RESUMO
BACKGROUND: The significance of cardiac troponin I (cTnI) elevation after trauma is debated. We therefore explored the association between cTnI elevation at admission after trauma and ICU mortality. METHODS: We performed a retrospective analysis from a prospectively constituted database, of patients admitted to ICU after trauma at a single centre, over a 36 month period. According to cTnI plasma concentration at admission, patients were categorised into three groups: normal (<0.05 ng ml-1), intermediate (0.05-0.99 ng ml-1), or high concentration (≥1.0 ng ml-1). Associations of pre-hospital conditions or cTnI elevation and mortality were analysed by multivariate logistic regression. RESULTS: Among the 994 patients, 177 (18%) had cTnI elevation at ICU admission. Of this total, 114 (11%) patients died in the ICU. The cTnI release was an independent predictor of ICU mortality with a concentration-response relationship [odds ratio (OR) 4.90 (2.19-11.16) and 14.83 (4.68-49.90) for intermediate and high concentrations, respectively] and Day 2 mortality [OR 2.23 (1.18-5.80) and 7.49 (2.77-20.12) for intermediate and high concentrations, respectively]. The severity of thoracic trauma [OR 2.25 (1.07-4.55) and 3.23 (2.00-5.27) for Abbreviated Injury Scale scores 1-2 and ≥3, respectively], out-of-hospital maximal heart rate ≥120 beats min-1 [OR 2.22 (1.32-3.69)], and out-of-hospital shock [OR 2.02 (1.20-3.38)] were independently associated with cTnI elevation. CONCLUSIONS: Release of cTnI was an independent predictor of ICU mortality, suggesting that this biomarker can be used in daily practice for early stratification of the risk of ICU death. Thoracic trauma was strongly associated with cTnI elevation.
Assuntos
Troponina I/sangue , Ferimentos e Lesões/diagnóstico , Adulto , Biomarcadores/sangue , Bases de Dados Factuais , Feminino , França/epidemiologia , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Ferimentos e Lesões/sangue , Adulto JovemRESUMO
BACKGROUND: Ulcerative colitis (UC) promotes cancer, and can be ameliorated by early appendicectomy for appendicitis. The aim of the study was to explore the effect of appendicectomy on colitis and colonic neoplasia in an animal model of colitis and a cohort of patients with UC. METHODS: Five-week old IL10/Nox1(DKO) mice with nascent colitis and 8-week-old IL10/Nox1(DKO) mice with established colitis underwent appendicectomy (for experimental appendicitis or no appendicitis) or sham laparotomy. The severity and extent of colitis was assessed by histopathological examination, and a clinical disease activity score was given. From a cohort of consecutive patients with UC who underwent colectomy, the prevalence of appendicectomy and pathological findings were collected from two institutional databases. RESULTS: Appendicectomy for appendicitis ameliorated experimental colitis in the mice; the effect was more pronounced in the 5-week-old animals. Appendicectomy in the no-appendicitis group was associated with an increased rate of colonic high-grade dysplasia (HGD) or cancer compared with rates in sham and appendicitis groups (13 of 20 versus 0 of 20 and 0 of 20 respectively; P < 0·001). Fifteen of 232 patients who underwent colectomy for UC had previously had an appendicectomy, and nine of these had colonic cancer or HGD. Thirty (13·8 per cent) of 217 patients with the appendix in situ had colonic neoplastic lesions. Multivariable analysis showed that previous appendicectomy was associated with colorectal neoplasia (odds ratio 16·88, 95 per cent c.i. 3·32 to 112·69). CONCLUSION: Appendicectomy for experimental appendicitis ameliorated colitis. The risk of colorectal neoplasia appeared to increase following appendicectomy without induced appendicitis in a mouse model of colitis, and in patients with UC who had undergone appendicectomy. Surgical relevance Appendicectomy for appendicitis protects against UC. In this murine model of colitis, appendicectomy for experimental appendicitis protected against colitis, but appendicectomy without appendicitis promoted colorectal carcinogenesis. In patients with ulcerative colitis who underwent colectomy, absence of the appendix (proof of previous appendicectomy) in the resection specimen was independently associated with colorectal neoplasia. Although patients with UC and a history of appendicectomy represent a small subset, they may need closer monitoring for colorectal neoplasia.
Assuntos
Apendicectomia , Colite Ulcerativa/etiologia , Neoplasias do Colo/complicações , Neoplasias Retais/complicações , Adulto , Animais , Doença Crônica , Colectomia/estatística & dados numéricos , Colite/patologia , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colite Ulcerativa/cirurgia , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Feminino , Humanos , Interleucina-10/deficiência , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Neoplasias Retais/patologia , Neoplasias Retais/cirurgiaRESUMO
BACKGROUND AND PURPOSE: Our aim was to characterize the clinical profile, temporal changes and outcomes of patients with severe encephalitis. METHODS: A retrospective cohort study was conducted on adult patients with encephalitis admitted to the medical intensive care unit (ICU) of a university hospital over a 20-year period. Patients' characteristics and outcomes were compared between two 10-year periods: (i) 1991-2001 and (ii) 2002-2012. Multivariate logistic regression was used to analyze factors associated with a poor outcome, as defined by a modified Rankin scale (mRS) score of 4-6 (severe disability or death) 90 days after admission. RESULTS: A total of 279 patients were studied. Causes of encephalitis were infections (n = 149, 53%), immune-mediated causes (n = 41, 15%) and undetermined causes (n = 89, 32%). The distribution of causes differed significantly between the two periods, with an increase in the proportion of encephalitis recognized to be of immune-mediated causes. At day 90, 208 (75%) patients had an mRS = 0-3 and 71 (25%) had an mRS = 4-6. After adjustment for functional status before admission, the following parameters were independently associated with a poor outcome: coma [odds ratio (OR) 7.09, 95% confidence interval (95% CI) 3.06-17.03], aspiration pneumonia (OR 4.02, 95% CI 1.47-11.03), a lower body temperature (per 1 degree, OR 0.72, 95% CI 0.53-0.97), elevated cerebrospinal fluid protein levels (per 1 g/l, OR 1.55, 95% CI 1.17-2.11) and delayed ICU admission (per 1 day, OR 1.04, 95% CI 1.01-1.07). CONCLUSIONS: Indicators of outcome in adult patients with severe encephalitis reflect both the severity of illness and systemic complications. Our data suggest that patients with acute encephalitis may benefit from early ICU admission.
Assuntos
Encefalite , Unidades de Terapia Intensiva/estatística & dados numéricos , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto , Encefalite/complicações , Encefalite/etiologia , Encefalite/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Removal of deposited eggs could be a useful control strategy for the damaging fish ectoparasite Argulus foliaceus, but focused control requires knowledge of egg-laying patterns. Here, we investigated diel changes in the egg-laying behaviour of a natural population of A. foliaceus. Data were collected from 17-28 May 2004. Days were divided into 3 time periods: 06:00-14:00, 14:00-22:00 and 22:00-06:00 h. Significantly more egg clutches were laid from 06:00-14:00 h than during the other 2 time periods, which were not significantly different from each other. Significantly more egg clutches per hour were laid during hours of daylight as compared to hours of darkness. Significantly more egg clutches were laid in the top 1 m of the water column than at the bottom, and this was consistent throughout all 3 time periods. It is suggested that the increase in egg-laying activity during daylight hours may be due to a higher motivation to search for hosts during the night and an increased ability to locate silhouetted egg-laying sites during the day. These data can provide information useful for egg removal and control strategies.
Assuntos
Arguloida/fisiologia , Ectoparasitoses/veterinária , Doenças dos Peixes/parasitologia , Oviposição/fisiologia , Animais , Ectoparasitoses/parasitologia , Ectoparasitoses/prevenção & controle , Doenças dos Peixes/prevenção & controle , Água Doce/parasitologia , Oncorhynchus mykiss/parasitologia , Óvulo/fisiologia , Fatores de TempoRESUMO
OBJECTIVES: To develop a diagnostic predictive model for the identification of patients with presumptive pulmonary tuberculosis (PTB) at high risk for active disease and those requiring nucleic acid amplification (NAAT) testing and/or preventive respiratory isolation in low-incidence, high-income countries. DESIGN: A 1:1 case-control study was conducted in consecutive immunocompetent patients with presumed PTB hospitalised between 2009 and 2012 in Paris, France. Cases were defined as individuals with culture-confirmed PTB, regardless of smear result. Those with presumed PTB and three smear- and culture-negative samples were selected as controls. A score was derived using conditional logistic regression. Internal validity of the score was assessed using the bootstrap method. RESULTS: A total of 354 patients were included in the analysis (177 cases, 177 controls). Among the 177 cases, 74 (42%) were smear-negative but culture-positive. Factors independently associated with PTB were age <50 years (adjusted OR [aOR] 4.7, 95%CI 1.8-12), diabetes (aOR 3.2, 95%CI 1.1-9.8), absence of cough with or without sputum (aOR 3.7, 95%CI 1.7-8.3), fever >15 days (aOR 3.5, 95%CI 1.3-9.5), apical infiltration without cavity (aOR 3.4, 95%CI 1.4-8.5) and cavitation or miliary pattern (aOR 19.7, 95%CI 7.6-51.1). Score C-index was 0.84 (95%CI 0.79-0.88). Calibration for the overall population (P = 0.770) and in smear-negative patients (P = 0.980) was appropriate. A score of î¶3.3 had 90% sensitivity, 50% specificity and 79% (IQR 28-95) median probability of PTB. CONCLUSIONS: This score could be used to build an algorithm to determine the need for respiratory isolation and/or NAAT use in PTB disease.
Assuntos
Modelos Estatísticos , Técnicas de Amplificação de Ácido Nucleico/métodos , Escarro/microbiologia , Tuberculose Pulmonar/diagnóstico , Adulto , Idoso , Estudos de Casos e Controles , Tosse/epidemiologia , Tosse/etiologia , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Paris/epidemiologia , Prevalência , Probabilidade , Sensibilidade e Especificidade , Tuberculose Pulmonar/epidemiologiaRESUMO
Since in nuclear power plants, risks of skin contact contamination by radiocobalt are significant, we focused on the impact of cobalt on a human cutaneous cell line, i.e. HaCaT keratinocytes. The present paper reports an interdisciplinary approach aimed at clarifying the biochemical mechanisms of metabolism and toxicity of cobalt in HaCaT cells. Firstly, a brief overview of the used instrumental techniques is reported. The following parts present description and discussion of results concerning: (i) toxicological studies concerning cobalt impact towards HaCaT cells (ii) structural and speciation fundamental studies of cobalt-bioligand systems, through X-ray absorption spectroscopy (XAS), ab initio and thermodynamic modelling (iii) preliminary results regarding intracellular cobalt speciation in HaCaT cells using size exclusion chromatography/inductively coupled plasma-atomic emission spectroscopy (SEC/ICP-AES) and direct in situ analysis by ion beam micropobe analytical techniques.
Assuntos
Cobalto/toxicidade , Queratinócitos/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cobalto/farmacocinética , Humanos , Mutagênicos/toxicidade , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologiaRESUMO
Argulus foliaceus is a damaging fish ectoparasite for which new control measures are being developed based on egg-removal. In an attempt to develop further understanding of seasonal and vertical egg-laying patterns in this parasite, egg-laying activity was monitored over the period 14 April to 17 November 2003 in 2 rainbow trout Oncorhynchus mykiss fisheries in Northern Ireland, UK. At Site 1, egg-laying was continuous from 21 April to 17 November, when water temperature was above 8 to 10 degrees C. At Site 2, egg-laying was continuous from 4 June to 29 October. In the early months of the season, egg-laying was recorded mainly within the top 1 m of the water column; however, a significant shift to deep water egg-laying was recorded between 7 July and 17 November at Site 1 and between 20 August and 29 October at Site 2. Egg clutches were preferentially laid at depths of up to 8.5 m during this time (Site 2), a feature of egg-laying hitherto unappreciated. Temperature and dissolved oxygen did not differ significantly among depths, but there was an increase in water clarity over time. However, the precise environmental triggers for deep water egg-laying are still unclear. These new insights into the reproductive behaviour of this species will be useful in developing control methods based on egg-removal.
Assuntos
Arguloida/fisiologia , Oviposição/fisiologia , Animais , Meio Ambiente , Feminino , Água Doce , Oncorhynchus mykiss/parasitologia , Óvulo , Oxigênio/análise , Reprodução/fisiologia , Estações do Ano , TemperaturaRESUMO
A comparison of three cellular irradiation techniques using the Monte Carlo simulation toolkit Geant4 is presented in this paper. They involve electrodeposited source of alpha particle-emitting radionuclides, random classical alpha beam irradiation and single cell targeted irradiation using a focused alpha microbeam line. The simulation allows the calculation of hit distributions among the cellular population as well as the absorbed dose for two typical cellular geometries.
Assuntos
Técnicas de Cultura de Células/métodos , Fenômenos Fisiológicos Celulares/efeitos da radiação , Modelos Biológicos , Método de Monte Carlo , Aceleradores de Partículas , Radiometria/métodos , Software , Partículas alfa , Simulação por Computador , Relação Dose-Resposta à Radiação , Modelos Estatísticos , Doses de Radiação , Reprodutibilidade dos Testes , Espalhamento de Radiação , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Beta-blockers may have to be interrupted in patients with cirrhosis. The concept of a rebound after interruption of beta-blockers is based on an animal study and on isolated case reports of variceal bleeding. AIM: To determine if a rebound occurs in patients with cirrhosis following abrupt interruption of beta-blockers. METHODS: We prospectively included all consecutive patients with cirrhosis undergoing right heart and hepatic vein catheterisation. Four groups were defined: 'no beta-blockers' including patients not receiving beta-blockers; '≤1 day', '2-3 days' and '≥4 days' classified according to the time patients had interrupted beta-blockers before catheterisation. Results were expressed as median (interquartile range). RESULTS: A total of 150 patients were included. Among the 25 patients in the groups '2-3 days' and '≥4 days', median duration of beta-blockers interruption was 4 (3-6) days. No gastrointestinal bleeding occurred during that period, nor during the following month. Hepatic venous pressure gradient was not different among patients in usually treated with beta-blockers. After adjustment, beta-blockers interruption was not associated with hepatic venous pressure gradient. Cardiac index was higher in the '≥4 days' group [4.6 L/min/m(2) (3.5-5.1)] than in the '≤1 day' group [3.4 (2.6-4.0); P = 0.001] or in the '2-3 days' group [3.1 (2.7-3.7); P = 0.007], but not different from the 'no beta-blockers' group. CONCLUSIONS: Abrupt interruption of beta-blockers is associated neither with an apparent increase in the risk of variceal bleeding nor with a haemodynamic rebound. Thus, interruption of beta-blockers in patients with cirrhosis may not require particular dosing or surveillance.
Assuntos
Antagonistas Adrenérgicos beta/efeitos adversos , Hemodinâmica/efeitos dos fármacos , Cirrose Hepática/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Veias Hepáticas/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Pressão na Veia Porta/efeitos dos fármacosRESUMO
Activation of the AP-1 transcription factor and TGF-beta1 growth factor by ionizing radiation was studied both in vivo in pig skin, and in vitro in human fibroblasts and keratinocytes. Three and 6 h after irradiation, the Fos and Jun proteins and their binding activity to an AP-1 consensus sequence were strongly induced by high doses of gamma-rays. c-Fos, c-Jun and JunB proteins were found to be present in gel-shift complexes by probing with specific antibodies. Both keratinocytes and fibroblasts exhibited heightened AP-1 activity following irradiation. As we previously found that TGF-beta1 is involved in the development of skin lesions induced by radiation, TGF-beta1 gene expression was also examined. Two and 6 h after irradiation, the levels of TGF-beta1 transcripts were increased in skin. By immunostaining, TGF-beta1 protein levels were found to be increased in fibroblasts, keratinocytes and endothelial cells. As the TGF-beta1 promoter contains AP-1 binding sites, the relation between AP-1 activity and TGF-beta1 induction was addressed. The -365 TGF-beta1 promoter fragment, which contains a high affinity AP-1 site, exhibited increased binding to Jun and Fos proteins following irradiation. These results suggest that stress-inducible TGF-beta1 expression is mediated by the activation of AP-1 transcription factor.
Assuntos
Pele/efeitos da radiação , Fator de Transcrição AP-1/metabolismo , Fator de Crescimento Transformador beta/biossíntese , Animais , Células Cultivadas , Sequência Consenso , Relação Dose-Resposta à Radiação , Expressão Gênica/efeitos da radiação , Humanos , Estresse Oxidativo , Regiões Promotoras Genéticas , Pele/metabolismo , Suínos , Fator de Crescimento Transformador beta/genéticaRESUMO
Inappropriate antibiotic therapy in ventilator-associated pneumonia (VAP) is associated with increased mortality. Using broad-spectrum antibiotics for 48 h until the results of conventional cultures and antimicrobial susceptibility testing (AST) are available, may promote the emergence of drug-resistant bacteria. Performing AST directly on clinical respiratory samples would hasten the process by at least 24 h. Here, we analysed the diagnostic performance of a rapid method combining mass spectrometry and direct AST (DAST), and compared it with the conventional method (mass spectrometry with conventional AST (CAST)). Additionally, we assessed its potential impact on antimicrobial use in patients. Over a period of 18 months, the two methods were performed on 85 bronchoalveolar lavages obtained from intensive care unit patients with suspected VAP, and in which Gram-negative bacilli were observed on direct examination. Only the CAST results were reported to the clinicians. DAST produced useable results in 85.9% of the patients. The sensitivity and negative predictive values of DAST were 100% for all antibiotics tested, except gentamicin (97.1%, (95% CI 93.3-101) and 97.4% (93.7-101), respectively) and amikacin (88.9% (81.7-96.1) and 96.4% (92.1-100.7), respectively), compared with CAST. Specificity and positive predictive values ranged from 82.9 (74.2-91.5) to 100%, and from 86.4 (78.5-94.2) to 100%, respectively. If the DAST results had been reported to the clinicians, treatment could have been optimized 24 h earlier in 35/85 (41.2%) patients, with 17 carbapenem patient-days saved. Overall, routine use of the DAST method could help optimize earlier antibiotic treatment in patients with suspected VAP.
Assuntos
Monitoramento de Medicamentos/métodos , Espectrometria de Massas/métodos , Testes de Sensibilidade Microbiana/métodos , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Fatores de TempoRESUMO
The lactose-assimilating yeast, Kluyveromyces lactis, has been developed as a microbial host for the synthesis and secretion of human proteins. Here, we report the use of multi-copy vectors based on the 2 mu-like plasmid pKD1 from Kluyveromyces drosophilarum [Chen et al., Nucleic Acids Res. 14 (1986) 4471-4481] for the secretion of recombinant human interleukin-1 beta (reIL-1 beta). High levels of reIL-1 beta were secreted into the growth medium when the structural gene was fused in-frame to a synthetic secretion signal derived from the 'pre'-region of the K. lactis killer toxin. N-terminal sequencing of the excreted protein showed highly efficient (greater than 95%) maturation of the signal sequence. Synthesis as prepro-IL-1 beta, the 'pro'-sequence being derived from the human serum albumin-encoding gene, resulted in equally efficient secretion of mature IL-1 beta. Cytoplasmic production of Met-IL-1 beta, without a secretion signal, was found to be toxic to K. lactis. As in Saccharomyces cerevisiae [Baldari et al., EMBO J. 6 (1987) 229-234], but unlike native human IL-1 beta, K. lactis reIL-1 beta is glycosylated. This glycosylation led to a 95% loss of its biological activity. Removal of the carbohydrate chains by endo-beta-N-acetyl-glucosamidase H treatment fully restored the biological activity. A modified form of IL-1 beta (Asn7----Gln7), in which the unique site for Asn-linked glycosylation was deleted, exhibited the same biological activity as native IL-1 beta. The level of secretion of mature recombinant IL-1 beta ws glycosylation-independent.
Assuntos
Interleucina-1/genética , Kluyveromyces/genética , Proteínas Recombinantes de Fusão/biossíntese , Sequência de Aminoácidos , Sequência de Bases , Northern Blotting , Southern Blotting , Western Blotting , Expressão Gênica/genética , Vetores Genéticos/genética , Glicosilação , Humanos , Interleucina-1/biossíntese , Interleucina-1/metabolismo , Fatores Matadores de Levedura , Cinética , Kluyveromyces/metabolismo , Dados de Sequência Molecular , Micotoxinas/genética , Plasmídeos/genética , Processamento de Proteína Pós-Traducional/fisiologia , Proteínas Recombinantes de Fusão/metabolismoRESUMO
Skin fibrosis is characterized by the proliferation and accumulation of activated fibroblasts called myofibroblasts. They exhibit specific cytoskeletal differentiation, overexpress the fibrogenic cytokine TGF-beta1, synthesize excess extracellular matrix compounds and exhibit a depleted antioxidant metabolism. Recently, SOD was successfully used as an antifibrotic agent in vivo, thus challenging the postulate of established fibrosis irreversibility. We postulated that myofibroblasts could be a direct target for this therapeutic effect. To test this hypothesis, we used three-dimensional co-culture models of skin, in which specific phenotypes of normal fibroblasts versus myofibroblasts are retained. These 3-D models were treated with liposomal and carrier-free Cu/Zn SOD, and examined for their effects on cell number, cell death, and phenotypic differentiation. The results show that SOD did not induce myofibroblast cell death, whereas it significantly reduced TGF-beta1 expression, thus demonstrating that SOD might be proposed as a potent antagonist of this major fibrogenic growth factor. We also found that SOD significantly lowered the levels of the myofibroblast marker alpha-sm actin, of beta-actin, and of the extracellular matrix components alpha1(I) collagen and tenascin-C. In conclusion, our results suggest that SOD antifibrotic action occurred in vitro through the reversion of myofibroblasts into normal fibroblasts.
Assuntos
Fibroblastos/patologia , Fenótipo , Pele/patologia , Superóxido Dismutase/uso terapêutico , Fator de Crescimento Transformador beta/fisiologia , Actinas/genética , Animais , Apoptose , Contagem de Células , Colágeno/genética , Fibroblastos/metabolismo , Fibrose , Regulação da Expressão Gênica/efeitos dos fármacos , Modelos Biológicos , Pele/metabolismo , Superóxido Dismutase/farmacologia , Suínos , Tenascina/genética , Fator de Crescimento Transformador beta/genéticaRESUMO
Transforming growth factor beta 1 (TGFB1) is a cytokine involved in the development of both acute and late cutaneous radiation syndromes. We previously demonstrated that ionizing radiation induces TGFB1 expression in vivo in pig skin within a few hours. The purpose of the present study was to develop an in vitro human model to identify the mechanisms of this early activation. Accordingly, human HaCaT keratinocytes were irradiated with a single dose of 20 Gy. First, radiation-induced TGFB1 overexpression was checked at both the transcriptional and transductional levels in HaCaT cells. Then electrophoretic mobility shift assays (EMSA) and transient transfection with various TGFB1 promoter constructs were used to identify the sequences involved in regulating this promoter. EMSA analysis showed the induction of nuclear protein binding activity by gamma irradiation to the -365 AP1 sequence (TGTCTCA), suggesting the involvement of AP1 sequences in the regulation of TGFB1 transcription. In gene reporter assays, maximal TGFB1 promoter activation was found for the longest construct, which contains two AP1 sequences. However, assays with constructs including deletions showed that these two AP1 sequences were not sufficient to confer TGFB1 inducibility. These results showed for the first time, to our knowledge, that transcriptional regulation is involved in radiation-induced activation of TGFB1 gene expression.
Assuntos
Queratinócitos/efeitos da radiação , Regiões Promotoras Genéticas , Fator de Crescimento Transformador beta/genética , Linhagem Celular , Raios gama , Humanos , Queratinócitos/metabolismo , Ligação Proteica , Fatores de Transcrição/metabolismo , Ativação Transcricional , Fator de Crescimento Transformador beta/metabolismoRESUMO
This study was designed for the histopathological, cellular and biochemical characterization of a skin lesion removed surgically from a young male several months after accidental exposure to cesium-137, with an emphasis on expression of transforming growth factor beta1 (TGFB1) and tumor necrosis factor alpha (TNFA) and the occurrence of apoptosis. Under a hypertrophic epidermis, a highly inhomogeneous inflammatory dermis was observed, together with fibroblastic proliferation in necrotic areas. Immunostaining revealed overexpression of TGFB1 and TNFA inside the keratinocytes of the hypertrophic epidermis as well as in the cytoplasm of the fibroblasts and connective tissue of the mixed fibrotic and necrotic dermis. Inside this dermis, the TUNEL assay revealed areas containing numerous apoptotic fibroblasts next to areas of normal viable cells. Overexpression of TGFB1 was found in the conditioned medium and cellular fractions of both hypertrophic keratinocytes and fibrotic fibroblasts. This overexpression lasted for at least three passages in tissue culture. The present observations were consistent with the central role of TGFB1 in the determination of chronic radiation-induced damage to the skin and a significant involvement of TNFA. In addition, programmed cell death appeared to take place during the remodeling of the mixed fibrotic and necrotic tissue.
Assuntos
Radioisótopos de Césio/efeitos adversos , Lesões por Radiação/etiologia , Lesões por Radiação/patologia , Liberação Nociva de Radioativos , Dermatopatias/etiologia , Dermatopatias/patologia , Adulto , Células Cultivadas , Humanos , Masculino , Lesões por Radiação/metabolismo , Dermatopatias/metabolismo , Síndrome , Fator de Crescimento Transformador beta/biossíntese , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Previous studies have indicated the beneficial influence of higher than normal ultimate pH (pH(u)) on the tenderness of cooked meat. Such benefits have been indirectly linked to the influence of increased pH on the water-holding capacity (WHC) of meat above the iso-electric point (IEP) of the myofibrillar proteins. In the present study, relationships between WHC and the tenderness of some beef muscles were investigated under pH conditions within and below the IEP of the myofibrillar proteins, such that the maximum range of meat swelling was achieved. It was found that increased WHC, as measured by swelling ratio in both raw and cooked meat, markedly influenced cooked meat tenderness, irrespective of the connective tissue content of the muscles. The results fitted a series of exponential decay equations relating swelling ratio to cooked meat toughness. Additionally, strong linear decreases in toughness were apparent over the pH range 4·6 to 4·1 for the three muscle types studied.
RESUMO
Several beef forequarter muscles were investigated for fibre-type composition, total pigments, total nitrogen, non-protein nitrogen, anserine, carnosine and inorganic phosphorus contents, ultimate pH (pH(u)) and acid buffering capacities. In general, the predominantly 'red' fibre-type muscles had significantly higher (P<0·05) pH(u) values and total pigment concentrations than the predominantly 'white' fibre-type muscles which had significantly higher (P< 0·05) total nitrogen, non-protein nitrogen and carnosine contents and also significantly higher (P< 0·05) acid buffering capacities. The relationships between the various biochemical parameters of all the muscles studied and their acid buffering capacities were investigated by correlation matrix. The higher buffering capacities of the 'white' fibre-type muscles over the pH range pH(u) to pH 5·0 were attributed to their higher contents of carnosine and inorganic phosphorus. However, over the pH ranges pH(u) to pH 4·5 down to pH(u) to pH 3·0, the higher buffering capacities of the 'white' fibre-type muscles were attributed primarily to their higher lactic acid concentrations, as indicated by their low pH(u) values, and also to their higher non-protein nitrogen contents.
RESUMO
Data concerning the efficiency of protein extraction from meat waste tissues are presented. The tissues investigated were the lungs, stomach and small and large intestines of the ox, sheep and pig. Practically all of the protein, with the exception of connective tissue proteins, was solubilised under optimum extraction conditions both with alkali and anionic detergent. The disadvantages of isoelectric precipitation of alkaline extracted proteins have been investigated in detail using polyacrylamide gel electrophoresis incorporating sodium dodecyl sulphate (SDS). The compositions of the protein isolates from the various tissues studied differed from those of the soluble extracts and supernatants or wheys. However, a component of MW 75,000 daltons was characteristic of the wheys from each tissue. The compositions of both isolates and wheys are discussed in the light of structural and cytoplasmic proteins present in smooth muscle tissues. The usefulness of anionic polysaccharides as a means of whey protein recovery is discussed, together with similar benefits achieved using SDS.
RESUMO
The water-holding capacities (WHC) of six different beef muscles were measured over the pH range 5·7 to 4·0. Corresponding changes in the morphology of muscle fibres and connective tissue were observed by light microscopy. WHC increased over the pH range 5·1 to 4·0 in all muscles, with the M. longissimus dorsi (LD) having significantly higher (p < 0·05) swelling ratios than the other muscles at pH 4·3 and pH 4·0. In all muscles, swelling increased across and along the muscle fibre axis between pH5·1 and pH4·4. However, towards pH4·0, increased muscle fibre swelling occurred in predominantly 'white' fibre-type muscles, in particular the LD, whereas muscle fibre shrinkage occurred in predominantly 'red' fibre-type muscles. Increased swelling of perimysial collagen and endomysial reticulin was observed in all muscles between pH4·5 and pH4·0, while the appearance of elastin was unaffected by pH. Consequently, interactions between muscle fibre swelling and connective tissue swelling determined the extent of total muscle swelling in different muscles between pH 4·5 and pH 4·0.
RESUMO
The supraspinatus tendon is composed of 5 different layers consisting of intertwining bundles. On a front portion of the tendon, the layers become coated bundles which insert on the trochanter. At the insertion, the superficial or bursal surface of the tendon corresponding to the tendon fibers in contact with the subacromial bursa can be distinguished from the deep surface corresponding to the fibers in contact with the glenohumeral joint. A tendon tear may involve partial or total disruption of the tendon fibers and is called full-thickness tear if it affects the entire tendon, and partial-thickness tear if it involves only part of the tendon. Partial-thickness tears of the supraspinatus tendon include lesions of the superficial, deep and central surface or tendon delamination.A contrast enhanced examination requires injection of contrast agent into the joint (arthrography followed by computed tomography (CT) or magnetic resonance imaging (MRI)) to study the deep surface, and injection into the subacromial bursa (bursography followed by CT) to study the superficial surface. MRI and ultrasound (US) examination allow the study of these different tendon layers without the use of contrast agent (which is not possible at CT).