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)

Foscarnet, licenced by Astra pharmaceutical products, is a pyrophosphate analogue that selectively inhibits replication of viruses in infected cells. It inhibits in vitro the replication of all herpes viruses, including human cytomegalovirus (HCMV) at concentrations of 100 to 300 mumol/l and has a dose-related inhibitory effect on HIV-1 virus, influenza virus and hepatitis B virus. It does not require intra-cellular phosphorylation for antiviral activity. Oral bioavailability of foscarnet is low (12-22%), and foscarnet must be administered intravenously. It is mainly eliminated unchanged by the kidneys. Mean half-life in plasma ranges from 3.4 to 5 h. For acute therapy, the currently recommended regimen is 60 mg/kg t.i.d. or 90-100 mg/kg b.i.d. In AIDS patients, foscarnet is an effective treatment of HCMV retinitis. Healing or stabilisation of lesions is obtained in 85-95% of patients after 2 weeks or 3 weeks therapy. For HCMV gastrointestinal disease, complete or partial response rates of 57-95% have been reported with foscarnet. The optimal maintenance dosage of foscarnet necessary in CMV infections in AIDS patients remains to be clearly established. Data from small samples size studies have shown that foscarnet decreased significantly circulating levels of HIV antigen in AIDS patients with HCMV disease. Foscarnet is an effective treatment for acyclovir-resistant herpes simplex virus and for acyclovir-resistant varicella-zoster virus (40 mg/kg every 8 h). In patients with immunosuppression not HIV-related HCMV infections, particularly interstitial pneumonia in transplant recipients, experience with foscarnet is limited. The major adverse effect of foscarnet is reversible renal dysfunction, due to acute tubular toxicity. In may be partially prevented by hyperhydratation during the treatment. Fluctuations in serum calcium and phosphore levels, with both increase and decrease are also frequent adverse reactions. Most clinical symptoms are related to decrease in ionized calcium levels. Hyperphosphatemia, a clinically benign phenomenom, reflects the incorporation of foscarnet in bone. Penile ulcerations have been described and may result from mococutaneous direct toxicity of foscarnet eliminated in urine. Although relapses frequently occur after a few months of maintenance therapy, foscarnet that shows a marked activity against HCMV in vitro, has allowed important progress in therapy of HCMV infections in AIDS patients.
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PMID:Pharmacology and clinical use of foscarnet. 1861 71

The hepatitis B virus-encoded X (HBx) protein coactivates transcription of a variety of viral and cellular genes and it is believed to play essential roles in viral replication and hepatocarcinogenesis. To examine the pleiotropic effects of HBx protein on host cell protein expression, we utilized 2-DE and MS analysis to compare and identify differentially expressed proteins between a stable HBx-transfected cell line (HepG2-HBx), constitutively expressing HBx, and vector control cells. Of the 60 spots identified as differentially expressed (+/- over 2-fold, p < 0.05) between the two cell lines, 54 spots were positively identified by MS/MS analysis. Several recent studies suggested that HBx was involved in regional hypermethylation of tumor suppressor genes and global hypomethylation of satellite 2 repeats during hepatocarcinogenesis; however, no specific gene has been reported as hypomethylated by HBx. Promoter methylation analysis was examined for those protein spots showing significant alterations, and our results revealed that specific genes, such as aldehyde dehydrogenase 1 (ALDH1), can be hypomethylated by HBx, and two calcium ion-binding proteins, S100A6 and S100A4, were hypermethylated by HBx and could be re-expressed by AZA (DNA methylase inhibitor) treatment. Moreover, via cluster and pathway analysis, we proposed a hypothetical model for the HBx regulatory circuit involving aberrant methylation of retinol metabolism-related genes and calcium homeostasis-related genes. In summary, we profiled proteome alterations between HepG2-HBx and control cells, and found that HBx not only induces regional hypermethylation but also specific hypomethylation of host cell genes.
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PMID:Proteomic profiling identifies aberrant epigenetic modifications induced by hepatitis B virus X protein. 1911 5

In acetate buffer solution, the reaction of H2O2 with KI was catalyzed by horseradish peroxidase (HRP) to form I3-. The I3- combined respectively with rhodamine S(RhS), rhodamine 6G(Rh6G), rhodamine B(RhB) and butyl-rhodamine B(b-RhB) to form RhS-I3, Rh6G-I3, RhB-I3 and b-RhB-I3 association particles, resulting in the fluorescence quenching at 580, 580, 554 and 554 nm, respectively. The effect of pH value, rhodamine dye concentration, KI concentration, H2O2 concentration, reaction temperature and time on the fluorescence quenching intensity (deltaF) of the four catalytic systems was considered respectively. For the RhS, Rh6G, RhB and b-RhB catalytic systems, pH 4.6-3.2 x 10(-5) mol x L(-1) RhS-4 x 10(-3) mol x L(-1) KI-1.30 x 10(-5) mol x L(-1) H2O2-25 degrees C-20 min, 4.8-2.4 x 10(-5) mol x L(-1) Rh6G-4 x 10(-3) mol x L(-1) KI-2.59 x 10(-5) mol x L(-1) H2O2-25 degrees C-20 min, 4.6-1.6 x 10(-5) mol x L(-1) RhB-4 x 10(-3) mol x L(-1) KI-2.16 x 10(-5) mol x L(-1) H2O2-25 degrees C-20 min, and 4.6-1.6 x 10(-5) mol x L(-1) b-RhB-4 X 10(-3) mol x L(-1) KI-3.02 x 10(-5) mol x L(-1) H2O2-25 degrees C-20 min were chosen for use respectively. Under the optimal conditions, the HRP linear range was 8-6 400 pg x mL(-1) for the RhS catalytic system, 40-4 000 pg x mL(-1) for the Rh6G catalytic system, 32-3 200 pg x mL(-1) for the RhB catalytic system and 40-6 400 pg x mL(-1) for the b-RhB catalytic system, with a detection limit of 3.2, 3.0, 2.4 and 3.7 pg x mL(-1) HRP, respectively. The regress equation of the four catalytic systems was deltaF = 0.061 1c+39.6, deltaF = 0.047 2c+50.4, deltaF = 0.138 6c+34.2 and deltaF = 0.026 25c+36.72, with a correlation coefficient of 0.997 9, 0.999 0, 0.997 3 and 0.996 9, respectively. The RhS catalytic system was most sensitive, and was chosen for the determination of HRP. The influence of foreign substance on the RhS assay of 3.5 ng x mL(-1) HRP was examined, with a relative error of +/- 10%. A 3000-times L-glutamic acid, L-lysine, Ca2+, Mg2+, Cu2+, Fe3+, Zn2+ and vitamin B6, 1000-times HAS etc did not interfere with the assay. This showed that the assay has good selectivity. The RhS fluorescence quenching assay was applied to the determination of HRP in the solution of hepatitis B surface antibody labeling HRP, with satisfactory results.
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PMID:[Fluorescence quenching assay of ultratrace horseradish peroxidase using rhodamine dye]. 1945 17

The HBx protein of human hepatitis B virus (HBV) activates a calcium-dependent kinase pathway which is essential for the viral replication. In this study, we found that HBx expression in the absence of other HBV proteins and in the context of HBV replication decreased the mitochondrial calcein-AM/CoCl(2) signals by 10% and 14% in HepG2 cells and by 15% and 10% in Huh7 cells, respectively. This indicates that HBx can induce mitochondrial permeability transition (MPT) and cause calcium effusion into the plasma. In addition, RNA interference of Cylophilin D decreased HBx-induced MPT and suppressed HBV DNA replication by 41% in HepG2 cells. Our results suggest that HBx expression can induce MPT and facilitate HBV DNA replication.
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PMID:Involvement of mitochondrial permeability transition in hepatitis B virus replication. 1968 11

End-stage renal disease has emerged as a major public health problem around the world. In recent decades, several important advances have been made in the therapy of hemodialysis (HD) with the introduction of international guidelines to ensure the delivery of optimum care to HD patients. An increased mortality risk in HD patients unable to meet six targets in different areas of HD practice has been reported by the Dialysis Outcomes and Practice Patterns Study investigators. In this retrospective study, we assessed the current practice patterns of care for HD patients in the Kaser El-Aini Nephrology and Dialysis Center in comparison with Dialysis Outcomes Quality Initiative Guidelines, European Best Practice Guidelines, Centers for Disease Control and Prevention guidelines for prevention of transmission of infections among HD patients, and American Association for Medical Instrumentation (AAMI) standards for dialysis water quality. The mean percent of urea reduction was 63 +/- 8.8% in prevalent HD patients. An arteriovenous fistula was the vascular access in 91% of prevalent HD patients, whereas a temporary catheter was used in 9% of cases mostly as a bridge till arteriovenous fistula creation/maturation. Bicarbonate was the base used in 80% of the cases. Ninty-seven percent patients had thrice-weekly sessions and 3% had two dialysis sessions/wk. The mean serum albumin was 4.19 +/- 0.39 g/dL; 66.66% of prevalent patients had serum albumin level >4 g/dL. The mean serum calcium was 8.66 +/- 1.4 mg/dL, phosphorus was 6.26 +/- 2.54 mg/dL, and approximately 60% of patients had a serum phosphorus level >5.5 mg/dL. The CaxPi product was higher than 55 in around 40% of the cases, and the parathyroid hormone level was in the range of 150 to 300 pg/mL in around 10% of prevalent patients. The mean hemoglobin was 9.23 +/- 7.18 g/dL in prevalent cases; around 70% of cases had a hemoglobin level <11 g/dL. Iron deficiency was prevalent as 18% of patients, with serum ferritin <200 ng/L, and 34% had total serum test <20%. Seventy percent of the patients were hepatitis C virus positive and 4% were hepatitis B surface antigen positive, and all were negative for the human immunodeficiency virus serological test. Dialysis water was monitored regularly for chemical and bacterial contamination as recommended by the American Association for Medical Instrumentation, but an endotoxin assay is currently not included in the monitoring checklist. The annual mortality rate was 8% in 2007. The current audit revealed a reasonable quality of care for HD patients in the fields of vascular access care, dialysis adequacy, and nutrition areas. It also reveals the need for improving anemia management and control of hyperphosphatemia with dietary counseling and more frequent dialysis. To fully meet the guideline targets, each patient should be treated in an individualized way with more counseling, nutritional education, and individualized dialysis prescription. Besides, the unit needs to adopt primary and secondary intervention strategies to prevent and promptly correct any deviation from the desired targets.
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PMID:Quality of care assessment and adherence to the international guidelines considering dialysis, water treatment, and protection against transmission of infections in university hospital-based dialysis units in Cairo, Egypt. 1975 97

Chronic inflammation can be a major risk factor for cancer development and may contribute to the high worldwide incidence of hepatocellular carcinoma (HCC). Cyclooxygenase-2 (COX-2) is known to be an important mediator of inflammatory responses; however, its link to hepatitis B virus (HBV)-mediated inflammatory responses has not been established. Here, we demonstrate that the expression of COX-2 mRNA and protein was significantly elevated in cells transfected by HBV replicon but not in cells transfected by HBV genome lacking the HBx gene. Notably, COX-2 induction was correlated with HBx's ability to increase reactive oxygen species (ROS) levels. Consistently with this, antioxidant treatment and ectopic expression of manganese superoxide dismutase or catalase completely abolished COX-2 induction. Interestingly, a mitochondria localization-defective mutant of HBx (HBx(Delta 68-117)) neither increased intracellular ROS levels nor induced COX-2 expression. HBx(68-117), which encodes only amino acids 68-117 and is sufficient for mitochondria localization, increased ROS levels but did not induce COX-2 expression. Similarly, HBx targeting to the outer membrane of mitochondria (Mito-HBx) increased ROS but also failed to increase COX-2 expression, suggesting that other cytoplasmic signaling pathways are involved in HBx-mediated COX-2 induction. Indeed, inhibition of cytoplasmic calcium signaling by cyclosporine A, blocking mitochondrial permeability transition pore, and herbimycin, and inhibition of calcium-dependent tyrosine kinase suppressed HBV-mediated COX-2 induction. Thus, the data indicate that both mitochondrial ROS and cytoplasmic calcium signaling are necessary for the COX-2 induction. Our studies revealed a pathophysiological link between HBV infection and hepatic inflammation, and this chain of events might contribute to early steps in HBV-associated liver carcinogenesis.
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PMID:HBx targeting to mitochondria and ROS generation are necessary but insufficient for HBV-induced cyclooxygenase-2 expression. 1994 Sep 73

Worldwide, there are over 350 million people who are chronically infected with the human hepatitis B virus (HBV); chronic HBV infections are associated with the development of hepatocellular carcinoma (HCC). The results of various studies suggest that the HBV X protein (HBx) has a role in the development of HBV-associated HCC. HBx can regulate numerous cellular signal transduction pathways, including those that modulate cell proliferation. Many previous studies that analyzed the impact of HBx on cell proliferation pathways were conducted using established or immortalized cell lines, and when HBx was expressed in the absence of HBV replication, and the precise effect of HBx on these pathways has often differed depending on experimental conditions. We have studied the effect of HBx on cell proliferation in cultured primary rat hepatocytes, a biologically relevant system. We demonstrate that HBx, both by itself and in the context of HBV replication, affected the levels and activities of various cell cycle-regulatory proteins to induce normally quiescent hepatocytes to enter the G(1) phase of the cell cycle but not to proceed to S phase. We linked HBx regulation of cell proliferation to cytosolic calcium signaling and HBx stimulation of HBV replication. Cumulatively, our studies suggest that HBx induces normally quiescent hepatocytes to enter the G(1) phase of the cell cycle and that this calcium-dependent HBx activity is required for HBV replication. These studies identify an essential function of HBx during HBV replication and a mechanism that may connect HBV infections to the development of HCC.
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PMID:The hepatitis B virus X protein modulates hepatocyte proliferation pathways to stimulate viral replication. 2005 44

We have described herein a 39-year-old male patient with hepatitis B virus-related cirrhosis (Child class C), showing a prolonged corrected QT interval, who developed torsades de pointes (TdP) in the neohepatic stage of liver transplantation (LT). There was no arrhythmia in the pre-anhepatic and anhepatic stages. Multiple premature ventricular complexes, ventricular tachycardia, and TdP suddenly developed at 16 minutes after graft reperfusion without any prodromal arrhythmia; they persisted for 118 seconds. Laboratory tests showed that serum potassium, calcium, and magnesium concentrations of 4.7 mmol/L, 1.05 mmol/L, and 1.85 mg/dL, respectively were within normal ranges. Likely causative factors for TdP in this patient included a prolonged corrected QT interval (553 msec), a low hematocrit (21%), and a low arterial blood pressure (systolic blood pressure, 80-90 mm Hg; diastolic blood pressure; 20-26 mm Hg) in the neohepatic stage. This case demonstrated the importance of optimal maintenance of coronary perfusion, with an adequate hematocrit level and electrolyte concentrations, to prevent the development of TdP in cirrhotic patients with a prolonged corrected QT interval during LT.
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PMID:Torsades de pointes triggered by severe diastolic hypotension with low hematocrit in the neohepatic stage of liver transplantation: a case report. 2062 May 55

Fanconi syndrome results from generalised renal tubular toxicity and, owing to phosphate wasting can cause hypophosphataemic osteomalacia. Large clinical trials advocated the safety of adefovir dipivoxil at a daily dose of 10 mg, the standard dose given to patients with hepatitis B. We diagnosed Fanconi syndrome in conjunction with severe osteomalacia in 2 hepatitis B-positive patients on standard-dose adefovir therapy. The first patient was a 40-year-old male with a 5 month history of bone pain involving his knees, ankles, and ribs. He had been receiving adefovir dipivoxil for 27 months before the development of hypophosphataemia, urinary phosphate wasting, and aminoaciduria. These abnormalities resolved within weeks of discontinuation of adefovir dipivoxil and supplementation with elemental phosphate, calcium carbonate, and cholecalciferol. The second patient was a 53-year-old female with a 6 month history of lethargy, cachexia, and generalized bone pain. She had been receiving adefovir for 64 months before the development of these symptoms. She had hypophosphataemia, hypocalcaemia, metabolic acidosis, and severe vitamin D deficiency, but initially no urinary phosphate wasting. Four months of high-dose cholecalciferol supplementation unmasked her Fanconi syndrome including significant urinary phosphate wasting. The patient improved within weeks of discontinuation of adefovir and supplementation with elemental phosphate, calcium carbonate, and calcitriol. Despite large clinical trials advocating the safety of adefovir dipivoxil at 10-mg daily, long-term use of this agent may be nephrotoxic and in rare cases, cause Fanconi syndrome and severe hypophosphataemic osteomalacia. Clinicians prescribing this drug should be aware of this potential complication.
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PMID:Hypophosphataemic osteomalacia in patients on adefovir dipivoxil. 2066 Nov 53

There are over 350 million people chronically infected with the Hepatitis B virus (HBV); chronic HBV infections are associated with the development of hepatocellular carcinoma (HCC). While the precise mechanism of HBV-associated HCC remains undefined, it is believed to involve a combination of the host immune response to infection and activities of HBV proteins including the nonstructural X protein (HBx). HBx is a multifunctional protein that can modulate various cellular processes including cell proliferation. The exact effect of HBx on cell proliferation has varied depending on the cell line and exact conditions used in the study. Our previously published reports have demonstrated that HBx modulates the levels of cell cycle regulatory proteins in primary rat hepatocytes; however, the effect of HBx on cell cycle regulatory proteins in primary human hepatocytes, the natural host for HBV infection, has not been studied. Here we have examined the effect of HBx on cell cycle regulatory proteins in cultured, primary human hepatocytes. We demonstrate that HBx decreases the levels of cell cycle proteins that prevent progression into G1 phase and increases the levels of cell cycle proteins active in G1 phase. We have also shown that HBx modulation of cell cycle regulatory proteins requires cytosolic calcium, similar to the results we previously obtained in primary rat hepatocytes. Cumulatively, our results are the first demonstration that HBx modulates the levels of cell cycle regulatory proteins in a calcium-dependent manner in primary human hepatocytes.
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PMID:The hepatitis B virus HBx protein modulates cell cycle regulatory proteins in cultured primary human hepatocytes. 2093 70


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