAg was stabilized by a protein stabilizer (trehalose) and an antacid (Mg(OH)2). The microspheres were prepared by the double emulsion method and characterized by scanning electron microscopy. To neutralize the acids liberated by the biodegradable lactic/glycolic acid based polymer, we coincorporated into the polymer an antacid, Mg(OH)2, which neutralized the acidity during degradation of the polymer and also prevented HBsAg structural losses and aggregation. The antigen integrity after encapsulation was examined by sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by silver staining, isoelectric focusing and Western blotting techniques, which confirmed that antigen remained intact after encapsulation. In-vitro release experiments were performed in phosphate-buffered saline (pH 7.4) and the release of antigen was found to be improved by the protein stabilizer (trehalose). In stability studies, performed at 37 degrees C, the microspheres were found to be stable for 16 days. The immunogenicity of stable microsphere formulations bearing HBsAg was compared with the conventional alum-absorbed HBsAg vaccine in a guinea-pig model. The antibody titre indicated that a single injection of stabilized HBsAg-PLGA microspheres produced a better immune response than two injections of alum-formulated HBsAg vaccine. The findings suggest that recombinant HBsAg can be stabilized by use of a protein stabilizer and antacid during entrapment, and this stabilized preparation can be useful for antigen delivery.
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PMID:Development of a single-dose stabilized poly(D,L-lactic-co-glycolic acid) microspheres-based vaccine against hepatitis B. 1548 38

A new single-injection combination vaccine against six diseases has been developed to accommodate the growing number of recommended paediatric vaccines. A pentavalent liquid diphtheria, tetanus, acellular pertussis (3-component), hepatitis B, and inactivated polio (types 1-3) combined vaccine (DTPa-HBV-IPV) is extemporaneously mixed with a lyophilized Haemophilus influenza type B (Hib) conjugate vaccine (polyribosyl-ribitol phosphate (PRP)-T) and given as a single-injection. A cohort of 368 healthy infants was initially studied to evaluate the immunogenicity and reactogenicity of this hexavalent combination given as a primary course at 2, 4, and 6 months of age. At 15 months of age, from this cohort, 219 children received a booster dose of a licensed DTPa/Hib (PRP-T) vaccine to assess the booster response, while 70 received a challenge dose of unconjugated PRP (PRP) vaccine (to evaluate Hib-specific memory) plus a separate DTPa vaccine. Seven to 10 days following plain PRP challenge, anti-PRP geometric mean antibody concentrations (GMCs) had increased 13-fold to 5.67 microg/ml, and thirty days after conjugated PRP booster vaccination, anti-PRP antibody GMCs increased 102-fold. Both responses are indicative of immune memory. Vaccination was well tolerated following all primary and booster doses, although 10.5% of booster recipients experienced >50-mm local swelling at the site of DTPa vaccination. We conclude that DTPa-HBV-IPV/Hib is safe and immunogenic for primary vaccination, and that Hib-specific memory is induced by primary vaccination.
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PMID:Antibody persistence, PRP-specific immune memory, and booster responses in infants immunised with a combination DTPa-HBV-IPV/Hib vaccine. 1551 2

Acyclovir is an antivirus drug which has a good in vitro activity against hepatitis B virus. But because of the low solubility and low distribution in liver, the clinical application of acyclovir in hepatitis B was limited. To increase the solubility and the distribution in liver, acyclovir-dextran conjugate was synthesized by formation of Schiff's base. The solubility of obtained conjugate was 12 times greater than free acyclovir. Acyclovir will be slowly released from the obtained conjugate in pH 7.4 phosphate buffer solution (PBS) at 37 degrees C with a rate constant of 0.0035 hr(-1). Pharmacokinetic studies of acyclovir and acyclovir-dextran conjugate were conducted in mice by i.v. administration. Acyclovir concentrations in plasma, liver and kidney were determined by HPLC method. Relatively higher distribution of acyclovir in liver was observed when i.v. acyclovir-dextran conjugate as compared with i.v. free acyclovir. The results of pharmacokinetic studies indicated that acyclovir-dextran conjugate will be a good candidate to treat hepatitis B.
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PMID:Studies on acyclovir-dextran conjugate: synthesis and pharmacokinetics. 1555 20

To probe the ways by which the antisense gene of hepatitis B virus (HBV) can be transferred and transcripted in eukaryotic cells to inhibit HBV replication and expression. Two retroviral vectors that carried antisense gene of hepatitis B virus (HBV) PreC/C or PreS/S region were constructed. The HBV ayw PreC/C and PreS/S fragments were inserted into the vector pDO. R cloning site in the sense or antisense orientation and the recombinant retroviral vectors were then transfected into PA317 packaging cells by calcium phosphate coprecipitation, respectively. The stably transformed G418-resistant PA317 cells were selected and the recombinant retroviruses released from transfected G418-resistant PA317 cells were assayed by G418 selection method, using NIH 3T3 cells as target cells. Southern blot and RNA Dot blot analysis showed that the recombinant retroviral vector sequences were stably integrated into the chromosome of transfected PA317 cells and the antisense RNA of HBV PreS/S or PreC/C gene also transcripted in the transduced NIH 3T3 cells. These results suggested that antisense gene of HBV can be successfully transferred and transcripted in target cells through retroviral vector mediated gene transfer and the antisense retroviral vectors may be potentially useful for anti-HBV gene therapy.
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PMID:[Transcription of antisense RNA of hepatitis B virus through retroviral mediated gene transfer]. 1561 39

Phenylmethylphosphor-L-alaninate pronucleotides 7a, 7b, 8a, and 8b, cyclic phosphates 10a and 10b, and phosphates 11a and 11b derived from 2,2-bis(hydroxymethyl)methylenecyclopropane analogues 1a, 1b, 2a, and 2b were synthesized and evaluated for their antiviral activity. An improved protocol for the synthesis of analogues 1a, 1b, 2a, and 2b is also described. Phosphate 11a was the most effective agent against human and murine cytomegalovirus (EC(50) 0.25-1.1 microM). The Z-pronucleotides 7a and 7b had EC(50) 3.6-25.2 and 3-18.4 microM, respectively. The EC(50) of cyclic phosphate 10a was 6.0-20 microM. The activity against Epstein-Barr (EBV) was assay-dependent. Pronucleotides 7a and 7b and phosphate 11a had EC(50) 2.3-3.4 microM against EBV/H-1, but 7b was cytotoxic (CC(50) 3.8 microM). Cyclic phosphate 10a was the only compound effective against EBV/Daudi (EC(50) 0.96 microM), but it was inactive in H-1 cells. Pronucleotide 7a was active against varicella zoster virus with EC(50) 6.3 and 7.3 microM, respectively, and hepatitis B virus (HBV, EC(50) 4.1 microM). Cyclic phosphate 10a was the most effective analogue against HBV (EC(50) 0.8 microM).
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PMID:Nucleotides and pronucleotides of 2,2-bis(hydroxymethyl)methylenecyclopropane analogues of purine nucleosides: synthesis and antiviral activity. 1563 3


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