AIM： To undertake analysis of hepatitis A viral load, alanine aminotransferase （ALT）, and viral genotypes with duration of viremia, and to correlate these parameters with CD4^＋/ CD8^＋ lymphocyte populations that ...AIM： To undertake analysis of hepatitis A viral load, alanine aminotransferase （ALT）, and viral genotypes with duration of viremia, and to correlate these parameters with CD4^＋/ CD8^＋ lymphocyte populations that control cell-mediated immunity. METHODS： Cell counts were carried out using fresh whole blood collected in EDTA vials using a fluorescence activated cell sorter. Hepatitis A virus （HAV） RNA was extracted from blood serum, reverse transcribed into cDNA and quantified by Real-Time polymerase chain reaction and was genotyped. RESULTS： Among 11 patients, 10 could be analyzed completely. Of these, 3 had severe acute hepatitis （s-AH） and the remainder had a self-limited acute hepatitis A （AHA）, with one patient with fulminant disease （encephalopathy Grade IV） dying on the 4^th d. The ALT level was significantly higher both in AHA （1070.9±894.3; P = 0.0014） and s-AH （1713.9±886.3; P = 0.001） compared to normal controls （23.6±7.2）. The prothrombin time in s-AH patients （21.0 ±2.0; P=0.02） was significantly higher than in AHA （14.3±1.1;P = 0.44）. The CD4^＋/CD8^＋ ratio in AHA patients （1.17 ＋ 0.11; P = 0.22） and s-AH （0.83 ＋ 0.12; P = 0.0002） were lower than seen in normal healthy controls （1.52）. Self-limited cases had peak viral load at the beginning of analysis while in s-AH patients this occurred at the 15TM or 30^th d. In acute and severe groups, one patient each belonged to genotype IA, with the remaining 8 cases belonging to genotype IIIA. The only fulminant hepatic failure case belonged to genotype IA. HAV viral load and AIT values collected during the entire course of the selflimited infection were directly correlated but this was not the case for s-AH patients.CONCLUSION： Based on a small-scale study, the persistently higher viral load of s-AH might be due to diminished cellular immunity and hemolysis. The duration of viremia was dependent on the host, as the viral genotype had no apparent role in clinical outcome of AVH and s-AH cases.展开更多
AIM： （1） To gain information on immune responses to an accelerated schedule of 0, 1, and 2 mo in paramedical staff and BDS students who are at an increased risk of getting hepatitis B infection and come under high ...AIM： （1） To gain information on immune responses to an accelerated schedule of 0, 1, and 2 mo in paramedical staff and BDS students who are at an increased risk of getting hepatitis B infection and come under high risk groups. （2） To assess the efficacy and safety of En/vac- HB in different age groups, using genetically modified yeast strain Pichia pastoris, a new recombinant hepatitis B accine developed and manufactured in India. METHODS： A prospective, comparative, and single blinded trial of rapid （0, 1, and 2 mo） hepatitis B immunization schedulewas reported. A total of three hundred and seven （212 females and 95 males） healthy volunteers divided into three age groups （18-29, 30-39, and 40-49） were enrolled after screening for markers of hepatitis B. All the volunteers received 20 mg of the vaccine intramuscularly at 0, 1, and 2 mo. RESULTS： Geometric mean titers were calculated pre and post vaccination. Before immunization the GMT was 0.0124 mIU/mL. One month after the administration of the third dose of recombinant vaccine 296/307 （96.5%） subjects achieved seroprotective levels of anti-HBs. The geometric mean anti-HBs titers achieved after one month of the third dose was 2 560.0 mIU/mL. The geometric mean anti-HBs titer of males was 2 029.0 mIU/mL, while that of the females was 2 759.0 mIU/mL. In the age group of 18-29 years, anti-HBs titer was 3 025.0 mIU/ mL, while that in the age group of 30-39 years was 2 096.0 mlU/mL. In third age group of 40-49 years, anti- HBs titer was 1 592.0 mIU/mL. Hyper-responses （anti-HBs≥100 mIU/mL） were shown in 88.0% （271/307） of subjects. Eleven （3.5%） subjects responded poorly to the vaccine in the age group of 40-49 years. There was only mild pain at the site of injection otherwise there were no other adverse drug reactions （ADRs）. CONCLUSION： This vaccine （Enivac-HB） is safe and efficacious, providing significant protection after the third dose and rapid hepatitis B immunization schedule of 0, 1, and 2 mo can be recommended whenever rapid protection is the goal.展开更多
BACKGROUND Sinapic acid(SA)has been shown to have various pharmacological properties such as antioxidant,antifibrotic,anti-inflammatory,and anticancer activities.Its mechanism of action is dependent upon its ability t...BACKGROUND Sinapic acid(SA)has been shown to have various pharmacological properties such as antioxidant,antifibrotic,anti-inflammatory,and anticancer activities.Its mechanism of action is dependent upon its ability to curb free radical production and protect against oxidative stress-induced tissue injuries.AIM To study the hepatoprotective effects of SA against lipopolysaccharide(LPS)/Dgalactosamine(D-GalN)-induced acute liver failure(ALF)in rats.METHODS Experimental ALF was induced with an intraperitoneal(i.p.)administration of 8μg LPS and 800 mg/kg D-GalN in normal saline.SA was administered orally once daily starting 7 d before LPS/D-GalN treatment.RESULTS Data showed that SA ameliorates acute liver dysfunction,decreases serum levels of alanine transaminase(ALT),and aspartate aminotransferase(AST),as well as malondialdehyde(MDA)and NO levels in ALF model rats.However,pretreatment with SA(20 mg/kg and 40 mg/kg)reduced nuclear factor kappalight-chain-enhancer of activated B cells(NF-κB)activation and levels of inflammatory cytokines(tumor necrosis factor-αand interleukin 6).Also,SA increased the activity of the nuclear factor erythroid-related factor 2/heme oxygenase-1(Nrf2/HO-1)signaling pathway.CONCLUSION In conclusion,SA offers significant protection against LPS/D-GalN-induced ALF in rats by upregulating Nrf2/HO-1 and downregulating NF-κB.展开更多
OBJECTIVE:To investigate the effect of black catechu(BC) on the pharmacokinetics of theophylline(CYP1A2 substrate,with narrow therapeutic index)in rabbits.METHODS:In the present investigation the effect of BC on the p...OBJECTIVE:To investigate the effect of black catechu(BC) on the pharmacokinetics of theophylline(CYP1A2 substrate,with narrow therapeutic index)in rabbits.METHODS:In the present investigation the effect of BC on the pharmacokinetics of theophylline,a CYP1A2 substrate was determined.In the study,BC(264 mg/kg,p.o.) or saline(control group) was given to rabbits for 7 consecutive days and on the 8^(th)day theophylline(16 mg/kg) was administered orally one hour after BC or saline treatment.Blood samples were withdrawn at different time intervals(0.5,1,1.5,2,3,4,6,8,12,24 and 36 h) from the marginal ear vein.RESULTS:The pretreatment of rabbits with BC resulted in a significant increase in maximum blood concentration,time of peak concentration and area under the concentration time profile curve until last observation which was about 41.32%,35.71%and 15.03%,respectively.While decreases in clearance,volume of distribution,and half-life were observed.It is suggested that BC pretreatment decreases the CYP1 A metabolic activity leading to increase in bioavailability and decrease in oral clearance of theophylline,which may be due to inhibition of CYP1 A.CONCLUSION:BC can significantly alter theophylline pharmacokinetics in vivo possibly due to inhibition of CYP1 A and P-glycoprotein activity.Based on these results,precaution should be exercised when administering BC with CYP1 A substrate.展开更多
文摘AIM： To undertake analysis of hepatitis A viral load, alanine aminotransferase （ALT）, and viral genotypes with duration of viremia, and to correlate these parameters with CD4^＋/ CD8^＋ lymphocyte populations that control cell-mediated immunity. METHODS： Cell counts were carried out using fresh whole blood collected in EDTA vials using a fluorescence activated cell sorter. Hepatitis A virus （HAV） RNA was extracted from blood serum, reverse transcribed into cDNA and quantified by Real-Time polymerase chain reaction and was genotyped. RESULTS： Among 11 patients, 10 could be analyzed completely. Of these, 3 had severe acute hepatitis （s-AH） and the remainder had a self-limited acute hepatitis A （AHA）, with one patient with fulminant disease （encephalopathy Grade IV） dying on the 4^th d. The ALT level was significantly higher both in AHA （1070.9±894.3; P = 0.0014） and s-AH （1713.9±886.3; P = 0.001） compared to normal controls （23.6±7.2）. The prothrombin time in s-AH patients （21.0 ±2.0; P=0.02） was significantly higher than in AHA （14.3±1.1;P = 0.44）. The CD4^＋/CD8^＋ ratio in AHA patients （1.17 ＋ 0.11; P = 0.22） and s-AH （0.83 ＋ 0.12; P = 0.0002） were lower than seen in normal healthy controls （1.52）. Self-limited cases had peak viral load at the beginning of analysis while in s-AH patients this occurred at the 15TM or 30^th d. In acute and severe groups, one patient each belonged to genotype IA, with the remaining 8 cases belonging to genotype IIIA. The only fulminant hepatic failure case belonged to genotype IA. HAV viral load and AIT values collected during the entire course of the selflimited infection were directly correlated but this was not the case for s-AH patients.CONCLUSION： Based on a small-scale study, the persistently higher viral load of s-AH might be due to diminished cellular immunity and hemolysis. The duration of viremia was dependent on the host, as the viral genotype had no apparent role in clinical outcome of AVH and s-AH cases.
基金Supported by the Panacea Biotec Limited, New Delhi 110044,India
文摘AIM： （1） To gain information on immune responses to an accelerated schedule of 0, 1, and 2 mo in paramedical staff and BDS students who are at an increased risk of getting hepatitis B infection and come under high risk groups. （2） To assess the efficacy and safety of En/vac- HB in different age groups, using genetically modified yeast strain Pichia pastoris, a new recombinant hepatitis B accine developed and manufactured in India. METHODS： A prospective, comparative, and single blinded trial of rapid （0, 1, and 2 mo） hepatitis B immunization schedulewas reported. A total of three hundred and seven （212 females and 95 males） healthy volunteers divided into three age groups （18-29, 30-39, and 40-49） were enrolled after screening for markers of hepatitis B. All the volunteers received 20 mg of the vaccine intramuscularly at 0, 1, and 2 mo. RESULTS： Geometric mean titers were calculated pre and post vaccination. Before immunization the GMT was 0.0124 mIU/mL. One month after the administration of the third dose of recombinant vaccine 296/307 （96.5%） subjects achieved seroprotective levels of anti-HBs. The geometric mean anti-HBs titers achieved after one month of the third dose was 2 560.0 mIU/mL. The geometric mean anti-HBs titer of males was 2 029.0 mIU/mL, while that of the females was 2 759.0 mIU/mL. In the age group of 18-29 years, anti-HBs titer was 3 025.0 mIU/ mL, while that in the age group of 30-39 years was 2 096.0 mlU/mL. In third age group of 40-49 years, anti- HBs titer was 1 592.0 mIU/mL. Hyper-responses （anti-HBs≥100 mIU/mL） were shown in 88.0% （271/307） of subjects. Eleven （3.5%） subjects responded poorly to the vaccine in the age group of 40-49 years. There was only mild pain at the site of injection otherwise there were no other adverse drug reactions （ADRs）. CONCLUSION： This vaccine （Enivac-HB） is safe and efficacious, providing significant protection after the third dose and rapid hepatitis B immunization schedule of 0, 1, and 2 mo can be recommended whenever rapid protection is the goal.
基金Deanship of Scientific Research at King Saud University,No.RG-1439-083.
文摘BACKGROUND Sinapic acid(SA)has been shown to have various pharmacological properties such as antioxidant,antifibrotic,anti-inflammatory,and anticancer activities.Its mechanism of action is dependent upon its ability to curb free radical production and protect against oxidative stress-induced tissue injuries.AIM To study the hepatoprotective effects of SA against lipopolysaccharide(LPS)/Dgalactosamine(D-GalN)-induced acute liver failure(ALF)in rats.METHODS Experimental ALF was induced with an intraperitoneal(i.p.)administration of 8μg LPS and 800 mg/kg D-GalN in normal saline.SA was administered orally once daily starting 7 d before LPS/D-GalN treatment.RESULTS Data showed that SA ameliorates acute liver dysfunction,decreases serum levels of alanine transaminase(ALT),and aspartate aminotransferase(AST),as well as malondialdehyde(MDA)and NO levels in ALF model rats.However,pretreatment with SA(20 mg/kg and 40 mg/kg)reduced nuclear factor kappalight-chain-enhancer of activated B cells(NF-κB)activation and levels of inflammatory cytokines(tumor necrosis factor-αand interleukin 6).Also,SA increased the activity of the nuclear factor erythroid-related factor 2/heme oxygenase-1(Nrf2/HO-1)signaling pathway.CONCLUSION In conclusion,SA offers significant protection against LPS/D-GalN-induced ALF in rats by upregulating Nrf2/HO-1 and downregulating NF-κB.
基金the Deanship of Scientific Research at King Saud University for funding this research group,No. RG-1435-041
文摘OBJECTIVE:To investigate the effect of black catechu(BC) on the pharmacokinetics of theophylline(CYP1A2 substrate,with narrow therapeutic index)in rabbits.METHODS:In the present investigation the effect of BC on the pharmacokinetics of theophylline,a CYP1A2 substrate was determined.In the study,BC(264 mg/kg,p.o.) or saline(control group) was given to rabbits for 7 consecutive days and on the 8^(th)day theophylline(16 mg/kg) was administered orally one hour after BC or saline treatment.Blood samples were withdrawn at different time intervals(0.5,1,1.5,2,3,4,6,8,12,24 and 36 h) from the marginal ear vein.RESULTS:The pretreatment of rabbits with BC resulted in a significant increase in maximum blood concentration,time of peak concentration and area under the concentration time profile curve until last observation which was about 41.32%,35.71%and 15.03%,respectively.While decreases in clearance,volume of distribution,and half-life were observed.It is suggested that BC pretreatment decreases the CYP1 A metabolic activity leading to increase in bioavailability and decrease in oral clearance of theophylline,which may be due to inhibition of CYP1 A.CONCLUSION:BC can significantly alter theophylline pharmacokinetics in vivo possibly due to inhibition of CYP1 A and P-glycoprotein activity.Based on these results,precaution should be exercised when administering BC with CYP1 A substrate.
