妥卡尼对豚鼠心室肌细胞钙电流和钾电流的抑制作用

利用酶分散的成年豚鼠心室肌细胞和全细胞电压钳技术,研究了妥卡尼(tocainide)对心室肌细胞钙电流(I_ca)、延迟整流钾电流(I_k)和ATP敏感性钾电流(Ik,ATP)的作用。结果表明,妥卡尼对I_ca和I_k均显示浓度相关的抑制作用,妥卡尼50umol·L^-1对I_ca和I_k的抑制率分别为16%和3%。这可能是妥卡尼有效抑制室上性心动过速和缩短心肌动作电位平台期的重要机制。     

Enantioselective hydroxylation of nortriptyline in human liver microsomes, intestinal homogenate, and patients treated with nortriptyline

The enantioselectivity of hydroxylation of nortriptyline (NT) to E-10-hydroxynortriptyline (E-10-OH-NT) was studied in human liver microsomes, intestinal homogenate, and patients treated with NT. The rate of formation of (-)-E-10-OH-NT was higher than that of (+)-E-10-OH-NT both in the liver microsomes and in the intestinal homogenate. Quinidine, a prototype competitive inhibitor of the cytochrome P450IID6 ("debrisoquin hydroxylase"), inhibited the formation of (-)-E-10-OH-NT in a concentration-dependent manner in liver microsomes, while the formation of (+)-E-10-OH-NT was hardly affected. This indicates that P450IID6 catalyzes the hydroxylation of NT in a highly enantioselective manner to (-)-E-10-OH-NT in the liver. Another P450 isozyme besides IID6 seems to be responsible for the formation of the (+)-enantiomer in the liver. In intestinal homogenate, the formation of both enantiomers of E-10-OH-NT was inhibited to about the same extent by quinidine, the maximum inhibition being much less than in the liver. In the urine of six patients treated with NT, the (-)-enantiomer accounted for 91 +/- 2% of the unconjugated E-10-OH-NT, and for 78 +/- 6% of the glucuronide conjugates. The study shows that NT is hydroxylated in a highly enantioselective way, probably catalyzed by the polymorphic P450IID6, to (-)-E-10-OH-NT both in vitro in human liver as well as in vivo in patients treated with the drug.     

Periodontal conditions among adults in Southern Thailand

OBJECTIVE: To describe the periodontal conditions among 30-39- and 50-59-year-old rural Thais from the Province of Songkhla, Southern Thailand. METHODS: A total of 359 dentate persons were given a clinical examination comprising recordings of plaque and calculus in six teeth, and bleeding on probing, attachment level and pocket depth in six sites of all teeth present, except third molars. The same examiner carried out all examinations. Information on religious faith, smoking habits and use of betel was obtained by interview. A subset consisting of 60 persons was reexamined for attachment level 6 months later by another examiner. RESULTS: The oral hygiene conditions were poor with abundant amounts of both plaque and calculus. Gingival bleeding was essentially ubiquitous. The prevalence of attachment loss > or = 4 mm was 92% among 30-39-year-olds and 100% among 50-59-year-olds. The average percentage of sites affected in the two age groups was 23.9% and 63.9%. Pockets > or = 4 mm were seen in 84% of the 30-39-year-olds and in 93% of the 50-59-year-olds. Older age, Thai Buddhist faith and a high percentage of sites with calculus were significant positive predictors of a high percentage of sites with attachment loss > or = 4 mm, whereas older age and Thai Buddhist faith were the only statistically significant predictors of a high percentage of sites with attachment loss > or = 7 mm. CONCLUSION: The results indicate that this Thai population may have more widespread and severe periodontal destruction than other Asian populations, but failed to confirm the contention that Muslim faith is associated with more severe periodontal destruction.     

Cytotoxicity of liquids and powders of chemically different dental materials evaluated using dimethylthiazol diphenyltetrazolium and neutral red tests

The purpose of this study was to assess and compare the cytotoxicity of liquid and powder components of chemically different dental materials using 2 basic unspecific cell culture methods. Three chemically cured glass ionomers (Fuji II, Lining cement, and Ketac Silver), 1 light-cured glass ionomer (Fuji II LC), and 2 chemically cured acrylates (Swedon and Super Bond) were tested. The liquids were diluted 1:10 in cell culture medium. The liquids from chemically cured acrylates were further diluted 1:100, 1:1000, and 1:10000. Extracts were made by incubating the powders in cell culture medium for 24 h at 37 degrees C according to the ISO standard 10993-12. The cytotoxicity was assessed in transformed mouse fibroblasts (L-929) using two viability assays, dimethylthiazol diphenyltetrazolium (MTT) and neutral red (NR). Severe cytotoxicity was observed when testing powder extracts of Swedon, Fuji II, and Lining cement, whereas powder extracts of Ketac Silver, Fuji LC, and Super Bond induced slight to non-cytotoxicity. All of the 1:10 liquid dilutions were severely cytotoxic in the MTT assay. In the NR assay, however, four 10% dilutions were severely cytotoxic and 4 moderately cytotoxic. Further dilution of the liquids of the chemically cured acrylates reduced the toxicity, while the Super Bond catalyst was severely cytotoxic even as the 1:100 dilutions.     

Craniofacial morphology and growth comparisons in children with Robin Sequence, isolated cleft palate, and unilateral complete cleft lip and palate.

OBJECTIVE: Comparison of early craniofacial morphology and growth in children with nonsyndromic Robin Sequence (RS), isolated cleft palate (ICP), and unilateral complete cleft lip and palate (UCCLP). SUBJECTS: One hundred eight children with cleft: 7 with RS, 53 with ICP, and 48 with UCCLP were included in the study. The children were drawn from the group of all Danish children with cleft born 1976 through 1981. METHOD: Three-projection infant cephalometry. RESULTS: The craniofacial morphology in the RS, ICP, and UCCLP groups had some common characteristics: a wide maxilla with decreased length and posterior height, wide nasal cavity, short mandible, bimaxillary retrognathia, and reduced pharyngeal airway. The shortest mandible was found in RS followed by ICP and UCCLP; the pharyngeal airway was reduced in RS and ICP, compared with UCCLP; and the maxillary complex and nasal cavity were wider in UCCLP than in the other groups. The amount of facial growth in all three groups was similar; however, the direction was more vertical in UCCLP than in RS and ICP. CONCLUSION: Except for a shorter RS mandible, the facial morphology of infants with RS and ICP was similar, as was the amount of facial growth and the growth pattern. The differences in facial morphology can be ascribed to the difference in the primary anomaly. The amount of facial growth was similar in the three groups; however, the growth pattern showed a more vertical direction in UCCLP than in RS and ICP. It is hypothesized that the mandibular retrognathia in RS represents the outer end of that of the ICP distribution.     

Differential diagnosis of chordoma, chondroid, and ependymal tumors as aided by anti-intermediate filament antibodies.

Six chordomas, nine chondrosarcomas, and three myxopapillary ependymomas of the filum terminale were evaluated immunohistochemically for the expression of intermediate filament proteins by the use of monospecific antibodies against intermediate filament proteins of keratin, vimentin, and glial fibrillary acidic protein (GFAP) type. All chordomas were positive for keratin but negative for GFAP, whereas chondrosarcomas and ependymomas were negative for keratin. Chondrosarcomas showed strong vimentin positivity, whereas ependymomas were positive for GFAP. Chordomas showed desmosomelike junctions by electron microscopy, whereas chondrosarcomas of different types showed no junctions or only primitive ones. By electron microscopy chordomas often showed prominent intermediate filaments also associated with desmosomes, and poorly differentiated chondrosarcomas also showed prominent intermediate filaments. Keratin positivity of chordomas suggests their epithelial nature, while vimentin positivity of chondrosarcomas is in line with their mesenchymal derivation. The results also show that antibodies against different intermediate filament proteins can be applied as diagnostic aids in making the distinction between chordomas, chondroid tumors, and ependymal tumors.     

A new checkerboard panel for testing bacterial markers in periodontal disease

BACKGROUND/AIMS: Various microbiological methods have been used for testing bacterial markers for periodontitis and periodontal disease progression. Most studies have used only a limited number of well recognized bacterial species. The purpose of the present study was to evaluate the association of 13 more recently identified bacterial species in a new panel in comparison with 12 previously more recognized periodontotopathogens ('old panel') using the 'checkerboard' DNA-DNA hybridization method. METHODS: Fifty individuals were chosen who showed at least one site with a probing pocket depth of 6 mm or more (disease) and bleeding on probing and at least one site with a probing pocket depth of 3 mm and without bleeding on probing (health). One diseased and one healthy site on each individual were sampled with the paperpoint technique and the samples were processed in the checkerboard technique against deoxigenin-labeled whole genomic probes to 25 subgingival species representing 12 well recognized and 13 newly identified periodontitis associated species. RESULTS: Twenty-four (out of 25) species were detected more frequently in the subgingival plaque of diseased than healthy sites both at score 1 (> 10(4)) and score 3 (> 10(5)). A significant difference at the higher score (score 3) was noticed for all species of the old panel except for three (Streptococcus intermedius, Selenomonas noxia, and Eikenella corrodens). Of the species in the new panel only Prevotella tannerae, Filifactor alocis, and Porphyromonas endodontalis showed a statistical significant difference between diseased and healthy sites. CONCLUSION: It was concluded that P. tannerae, F. alocis, and P. endodontalis should be added to the 12 species used for routine diagnostics of periodontitis-associated bacterial flora.     

Unfavorable presenting clinical and laboratory features are associated with CALLA-negative non-T, non-B lymphoblastic leukemia in children

Twenty-four (5.7%) of 424 children with newly diagnosed acute lymphoblastic leukemia (ALL) were found to have blast cells that expressed HLA-DR antigens but not the common ALL antigen (CALLA), E-rosette receptors, T-cell antigens, or cytoplasmic or surface immunoglobulins. Each of the eight cases tested expressed the B-cell associated antigen B4, but not B1 or B2 antigen. Myeloid-associated antigens were not present in any of the 10 cases tested. By comparison with common (CALLA+ B-cell precursor) ALL, patients having this immunophenotype were more likely to be children less than 2 yr of age (p less than 0.001), to have higher initial leukocyte counts (p less than 0.001), and to have blast cells with a DNA index less than 1.16 (p = 0.05), a pseudodiploid karyotype (p = 0.01) and a chromosomal translocation (p = 0.003). The presence of any chromosomal translocation in these CALLA- ALL was related to measures of increased leukemic cell burden including higher leukocyte counts, larger liver and spleen sizes and higher serum lactic dehydrogenase levels. While the patients were entered into several treatment arms of two protocols, the CALLA- cases appeared to have lower remission rate (p = 0.06) and shorter event-free survival time (p = 0.05) than did those with common ALL. The association with clinical and laboratory features of known adverse prognostic significance provides some explanation for the poor treatment outcome of CALLA- ALL.     

Case-control study of risk factors for cervical neoplasia in Denmark. II. Role of sexual activity,reproductive factors,and venereal infections

Sexual, reproductive and venereal risk factors for cervical neoplasia were investigated in a population-based case-control study of 586 women with histologically verified, cervical squamous-cell carcinoma in situ, and 59 women with invasive squamous-cell cervical cancer, diagnosed from 1985 to 1986 in Copenhagen. Cases were identified from the computerized Danish Cancer Registry. An age-stratified control group (n=614) was drawn at random from the female population in the study area by means of the Danish Central Population Register. A structured questionnaire was mailed to cases as well as controls. Increasing number of sexual partners exerted a significant effect on the risk both for carcinoma in situ, and invasive cancer, independently of age at first intercourse and other potential confounders. Conversely, the association with early age at first intercourse became statistically insignificant after allowance for other risk factors, although an increasing risk was still observed with decreasing age at sexual debut. Early age at first episode with genital warts was a significant risk factor for carcinoma in situ, perhaps indicating a possible increased susceptibility of the cervix epithelium during adolescence. A history of genital warts was a good predictor of risk for carcinoma in situ, whereas a history of previous gonorrhea was associated with an increased risk for invasive carcinoma. Women with multiple births had a significantly increased adjusted risk, especially for carcinoma in situ, although some association was also observed with invasive cervical cancer. The study supports the hypothesis of cervical neoplasia being a sexually transmitted disease, and that carcinoma in situ and invasive cervical carcinoma, to a high degree, have similar patterns of risk factors.Drs Kjaer, Engholm, and Lynge are with the Danish Cancer Registry. Dr Dahl is with the Department of Surgery, Slagelse Hospital, Denmark. Dr Bock is with the Department of Gynecology, Rigshospitalet, Copenhagen, Denmark. Dr Jensen, formerly with the Danish Cancer Registry, is deceased. Address correspondence to Dr Kjaer, Danish Cancer Registry, Institute of Cancer Epidemiology, Danish Cancer Society, Rosenvengets Hovedvej 35, Box 839, Copenhagen. Denmark. The Danish Cancer Society supported this study through grants.     

Species differences in urinary butadiene metabolites; identification of 1,2-dihydroxy-4-(N-acetylcysteinyl)butane, a novel metabolite of butadiene.

1,3-Butadiene (BD) is used in the manufacture of styrene-BD and polybutadiene rubber. Differences seen in chronic toxicity studies in the susceptibility of B6C3F1 mice and Sprague-Dawley rats to BD raise the question of how to use the rodent toxicology data to predict the health risk of BD in humans. The purpose of this study was to determine if there are species differences in the metabolism of BD to urinary metabolites that might help to explain the differences in the toxicity of BD. The major urinary metabolites of BD in F344/N rats, Sprague-Dawley rats, B6C3F1 mice, Syrian hamsters, and cynomolgus monkeys were identified as 1,2-dihydroxy-4-(N-acetylcysteinyl)-butane (I) and the N-acetylcysteine conjugate of BD monoxide [1-hydroxy-2-(N-acetylcysteinyl)-3-butene] (II). These mercapturic acids are formed by addition of glutathione at either the double bond (I) or the epoxide (II) respectively. When exposed to approximately 8000 p.p.m. of BD for 2 h, the mice excreted 3-4 times as much metabolite II as I, the hamster and the rats produced approximately 1.5 times as much metabolite II as I, while the monkeys produced primarily metabolite I. The ratio of formation of metabolite I to the total formation of the two mercapturic acids correlated well with the known hepatic epoxide hydrolase activity in the different species. These data suggest that (i) the availability of the monoepoxide for conjugation with glutathione is highest in the mouse, followed by the hamster and the rat, and is lowest in the monkey; and (ii) the epoxide availability is inversely related to the hepatic activity of epoxide hydrolase, the enzyme that removes the epoxide by hydrolysis. The ratio of the two mercapturic acids in human urine following BD exposure may indicate the pathways of BD metabolism in humans and may aid in the determination of the most appropriate animal model for BD toxicity.