Previous research updated the mortality experience of North American synthetic rubber industry workers during the period 1944-1998, determined if leukemia and other cancers were associated with several employment factors and carried out Poisson regression analysis to examine exposure-response associations between estimated exposure to 1,3-butadiene (BD) or other chemicals and cancer. The present study used Cox regression procedures to examine further the exposure-response relationship between several unlagged and lagged, continuous, time-dependent BD exposure indices (BD parts per million (ppm)-years, the total number of exposures to BD concentrations >100 ppm ("peaks") and average intensity of BD) and leukemia, lymphoid neoplasms and myeloid neoplasms. All three BD exposure indices were associated positively with leukemia. Using continuous, untransformed BD ppm-years the regression coefficient (beta) from an analysis that controlled only for age was 2.9 x 10(-4) (p
Alkaline phosphatases are non-specific phosphomonoesterases that are distributed widely in species ranging from bacteria to man. This study has concentrated on the tissue-nonspecific alkaline phosphatase from arctic shrimps (shrimp alkaline phosphatase, SAP). Originating from a cold-active species, SAP is thermolabile and is used widely in vitro, e.g. to dephosphorylate DNA or dNTPs, since it can be inactivated by a short rise in temperature. Since alkaline phosphatases are zinc-containing enzymes, a multiwavelength anomalous dispersion (MAD) experiment was performed on the zinc K edge, which led to the determination of the structure to a resolution of 1.9 A. Anomalous data clearly showed the presence of a zinc triad in the active site, whereas alkaline phosphatases usually contain two zinc and one magnesium ion per monomer. SAP shares the core, an extended beta-sheet flanked by alpha-helices, and a metal triad with the currently known alkaline phosphatase structures (Escherichia coli structures and a human placental structure). Although SAP lacks some features specific for the mammalian enzyme, their backbones are very similar and may therefore be typical for other higher organisms. Furthermore, SAP possesses a striking feature that the other structures lack: surface potential representations show that the enzyme's net charge of -80 is distributed such that the surface is predominantly negatively charged, except for the positively charged active site. The negatively charged substrate must therefore be directed strongly towards the active site. It is generally accepted that optimization of the electrostatics is one of the characteristics related to cold-adaptation. SAP demonstrates this principle very clearly.
BACKGROUND: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has a long half-life of 5-10 years in human beings as a result of its high lipophilicity, and little or no metabolism. We monitored TCDD, its form, distribution, and elimination in Victor Yushchenko after he presented with severe poisoning. METHODS: In late December, 2004, a patient presented with TCDD poisoning; the levels in his blood serum (108000 pg/g lipid weight) were more than 50 000-fold greater than those in the general population. We identified TCDD and its metabolites, and monitored their levels for 3 years using gas chromatography and high-resolution mass spectrometry in samples of blood serum, adipose tissue, faeces, skin, urine, and sweat, after they were extracted and cleaned with different organic solvents. FINDINGS: The amount of unmodified TCDD in the samples that were analysed accounted for about 60% of TCDD eliminated from the body during the same period. Two TCDD metabolites-2,3,7-trichloro-8-hydroxydibenzo-p-dioxin and 1,3,7,8-tetrachloro-2-hydroxydibenzo-p-dioxin-were identified in the faeces, blood serum, and urine. The faeces contained the highest concentration of TCDD metabolites, and were the main route of elimination. Altogether, the different routes of elimination of TCDD and its metabolites accounted for 98% of the loss of the toxin from the body. The half-life of TCDD in our patient was 15.4 months. INTERPRETATION: This case of poisoning with TCDD suggests that the design of methods for routine assessment of TCDD metabolites in human beings should be a main aim of TCDD research in the metabolomic era. FUNDING: University of Geneva Dermatology Fund, and Swiss Centre for Applied Human Toxicology.
Comment In: Lancet. 2009 Oct 3;374(9696):1131-219660808
[2nd place in the contest for young scientists on gastroenterology in the 17th Congress "Man and Medicine" (April 2010, Moscow). Erosive esophagitis in children: characteristics of 24-hour pH monitoring in the the esophagus].
A new class of antitumor agents, having structural analogy to amonafide, but differing by the addition of a fourth ring in the nucleus, was synthesized conveniently from anthracene. Compounds with a variety of substituents, containing a basic nitrogen atom and located on the imide nitrogen, were prepared. Thirteen of 19 new compounds had greater growth inhibitory potency than amonafide in a panel of cultured murine and human tumor cells using the sulforhodamine B and MTT dye assays. The most active agents were similarly more toxic than amonafide to normal neonatal rat myocytes in vitro, but they had better chemotherapeutic indexes. From these compounds, the one with a 2-(dimethylamino)ethyl side chain (named azonafide) was chosen for further study. It showed high potency against a panel of cultured human colon cancer cells and it was active against ip P388 leukemia and subcutaneous B16 melanoma in mice. Preliminary structure-activity correlations suggest that the basicity of the side-chain nitrogen and the length of side chain are important determinants of antitumor potency in vitro. Steric hindrance and rigidity of the side chains might be other determinants.
PURPOSE: To evaluate the clinical performance of Helioseal-F, a fluoride-containing fissure sealant, in school children at caries risk. MATERIALS AND METHODS: A caries risk assessment based on past caries experience, saliva microbial tests, buffer capacity and frequency of sugar intake was carried out in 204 healthy children, 6-7 years of age. Children exhibiting one or more risk factors were considered at caries risk (n = 121) and their permanent molars were sealed with a fluoride-containing fissure sealant, thus forming a fissure sealant group (FSG). The remaining 83 children with low caries risk received no fissure sealants and constituted a reference group (RG). Both groups were followed for 2 years. From 15 children of both groups, unstimulated whole saliva was collected 1 month after sealant placement in order to determine fluoride levels. In another 20 children, a split-mouth study design was utilized to compare the colonization of mutans streptococci adjacent to and on F-containing sealants and conventional controls. The sealants were placed by dental hygienists according to the manufacturers' instructions. RESULTS: A total of 431 fissure sealants were placed at baseline. Complete retention was found in 76.6% during the study period while 22.0% were partially lost. Six sealants (1.4%) were completely lost. The enamel caries incidence was 45% lower (P
The trypanosomatid parasite Trypanosoma brucei synthesizes fatty acids in the mitochondrion using the type II fatty acid synthesis (FAS) machinery. When mitochondrial FAS was characterized in T. brucei, all of the enzymatic components were identified based on their homology to yeast mitochondrial FAS enzymes, except for 3-hydroxyacyl-ACP dehydratase. Here we describe the characterization of T. brucei mitochondrial 3-hydroxyacyl-ACP dehydratase (TbHTD2), which was identified by its similarity to the human mitochondrial dehydratase. TbHTD2 can rescue the respiratory deficient phenotype of the yeast knock-out strain and restore the lipoic acid content, is localized in the mitochondrion and exhibits hydratase 2 activity.
The purpose of this study was to evaluate the clinical performance of preformed beta-quartz glass-ceramic insert restorations.
Nine Class I and 30 Class II beta-quartz glass-ceramic insert restorations were placed in 16 patients who were seen regularly by personnel at Umeå University Dental School. The California Dental Association criteria were used to evaluate the restorations at baseline, 6 months, and 1, 2, and 3 years after luting. The occurrence of postoperative sensitivity, the time taken to manufacture each restoration, and certain periodontal conditions were also evaluated.
Sixty-nine percent of the restorations were rated satisfactory at the 3-year examination. During the follow-up period, 4 became loose and 7 were fractured or had flaking surfaces. Caries was registered in connection with 1 restoration. Excellent ratings were obtained for marginal integrity, anatomic form, surface, and color in 62%, 84%, 32%, and 44% of the restorations, respectively. There was no statistically significant difference in the occurrence of plaque and bleeding on probing in comparison with the controls. The mean overall time for placement was 38 minutes. The estimated survival rate (Kaplan-Meier) was 59% after 3.5 years.
The quality of the beta-quartz glass-ceramic restorations in the present study was inferior to that presented in most earlier studies of ceramic or resin composite posterior restorations placed in patients treated at university clinics. Both the technique and the beta-quartz glass-ceramic inserts have to be evaluated in more long-term studies to assess the possibility of their serving as an alternative restorative technique.