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Background: We investigated and evaluated the cost effectiveness of coding by health care economists in a centre for orthopaedics and trauma surgery in Germany, by quantifying and comparing the financial efficiency of physicians with basic knowledge of the DRG-system with the results of healthcare economists with in-depth knowledge (M.Sc.). In addition, a hospital survey was performed to establish how DRG-coding is being performed and the identity of the persons involved. Material and Methods: In a prospective and controlled study, 200 in-patients were coded by a healthcare economist (study group). Prior to that, the same cases were coded by physicians with basic training in the DRG-system, who made up the control group. All cases were picked randomly and blinded without informing the physicians coding the controls, in order to avoid any Hawthorne effect. We evaluated and measured the effective weighting within the G-DRG, the DRG returns per patient, the overall DRG return, and the additional time needed. For the survey, questionnaires were sent to 1200 German hospitals. The completed questionnaire was analysed using a statistical program. Results: The return difference per patient between controls and the study group was significantly greater (2472 ± 337 ; p < 0.05); the overall return was raised by 494,500 . The mean additional time needed was 11.32 ± 0.8 min per case, resulting in an increase in proceeds of 218 ± 38 per minute. 2.5â% of all cases had to be devaluated by the health economist after the initial coding by the control group. Returned sheets of 60 hospitals were evaluated. The median level of DRG case reports was 1277 (2500-62,300). Coding was performed in 69â% of cases by doctors, 19â% by skilled specialists for DRG coding and in 8â% together. Overall satisfaction with the DRG was described by 61â% of respondents as good or excellent. Conclusion: Our prospective and controlled study quantifies the cost efficiency of health economists in a centre of orthopaedics and trauma surgery in Germany for the first time. We provide some initial evidence that health economists can enhance the CMI, the resulting DRG return per patient as well as the overall DRG return. Data from the survey shows that in many hospitals there is great reluctance to leave the coding to specialists only.
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Centros Médicos Académicos/economía , Análisis Costo-Beneficio/economía , Grupos Diagnósticos Relacionados/economía , Grupos Diagnósticos Relacionados/estadística & datos numéricos , Eficiencia Organizacional/economía , Modelos Económicos , Médicos/economía , Simulación por Computador , Análisis Costo-Beneficio/métodos , AlemaniaAsunto(s)
Aberraciones Cromosómicas , Análisis Mutacional de ADN , Mutación del Sistema de Lectura/genética , Genes Recesivos/genética , Enfermedad de Niemann-Pick Tipo A/diagnóstico , Enfermedad de Niemann-Pick Tipo A/genética , Esfingomielina Fosfodiesterasa/genética , Femenino , Tamización de Portadores Genéticos , Humanos , LactanteRESUMEN
Auto-antibodies to apolipoprotein A-1 (anti-apoA-1 IgG) were shown to promote inflammation and atherogenesis, possibly through innate immune receptors signalling. Here, we aimed at investigating the role of Toll-like receptors (TLR) 2 and 4 on anti-apoA-1 IgG-induced atherosclerotic plaque vulnerability, myocardial necrosis and mortality in mice. Adult male apolipoprotein E knockout (ApoE)-/- (n=72), TLR2-/-ApoE-/- (n=36) and TLR4-/-Apo-/- (n=28) mice were intravenously injected with 50 µg/mouse of endotoxin-free polyclonal anti-apoA-1 IgG or control isotype IgG (CTL IgG) every two weeks for 16 weeks. Atherosclerotic plaque size and vulnerability were assessed by histology. Myocardial ischaemia and necrosis, respectively, were determined by electrocardiographic (ECG) changes assessed by telemetry and serum troponin I (cTnI) measurements. Impact on survival was assessed by Kaplan-Meier analyses. In ApoE-/- mice, anti-apoA-1 IgG passive immunisation enhanced histological features of atherosclerotic plaque vulnerability (increase in neutrophil and MMP-9 and reduction in collagen content), induced a substantial cTnI elevation (p=0.001), and increased mortality rate by 23 % (LogRank, p=0.04) when compared to CTL IgG. On a subgroup of ApoE-/- mice equipped with telemetry (n=4), a significant ST-segment depression was noted in anti-apoA-1 IgG-treated mice when compared to CTL IgG recipients (p< 0.001), and an acute ST-segment elevation myocardial infarction preceding mouse death was observed in one case. The deleterious effects of anti-apoA-1 IgG on atherosclerotic plaque vulnerability, myocardial necrosis and death were partially reversed in TLR2-/-ApoE-/- and TLR4-/-ApoE-/- backgrounds. In conclusion, anti-apoA-1 auto-antibodies seem to be active mediators of atherosclerotic plaque vulnerability, myocardial necrosis, and mortality in mice through TLR2- and TLR4-mediated pathways.
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Apolipoproteína A-I/antagonistas & inhibidores , Autoanticuerpos/efectos adversos , Inmunoglobulina G/efectos adversos , Isquemia Miocárdica/etiología , Miocardio/patología , Placa Aterosclerótica/inmunología , Receptor Toll-Like 2/fisiología , Receptor Toll-Like 4/fisiología , Animales , Enfermedades de la Aorta/patología , Apolipoproteína A-I/inmunología , Apolipoproteínas E/deficiencia , Colágeno/análisis , Susceptibilidad a Enfermedades , Inmunización Pasiva/efectos adversos , Lípidos/análisis , Masculino , Ratones , Ratones Noqueados , Infarto del Miocardio/etiología , Infarto del Miocardio/inmunología , Infarto del Miocardio/patología , Isquemia Miocárdica/sangre , Isquemia Miocárdica/inmunología , Isquemia Miocárdica/patología , Necrosis , Placa Aterosclerótica/genética , Placa Aterosclerótica/metabolismo , Transducción de Señal/inmunología , Telemetría , Receptor Toll-Like 2/deficiencia , Receptor Toll-Like 2/genética , Receptor Toll-Like 4/deficiencia , Receptor Toll-Like 4/genética , Troponina I/sangreRESUMEN
OBJECTIVES: We have recently shown that CRP induces chemokine secretion and adhesion molecule up-regulation in human primary monocytes cultured in adherence. Given the increasing evidence on direct immunomodulatory properties of statins, we investigated their possible anti-inflammatory role on CRP-treated human monocytes. METHODS: Monocytes were isolated by Ficoll-Percoll gradients and cultured in adherence to polystyrene. Chemokine secretion and adhesion molecule expression were detected by ELISA and flow cytometry. Migration assays were performed in modified Boyden chambers. Intracellular kinase activation was assessed by western blot. RESULTS: Treatment with simvastatin or atorvastatin decreased CRP-induced release of CCL2, CCL3 and CCL4. In addition, both statins reduced CRP-induced intercellular adhesion molecule (ICAM-1) up-regulation, but had no effects on CD11b and CD18. Treatments with 1 microM simvastatin or atorvastatin significantly inhibited monocyte migration in response to CRP. CD32 and CD64 (CRP receptors) expression on monocytes was not affected by statins. Statin-induced inhibition of CRP-mediated chemokine secretion, ICAM-1 up-regulation and migration occurred through the inhibition of extracellular signal-regulated kinase (ERK) 1/2. Treatment with L-mevalonate or farnesylpyrophosphate, but not geranylgeranyl-pyrophosphate reversed the statin-induced effect on CRP-mediated functions and ERK 1/2 phosphorylation, confirming that statins blocked CRP-induced ERK 1/2 phosphorylation through the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. CONCLUSIONS: Statins inhibited CRP-induced chemokine secretion, ICAM-1 up-regulation and migration in human adherent monocytes, through the inhibition of HMG-CoA reductase-ERK 1/2 pathway. This pathway could represent a very promising target to reduce CRP-induced activities in monocyte-mediated diseases, such as atherosclerosis or RA.
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Proteína C-Reactiva/antagonistas & inhibidores , Quimiocinas/metabolismo , Quimiotaxis de Leucocito/efectos de los fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Molécula 1 de Adhesión Intercelular/biosíntesis , Proteína C-Reactiva/farmacología , Adhesión Celular/fisiología , Células Cultivadas , Relación Dosis-Respuesta a Droga , Activación Enzimática/fisiología , Humanos , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Monocitos/efectos de los fármacos , Monocitos/fisiología , Receptores Inmunológicos/efectos de los fármacos , Receptores Inmunológicos/metabolismo , Proteínas Recombinantes/farmacología , Regulación hacia Arriba/efectos de los fármacosRESUMEN
AIMS/HYPOTHESIS: This study compared the pharmacokinetics and pharmacodynamics of insulin glulisine, insulin lispro, and regular human insulin in obese subjects. METHODS: In this single-dose, randomized, double-blind, crossover euglycaemic clamp study, 18 non-diabetic subjects (mean body mass index [BMI] 34.7 kg . m (-2)) were randomized to receive subcutaneous injections of each insulin (0.3 U . kg (-1)) in pre-determined sequences. RESULTS: Insulin glulisine and insulin lispro had more rapid-acting profiles than regular human insulin. Fractional glucose infusion rate (GIR)-area under curves (AUC) of the GIR curve and maximum GIR were greater for insulin glulisine and insulin lispro versus regular human insulin. Total glucose disposal was slightly greater with insulin glulisine than with regular human insulin, and was comparable to insulin lispro, although it decreased with increasing insulin resistance (HOMA index) with all insulins. Time to 20 % (early glucose disposal) and 80 % (bulk of activity) of total GIR-AUC were shorter for insulin glulisine and insulin lispro versus regular human insulin. This was corroborated by more rapid and shorter residing pharmacokinetic profiles of insulin glulisine and insulin lispro versus regular human insulin, evidenced by shorter times to 20 % of total INS-AUC, INS-C (max) (INS-t (max)), and mean residence time. Moreover, time to 20 % of total GIR-AUC demonstrated a less rapid-acting profile for insulin lispro versus insulin glulisine, which was consistent with the slightly less rapid pharmacokinetic profile of insulin lispro. There was no significant correlation between BMI or subcutaneous fat thickness and pharmacokinetic or pharmacodynamic profiles for insulin glulisine, unlike insulin lispro and regular human insulin. CONCLUSIONS/INTERPRETATION: Insulin glulisine and insulin lispro demonstrated substantially more rapid time-action profiles than regular human insulin in obese non-diabetic subjects, which prevailed with insulin glulisine irrespective of BMI and subcutaneous fat thickness.
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Hipoglucemiantes/farmacocinética , Insulina/análogos & derivados , Obesidad , Adulto , Glucemia/efectos de los fármacos , Método Doble Ciego , Femenino , Humanos , Hipoglucemiantes/administración & dosificación , Inyecciones Subcutáneas , Insulina/administración & dosificación , Insulina/farmacocinética , Insulina Lispro , Masculino , Persona de Mediana Edad , Obesidad/sangre , TiempoRESUMEN
Insulin glulisine is a new rapid-acting insulin analog. The aim of this study was to assess the glucodynamic efficacy of insulin glulisine compared with regular human insulin (RHI) using a manual euglycemic clamp technique. Steady-state pharmacokinetics of insulin glulisine, and its cardiac safety (ECG) and tolerability after intravenous administration, were also determined. This was a single center, randomized, open-label, two-way crossover study in healthy male subjects (n = 16). At the treatment visits subjects received an intravenous infusion of the study drug at a rate of 0.8 mU kg (-1) . min (-1) for 2 hours. Individual baseline glucose concentrations were targeted for euglycaemia and maintained with a manual adjusted 20 % glucose solution over the clamp period of a maximum 6 hours. A glulisine-specific antibody was used to quantify glulisine concentrations by radioimmunoassay, while a non-specific insulin antibody and C-peptide based correction for endogenous insulin was used to estimate exogenous human insulin (RHI). At steady state (90 - 120 min), insulin glulisine and RHI had equivalent glucose utilization (GIR-AUC (SS), 209 [corrected] mg . kg (-1) for glulisine, 214 [corrected] mg . kg (-1) for RHI) and infusion rates (GIR (SS), 7.0 and 7.2 [corrected] mg . kg (-1) . [corrected] min (-1) . kg (-1)). Both insulins also presented equal total glucose disposal (GIR-AUC (0 - clamp end), 995 and 1050 [corrected] mg . kg (-1)) and onset of activity within 20 min. Insulin glulisine and RHI showed parallel time concentration profiles with similar distribution and elimination, but the different antibodies employed for radioimmunoassay impeded a quantitative comparison. There were no noteworthy individual or within-group changes in cardiac repolarisation parameters measured by 12-lead ECG during insulin glulisine infusion. In conclusion, insulin glulisine and RHI show similar distribution and elimination profiles and equivalent glucodynamic efficacy on a molar, unit-per-unit basis.
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Técnica de Clampeo de la Glucosa , Insulina/análogos & derivados , Insulina/farmacología , Insulina/farmacocinética , Adulto , Glucemia/análisis , Estudios Cruzados , Humanos , Cinética , Masculino , Proteínas RecombinantesRESUMEN
Radiation as well as mechanical treatments induced in drugs and excipients radicals, which can be studied by electron paramagnetic resonance. A special attention is pointed about the use of electron paramagnetic resonance (EPR) to bring the proof whether or not a drug has been irradiated or not. We also discuss of other methods (thermoluminescence (TL), gas phase chromatography (GPC)) which can be used to bring the same proof in case of irradiated drugs, excipients and cosmetic products.
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Espectroscopía de Resonancia por Spin del Electrón/métodos , Aminoácidos , Ampicilina/farmacología , Antibacterianos/farmacología , Cromatografía de Gases , Radicales Libres , Rayos gamma , Calor , Aceite de Oliva , Aceites de Plantas/farmacología , Temperatura , Rayos UltravioletaRESUMEN
The alpha(6) integrin is a 140-kDa (nonreduced) laminin receptor. We have identified a novel 70-kDa (nonreduced) form of the alpha(6) integrin called alpha(6)p for the latin word parvus, meaning small. The variant was immunoprecipitated from human cells using four different alpha(6)-specific monoclonal antibodies but not with alpha(3) or alpha(5) antibodies. The alpha(6)p integrin contained identical amino acid sequences within exons 13--25, corresponding to the extracellular "stalk region" and the cytoplasmic tail of the alpha(6) integrin. The light chains of alpha(6) and alpha(6)p were identical as judged by alpha(6)A-specific antibodies and electrophoretic properties. The alpha(6)p variant paired with either beta(1) or beta(4) subunits and was retained on the cell surface three times longer than alpha(6). Reverse transcription/polymerase chain reaction analysis revealed a single polymerase chain reaction product. The alpha(6)p variant was found in human prostate (DU145H, LnCaP, PC3) and colon (SW480) cancer cell lines but not in normal prostate (PrEC), breast cancer (MCF-7), or lung cancer (H69) cell lines or a variant of a prostate carcinoma cell line (PC3-N). Protein levels of alpha(6)p increased 3-fold during calcium-induced terminal differentiation in a normal mouse keratinocyte model system. A novel form of the alpha(6) integrin exists on cell surfaces that contains a dramatically altered extracellular domain.
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Integrinas/análisis , Secuencia de Aminoácidos , Humanos , Integrinas/química , Integrinas/genética , Datos de Secuencia Molecular , Especificidad de ÓrganosRESUMEN
Formation of the lipoxygenase-catalyzed metabolites of arachidonic acid, 8-hydroxyeicosatetraenoic acid (8-HETE) and 12-hydroxyeicosatetraenoic acid (12-HETE), and of the exocyclic DNA adducts 1,N(6)-ethenodeoxyadenosine (epsilondA) and 3, N(4)-ethenodeoxycytidine (epsilondC) was investigated in NMRI mouse skin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA) and promoted by 12-O-tetradecanoylphorbol-13-acetate (TPA). In reversible papillomas obtained after 20 weeks of TPA treatment, 15- and 68-fold higher contents of 8-HETE and 12-HETE, respectively, were observed, which were paralleled by 12- and 9-fold increased amounts of epsilondA and epsilondC, respectively. When compared to the level in vehicle-treated control skin, these elevations were statistically significant. In irreversible papillomas harvested 20 weeks after the last TPA treatment, the levels of HETEs and etheno-DNA adducts were found to be slightly reduced, as compared to those in reversible papillomas, but were still increased over control levels in age-matched mice. Comparison of mean group values by simple regression analysis showed a close positive correlation between HETE and etheno-DNA adduct levels. Consistent with the miscoding properties of epsilondA causing mainly A --> T transversions, its increased formation in papillomas could thus contribute to this type of mutation in codon 61 of cHa-ras, shown to be a hallmark of DMBA-initiated and TPA-promoted mouse skin carcinogenesis. Although direct evidence that etheno adducts are derived from lipoxygenase-catalyzed metabolites of arachidonic acid is missing, our results implicate DNA damage by oxidative stress and lipid peroxidation as a cause of genetic instability observed at late stages of tumor promotion in mouse skin carcinogenesis.
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Ácido Araquidónico/metabolismo , Aductos de ADN/biosíntesis , Desoxiadenosinas/metabolismo , Desoxicitidina/análogos & derivados , Lipooxigenasa/metabolismo , Papiloma/metabolismo , Neoplasias Cutáneas/metabolismo , Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico/análisis , Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico/metabolismo , Animales , Cromatografía Líquida de Alta Presión , Aductos de ADN/análisis , ADN de Neoplasias/análisis , Desoxiadenosinas/análisis , Desoxicitidina/análisis , Desoxicitidina/metabolismo , Femenino , Cromatografía de Gases y Espectrometría de Masas , Ácidos Hidroxieicosatetraenoicos/análisis , Ácidos Hidroxieicosatetraenoicos/metabolismo , Ratones , Mutagénesis , Papiloma/inducido químicamente , Papiloma/genética , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/genética , Regulación hacia ArribaRESUMEN
Ribosome biogenesis requires, in addition to rRNA molecules and ribosomal proteins, a multitude of trans-acting factors. Recently it has become clear that in the yeast Saccharomyces cerevisiae many RNA helicases of the DEAD-box and related families are involved in ribosome biogenesis. Here we show that the previously uncharacterised open reading frame YDL031w (renamed DBP10 for DEAD-box protein 10) encodes an essential putative RNA helicase that is required for accurate ribosome biogenesis. Genetic depletion of Dbp10p results in a deficit in 60S ribosomal subunits and an accumulation of half-mer polysomes. Furthermore, pulse-chase analyses of pre-rRNA processing reveal a strong delay in the maturation of 27SB pre-rRNA intermediates into 25S rRNA and 7S pre-rRNA. Northern blot analyses indicate that this delay leads to higher steady-state levels of 27SB species and reduced steady-state levels of 7S pre-rRNA and 25S/5.8S mature rRNAs, thus explaining the final deficit in 60S subunit and the formation of half-mer polysomes. Consistent with a direct role in ribosome biogenesis, Dbp10p was found to be located predominantly in the nucleolus.
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ARN Helicasas/genética , Ribosomas/fisiología , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/enzimología , Saccharomyces cerevisiae/genética , Secuencia de Aminoácidos , Secuencia de Bases , Nucléolo Celular/fisiología , ARN Helicasas DEAD-box , Eliminación de Gen , Datos de Secuencia Molecular , Oligodesoxirribonucleótidos , Sistemas de Lectura Abierta , Fenotipo , ARN Helicasas/metabolismo , ARN Ribosómico/genética , ARN Ribosómico 5.8S , Ribosomas/genética , Saccharomyces cerevisiae/crecimiento & desarrolloRESUMEN
A quantitative stereochemical analysis of the products generated by recombinant mouse (12S)-lipoxygenase isoenzymes was performed with arachidonic acid and linoleic acid as substrates. The leucocyte-type (12S)-lipoxygenase generated, in addition to 12-hydroxyeicosatetraenoic acid (12-HETE) as the main product, 15- and 8-HETE from arachidonic acid and 13- and 9-hydroxyoctadecadienoic acid (13- and 9-HODE) from linoleic acid. The platelet-type enzyme oxygenated arachidonic acid to 12- and 8-HETE and linoleic acid to 13- and 9-HODE, whereas the epidermis-type (12S)-lipoxygenase reaction was essentially mono-specific with arachidonic acid but oxygenated linoleic acid to both 13- and 9-HODE. 12-HETE and 13-HODE were almost exclusively the S enantiomers. 8-HETE was the R enantiomer as a side-product of the platelet-type (12S)-lipoxygenase reaction but the S enantiomer as a side-product of the leucocyte-type reaction. 9-HODE was generated as the R enantiomer by the platelet-type and the epidermis-type isoenzymes and as the S enantiomer by the leucocyte-type (12S)-lipoxygenase. On the basis of published models of lipoxygenase-substrate interaction, the stereochemistry of the products generated by the platelet- and epidermis-type (12S)-lipoxygenases is in agreement with a fixed 'tail-to-head' orientation of the substrate fatty acid in the binding pocket of these enzymes, whereas that of the reaction products of the leucocyte-type (12S)-lipoxygenase can be explained only when the inverse orientation of the substrate or a rotational isomerism along the longitudinal axis of the substrate is allowed. Both the product spectra generated and the sensitivity towards the 12-lipoxygenase selective inhibitors N-benzyl-N-hydroxy-4-phenylpentanamide and cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate indicated the platelet-type and the epidermis-type isoenzymes to be biochemically more related to each other than to the leucocyte-type (12S)-lipoxygenase.
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Araquidonato 12-Lipooxigenasa/metabolismo , Ácidos Linoleicos Conjugados , Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico/metabolismo , Animales , Ácido Araquidónico/metabolismo , Plaquetas/enzimología , Línea Celular , Epidermis/enzimología , Humanos , Isoenzimas/metabolismo , Cinética , Leucocitos/enzimología , Ácidos Linoleicos/metabolismo , Ratones , Modelos Químicos , Proteínas Recombinantes/metabolismo , Estereoisomerismo , Especificidad por Sustrato , TransfecciónRESUMEN
The expression pattern, enzymatic activity, and products of 8-lipoxygenase (LOX) were analyzed in normal and neoplastic skin of NMRI mice. While barely detectable in normal epidermis, 8-LOX was transiently induced by 12-O-tetradecanoylphorbol-13-acetate and constitutively expressed in papillomas but not carcinomas obtained by the initiation-promotion protocol of mouse skin carcinogenesis. The product profile and chirality of both the native and the recombinant protein produced the S enantiomers of 8-hydroxy-5Z,9E,11Z,14Z-eicosatetraenoic acid (8-HETE) and 9-hydroxy-10E,12Z-octadecadienoic acid (9-HODE) as the main arachidonic acid- and linoleic acid-derived metabolites. As compared with normal epidermis, papillomas exhibited 25- and 4-fold elevated levels of 8-HETE and 9-HODE, respectively. However, the varying S to R ratios of 8-HETE and the predominance of 9(R)-HODE indicated that in addition to 8(S)-LOX, other enzymes yet to be defined may be involved in 8-HETE and 9-HODE production. The massive accumulation of both 8-HETE and 12-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12-HETE) point to a critical role of these LOX pathways in epidermal tumor development, in particular in the papilloma stage. Here we showed that 8- and 12-hydroperoxyeicosatetraenoic acids and 8- and 12-HETE induce chromosomal alterations in cycling primary basal keratinocytes.
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Araquidonato Lipooxigenasas/biosíntesis , Ácido Araquidónico/metabolismo , Ácidos Linoleicos Conjugados , Papiloma/metabolismo , Neoplasias Cutáneas/metabolismo , Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico/metabolismo , Animales , Femenino , Ácidos Hidroxieicosatetraenoicos/metabolismo , Queratinocitos/metabolismo , Ácidos Linoleicos/metabolismo , Masculino , Ratones , Papiloma/patología , Neoplasias Cutáneas/patologíaRESUMEN
Psychiatric and developmental disorders with onset in early childhood are often missed and commonly overlooked by adult psychiatrists. These disorders have important continuities into adulthood and are powerful predictors of chronicity, comorbidity, and severity. It is essential that they are recognized and taken into account in the assessment and treatment of the adult patient.
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Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastornos de la Conducta Infantil/diagnóstico , Trastornos Generalizados del Desarrollo Infantil/diagnóstico , Discapacidades del Desarrollo/diagnóstico , Errores Diagnósticos , Trastornos del Humor/diagnóstico , Trastornos por Estrés Postraumático/diagnóstico , Adolescente , Adulto , Niño , Femenino , Humanos , Discapacidades para el Aprendizaje/diagnóstico , Masculino , Persona de Mediana Edad , Temperamento/fisiología , Trastornos de Tic/diagnóstico , Resultado del TratamientoRESUMEN
Using a combination of conventional screening procedures and polymerase chain reaction cloning, we have isolated a cDNA encoding an epidermis-type 12-lipoxygenase (e12-lipoxygenase) from mouse epidermis. The open reading frame corresponds to a protein of 662 amino acids and was found to be 99.8% identical to the ORF of an epidermal lipoxygenase gene Aloxe, described recently [Van Dijk et al. (1995) Biochim. Biophys. Acta 1259, 4-8]. When expressed in human embryonic kidney cells the recombinant protein could be shown to synthesize 12(S)-HETE from arachidonic acid. By fluorescence in situ hybridization the e12-lipoxygenase gene was localized to chromosome band 11 B1-B3.
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Araquidonato 12-Lipooxigenasa/biosíntesis , Araquidonato 12-Lipooxigenasa/genética , Mapeo Cromosómico , Isoenzimas/biosíntesis , Piel/enzimología , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Línea Celular , Clonación Molecular , Cartilla de ADN , ADN Complementario , Humanos , Hibridación Fluorescente in Situ , Isoenzimas/genética , Riñón , Ratones , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Biosíntesis de Proteínas , TransfecciónRESUMEN
The study undertook to ascertain the effect of a subnormal dietary intake of vitamin B6 on plasma levels of total cholesterol, high density lipoproteins, low density lipoproteins and triglycerides. Plasma samples were assessed after 8 weeks in 3 groups of young male Wistar rats receiving a daily pyridoxine hydrochloride intake of 60 (normal control group, A) and 20 micrograms (experimental group C). Group B was the pair-fed control. Vitamin B6 status of all groups was confirmed by measuring plasma pyridoxal-5'-phosphate and pyridoxal. All groups were still in the growth phase at the end of 8 weeks, and since the mean mass for all groups remained within the norm for male Wistar rats, it would appear that caloric intake was not compromised. The fasting triglyceride levels in the normal control group were significantly higher than those of the experimental and pair-fed control groups, although all values remained within the normal range for rats. A subnormal intake of pyridoxine hydrochloride made no significant difference in the high density lipoprotein levels although it contributed to a significant increase in low density lipoprotein and total cholesterol levels. The plasma pyridoxal-5'-phosphate and pyridoxal values were in accordance with the pyridoxine hydrochloride intake of the different groups.
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Avitaminosis/fisiopatología , Lípidos/sangre , Piridoxina/farmacología , Análisis de Varianza , Animales , Peso Corporal/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Metabolismo de los Lípidos , Masculino , Piridoxal/sangre , Piridoxal/metabolismo , Fosfato de Piridoxal/sangre , Fosfato de Piridoxal/metabolismo , Ratas , Ratas WistarRESUMEN
Tissue zinc (Zn), copper (Cu) and iron (Fe) were determined in three groups of young male Wistar rats that received a daily pyridoxine hydrochloride (PN.HCl) intake of 45, 23 and 0 micrograms respectively in their diets over 8 weeks. No significant differences were found in the Zn and Cu levels in the liver, kidney, skeletal and cardiac tissue of all 3 groups. The Fe levels were significantly higher in the heart and liver and significantly lower in the skeletal muscle of the group receiving no PN.HCl in the diet (P < 0.05). This study indicates that the increased fecal excretion of Zn and Cu observed during a previous balance study on the above vitamin B6 deficient group of animals may be due to a decreased absorption of these elements from the diet rather than their excretion from tissue stores. The changes in Fe levels in the heart, liver and skeletal muscle points towards some alteration in tissue stores of this element during a vitamin B6 deficiency.
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Cobre/metabolismo , Hierro/metabolismo , Deficiencia de Vitamina B 6/metabolismo , Zinc/metabolismo , Animales , Riñón/química , Riñón/metabolismo , Hígado/química , Hígado/metabolismo , Masculino , Músculo Esquelético/química , Músculo Esquelético/metabolismo , Miocardio/química , Miocardio/metabolismo , Ratas , Ratas Wistar , Oligoelementos/metabolismo , Xanturenatos/metabolismo , Xanturenatos/orinaRESUMEN
In order to find further genes of the mitochondrial fatty acid synthase, we searched the genome of Saccharomyces cerevisiae for sequences that are homologous to conserved regions of bacterial fatty acid synthase genes. We found the gene products of ORF YKL055c (EMBL Accession No. X75781) and of YOR221C (EMBL Accession No. X92441) to be homologous to bacterial 3-oxoacyl-(acyl carrier protein) reductases and to malonyl-CoA:ACP-transferases, respectively. We disrupted these two genes which in both cases led to a respiratory deficient phenotype, as is the case for the genes encoding a mitochondrial acyl carrier protein and a beta-ketoacyl-ACP synthase. We propose to call the above mentioned genes OAR1 [3-oxo-acyl-(acyl carrier protein) reductase] and MCT1 (malonyl-CoA:ACP transferase). They are presumed to be part of a type-II mitochondrial fatty acid synthase, a relic of the endosymbiontic origin of mitochondria, delivering substrates for phospholipid re-modelling and/or repair.
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Ácido Graso Sintasas/genética , Genes Fúngicos/genética , Mitocondrias/enzimología , Saccharomyces cerevisiae/genética , 3-Oxoacil-(Proteína Transportadora de Acil) Reductasa , S-Maloniltransferasa de la Proteína Transportadora de Grupos Acilo , Aciltransferasas/genética , Oxidorreductasas de Alcohol/genética , Secuencia de Aminoácidos , Prueba de Complementación Genética , Mitocondrias/metabolismo , Datos de Secuencia Molecular , Fosforilación Oxidativa , Saccharomyces cerevisiae/enzimología , Homología de Secuencia de AminoácidoRESUMEN
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder with a great degree of phenotypic variability. Given the presence of two gene loci underlying this disorder, locus heterogeneity may account for some of the variability. However, significant within family variation suggests that different genes do not explain the majority of this variation. The purpose of this research is to identify physical and behavioural variation in expression of TSC in a single large extended kindred. TSC in this kindred is cosegregating with markers localised to chromosome 16p13.3. The expression of TSC in this kindred is quite variable with a substantial proportion of persons showing very mild physical expression of TSC. In contrast to very mild physical expression of TSC in some family members, there is a significant clustering of psychiatric disorders among persons affected with TSC compared to their unaffected relatives. This finding, coupled with the mild physical expression of TSC in some family members, supports a hypothesis that the TSC2 gene may present phenotypically as mild skin signs and significant behavioural problems.
Asunto(s)
Cromosomas Humanos Par 16 , Variación Genética , Esclerosis Tuberosa/genética , Adolescente , Adulto , Mapeo Cromosómico , Femenino , Humanos , Entrevistas como Asunto , Escala de Lod , Masculino , Trastornos Mentales/epidemiología , Trastornos Mentales/genética , Pruebas Neuropsicológicas , Fenotipo , Examen Físico , Esclerosis Tuberosa/fisiopatología , Esclerosis Tuberosa/psicologíaRESUMEN
Zinc (Zn), copper (Cu) and iron (Fe) balance was assessed over 8 weeks in 3 groups of young male Wistar rats receiving a daily pyridoxine hydrochloride (PN-HCl) intake of 45, 23 and 0 micrograms respectively. Although all 3 groups remained in a positive balance throughout the study the Zn and Cu balance, growth and food intake was significantly lower in the group receiving no PN-HCl (p < 0.05). The lowered Zn and Cu balance in this group resulted from a decreased food intake coupled with an increased excretion of Zn and Cu. The group receiving 23 micrograms/d of PN-HCl showed no significant difference in growth, food intake and Zn and Cu balance when compared to the group receiving 45 micrograms/d, indicating that subminimal levels of vitamin may still be exerting beneficial effects on the balance of these trace elements.