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)

The influence of octreotide and somatostatin on liver metabolic activity were studied in 16 patients with cirrhosis that was positive for hepatitis B surface antigen (HBsAg). In patients receiving a 50 micrograms bolus and a 50 micrograms/hr infusion of octreotide, the hepatic blood flow, hepatic clearance, and the maximum velocity/metabolic elimination rate constant (Vmax/km) were significantly reduced after octreotide infusion compared with basal values. Similarly, the hepatic blood flow, hepatic clearance, and Vmax/km were significantly decreased in patients receiving a 250 micrograms bolus and a 250 micrograms/hr infusion of somatostatin. The extraction ratio and the systemic hemodynamic values, including cardiac index, heart rate, mean arterial pressure, and systemic vascular resistance, showed no significant changes in patients receiving either octreotide or somatostatin. These findings suggest that, as with somatostatin, octreotide reduced hepatic blood flow and impaired liver metabolic activity in patients with HBsAg-positive cirrhosis. These effects may have important clinical implications in the management of bleeding esophageal varices in patients with cirrhosis.
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PMID:Octreotide decreased liver metabolic activity in patients with hepatitis B surface antigen-positive cirrhosis. 135 73

The X gene product encoded by the hepatitis B virus, termed pX, is a promiscuous transactivator of a variety of viral and cellular genes under the control of diverse cis-acting elements. Although pX does not appear to directly bind DNA, pX-responsive elements include the NF-kappa B, AP-1, and CRE (cAMP response element) sites. Direct protein-protein interactions occur between viral pX and the CRE-binding transcription factors CREB and ATF. Here we examine the mechanism of the protein-protein interactions occurring between CREB and pX by using recombinant proteins and in vitro DNA-binding assays. We demonstrate that pX interacts with the basic region-leucine zipper domain of CREB but not with the DNA-binding domain of the yeast transactivator protein Gal4. The interaction between CREB and pX increases the affinity of CREB for the CRE site by an order of magnitude, although pX does not alter the rate of CREB dimerization. Methylation interference footprinting reveals differences between the CREB DNA and CREB-pX DNA complexes. These experiments demonstrate that pX titers the way CREB interacts with the CRE DNA and suggest that the basic, DNA-binding region of CREB is the target of pX. Transfection assays in PC12 cells with the CREB-dependent somatostatin promoter demonstrate a nearly 15-fold transcriptional induction after forskolin stimulation in the presence of pX. These results support the significance of the CREB-pX protein-protein interactions in vivo.
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PMID:The hepatitis B virus X protein targets the basic region-leucine zipper domain of CREB. 773 90

The chemically synthesized somatostatin (ss) gene was fused in phase with the 3'-end of hepatitis B virus surface antigen (HBsAg) gene. The fusion gene HBs/ss was then recombined into the genome of vaccinia virus. This recombinant virus (vv-HBs/ss) can express hybrid HBsAg/ss particles which present as determinants on their surfaces, thereby bearing a good immunogenicity. This new strategical vaccine of ss can elicit the production of antibody capable of neutralizing ss in the plasma, and consequently enhance the growth of animals.
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PMID:A new genetically engineered vaccine for animal growth promotion. 786 23

Somatostatin has been used to effectively control acute variceal haemorrhage, with conjectured mechanisms on portal hypertension. We, therefore, evaluated the effects of somatostatin on hepatic and systemic haemodynamics in 15 patients with hepatitis B-related cirrhosis and portal hypertension. All patients received an intravenous, continuous infusion of somatostatin 250 micrograms/h, following a bolus injection of 250 micrograms. In systemic haemodynamics, the mean arterial pressure (MAP) increased (P < 0.05), associated with a reflex bradycardia within 3 min following bolus injections, compared with basal values. The right atrial pressure, pulmonary capillary wedge pressure, inferior vena cava pressure, cardiac index, and systemic vascular resistance remained unaffected after drug infusion. In hepatic haemodynamics, the wedge hepatic vein pressure remained unchanged after drug administration. However, there was an increase in free hepatic vein pressure (FHVP; P < 0.05), and a trend toward a decrease in the hepatic vein pressure gradient (HVPG; P = 0.063), within 3 min after bolus injection. Furthermore, the hepatic blood flow decreased significantly at 10 and 30 min after somatostatin infusion (P < 0.05). The effective sinusoidal perfusion assessed by indocyanine green infusion also decreased progressively at 10 min (P = 0.057) and 30 min (P < 0.05). We concluded that somatostatin, at the dose used in this study, caused a transient and bolus-related vasoconstrictive effect, resulting in increases in MAP and FHVP, a decrease in heart rate, and a trend toward lower HVPG. In addition, somatostatin reduced the hepatic blood flow and effective sinusoidal perfusion which may be hazardous to cirrhotic patients during variceal haemorrhage.
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PMID:Changes of hepatic and systemic haemodynamics following somatostatin administration in patients with hepatitis B-related cirrhosis. 809 83

Hepatocellular carcinoma is responsible in France for approximately 5,500 deaths per year. Incidence rates are growing and the general status of patients is improving mainly because of earlier diagnosis and improvement in the treatment of complications of liver cirrhosis. In most of the cases the severity of the underlying liver disease is the prominent prognostic factor. Its treatment remains a difficult challenge for oncologists. Unfortunately surgery is usually contraindicated. Most trials of systemic chemotherapy are disappointing with poor response rates and severe side effects; new drugs and direct delivery in the hepatic artery appear to be of interest. Results with interferon are interesting but requires more studies. The lack of efficacy of antiandrogenic and antiestrogenic treatments were recently demonstrated; a recent randomized study showing the interest of somatostatin requires confirmation. Reports on radiotherapy are anecdotals. A lot of studies using liver directed therapies were conducted worldwide. Percutaneous ethanol injections (PEI) are well tolerated and are highly effective in small solitary tumors (> 70% of complete necrosis) but less in larger tumors; recurrences are frequent. No randomized trial have been performed concerning PEI but survival rates seem similar to those of surgery. A randomized controlled trial recently demonstrates that injection of acetic acid is more effective than injection of ethanol. Chemoembolization was extensively studied because of the demonstration of objective responses but all trials failed to demonstrate an improvement in survival. Intraarterial injection of radioactive Lipiodol achieves the same response rate and the same survival than chemoembolization but is significantly best tolerated. This treatment is superior to best supportive cares in patients with portal vein thrombosis. In conclusion, despite the fact that this disease is very frequent we have currently too many treatment options and are lacking of simple rules. The best treatment remains prevention, and the efficacy of hepatitis B vaccination was recently demonstrated in Taiwan.
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PMID:[Nonsurgical treatment of hepatocellular carcinoma]. 1041 27

Significant progress is being made in the prevention of hepatitis B-related hepatocellular carcinoma (HCC) but hepatitis C-related HCC is increasing in the West and therapeutic advances in established disease have been modest. Although ablative therapies, including surgical resection, seem effective in patients with small tumours these only represent a minority of patients. For the majority with advanced disease there is some evidence for survival benefit for transarterial chemoembolisation but only in very carefully selected patients. Systemic chemotherapy is of unproven benefit and is now largely confined to clinical trials. In contrast, there has been a steady improvement in the outlook of patients with established metastatic liver cancer when the primary site is colorectal. Survival has increased from around six months to almost two years with the introduction of new cytotoxic agents, irinotecan and oxaliplatin. Somatostatin analogues have had a dramatic impact on the symptomatic control of neuroendocrine tumours, metastatic to the liver that result in the carcinoid syndrome.
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PMID:New medical options for liver tumours. 1788 51

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death, and its incidence is increasing worldwide. Due to the known risk factors (mainly hepatitis B and C viruses), we believe there is a rationale for a chemopreventive approach to treat HCC. Here, based on described in vitro data, we evaluated the preventive effects of lanreotide, a somatostatin analog, on the induction of early carcinogenic events. We monitored preneoplastic foci induced by a two-stage initiation/promotion model of hepatocarcinogenesis in male Wistar rats, using diethylnitrosamine and 2-acetylaminofluorene. Lanreotide was given starting the day after the first diethylnitrosamine injection. By quantitative morphometry, we showed that lanreotide significantly decreases the size of induced preneoplastic foci. Analysis of proliferation and apoptosis assessed by immunohistochemistry, showed decreased proliferation and increased cell death in rats treated with lanreotide. As these events were associated with a significant decreased expression of the cell cycle regulator cyclin D1 and an increased expression of the cyclin-dependent kinase inhibitor p27(kip1) compared to the non-treated group, it is tempting to speculate that these factors are involved in the favorable effect of lanreotide. In conclusion, lanreotide significantly decreases early carcinogenic transformation in a two-step rat model. As lanreotide has a low toxicity profile, we believe it would be interesting to evaluate its effect in chemoprevention of HCC.
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PMID:Inhibition of early preneoplastic events in the rat liver by the somatostatin analog lanreotide. 1790 Mar 9

Somatostatin (SS) and growth hormone-releasing hormone (GHRH) are synthesized and secreted by the hypothalamus, which can control the synthesis and secretion of the growth hormone (GH) from the hypophysis as well as regulate the GH concentrations in animals and humans. In this article, we describe the regulation of animal growth using plasmid DNA encoding both the GHRH gene and the SS gene fused with the hepatitis B surface antigen (HBsAg) gene. We constructed a series of expression plasmids to express the GHRH and HBsAg-SS fusion genes individually as well as collectively. The fusion gene and GHRH were successfully expressed in Chinese hamster ovary (CHO) cells, as proven by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoblotting tests. Poly D, L-lactide-co-glycolic acid (PLGA) plasmid-encapsulating microspheres were prepared and injected intramuscularly into the leg skeletal muscles of rabbits. Weight gain/day and the levels of insulinlike growth factor-I (IGF-I), SS, and hepatitis B surface antibody (HBsAb) were monitored. During days 30 postinjection, increase in weight gain/day and IGF- I concentration and decrease in SS were observed in treatment groups. From days 15 to 30 postinjection, the weight gain/day significantly increased (P < 0.05) by 129.13%, 106.8%, and 72.82% relative to the control group in the co-expression GHRH and fusion gene (named P-G-HS), fusion gene (named P-HS), and GHRH (named P-G) groups, respectively. And most importantly, the P-G-HS group showed significant weight gain/day (P < 0.05) relative to the P-G and P-HS groups. A significant increase in the IGF-I concentration and decrease in the SS level relative to the control group were also observed. The results indicated that the combination of plasmid-mediated GHRH supplementation and positive immunization against SS led to more robust weight gain/day in rabbits.
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PMID:Simultaneous expression of growth hormone releasing hormone (GHRH) and hepatitis B surface antigen/somatostatin (HBsAg/SS) fusion genes in a construct in the skeletal muscle enhances rabbit weight gain. 1843 1

The aim of current study was to evaluate the prospects of somatostatin DNA vaccine. Two copies of somatostatin (SS) genes were fused with the hepatitis B surface antigen (HBsAg) S gene using genetic engineering methods, the identified recombinant plasmid designated as pcS/2SS was transfected into HeLa cells to detect expression and antigenicity of target fusion protein, and its immunoreaction as well as safety was evaluated with animal experiments. The expressed target protein had a specific reaction with somatostatin antibody and showed a single strip result. A single injection of this vector stimulated long-term antigen-specific antibody responses in rats, and peak antibody levels occurred at the 2nd week of the initial injection. Additionally, the 50 microg immunized group resulted in a 13.5% increase in growth rate as compared with control group (111.7 g vs. 98.4 g). The genomic DNA was assayed for integrated plasmid using a sensitive PCR method, and the risk of mutation due to integration of pcS/2SS plasmid following intramuscular injection in mice was negligible. The successful construction of pcS/2SS DNA vaccine with good immunogenicity and safety has prospects to promote growth of animals.
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PMID:Construction and evaluation of the eukaryotic expression plasmid encoding two copies of somatostatin genes fused with hepatitis B surface antigen gene S. 1845 80

In the current work, the fusion gene including somatostatin (SS) and the hepatitis B surface antigen gene was cloned into a balanced lethal system plasmid (pYA3493), and then transformed into asd- attenuated Salmonella choleraesuis C500 strain, the positive transformant without antibiotic resistance gene was confirmed by restriction analysis and DNA sequencing, designated as pYA-SS. The expression and immunogenicity of fusion protein were detected by SDS-PAGE and Western blot analysis. These results show that the recombinant prokaryotic expression plasmid pYA-SS could express the SS fusion protein with good immunogenicity in C500 strain. In above all, this study could provide reliable materials to develop novel, good and safe vaccine in enhancing the growth of animals.
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PMID:[Construction and characterization of a novel somatostatin prokaryotic expression]. 1880 81


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