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OBJECTIVES: Current repair procedures for articular cartilage (AC) cannot restore the tissue's original form and function because neither changes in its architectural blueprint throughout life nor the respective biological understanding is fully available. We asked whether two unique elements of human cartilage architecture, the chondrocyte-surrounding pericellular matrix (PCM) and the superficial chondrocyte spatial organization (SCSO) beneath the articular surface (AS) are congenital, stable or dynamic throughout life. We hypothesized that inducing chondrocyte proliferation in vitro impairs organization and PCM and induces an advanced osteoarthritis (OA)-like structural phenotype of human cartilage. METHODS: We recorded propidium-iodine-stained fetal and adult cartilage explants, arranged stages of organization into a sequence, and created a lifetime-summarizing SCSO model. To replicate the OA-associated dynamics revealed by our model, and to test our hypothesis, we transduced specifically early OA-explants with hFGF-2 for inducing proliferation. The PCM was examined using immuno- and auto-fluorescence, multiphoton second-harmonic-generation (SHG), and scanning electron microscopy (SEM). RESULTS: Spatial organization evolved from fetal homogeneity, peaked with adult string-like arrangements, but was completely lost in OA. Loss of organization included PCM perforation (local micro-fibrillar collagen intensity decrease) and destruction [regional collagen type VI (CollVI) signal weakness or absence]. Importantly, both loss of organization and PCM destruction were successfully recapitulated in FGF-2-transduced explants. CONCLUSION: Induced proliferation of spatially characterized early OA-chondrocytes within standardized explants recapitulated the full range of loss of SCSO and PCM destruction, introducing a novel in vitro methodology. This methodology induces a structural phenotype of human cartilage that is similar to advanced OA and potentially of significance and utility.
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Osteoartrite , Cartilagem Articular , Condrócitos , Matriz Extracelular , Fator 2 de Crescimento de Fibroblastos , HumanosRESUMO
STUDY QUESTION: How are protamine deficiencies associated with sperm head morphology in subfertile men? SUMMARY ANSWER: The prevalence of morphological variations and large nuclear vacuoles was slightly higher in protamine-deficient spermatozoa than in non-deficient spermatozoa. WHAT IS KNOWN ALREADY: A protamine deficiency was previously reported to be associated with an abnormal sperm morphology; however, how they are related to each other remains unclear. This is further confounded by a number of protamine-deficient spermatozoa having a normal head morphology. STUDY DESIGN, SIZE, DURATION: This is a cross-sectional study, including 36 men diagnosed with male factor infertility or participating in an assisted reproduction program. To assess sperm head morphology, this study analyzed 2400 spermatozoa with a protamine deficiency and 2400 spermatozoa with a normal protamine status. An additional 21 men were analyzed to examine DNA fragmentation and its relationship with protamine deficiencies and sperm head morphologies. PARTICIPANTS/MATERIALS, SETTING, METHODS: The morphology of the sperm head was evaluated based on its shape, size and nuclear vacuoles at a magnification of >6000×. Using elliptic Fourier analysis, the shape was summarized into four numeric variables. The protamine status was evaluated with chromomycin A3 (CMA3). Sperm head size, vacuoles and shape were compared between protamine-deficient and non-deficient spermatozoa. DNA fragmentation was evaluated with the terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) assay. The percentages of protamine-deficient spermatozoa and DNA fragmentation were compared between spermatozoa with morphologically normal heads and those with abnormal heads. MAIN RESULTS AND THE ROLE OF CHANCE: Variations in head size (P < 0.0001) and shape (P < 0.0001) were significantly higher, with narrower (P < 0.001), more fan-shaped (P < 0.01) and more square-shaped forms (P < 0.001) in protamine-deficient spermatozoa than in non-deficient spermatozoa; however, the distribution of morphological variations markedly overlapped. Protamine deficiencies were more frequently observed in spermatozoa with large nuclear vacuoles than in those without them (32.0 ± 3.1 versus 39.4 ± 2.9%, P < 0.001). The percentage of protamine-deficient spermatozoa was significantly lower in spermatozoa with a normal head morphology than in those with an abnormal head morphology (25.4 ± 2.6 versus 38.0 ± 2.5%, P < 0.001). The percentage of DNA fragmentation was significantly higher in protamine-deficient spermatozoa than in non-deficient spermatozoa (11.3 ± 2.1 versus 1.6 ± 0.6%, P < 0.001), and was lower in spermatozoa with a normal head morphology than in those with an abnormal head morphology (2.6 ± 0.7 versus 6.4 ± 0.2%, P < 0.001). LIMITATIONS, REASONS FOR CAUTION: We were unable to discriminate the kind of protamines or quantify the extent of the protamine deficiency in spermatozoa using the CMA3 staining method. WIDER IMPLICATIONS OF THE FINDINGS: This study provided a novel insight into how abnormal protamination affects sperm head morphology as well as the relationship between sperm head morphology and its own molecular integrity. Our results will contribute to a deeper understanding of the benefits and limitations of the morphological selection of spermatozoa for ICSI. STUDY FUNDING/COMPETING INTERESTS: This study was supported by a JSPS Grant-in-Aid for the Encouragement of Scientists (25931009, 26931010). All authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: N/A.
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Infertilidade Masculina/patologia , Protaminas/metabolismo , Espermatozoides/patologia , Vacúolos/patologia , Adulto , Forma Celular , Estudos Transversais , Fragmentação do DNA , Humanos , Infertilidade Masculina/metabolismo , Masculino , Pessoa de Meia-Idade , Cabeça do Espermatozoide/metabolismo , Cabeça do Espermatozoide/patologia , Espermatozoides/metabolismo , Vacúolos/metabolismoRESUMO
This study investigated the temperature elevation in the eye of anatomically based human head models for plane-wave exposures. The finite-difference time-domain method is used for analyzing electromagnetic absorption and temperature elevation. The eyes in the anatomic models have average dimensions and weight. Computational results show that the ratio of maximum temperature in the lens to the eye-average SAR (named 'heating factor for the lens') is almost uniform (0.112-0.147 degrees C kg W(-1)) in the frequency region below 3 GHz. Above 3 GHz, this ratio increases gradually with an increase of frequency, which is attributed to the penetration depth of an electromagnetic wave. Particular attention is paid to the difference in the heating factor for the lens between this study and earlier works. Considering causes clarified in this study, compensated heating factors in all these studies are found to be in good agreement.
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Cabeça/efeitos da radiação , Imagens de Fantasmas , Temperatura Corporal , Simulação por Computador , Feminino , Cabeça/patologia , Temperatura Alta , Humanos , Masculino , Modelos Anatômicos , Radiação , Doses de Radiação , Radiometria , Software , Temperatura , Distribuição TecidualRESUMO
INTRODUCTION: Student tutors in the dissection course are expected to meet high demands in their job, to fulfill these expectations they receive training. Combined tutor training is well accepted by tutors and tutees, however, it is not known how tutor training influences student learning. Deduced from the learning goals of the tutor training, a randomized, controlled, single-blinded study was set up with a quantitative cross-sectional analysis to compare student learning behavior. METHODS: A total of 197 medical students, coached either by ten trained or ten untrained tutors, were enlisted in the study. To assess the students' learning behavior we employed the LIST questionnaire. A common factor analysis was calculated to extract dimensions. Factor scores of the extracted dimensions were calculated for both groups to estimate differences in learning behavior. RESULTS: Factor analysis of the LIST questionnaire revealed eight factors explaining 47.57% of the overall variance. The eight factors comprise: deep learning, attention, learning organization, cooperative learning, time management, learning effort, superficial learning and learning environment. Comparing the factor scores of the extracted dimensions, students coached by trained tutors learned significantly more with their fellow students (factor score in cooperative learning 0.194 vs. -0.205, p<0.05), than students trained by untrained tutors. Students coached by trained tutors also tend to be better organized in their learning (factor score in learning organization 0.115 vs. -0.122, p=0.16). CONCLUSION: The learning behavior of students coached by trained tutors differs from the learning behavior of students coached by untrained tutors. Students coached by trained tutors learn significantly more often in teams than their colleagues and are better organized.
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Anatomia/educação , Dissecação/estatística & dados numéricos , Avaliação Educacional/estatística & dados numéricos , Grupo Associado , Estudantes de Medicina/estatística & dados numéricos , Capacitação de Professores/estatística & dados numéricos , Adulto , Currículo , Método Duplo-Cego , Docentes/estatística & dados numéricos , Feminino , Alemanha , Humanos , Masculino , Capacitação de Professores/métodos , Ensino , Adulto JovemRESUMO
OBJECTIVES: Cement augmentation of pedicle screws could be used to improve screw stability, especially in osteoporotic vertebrae. However, little is known concerning the influence of different screw types and amount of cement applied. Therefore, the aim of this biomechanical in vitro study was to evaluate the effect of cement augmentation on the screw pull-out force in osteoporotic vertebrae, comparing different pedicle screws (solid and fenestrated) and cement volumes (0 mL, 1 mL or 3 mL). MATERIALS AND METHODS: A total of 54 osteoporotic human cadaver thoracic and lumbar vertebrae were instrumented with pedicle screws (uncemented, solid cemented or fenestrated cemented) and augmented with high-viscosity PMMA cement (0 mL, 1 mL or 3 mL). The insertion torque and bone mineral density were determined. Radiographs and CT scans were undertaken to evaluate cement distribution and cement leakage. Pull-out testing was performed with a material testing machine to measure failure load and stiffness. The paired t-test was used to compare the two screws within each vertebra. RESULTS: Mean failure load was significantly greater for fenestrated cemented screws (+622 N; p ⩽ 0.001) and solid cemented screws (+460 N; p ⩽ 0.001) than for uncemented screws. There was no significant difference between the solid and fenestrated cemented screws (p = 0.5). In the lower thoracic vertebrae, 1 mL cement was enough to significantly increase failure load, while 3 mL led to further significant improvement in the upper thoracic, lower thoracic and lumbar regions. CONCLUSION: Conventional, solid pedicle screws augmented with high-viscosity cement provided comparable screw stability in pull-out testing to that of sophisticated and more expensive fenestrated screws. In terms of cement volume, we recommend the use of at least 1 mL in the thoracic and 3 mL in the lumbar spine.Cite this article: C. I. Leichtle, A. Lorenz, S. Rothstock, J. Happel, F. Walter, T. Shiozawa, U. G. Leichtle. Pull-out strength of cemented solid versus fenestrated pedicle screws in osteoporotic vertebrae. Bone Joint Res 2016;5:419-426.
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INTRODUCTION: Medical professionalism is an increasingly important issue in medical education. The dissection course represents a profound experience for undergraduate medical students, which may be suitable to address competencies such as self-reflection and professional behavior. MATERIAL AND METHODS: Based on a needs assessment, a seminar on medical professionalism was developed to parallel the dissection course. The conceptual framework for the teaching intervention is experiential learning. Specific learning goals and an interview guideline were formulated. After a pilot run, peer-teaching was introduced. RESULTS: Over three terms (winter 2012/13, 2013/14, 2014/15), an average of 129 students voluntarily participated in the seminar, corresponding to 40% of the student cohort. The evaluation (n=38) shows a majority of students agreeing that the seminar offers support with this extraordinary situation in general and also that the seminar helps them to become first impressions on how to cope with death and dying in their later professional life as a doctor, and, that it also provides them the means to reflect upon their own coping mechanisms. CONCLUSION: Although not yet implemented as an obligatory course, the seminar is appreciated and positively evaluated. Medical professionalism is an implicit aspect of the dissection course. To emphasize its importance, a teaching intervention to explicitly discuss this topic is advisable.
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Anatomia/educação , Anatomia/ética , Dissecação/educação , Dissecação/ética , Ética Médica/educação , Profissionalismo/educação , Currículo , Dissecação/psicologia , Alemanha , Profissionalismo/ética , EnsinoRESUMO
We describe the synthesis of biodegradable poly(ethyleneglycol)-coupled galactolipids in which the galactose moiety is separated from a diacylglyceride lipid anchor by poly(ethylene glycol) chains of 10, 20 or 40 oxyethylene residues (PEG10/20/40). These Gal-PEG lipids (Gal-PEG-Lip) were incorporated in the bilayer of liposomes. The surface exposure of the galactose was investigated by aggregation experiments with ricinus communis agglutinin 120. Only the liposomes containing the PEG10 galactolipid aggregated with the lectin. Therefore liposomes were prepared containing Gal-PEG10-Lip and a trace amount of [3H]cholesteryl oleyl ether with an average diameter of approximately 100 nm and injected intravenously into rats. The Gal-PEG10-Lip liposomes were cleared from plasma with a T1/2 of 0.3 h. Identically sized and composed control liposomes without the Gal-PEG10-Lip had a T1/2 of approximately 12 h. The rapid plasma elimination of the Gal-PEG10-Lip liposomes could be attributed entirely to increased uptake by the liver amounting to more than 90% of injected dose. Uptake by the spleen was decreased to less than 1% of injected dose. A single injection of N-acetylgalactosamine 1 min prior to Gal-PEG-Lip liposome administration reduced the initial rate of plasma clearance to control levels. The increased liver uptake was almost entirely attributable to increased uptake by the Kupffer cells. Incorporation of PEG-DSPE in the Gal-PEG10-Lip liposomes only partially reversed the effect of the galactolipid with respect to liver and spleen uptake as well as intrahepatic distribution. These experiments demonstrate that liposome surface-exposed galactose residues, even if attached at the distal end of a poly(ethyleneglycol) chain anchored in the liposomal bilayer are effectively recognized by the galactose particle receptor on the Kupffer cells but fail to achieve significant targeting to the asialoglycoprotein receptor on the hepatocytes.
Assuntos
Galactose/metabolismo , Glicolipídeos/metabolismo , Lipossomos/metabolismo , Lectinas de Plantas , Polietilenoglicóis/metabolismo , Acetilgalactosamina/farmacologia , Animais , Diglicerídeos/metabolismo , Galactolipídeos , Glicolipídeos/síntese química , Células de Kupffer/metabolismo , Lectinas/farmacologia , Bicamadas Lipídicas , Lipossomos/química , Lipossomos/farmacocinética , Fígado/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Fosfatidiletanolaminas/metabolismo , Ratos , Receptores de Superfície Celular/metabolismo , Baço/metabolismoRESUMO
Progestins are known to suppress the growth of normal human endometrial glands and endometrial carcinomas possessing PRs. To elucidate the molecular mechanisms of progestin-induced growth inhibition, the expression and functional involvement of p27Kip1 (p27), a cyclin-dependent-kinase inhibitor, was investigated using cultured normal endometrial glandular cells and endometrial carcinoma cell lines (Ishikawa; PR-positive, KLE; PR-negative). Growth of the normal endometrial glandular cells and Ishikawa cells was suppressed by treatment with progesterone and medroxyprogesterone acetate, respectively, in association with an increase in p27 protein expression. Immunoprecipitation revealed that progestins accelerated the complex formation of p27 and cdk2 in both types of cells. However, treatment with progestins did not show any marked alterations in the mRNA expression of p27 in either normal glandular cells or Ishikawa cells. On the other hand, p27 protein degradation experiments indicated that treatment with progesterone and medroxyprogesterone acetate prolonged the degradation time of the normal endometrial glandular cells and Ishikawa cells, respectively. Forced expression of the p27 protein using a p27 expression plasmid reduced the growth activity of normal endometrial glandular cells. These findings suggest that p27 is functionally involved in progestin-induced growth suppression of normal and malignant endometrial epithelial cells and that up-regulation of the p27 protein by progestins possibly occurs via posttranslational mechanisms.
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Proteínas de Ciclo Celular/fisiologia , Neoplasias do Endométrio/fisiopatologia , Endométrio/fisiologia , Neoplasias Epiteliais e Glandulares/fisiopatologia , Proteínas Supressoras de Tumor , Divisão Celular/efeitos dos fármacos , Divisão Celular/fisiologia , Células Cultivadas , Inibidor de Quinase Dependente de Ciclina p27 , Neoplasias do Endométrio/patologia , Endométrio/citologia , Feminino , Humanos , Neoplasias Epiteliais e Glandulares/patologia , Progestinas/farmacologia , Progestinas/fisiologia , Regulação para Cima/efeitos dos fármacosRESUMO
The CbpA protein is an analog of the DnaJ molecular chaperone of Escherichia coli. The dnaJ- cbpA- double-null mutant exhibits severe defects in cell growth, namely, a very narrow temperature range for growth. To gain insight into the functions of CbpA as well as DnaJ, we isolated a multicopy suppressor gene that permits this dnaJ- cbpA- mutant to grow normally at low temperatures. The suppressor gene was identified as rpoD, the gene that encodes the major sigma 70. The biological implications of this finding are examined and discussed.
Assuntos
Proteínas de Bactérias/genética , Proteínas de Escherichia coli , Escherichia coli/genética , Genes Bacterianos , Chaperonas Moleculares/genética , Proteínas de Ligação a DNA/genética , RNA Polimerases Dirigidas por DNA/genética , Amplificação de Genes , Proteínas de Choque Térmico HSP40 , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico/genética , Mutação , Fator sigma/genética , Supressão GenéticaRESUMO
Harman and norharman are widely distributed in the environment and consequently contaminate in domestic waste-water. It has been reported that they have co-mutagenic activity in the presence of non- mutagenic aromatic amines such as aniline and o-toluidine with S9 mix. When these beta-carbolines were treated with sodium hypochiorite under mild conditions, chlorinated derivatives were produced. Among them, 6-chloroharman and 6-chloronorharman showed much more potent co-mutagenic activities than harman and norharman in the presence of o-toluidine toward Salmonella typhimurium TA98 with S9 mix. These results suggest that the chlorination of harman and norharman occurs during disinfection at the sewage plant to produce potent co-mutagens that contaminate river water.
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Harmina/análogos & derivados , Harmina/química , Mutagênicos/toxicidade , Hipoclorito de Sódio/química , Biotransformação , Carbolinas , Harmina/toxicidade , Testes de Mutagenicidade , Mutagênicos/química , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genéticaRESUMO
Mutagenicity of 6-aminoquinoxaline derivatives was tested with Salmonella typhimurium strains TA98 and TA100 in the presence and absence of S9 mix from the viewpoint that the 6-aminoquinoxaline skeleton is a common unit of mutagenic imidazoquinoxalines. We tested nine compounds: 5-methyl-6-methylaminoquinoxaline (1), 3,5-dimethyl-6-methylaminoquinoxaline (2), 2,5-dimethyl-6-methylaminoquinoxaline (3), 6-methylamino-2,3,5-trimethylquinoxaline (4), 2,3-diethyl-5-methyl-6-methylaminoquinoxaline (5), 5-methyl-6-methylamino 3-phenylquinoxaline (6), 6-amino-2,3,5-trimethylquinoxaline (7), 6-dimethylamino-2,3,5- trimethylaminoquinoxaline (8), 6-amino-2,3-dimethylquinoxaline (9). These compounds showed the mutagenic activity for both TA98 and TA100 in the presence of S9 mix, where they were more sensitive for TA100 strain. Methyl groups at the 2, 3 and/or 5 positions increased the potency of mutagenicity (1 < 2 < 3 << 4, 9 < 7). However, ethyl groups at the 2 and 3 positions lowered the mutagenicity of the methyl substitute but elevated it of the parental compound (1 < 5 < 4). A methyl group at the N6 position decreased the mutagenicity (7 > 4 > 8).
Assuntos
Aminas/toxicidade , Mutagênicos/toxicidade , Quinoxalinas/toxicidade , Aminas/síntese química , Relação Dose-Resposta a Droga , Testes de Mutagenicidade , Mutagênicos/síntese química , Quinoxalinas/síntese química , Salmonella typhimurium , Relação Estrutura-AtividadeRESUMO
A mutagen, 2-[2-(acetylamino)-4-[bis(2-methoxyethyl)amino]-5-methoxyphenyl]5-ami no-7-bromo-4-chloro-2H-benzotriiazole (PBTA-1), isolated from water of the Nishitakase River in Kyoto exhibits potent mutagenic activity in Salmonella typhimurium TA98 with S9 mix and has characteristic moieties, including bromo, chloro, acetylamino, bis(2-methoxyethyl)amino and primary amino groups on a 2-phenylbenzotriazole skeleton. The mutagenicities of PBTA-1, its congeners and five related 2-phenylbenzotriazoles were examined in S. typhimurium TA98 with S9 mix in order to elucidate the structure-activity relationships. The data obtained suggest that a primary amino group plays an essential role in the mutagenic activity as do aromatic amines including heterocyclic amines in cooked foods. The effect of planarity of the 2-phenylbenzotriazole ring was significant, and in addition, halogen groups of PBTA-1 influenced the enhancement of the mutagenic activity.
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Mutagênicos/toxicidade , Triazóis/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Masculino , Microssomos Hepáticos/efeitos dos fármacos , Testes de Mutagenicidade , Mutagênicos/química , Ratos , Ratos Sprague-Dawley , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Relação Estrutura-Atividade , Triazóis/químicaRESUMO
We have previously isolated five mutagens in blue rayon-adsorbed substances from water at a site below sewage plants in the Nishitakase River, in Kyoto, Japan, and identified two of them as 2-phenylbenzotriazole derivatives, 2-[2-(acetylamino)-4-[bis(2-methoxyethyl)amino]-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-1) and 2-[2-(acetylamino)-4-[(2-cyanoethyl)ethylamino]-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-2). In the present study, we collected adsorbed materials on blue cotton (3 kg x 9 times) at the same location, and isolated a sufficient amount (97 microg) of one of the remaining three mutagens other than PBTA-1 and PBTA-2, for structural analysis, by multiple column chromatography. The structure of mutagen, accounting for 12% of the total mutagenicity of the blue rayon-adsorbed substances, was determined to be a PBTA-1 analogue, 2-[2-(acetylamino)-4-amino-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-4). PBTA-4 is a potent mutagen, inducing 190,000 and 7,800,000 revertants of Salmonella typhimurium TA98 and YG1024 per microgram, respectively, in the presence of S9 mix. In addition to the water of the Nishitakase River, PBTA-4 was detected in water samples from two rivers that flow through other regions where textile-dyeing industries have been developed. Like other PBTA analogues, PBTA-4 might also be produced from azo dyes during industrial processes in dyeing factories and treatment at sewage plants.
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Compostos Azo/análise , Água Doce/química , Mutagênicos/análise , Triazóis/análise , Animais , Cromatografia Líquida de Alta Pressão , Corantes/análise , Masculino , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Testes de Mutagenicidade , Mutagênicos/toxicidade , Ratos , Ratos Sprague-Dawley , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Espectrofotometria Ultravioleta , Triazóis/síntese químicaRESUMO
The pharmacokinetics of DP-1904, a new potent and selective thromboxane synthetase inhibitor, and its effects on ex-vivo prostanoid formation have been studied in groups of Japanese normal male volunteers, who received repeated oral doses of 200 mg every 12 h for 4 doses, or 400 mg every 24 h for 2 doses, or 200 mg every 12 h for 14 doses. The drug was well tolerated by all subjects without evidence of adverse reactions. Repeated administration showed no significant changes in half-lives, tmax values, cmax values and AUC values. DP-1904 did not exhibit time-dependent kinetics. Its plasma levels were lower than the quantifiable level (50 ng mL-1) at 12 h after each dose. These data suggest no significant accumulation of DP-1904 in normal volunteers. DP-1904 reduced the serum thromboxane B2 by about 80% during the medication, the serum concentrations returning to about 44, 75 and 20% of the predrug control values at 36 h after the last 200 mg doses and 48 h after the last 400 mg dose.
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Imidazóis/farmacocinética , Tetra-Hidronaftalenos/farmacocinética , Tromboxano-A Sintase/antagonistas & inibidores , Administração Oral , Adulto , Cromatografia Líquida de Alta Pressão , Meia-Vida , Humanos , Imidazóis/administração & dosagem , Imidazóis/farmacologia , Masculino , Taxa de Depuração Metabólica , Tetra-Hidronaftalenos/administração & dosagem , Tetra-Hidronaftalenos/farmacologia , Tromboxano B2/biossíntese , Tromboxano B2/sangueRESUMO
The pharmacokinetics of DP-1904, a new potent and selective thromboxane synthetase inhibitor and its effects on ex-vivo prostanoid formation were studied in Japanese normal male volunteers, who received orally a single 10, 20, 50, 100, 200, 400 or 800 mg dose. The drug was well tolerated by all subjects without evidence of any adverse reactions. The absorption of DP-1904 from gastro-intestinal tract was rapid. After oral doses of 10-800 mg of the drug given to volunteers in the fasted state, the mean maximum drug concentrations in plasma (Cmax) (mean +/- s.e., n = 5) of 0.215 (+/- 0.041), 0.399 (+/- 0.037), 1.47 (+/- 0.22), 2.86 (+/- 0.22), 4.66 (+/- 0.58), 7.28 (+/- 0.72) and 16.9 (+/- 2.6) micrograms mL-1 were reached within 1 h. DP-1904 concentrations declined monophasically after Cmax with half lives of 30-40 min. These half lives were independent of the administered doses. The mean area under the concentration-time curves (AUCs) increased from 0.398 (+/- 0.038) to 30.0 (+/- 2.7) micrograms h mL-1 as the dose increased from 10 to 800 mg. Linear relations between the doses and Cmax and AUCs were observed. The correlation coefficients for Cmax and AUC were 0.930 and 0.960, respectively. The apparent oral clearance (CL/F) and renal clearance (CLR) did not change significantly as dose increased from 10 to 800 mg. The kinetics of DP-1904 proved to be linear in the dose range studied.(ABSTRACT TRUNCATED AT 250 WORDS)
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Imidazóis/farmacocinética , Naftalenos/farmacocinética , Tetra-Hidronaftalenos/farmacocinética , Administração Oral , Adulto , Humanos , Imidazóis/administração & dosagem , Imidazóis/farmacologia , Masculino , Pessoa de Meia-Idade , Tetra-Hidronaftalenos/administração & dosagem , Tetra-Hidronaftalenos/farmacologia , Tromboxano B2/sangue , Tromboxano-A Sintase/antagonistas & inibidoresRESUMO
Chlorinated derivatives of bisphenol A were detected in the final effluents of eight paper manufacturing plants in Shizuoka, Japan, where thermal paper and/or other printed paper is used as the raw material. Their amounts were determined by gas chromatography/mass spectrometry (GC/MS) after treatment with N, O-bis(trimethylsilyl)trifluoroacetamide, and ranged from traces to 2.0 microg/l. They are likely produced by chlorination of bisphenol A, which was released into the effluents from the pulping process of wastepaper, during or after bleaching with chlorine.
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Conservação dos Recursos Naturais , Estrogênios não Esteroides/análise , Fenóis/análise , Eliminação de Resíduos , Eliminação de Resíduos Líquidos , Compostos Benzidrílicos , Cloro/química , Monitoramento Ambiental , Cromatografia Gasosa-Espectrometria de Massas , Resíduos Industriais , Papel , Purificação da ÁguaRESUMO
Recently, the therapeutic guideline has been mentioned in opportunistic infection of the compromised host, and many observations regarding complication of infection in these hosts have been reported. However, there were few reports in the relationship between infection and immune function or nutritional status. In this study, we confirmed that the nutritional status influences immune function in patients with lung cancer, hepatoma and renal failure, and that malnutrition markedly reduces their immunity. In patients after operation who where the pre-operative assessment of the nutritional status was performed an attempt to improve the nutritional status has been already made to improve their prognosis. Therefore, we emphasize that the management of the nutritional status even in hosts with many other diseases is thought to be important in protection against infection and prognosis of the disease.
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Infecções/etiologia , Distúrbios Nutricionais/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Tolerância Imunológica , Masculino , Pessoa de Meia-IdadeRESUMO
A 61-year-old woman was hospitalized because of ulcerative colitis which had caused fever, vomiting and diarrhea since June 16, 1992. Then she developed toxic megacolon, and was transferred to our hospital on the 1st of July and underwent subtotal colectomy the same day. After surgery, she received intravenous hyperalimentation (IVH) which contained 1,000 Kcal/day without vitamin supplementation. From the 8th to the 13th post-operative days, she took 3/4 or more of the liquid diet which contained 1,050 Kcal, protein 35 g, carbohydrate 166 g and vitamin B1 0.59 mg per day. From the 14th to the 23rd post-operative days, she ate 4/5 or more of the oral diet which contained 1,700 Kcal/day, protein 68 g, carbohydrate 236 g and vitamin B1 0.93 mg per day. During the 7th to the 23rd day, the IVH was reduced to 800 Kcal and then 500 Kcal per day. She talked less on the 19th post-operative day, and in a few days, her level of consciousness began to decline progressively. On the 27th post-operative day, neurological examinations revealed the following: semi-coma, almost fixed pupils which were 3 mm in diameter, absent doll's eye movement to all directions, flaccid extremities with abolished deep tendon reflexes. Pertinent abnormalities on laboratory data at that time consisted of hemoglobin 7.8 g/dl and serum total protein 5.4 g/dl. Lumbar puncture revealed normal cerebrospinal fluid under normal opening pressure. Cranial magnetic resonance imaging (MRI) taken on the 27th post-operative day demonstrated, on T2-weighted images, symmetrical high intensity lesions in the periventricular areas of the third and fourth ventricles, and periaqueductal area of the midbrain.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Colectomia , Colite Ulcerativa/cirurgia , Encefalopatia de Wernicke/etiologia , Dieta , Feminino , Humanos , Pessoa de Meia-Idade , Nutrição Parenteral Total , Complicações Pós-Operatórias , Deficiência de Tiamina/etiologiaRESUMO
A 39-year-old woman presented with disturbed consciousness, left hemiparesis and headache. CT scan revealed subcortical hemorrhage in the right parietal region, which had lower density than usual intracerebral hemorrhage and was associated with irregular perifocal edema. Cerebral angiograms revealed narrowed cortical vein with irregular wall in the right parietal region, where delayed local blood flow into the deep cerebral veins through collateral vessels was noted. The diagnosis was subcortical hemorrhage due to thrombosis of cortical vein. Her symptoms and brain edema were progressive. To reduce intracranial pressure, evacuation of the hematoma was performed. The hematoma which existed 1cm under the right parietal cortex was about 20g in weight. She remarkably improved soon after operation. Frequency of sinovenous thrombosis has been reported to be about 10% of all cerebral ischemic diseases, however, localized venous thrombosis is rare among them. This is because it is not always symptomatic and it is difficult to make accurate diagnosis. Six cases of localized venous thrombosis were reviewed, in which accurate diagnosis were established by cerebral angiograms, CT scan and/or autopsy. Clinical and radiological features of this case were presented.
Assuntos
Hemorragia Cerebral/complicações , Trombose dos Seios Intracranianos/complicações , Adulto , Córtex Cerebral/irrigação sanguínea , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/cirurgia , Feminino , Humanos , Radiografia , Trombose dos Seios Intracranianos/diagnóstico por imagem , VeiasRESUMO
A primary cerebral rhabdomyosarcoma is reported in a 51-year-old female. She noticed progressive weakness of the left leg in September 1977 and underwent craniotomy for a brain tumor in Tokyo Metropolitan Okubo General Hospital. At the operation the tumor was located on the medial aspect of the right frontal lobe, being attached to the falx. The tumor was 6.0 x 5.0 x 4.0cm in size and subtotally removed. Shortly after operation, she developed a left-sided hemiplegia and was referred to our Kanagawa Rehabilitation Center. During rehabilitation she developed disturbance in recent memory, orientation and speaking. A second operation was done in June 1978, revealing obvious recurrence. A well demarcated extramedullary gray and soft tumor, 7.0 x 5.0 x 3.5cm in size, was found in the previously operated site, being attached to the falx. It was subtotally again. Following surgery her clinical condition was temporally improved. Four months following surgery, however, she developed signs of increased intracranial pressure and died in October 1978 in spite of having chemotherapy and irradiation. Autopsy was not permitted. The tumor was diagnosed as rhabdomyosarcoma with light and electron microscopies and several investigation revealed no primary lesion in elswhere except for the cranium. The histological documentation is also presented and discussed.