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Objective To compare the hepatotoxicity of matrine (MT) and oxymatrine (OMT) and explore the severity and characteristics of their toxicity, and to preliminarily elucidate their toxic mechanisms. Methods Liver cell line LO-2 cells were treated with acetaminophen (APAP), matrine and oxymatrine for 24 h, and the IC values, the contents of enzymes in the liver cells, the pathological changes, the contents of malondialdehyde (MDA) and glutathione (GSH) and the cell apoptosis rate were detected. In addition, adult zebrafish were treated with APAP, matrine and oxymatrine for 96 h, and the LC50 values, the pathological morphology of the liver cells, the contents of MDA and GSH and the apoptosis rate were detected. Meanwhile, the expression of oxidative stress-related gene, zgc: 136383, and the apoptosis-related genes, EIF4EBP3 and zgc: 123120, was also detected. Results Matrine and oxymatrine had toxic effects on liver cells in vitro. The IC50 value of matrine was 5. 3 mmol/L, and that of oxymatrine was ＞ 19 mmol/L. The contents of alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in the liver cells treated with matrine or oxymatrine were increased, and the cells appeared swollen, with an increase in the MDA level and a decrease in the GSH level. The cell apoptosis rate was also increased (P ＜ 0. 05). Furthermore, matrine and oxymatrine had toxic effects on the zebrafish. The LC50 value of matrine was 0. 41 mmol/L, and that of oxymatrine was ＞3. 8 mmol/L. The hepatocytes of zebrafish treated with matrine and oxymatrine appeared vacuolization in a mild to moderate degree, with an increase of the MDA content and a decrease of the GSH content. The cell apoptosis rate was increased (P ＜0. 05 for all). Expression of the oxidative stress-related gene zgc: 136383 (P ＜ 0. 05) and the apoptosis-resistant gene EIF4EBP3 (P ＜ 0. 05) was down-regulated by matrine, but that of the apoptosis-promoting gene zgc: 123120 was up-regulated (P ＜ 0. 05). Conclusions Results of the experiments using liver cells in vitro are consistent with those using the in vivo zebrafish model. Matrine (MT) and oxymatrine (OMT) both have hepatotoxicity, with similar toxic characteristics, and the toxicity of matrine is greater than oxymatrine. The mechanism of their hepatotoxicity is related with oxidative stress and cell apoptosis. Matrine reduces lipid transportation and activates oxidative stress reactions through down-regulation of gene zgc: 136383. In addition, matrine induces apoptosis in the liver cells via up-regulation of the apoptosis-promoting gene zgc: 123120 and down-regulation of the apoptosis-resistant gene EIF4EBP3.
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Objective To discuss the role of therapeutic drug monitoring (TDM) in pharmaceutical care by successful intervention of severe drug-drug interaction in 3 patients with hematological disease treated with voriconazole and rifampin.Methods Three patients with hematological disease were monitored for the plasma concentration of voriconazole before,during,and after the concomitant use of rifampin.The severity of this drug interaction was revealed,risks for developing invasive fungal infection and tuberculosis dissemination after chemotherapy were evaluated based on the TDM results,and alternative regimens were recommended.Results Voriconazole plasma concentration was normal at baseline but significantly depressed after combination with rifampin in all 3 cases.Concomnitant use of rifampin leads to a rapid decline in plasma concentration of voriconazole in 2-3 days,and withdraw of this enzyme induction effect takes 8-10 days after discontinuation of rifampin.Conclusion TDM is a helpful tool for providing pharmaceutical care,it helps to objectively visualize the degree of clinically important drug-drug interactions.Clinical evidence together with TDM results suggests high risk for developing invasive fungal infection and tuberculosis dissemination in hematology patients while using this combination therapy.Discontinuation of rifampin was suggested and accepted.For these patients,combination of voriconazole and rifampin should be avoided.
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Objective: To evaluate the clinical effect of transpedical interbody bone grafting in the treatment of i senile osteoporotic vertebral fracture
Methods: Eighty-six elders with osteoporotic vertebral fracture were selected and divided into a control group and a test group using random double-blind method. Patients in the control group were treated by short-segment transpedicular screw system internal fixation, while patients in the test group were treated by short-segment transpedicular screw system internal fixation in combination with transpedical interbody bone grafting. Operation related indexes and fracture recovery condition were compared between the two groups
Results: The overall effective rate of the test group was 93.02%, much higher than the control group [76.74%] [P<0.05]. The difference of operation duration, intraoperative bleeding volume, length of hospital | stay, fracture healing time, preoperative vertebral height loss and preoperative Cobb's angle between! the two groups had no statistical significance [P>0.05]. The postoperative pain score of the test group | was lower than that of the control group, and the difference was statistically significant [P<0.05]. The; vertebral height loss and Cobb's angle of the test group were superior to those of the control group at the last follow up, and the difference had statistical significance [P<0.05]. The incidence of internal fixator loosening of the test group was much lower than that of the control group [P<0.05]
Conclusion: Short-segment transpedicular screw system internal fixation in combination with transpedical interbody bone grafting shows favorable effects in the treatment senile osteoporotic vertebral fracture, resulting in mild pain and less loss of vertebral height and angle; hence it is worth promotion in clinic
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Humans , Male , Female , Aged , Bone Transplantation , Treatment Outcome , Pain, Postoperative , Spinal Fractures/therapyABSTRACT
9α-hydroxy-4-androstene-3,17-dione (9-OH-AD) is an important intermediate in the steroidal drugs production. 3-ketosteroid-9α-hydroxylase (KSH), a two protein system of KshA and KshB, is a key-enzyme in the microbial steroid ring B-opening pathway. KSH catalyzes the transformation of 4-androstene-3,17-dione (AD) into 9-OH-AD specifically. In the present study, the putative KshA and KshB genes were cloned from Mycobacterium smegmatis mc(2)155 and Gordonia neofelifaecis NRRL B-59395 respectively, and were inserted into the expression vector pNIT, the co-expression plasmids of kshA-kshB were obtained and electroporated into Mycobacterium sp. NRRL B-3805 cells. The recombinants were used to transform steroids, the main product was characterized as 9α-hydroxy-4-androstene-3,17-dione (9-OH-AD), showing that kshA and kshB were expressed successfully. Different from the original strain Mycobacterium sp. NRRL B-3805 that accumulates 4-androstene-3,17-dione, the recombinants accumulates 9α-hydroxy-4-androstene-3,17-dione as the main product. This results indicates that the putative genes kshA, kshB encode active KshA and KshB, respectively. The process of biotransformation was investigated and the results show that phytosterol is the most suitable substrate for biotransformation, kshA and kshB from M. smegmatis mc(2)155 seemed to exhibit high activity, because the resultant recombinant of them catalyzed the biotransformation of phytosterol to 9-OH-AD in a percent conversion of 90%, which was much higher than that of G. neofelifaecis NRRL B-59395. This study on the manipulation of the ksh genes in Mycobacterium sp. NRRL B-3805 provides a new pathway for producing steroid medicines.
Subject(s)
Androstenedione , Bacterial Proteins , Genetics , Metabolism , Biotransformation , Ketosteroids , Mixed Function Oxygenases , Genetics , Metabolism , Mycobacterium , Metabolism , Mycobacterium smegmatis , PlasmidsABSTRACT
Objective:To compare the efficacy and adverse reactions of omeprazole and pantoprazole in the treatment of patients with peptic ulcer bleeding. Methods: Totally 362 cases of peptic ulcer bleeding were randomly divided into the control group and the observation group with 181 ones in each. The control group was treated by omeprazole 40mg in 0. 9% sodium chloride injection 100ml, ivd, bid, and the observation group was given pantoprazole 80mg in 0. 9% sodium chloride injection 100ml, ivd, bid. The treatment course was 3-6 days. The times of vomiting and melena, bleeding situation and bleeding stopping time in the two groups were observed and recorded, and the clinical efficacy, adverse drug reactions during the treatment and the expense of the two groups were also compared. Results:The bleeding amount on the first and third day in the observation group was significantly lower than that in the control group (P 0. 05). The average daily cost of the observation group was significantly lower than that of the control group (P 0. 05). Conclusion:The efficacy of omeprazole and pantoprazole in the treatment of peptic ulcer bleeding was similar with high security. However, pantoprazole may reduce the times of vomiting and melena, shorten the bleeding time and decrease the treatment cost.
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Objective To study the rhythmic changes of 24 h ambulatory blood pressure in pre-eclampsia(PE)patients and come up with coping strategies. Method The levels and circadian variations of blood pressures in 240 pre-eclampsia patients were monitored and observed with 24 h ambulatory blood pressure monitoring. Results Among the 240 PE cases,121 were diagnosed as mild PE and 119 as severe PE.There were significant differences in the average of 24 h circadian variation,the average of date time variation,decreased blood pressure at night time between the two groups(all P<0.05). Conclusion Through ambulatory blood pressure monitoring,nurses can monitor the rhythmic changes of 24 h ambulatory blood pressure,make reasonable arrangements for the treatment and care operations,reduce the factors that induce eclampsia and ensure the safety of mother and baby .
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Objective To evaluate the effects of carvedilol on left ventricular function by MPI in patients with heart failure.Methods All the cases came from the first Affiliated Hospital of Harbin Medical University during 2004 to 2006.There were two groups:45 Carvedilol treated patients and 50 placebo controlled patients.The patients with heart failure were detected the conventional Tei index(c-Tei),the tissue Doppler Tei index(t-Tei)and left ventricular ejection fraction pretherapy and post-treatment 1 month and 6 month.Results The patients with heart failure were higher in LVEDd,c-Tei,t-Tei and lower in LVEF compared with the controlled patients(P
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Objective To evaluate the images of MRCP acquired by adjusting 0.3 Tesla MR unit heavy T 2-weighted scanning parameters and altering scanning angle and diagnostic correctivity to biliary obstructive disease.Methods Routine MR T 1WI,T 2WI scanning were performed axial in 50 cases of patients with biliary obstruction.All of them were divided into two groups,20 cases of them were scanned coronal with FSE T 2-weighted fixed parameters,30 cases of them were scanned with altering scanning angle,increasing scanning slices,decreasing distance of two near slices,reducing signal collection times(NSA),shortening scanning time.Results The acquired images through adjusting FSE T 2-weighted scanning parameters were visualized clearly.The boundary of cholangiopancreatie ducts were showed clearly.The display rate of biliary and pancreatie ducts was elevaled from 20% to 83.3%.The accuracy of it for evaluating the causes of obstruction was increased from 88.9% to 93.3%.The accuracy of it in the detection of the location of bile duct obstruction was 100%.Conclusion Through adjusting scanning purameters low field MRCP is very helpful in improved images quality and reflecting veliable signs of biliary and pancreatie duct obstruction disease combined with MRI T 1-weighted T 2-weighted message.This method can increased the diagnostic accuracy of the causes of obseruction and supply the reliable ground for clinical treatment.