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排序方式: 共有244条查询结果,搜索用时 31 毫秒
1.
Carbamazepine, diuretics, and hyponatremia: a possible interaction   总被引:1,自引:0,他引:1  
Although carbamazepine is known to cause hyponatremia, no previous reports have indicated an interaction between carbamazepine and a diuretic. Two patients are described who were treated with this combination and developed symptomatic hyponatremia, which cleared when both drugs were discontinued in one patient and when the diuretic was discontinued in the second patient. The possible mechanisms of action of carbamazepine-induced hyponatremia are discussed.  相似文献   
2.
Liver homogenates from rats fed tamoxifen (TAM) in the diet were shared among four different laboratories. TAM-DNA adducts were assayed by high pressure liquid chromatography-electrospray tandem mass spectrometry (HPLC-ES-MS/MS), TAM-DNA chemiluminescence immunoassay (TAM-DNA CIA), and (32)P-postlabeling with either thin layer ((32)P-P-TLC) or liquid chromatography ((32)P-P-HPLC) separation. In the first study, rats were fed a diet containing 500 p.p.m. TAM for 2 months, and the values for measurements of the (E)-alpha-(deoxyguanosin-N(2)-yl)-tamoxifen (dG-N(2)-TAM) adduct in replicate rat livers varied by 3.5-fold when quantified using 'in house' TAM-DNA standards, or other approaches where appropriate. In the second study, rats were fed 0, 50, 250 or 500 p.p.m. TAM for 2 months, and TAM-DNA values were quantified using both 'in house' approaches as well as a newly synthesized [N-methyl-(3)H]TAM-DNA standard that was shared among all the participating groups. In the second study, the total TAM-DNA adduct values varied by 2-fold, while values for the dG-N(2)-TAM varied by 2.5-fold. Ratios of dG-N(2)-TAM:(E)-alpha-(deoxyguanosin-N(2)-yl)-N-desmethyltamoxifen (dG-N(2)-N-desmethyl-TAM) in the second study were approximately 1:1 over the range of doses examined. The study demonstrated a remarkably good agreement for TAM-DNA adduct measurements among the diverse methods employed.  相似文献   
3.
N-Hydroxy-2-acetylaminofluorene (N-OH-AAF) is the proximate carcinogenic metabolite of the powerful rat liver carcinogen 2-acetylaminofluorene. In this study, transgenic Big Blue(R) rats were used to examine the relationship between in vivo mutagenicity and DNA adduct formation by N-OH-AAF in the target liver compared with that in nontarget tissues. Male rats were given one, two, or four doses of 25 mg N-OH-AAF/kg body weight by i.p. injection at 4-day intervals, and groups of treated and control rats were euthanized up to 10 weeks after beginning the dosing. Mutant frequencies were measured in the spleen lymphocyte hprt gene, and lacI mutant frequencies were determined in the liver and spleen lymphocytes. At 6 weeks after beginning the dosing, the hprt mutant frequency in spleen lymphocytes from the four-dose group was 16.5 x 10(-6) compared with 3.2 x 10(-6) in control animals. Also at 6 weeks, rats given one, two, or four doses of N-OH-AAF had lacI mutant frequencies in the liver of 97.6, 155.6, and 406.8 x 10(-6), respectively, compared with a control frequency of 25.7 x 10(-6); rats given four doses had lacI mutant frequencies in spleen lymphocytes of 55.8 x 10(-6) compared with a control frequency of 20.4 x 10(-6). Additional rats were evaluated for DNA adduct formation in the liver, spleen lymphocytes, and bone marrow by (32)P-postlabeling. Adduct analysis was conducted 1 day after one, two, and four treatments with N-OH-AAF, 5 days after one treatment, and 9 days after two treatments. N-(Deoxyguanosin-8-yl)-2-aminofluorene was the major DNA adduct identified in all the tissues examined. Adduct concentrations increased with total dose to maximum values in samples taken 1 day after two doses, and remained essentially the same after four doses. In samples taken after four doses, adduct levels were 103, 28, and 7 fmol/microg of DNA in liver, spleen lymphocytes, and bone marrow, respectively. The results indicate that the extent of both DNA adduct formation and mutant induction correlates with the organ specificity for N-OH-AAF carcinogenesis in the rat. Environ. Mol. Mutagen. 37:195-202, 2001. Published 2001 Wiley-Liss, Inc.  相似文献   
4.
Hepatitis C infection is associated with autoimmune disorders, such as the production of autoantibodies. Anti-LKM1 and anti-LC1, immunomarkers of type 2 autoimmune hepatitis, have been previously associated with a HCV infection. Anti-Soluble-Liver-Antigen autoantibodies (SLA) are specifically associated with type 1 and type 2 autoimmune hepatitis and more closely related to patients who relapse after steroid therapy. The recent molecular cloning of the soluble liver antigen provides the opportunity to develop more specific tests for the detection of antibodies against it. The aim of this work is to characterize anti-soluble-liver autoantibodies in sera from patients chronically infected by HCV. A recombinant cDNA from activated Jurkat cells coding for the full length tRNP(Ser)Sec/SLA antigen was obtained. ELISA, Western Blot and immunoprecipitation tests were developed and used to search for linear and conformational epitopes recognized by anti-SLA antibodies in sera from patients chronically infected by HCV. Anti-soluble liver antigen antibodies were found in sera from 10.4% of HCV-infected patients. The prevalence was significantly increased to 27% when anti-LKM1 was also present. Most anti-SLA reactivity was directed against conformational epitopes on the antigen. The means titers by ELISA were lower than those obtained in type 2 AIH. The result of autoantibody isotyping showed a subclass restriction to IgG1 and also IgG4. This study shows the presence of anti-SLA antibodies in approximately 10% of HCV infected patients. The prevalence of SLA autoantibodies in HCV infected patients increases when LKM1 autoantibodies are also present. The relationship between the prevalence of this characteristic autoimmune hepatitis autoantibody and the implication of an autoimmune phenomenon in the liver injury of patients chronically infected by HCV needs further investigation.  相似文献   
5.
The presence of relatively high levels of prostaglandin H synthase(PHS) in the dog urinary bladder and its ability to mediatethe activation of carcinogenic arylamines to DNA-bound productsin vitro suggests the involvement of this enzyme in arylamine-inducedbladder carcinogenesis. Since the PHS-dependent metabolism of2-naphthylamine (2-NA) had been shown to yield both ring- andN-oxidation products in vitro, we compared the reactivity of3H-labeled N-hydroxy-2-naphthylamine (N-OH-2-NA), 2-nitrosonaphthalene,and 2-amino-1-naphthol (2-AN) toward DNA and protein. In thePHS-incubation system, all three derivatives bound at high levelsto protein, but only N-OH-2-NA and 2-AN bound appreciably toDNA. Though ring-oxidation has usually been considered a detoxificationpathway, the covalent binding of [3H]2-AN to DNA was found tooccur readily under aerobic conditions and was enhanced at acidicpH. At pH 5 in air, the reactivity of [3H]2-AN with nucleicacids and protein was in the order: serum albumin > tRNA> poly G > poly C > DNA > poly A > rRNA >poly U. Enzymatic hydrolysis of DNA reacted with [3H]2-AN andsubsequent analysis by h.p.l.c. indicated the presence of severalcarcinogen-nucleoside adducts. The major product was characterizedas N4-(deoxyguanosin-N2-yl)-2-amino-1,4-naphthoquinoneimine;and two minor products were tentatively identified as N4-(deoxyadenosin-N6-yl)-2-amino-1,4-naphthoquinoneimineand a deoxyguanosin-N2-yl adduct of a naphthoquinoneimine dimer.These adducts accounted for 60% of the total DNA binding obtainedby incubation of [3H]2-NA with PHS in vitro and for 20% of the[3H]2-NA bound to dog urothelial DNA in vivo. The remainingadducts were identical to those previously reported as productsof the reaction of N-OH-2-NA with DNA. These results suggestthat a minor proportion of the DNA adducts found in vivo maybe formed by PHS-activation of 2-NA in the target tissue. Furthermore,the reactivity of 2-AN with cellular nucleophiles, presumablythrough formation of 2-imino-1-naphthoquinone or a protonated4-naphthocarbenium ion, indicates that ring-oxidation productsof arylamines and of other carcinogenic aryl compounds shouldbe evaluated as proximate carcinogenic metabolites.  相似文献   
6.
Fu PP  Beland FA  Yang SK 《Carcinogenesis》1980,1(8):725-727
Cyclopenta-polycyclic aromatic hydrocarbons (cyclopenta-PAHs) are a group of compounds that have been detected as environmental pollutants. Perturbation molecular orbital (PMO) calculations on their presumed ultimate carcinogenic metabolites, the cyclopenta-PAH expoxides, predict that they may have a greater biological hazard than the classic PAHs.  相似文献   
7.
The probable ultimate urinary bladder carcinogen, N-hydroxy-2-naphthylamine(N-HO-2-NA), reacted with nucleic acids and proteins under mildlyacidic conditions (pH 5) to form covalently bound derivatives.The extent of reaction was in the order: poly-guanylic acid>DNA protein rRNA >tRNA >polyadenylic acid, polyuridylicacid >polycytidylic acid. At pH 7, appreciable reaction occurredonly with protein. Enzymatic hydrolyses of the DNA, which contained1.5 naphthyl residues/1000 nucleotides, yielded 3 nucleoside-arylamineadducts. From chemical, u.v., n.m.r., and mass spectrometricanalyses, the adducts were identified as 1-(deoxy-guanosin-N2-yl)-2-naphthylamine,1-(deoxyadeno-sin-N6-yl)-2-naphthylamine, and a purine ring-openedderivative of N-(deoxyguanosin-8-yl)-2-naphthylamine, tentativelyidentified as 1-[5-(2,6-diamino-4-oxopyrimidinyl-N6-deoxyriboside)]-3-(2-naphthyl)urea.The properties of these adducts and their possible role in theinitiation of carcinogenesis are discussed.  相似文献   
8.
9.
Hepatitis C infection is associated with autoimmune disorders, such as the production of autoantibodies. Anti-LKM1 and anti-LC1, immunomarkers of type 2 autoimmune hepatitis, have been previously associated with a HCV infection. Anti-Soluble-Liver-Antigen autoantibodies (SLA) are specifically associated with type 1 and type 2 autoimmune hepatitis and more closely related to patients who relapse after steroid therapy. The recent molecular cloning of the soluble liver antigen provides the opportunity to develop more specific tests for the detection of antibodies against it. The aim of this work is to characterize anti-soluble-liver autoantibodies in sera from patients chronically infected by HCV. A recombinant cDNA from activated Jurkat cells coding for the full length tRNP(Ser)Sec/SLA antigen was obtained. ELISA, Western Blot and immunoprecipitation tests were developed and used to search for linear and conformational epitopes recognized by anti-SLA antibodies in sera from patients chronically infected by HCV. Anti-soluble liver antigen antibodies were found in sera from 10.4% of HCV-infected patients. The prevalence was significantly increased to 27% when anti-LKM1 was also present. Most anti-SLA reactivity was directed against conformational epitopes on the antigen. The means titers by ELISA were lower than those obtained in type 2 AIH. The result of autoantibody isotyping showed a subclass restriction to IgG1 and also IgG4. This study shows the presence of anti-SLA antibodies in approximately 10% of HCV infected patients. The prevalence of SLA autoantibodies in HCV infected patients increases when LKM1 autoantibodies are also present. The relationship between the prevalence of this characteristic autoimmune hepatitis autoantibody and the implication of an autoimmune phenomenon in the liver injury of patients chronically infected by HCV needs further investigation.  相似文献   
10.
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