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Cálculos Biliares/complicações , Hiperparatireoidismo Primário/complicações , Idoso , Colecistectomia , Comorbidade , Feminino , Cálculos Biliares/epidemiologia , Cálculos Biliares/cirurgia , Humanos , Hipercalcemia/etiologia , Hiperparatireoidismo Primário/epidemiologia , Japão/epidemiologia , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos RetrospectivosRESUMO
Thymic stromal lymphopoietin (TSLP) has been suggested recently to play an important role in the pathophysiology of rheumatoid arthritis (RA). However, there is little information on serum TSLP concentrations in RA and its clinical significance. The present study investigated whether serum TSLP concentrations were affected in patients with RA. Using an enzyme-linked immunosorbent assay (ELISA), we measured TSLP concentrations in the serum obtained from 100 patients with RA, 60 patients with osteoarthritis (OA) and 34 healthy volunteers. We also investigated the correlation between serum TSLP concentrations and clinical parameters of disease activity in RA [disease activity score using 28 joint counts (DAS28)-C-reactive protein (CRP), DAS28-erythrocyte sedimentation rate (ESR), Clinical Disease Activity Index (CDAI]), patient's/-physician's Visual Analogue Scale (VAS), swollen joints count, tender joints count, CRP, ESR and matrix metalloproteinase-3 (MMP-3) concentrations]. In addition, we investigated the correlation between serum TSLP concentrations and anti-citrullinated peptide antibody (ACPA) and serum tumour necrosis factor (TNF)-α. Serum TSLP levels in patients with RA were significantly higher than those in patients with OA and in healthy volunteers. Interestingly, serum TSLP concentrations were correlated significantly with ACPA titres, but not with other clinical parameters. There was a significant increase in serum TSLP concentrations in patients with RA, which was correlated positively with serum ACPA titres. These findings suggest that in patients with RA, TSLP may play a role in ACPA production by B cells.
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Artrite Reumatoide/imunologia , Autoanticorpos/sangue , Citocinas/imunologia , Osteoartrite/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/sangue , Artrite Reumatoide/patologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Linfócitos B/patologia , Sedimentação Sanguínea , Proteína C-Reativa/imunologia , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Citocinas/sangue , Citocinas/genética , Feminino , Expressão Gênica , Humanos , Articulações/imunologia , Articulações/metabolismo , Articulações/patologia , Masculino , Metaloproteinase 3 da Matriz/sangue , Metaloproteinase 3 da Matriz/genética , Metaloproteinase 3 da Matriz/imunologia , Pessoa de Meia-Idade , Osteoartrite/sangue , Osteoartrite/patologia , Peptídeos Cíclicos/sangue , Peptídeos Cíclicos/imunologia , Índice de Gravidade de Doença , Transdução de Sinais , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Linfopoietina do Estroma do TimoRESUMO
Symptoms and laboratory parameters of allergic diseases exhibit prominent ~24-h variations. For instance, in most allergic rhinitis patients, symptoms worsen overnight or early in the morning. Accordingly, there are benefits to nighttime dosing of anti-allergy medications in such patients. Although the circadian pathophysiology of allergic diseases is well documented, the biological basis of this phenomenon remains poorly understood. Recent studies have begun to reveal that the internal timekeeping system termed the circadian clock plays a key role in temporal regulation of allergic reaction, and may therefore underlie the circadian pathophysiology of allergic diseases. Here, we review new knowledge that highlights the emerging role of the circadian clock as a potent regulator of allergic reactions. Given the strong influence of circadian rhythms on allergic diseases, we believe that research on how the time of day impacts allergic reaction which we may call 'chronoallergology' will provide new insight into previously unknown aspects of the biology of allergies. Such knowledge should facilitate novel strategies for prevention and treatment of these diseases.
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Relógios Circadianos/fisiologia , Hipersensibilidade/imunologia , Animais , HumanosRESUMO
It remains poorly understood how symptoms in allergic rhinitis are most severe during overnight or early in the morning. The circadian clock consisting of a network of several 'clock genes' including Clock drives daily rhythms in physiology. This study showed that allergen-induced surface CD203c expression on basophils in seasonal allergic rhinitis caused by Japanese cedar pollen exhibited a time-of-day-dependent variation associated with temporal variations in canonical circadian clock gene expression. We also found that bone-marrow-derived basophils (BM basophils) generated from wild-type mice exhibited a time-of-day-dependent variation in IgE-mediated IL-4 and histamine production, which was not observed in BM basophils generated from Clock-mutated mice. Therefore, allergen-specific basophil reactivity shows daily variations depending on the circadian clock activity in basophils, which could partly explain temporal symptomatic variations in allergic rhinitis. Additionally, circadian variations in CD203c expression should be considered for interpretation of this biomarker in clinical research.
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Alérgenos/imunologia , Basófilos/imunologia , Basófilos/metabolismo , Relógios Circadianos/genética , Rinite Alérgica Sazonal/genética , Rinite Alérgica Sazonal/imunologia , Adulto , Animais , Proteínas CLOCK/genética , Proteínas CLOCK/metabolismo , Regulação da Expressão Gênica , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Mutação , Proteínas Circadianas Period/genética , Proteínas Circadianas Period/metabolismo , Diester Fosfórico Hidrolases/genética , Diester Fosfórico Hidrolases/metabolismo , Pólen/imunologia , Pirofosfatases/genética , Pirofosfatases/metabolismo , Fatores de Tempo , Adulto JovemRESUMO
We investigate the photophysical and amplified spontaneous emission properties of a series of monodisperse solution-processable oligofluorenes functionalized with hexyl chains at the C9 position of each fluorene unit. Thin films of these oligofluorenes are then used in organic field-effect transistors and their charge transport properties are examined. We have particularly focused our attention on the influence of oligofluorene length on the absorption and steady-state fluorescence spectra, on the HOMO/LUMO energy levels, on the photoluminescence lifetime and quantum yield as well as on the amplified spontaneous emission properties and the charge carrier mobilities. Differential scanning calorimetry and X-ray diffraction measurements demonstrate that, among all oligofluorene derivatives used in this study, only the structure and morphology of the pentafluorene film is significantly modified by a thermal treatment above the glass transition temperature, resulting in a 9 nm blue-shift of the fluorescence spectrum without significant changes in the photoluminescence quantum yield and in the amplified spontaneous emission threshold. In parallel, hole field-effect mobility is significantly increased from 8.6 × 10(-7) to 3.8 × 10(-5) cm(2) V(-1) s(-1) upon thermal treatment, due to an increase of crystallinity. This study provides useful insights into the morphological control of oligofluorene thin films and how it affects their photophysical and charge transport properties. Moreover, we provide evidence that, because of the low threshold, the tunability of the amplified spontaneous emission and the photostability of the films, these oligofluorenes are promising candidates for organic solid-state laser applications.
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BACKGROUND: Peritoneal lavage cytology (CY) is used in the diagnosis and staging of various cancers. The clinical significance of positive cytology results in patients with pancreatic cancer is yet to be determined. METHODS: Peritoneal washing samples were collected from consecutive patients with pancreatic cancer between July 1991 and December 2012. The correlations between cytology results, clinicopathological parameters and recurrence patterns were evaluated. The prognostic impact of CY status, regarding resectability and the effectiveness of adjuvant chemotherapy, were analysed. RESULTS: Of 523 included patients, 390 underwent resection. Patients with tumours at least 2 cm in diameter were more likely to have CY+ status than patients with tumours smaller than 2 cm (48 of 312 versus 3 of 78 respectively; P = 0·005) and there was a significant correlation between CY+ status and tumour invasion of the anterior pancreatic capsule (43 of 276 versus 8 of 113 with no invasion of the capsule; P = 0·030). Although the overall survival of patients with resected CY+ tumours was worse than that of patients with resected CY- tumours, it was significantly better than the survival of unresected patients regardless of CY status. Multivariable analysis of all patients who had pancreatectomy did not identify CY+ as an independent prognostic factor. Patients with CY+ tumours tended to develop peritoneal metastasis more often than those with CY- tumours, although not significantly so. The median survival time of 34 patients with resected CY+ tumours who received adjuvant chemotherapy was better than that of 17 patients who had surgery alone, although this was not statistically significant (15·3 versus 10·0 months; P = 0·057). CONCLUSION: CY+ status is not clinically equivalent to gross peritoneal metastasis in patients with pancreatic cancer. Curative resection is still recommended regardless of CY status.
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Neoplasias Pancreáticas/patologia , Lavagem Peritoneal/métodos , Peritônio/patologia , Quimioterapia Adjuvante , Citodiagnóstico/métodos , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Neoplasias Peritoneais/secundárioRESUMO
BACKGROUND: Immediate-type skin allergic reactions, such as passive cutaneous anaphylactic reaction, are associated with circadian rhythm, but the role of circadian mechanisms on delayed-type skin allergic reactions, such as contact hypersensitivity (CHS), remains uncertain. In mice, CHS, a T-cell-mediated immune response, is a classic model of human allergic contact dermatitis. OBJECTIVES: We investigated whether biological clock dysfunction affects CHS pathogenesis in CLOCK mutant mice compared with wild-type (WT) mice. METHODS: Mice were treated with 2,4,6-trinitro-1-chlorobenzene (TNCB) on the abdominal skin on day 0 (sensitization) and then treated with TNCB on the ears on day 5 (challenge). RESULTS: We found that biological clock dysfunction resulted in severe inflammation. Ear swelling, serum immunoglobulin E level and mast cell number were significantly increased in CLOCK mutant mice compared with WT mice. These results provide evidence that CLOCK mutation promotes the T-helper type 2 immune response and exacerbates CHS. Corticosterone has a protective effect on CHS. The serum corticosterone level lost rhythmicity and showed a decreased daily level in CLOCK mutant mice compared with WT mice, supporting the exacerbating effect of CLOCK mutation on CHS. Adrenalectomy markedly worsened TNCB-induced CHS in WT mice but not in CLOCK mutant mice. In addition, dramatic dexamethasone-induced protection of CHS was observed in CLOCK mutant mice compared with WT mice. CONCLUSIONS: The present results suggest that circadian rhythm might be an important factor in the regulation of CHS via corticosterone rhythmicity and/or level.
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Relógios Biológicos , Transtornos Cronobiológicos/complicações , Dermatite de Contato/etiologia , Hipersensibilidade Tardia/etiologia , Córtex Suprarrenal/fisiologia , Adrenalectomia , Animais , Anti-Inflamatórios/farmacologia , Relógios Biológicos/genética , Corticosterona/metabolismo , Dermatite de Contato/imunologia , Dexametasona/farmacologia , Hipersensibilidade Tardia/imunologia , Imunidade Celular/fisiologia , Irritantes , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Mutantes , Mutação , Cloreto de PicrilaRESUMO
Ischemia/reperfusion injury (IRI) is the most common cause of early mortality following lung transplantation (LTx). We hypothesized that nitrite, an endogenous source of nitric oxide (NO), may protect lung grafts from IRI. Rat lung grafts were stored in preservation solution at 4°C for 6 hours. Both grafts and recipients were treated with nitrite. Nitrite treatment was associated with significantly higher levels of tissue oxygenation, lower levels of cytokines and neutrophil/macrophage infiltration, lower myeloperoxidase activity, reduced oxidative injury and increased cGMP levels in grafts than in the controls. Treatment with either a nitric oxide scavenger or a soluble guanylyl cyclase (sGC) inhibitor diminished the beneficial effects of nitrite and decreased cGMP concentrations. These results suggest that nitric oxide, generated from nitrite, is the molecule responsible for the effects of nitrite via the nitric oxide/sGC/cGMP pathway. Allopurinol, a xanthine oxidoreductase (XOR) inhibitor, abrogated the protective effects of nitrite, suggesting that XOR is a key enzyme in the conversion of nitrite to nitric oxide. In vitro experiments demonstrated that nitrite prevented apoptosis in pulmonary endothelial cells. Nitrite also exhibits longer survival rate in recipients than control. In conclusion, nitrite inhibits lung IRI following cold preservation and had higher survival rate in LTx model.
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Lesão Pulmonar Aguda/prevenção & controle , Transplante de Pulmão/efeitos adversos , Nitritos/farmacologia , Estresse Oxidativo/fisiologia , Traumatismo por Reperfusão/prevenção & controle , Lesão Pulmonar Aguda/etiologia , Animais , Modelos Animais de Doenças , Rejeição de Enxerto , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Pulmão/métodos , Masculino , Óxido Nítrico/metabolismo , Peroxidase/metabolismo , Distribuição Aleatória , Ratos , Ratos Endogâmicos Lew , Ratos Sprague-Dawley , Valores de ReferênciaRESUMO
Bright, short-pulsed neutron beams from laser-driven neutron sources (LANSs) provide a new perspective on material screening via fast neutron activation analysis (FNAA). FNAA is a nondestructive technique for determining material elemental composition based on nuclear excitation by fast neutron bombardment and subsequent spectral analysis of prompt γ-rays emitted by the active nuclei. Our recent experiments and simulations have shown that activation analysis can be used in practice with modest neutron fluences on the order of 105 n/cm2, which is available with current laser technology. In addition, time-resolved γ-ray measurements combined with picosecond neutron probes from LANSs are effective in mitigating the issue of spectral interference between elements, enabling highly accurate screening of complex samples containing many elements. This paper describes the predictive capability of LANS-based activation analysis based on experimental demonstrations and spectral calculations with Monte Carlo simulations.
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AIMS/HYPOTHESIS: It is difficult to use HbA(1c) as an indicator of glycaemic control in patients with neonatal diabetes mellitus (NDM) because of high levels of fetal haemoglobin (HbF) remaining in the blood. In this study, glycated albumin (GA), which is not affected by HbF, and HbA(1c) were compared to evaluate whether they reflect glycaemic control in patients with NDM. METHODS: This study included five patients with NDM. Age at diagnosis was 38 ± 20 days. Insulin therapy was started in all patients, and levels of GA, HbA(1c) and HbF were measured monthly for 6 months. One-month average preprandial plasma glucose (aPPG) was calculated using self-monitoring of blood glucose. RESULTS: Plasma glucose and GA were elevated (29.7 ± 13.1 mmol/l [n = 5] and 33.3 ± 6.9% [n = 3], respectively) but HbA(1c) was within normal limits (5.4 ± 2.6% [35.5 ± 4.9 mmol/mol]; n = 4) at diagnosis. With diabetes treatment, aPPG (r = -0.565, p = 0.002), GA (r = -0.552, p = 0.003) and HbF (r = -0.855, p < 0.0001) decreased with age, whereas HbA(1c) increased (r = 0.449, p = 0.004). GA was strongly positively correlated with aPPG (r = 0.784, p < 0.0001), while HbA(1c) showed no correlation with aPPG (r = 0.221, p = 0.257) and was significantly inversely correlated with HbF (r = -0.539, p = 0.004). CONCLUSIONS/INTERPRETATION: GA is a useful indicator of glycaemic control in patients with NDM, whereas HbA(1c) is influenced by age-related changes in HbF and does not accurately reflect glycaemic control.
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Glicemia/metabolismo , Diabetes Mellitus/metabolismo , Hemoglobinas Glicadas/metabolismo , Albumina Sérica/metabolismo , Biomarcadores/metabolismo , Diabetes Mellitus/tratamento farmacológico , Feminino , Produtos Finais de Glicação Avançada , Hemoglobinas/metabolismo , Humanos , Lactente , Recém-Nascido , Insulina/uso terapêutico , Masculino , Resultado do Tratamento , Albumina Sérica GlicadaRESUMO
BACKGROUND: Nutritional status plays an important role in the incidence of postoperative complications and the prognosis of various tumours. The prognostic value of preoperative nutritional factors in patients with pancreatic cancer is not known. METHODS: This retrospective study included 268 patients who underwent resection for adenocarcinoma of the pancreas. The predictive value of preoperative nutritional status for postoperative outcome (survival, complications) was assessed. Nutritional factors included the three constitutional indices, serum albumin and Onodera's prognostic nutrition index (PNI), calculated as 10 × serum albumin (g/dl) + 0·005× total lymphocyte count (per mm(3)). RESULTS: In multivariable analysis preoperative low PNI (but not low albumin) was an independent prognostic factor for poor survival: hazard ratio (HR) 1·73 (95 per cent confidence interval (c.i.) 1·21 to 2·47). The accuracy of a PNI value of less than 45 as cut-off for clinically significant preoperative malnutrition in predicting 1- or 2-year survival after surgery was, however, limited (66·4 and 56·3 per cent respectively). Low preoperative albumin concentration and PNI were significantly associated with postoperative complications: odds ratio 1·98 (95 per cent c.i. 1·18 to 3·32) and 2·14 (1·23 to 3·73) respectively. Low PNI and low body mass index were independently associated with pancreatic fistula: HR 2·52 (1·37 to 4·63) and 0·40 (0·17 to 0·93) respectively. CONCLUSION: The PNI is associated with overall survival and postoperative complications, in particular pancreatic fistula, in patients with pancreatic cancer. The moderate accuracy of PNI as a predictor of survival limits its clinical use.
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Estado Nutricional , Neoplasias Pancreáticas/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Cuidados Pré-Operatórios/mortalidade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
Synchrotron x-ray diffraction experiment shows that the metal-insulator transition occurring in a ferromagnetic state of a hollandite K(2)Cr(8)O(16) is accompanied by a structural distortion from the tetragonal I4/m to monoclinic P112(1)/a phase with a â2×â2×1 supercell. Detailed electronic structure calculations demonstrate that the metal-insulator transition is caused by a Peierls instability in the quasi-one-dimensional column structure made of four coupled Cr-O chains running in the c direction, leading to the formation of tetramers of Cr ions below the transition temperature. This provides a rare example of the Peierls transition of fully spin-polarized electron systems.
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Transforming growth factor (TGF)-beta has been implicated in immunosuppression. However, it remains obscure whether regulation of T cells by TGF-beta contributes to the immunosuppression in vivo. To address this issue, we developed transgenic mice expressing Smad7, an intracellular antagonist of TGF-beta/Smad signaling, selectively in mature T cells using a plasmid construct coding a promoter element (the distal lck promoter) that directs high expression in peripheral T cells. Peripheral T cells were not growth inhibited by TGF-beta in Smad7 transgenic mice. Although Smad7 transgenic mice did not spontaneously show a specific phenotype, antigen-induced airway inflammation and airway reactivity were enhanced in Smad7 transgenic mice associated with high production of both T helper cell type 1 (Th1) and Th2 cytokines. Thus, blockade of TGF-beta/Smad signaling in mature T cells by expression of Smad7 enhanced airway inflammation and airway reactivity, suggesting that regulation of T cells by TGF-beta was crucial for negative regulation of the inflammatory (immune) response. Our findings also implicated TGF-beta/Smad signaling in mature T cells as a regulatory component of allergic asthma.
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Asma/etiologia , Hiper-Reatividade Brônquica/etiologia , Proteínas de Ligação a DNA/fisiologia , Linfócitos T/fisiologia , Traqueia/patologia , Transativadores/fisiologia , Fator de Crescimento Transformador beta/fisiologia , Animais , Linfócitos B/fisiologia , Citocinas/biossíntese , Ativação Linfocitária , Camundongos , Camundongos Transgênicos , Ovalbumina/imunologia , Proteína Smad7RESUMO
I/R injury is a major deleterious factor of successful kidney transplantation (KTx). Carbon monoxide (CO) is an endogenous gaseous regulatory molecule, and exogenously delivered CO in low concentrations provides potent cytoprotection. This study evaluated efficacies of CO exposure to excised kidney grafts to inhibit I/R injury in the pig KTx model. Porcine kidneys were stored for 48 h in control UW or UW supplemented with CO (CO-UW) and autotransplanted in a 14-day follow-up study. In the control UW group, animal survival was 80% (4/5) with peak serum creatinine levels of 12.0 +/- 5.1 mg/dL. CO-UW showed potent protection, and peak creatinine levels were reduced to 6.9 +/- 1.4 mg/dL with 100% (5/5) survival without any noticeable adverse event or abnormal COHb value. Control grafts at 14 days showed significant tubular damages, focal fibrotic changes and numerous infiltrates. The CO-UW group showed significantly less severe histopathological changes with less TGF-beta and p-Smad3 expression. Grafts in CO-UW also showed significantly lower early mRNA levels for proinflammatory cytokines and less lipid peroxidation. CO in UW provides significant protection against renal I/R injury in the porcine KTx model. Ex vivo exposure of kidney grafts to CO during cold storage may therefore be a safe strategy to reduce I/R injury.
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Monóxido de Carbono/administração & dosagem , Transplante de Rim , Traumatismo por Reperfusão/prevenção & controle , Animais , Western Blotting , Carboxihemoglobina/metabolismo , Modelos Animais de Doenças , Sobrevivência de Enxerto , Malondialdeído/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Soluções , SuínosRESUMO
The increasing prevalence of allergic diseases in infants and children as well as adults has become an important issue in public health in industrial countries. However, few preventive measures are available to reduce the risk of allergic diseases in infants; e.g. the avoidance of smoking and alcohol consumption during pregnancy and lactation. Therefore, there is an enthusiasm to identify certain factors in foods, nutrients, and environment responsible for the primary prevention of allergic diseases during infancy. In the last decade, TGF-beta in maternal milk has been implicated in the prevention of allergic diseases in infants and young children. This review summarizes the relevant epidemiological reports and highlights the recent animal studies to support the preventive role of orally administered TGF-beta, such as TGF-beta in human milk, in the development of allergic diseases in infants. We also provide suggestions for the potential use of dietary (oral) TGF-beta for the primary prevention of allergic diseases. Further studies to address the scientific validity and mechanistic insight to this Mother Nature-inspired concept are clearly required and will be important to develop new approaches to prevent allergic diseases.
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Hipersensibilidade/prevenção & controle , Complicações na Gravidez/prevenção & controle , Fator de Crescimento Transformador beta/administração & dosagem , Animais , Alimentação com Mamadeira/normas , Feminino , Humanos , Hipersensibilidade/dietoterapia , Lactente , Camundongos , Leite Humano/imunologia , Gravidez , Complicações na Gravidez/dietoterapia , Probióticos/administração & dosagemRESUMO
BACKGROUND AND AIMS: Intestinal manipulation triggers an inflammatory cascade within the muscularis causing postoperative ileus (POI). The aim of this study was to investigate the recovery and therapeutic potential of interleukin 10 (IL10) for POI. METHODS: POI was induced by bowel surgical manipulation (SM) in wild-type, IL10(-/-) and recombinant murine IL10 (rmIL10)-treated mice. Immunohistochemistry localised IL10 in the muscularis externa, histochemistry quantified neutrophil recruitment, and quantitative PCR quantified alterations in mRNA. Luminex multiplex analysis, Griess reaction and ELISA measured proteins, nitric oxide (NO) and prostanoid release from the muscularis externa, respectively, in 24 h organ culture. Gastrointestinal transit and jejunal circular muscle organ bath techniques assessed gastrointestinal function. RESULTS: In IL10 knockouts compared with the wild type, the expression of numerous proinflammatory mRNAs (IL6, IL1 beta, chemokine C-C motif ligand 2 (CCL2) and haem oxygenase-1) and proteins (IL6, IL1 alpha, IL12, IL17, interferon gamma, tumour necrosis factor alpha, CCL2, interferon-inducible protein-10 and granulocyte-macrophage colony-stimulating factor (GM-CSF)) were accentuated, and release of muscle inhibitors NO and prostanoids was increased; motility never recovered from manipulation and mortality rate was 87.5%. In wild types, complete functional recovery occurred in 7 days with no mortality. SM delay in transit and suppression in jejunal circular muscle contractions were significantly improved by rmIL10 treatment. Upregulation in IL1 beta, IL6 and CCL2 mRNAs and inflammatory mediators (IL1 alpha, IL6, CCL2, macrophage inflammatory protein-1 alpha, GM-CSF, NO and prostaglandin) after SM were significantly less with rmIL10 treatment, which resulted in a decrease in neutrophil recruitment compared with SM controls. CONCLUSION: IL10 plays an obligatory role in postoperative intestinal recovery, and exogenous IL10 prevents its development. Pre-emptive exogenous recombinant human IL10 could be a treatment for the prevention of clinical POI.
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Trânsito Gastrointestinal/fisiologia , Íleus/fisiopatologia , Interleucina-10/fisiologia , Complicações Pós-Operatórias/fisiopatologia , Animais , Feminino , Trânsito Gastrointestinal/efeitos dos fármacos , Íleus/metabolismo , Íleus/prevenção & controle , Imuno-Histoquímica , Mediadores da Inflamação/metabolismo , Interleucina-10/uso terapêutico , Jejuno/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia , Complicações Pós-Operatórias/metabolismo , Complicações Pós-Operatórias/prevenção & controle , RNA Mensageiro/análise , Proteínas Recombinantes/uso terapêuticoRESUMO
BACKGROUND: This multicentre randomised phase III trial was designed to determine whether adjuvant chemotherapy with gemcitabine improves the outcomes of patients with resected pancreatic cancer. METHODS: Eligibility criteria included macroscopically curative resection of invasive ductal carcinoma of the pancreas and no earlier radiation or chemotherapy. Patients were randomly assigned at a 1 : 1 ratio to either the gemcitabine group or the surgery-only group. Patients assigned to the gemcitabine group received gemcitabine at a dose of 1000 mg m(-2) over 30 min on days 1, 8 and 15, every 4 weeks for 3 cycles. RESULTS: Between April 2002 and March 2005, 119 patients were enrolled in this study. Among them, 118 were eligible and analysable (58 in the gemcitabine group and 60 in the surgery-only group). Both groups were well balanced in terms of baseline characteristics. Although heamatological toxicity was frequently observed in the gemcitabine group, most toxicities were transient, and grade 3 or 4 non-heamatological toxicity was rare. Patients in the gemcitabine group showed significantly longer disease-free survival (DFS) than those in the surgery-only group (median DFS, 11.4 versus 5.0 months; hazard ratio=0.60 (95% confidence interval (CI): 0.40-0.89); P=0.01), although overall survival did not differ significantly between the gemcitabine and surgery-only groups (median overall survival, 22.3 versus 18.4 months; hazard ratio=0.77 (95% CI: 0.51-1.14); P=0.19). CONCLUSION: The current results suggest that adjuvant gemcitabine contributes to prolonged DFS in patients undergoing macroscopically curative resection of pancreatic cancer.
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Antimetabólitos Antineoplásicos/uso terapêutico , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/terapia , Adulto , Idoso , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Taxa de Sobrevida , GencitabinaRESUMO
In the current review article, evidences on radical surgery for gastric cancer reported in the literature are highlighted. The authors conclude that extended lymphadenectomy offers a statistically significant survival benefit. This benefit is only evident if the operative mortality is less than 2%, as obtained in centers of excellence with a high-volume experience of resection of gastric cancer. Lymphadenectomy should no longer be considered only as a tool for cancer-staging, but also as a beneficial therapeutic measure.
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Procedimentos Cirúrgicos do Sistema Digestório , Excisão de Linfonodo/métodos , Neoplasias Gástricas/cirurgia , Quimioterapia Adjuvante , Humanos , Metástase Linfática , Pancreatectomia , Radioterapia Adjuvante , Ensaios Clínicos Controlados Aleatórios como Assunto , Esplenectomia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/radioterapiaRESUMO
Alteration in transforming growth factor-beta signalling pathway is one of the main causes of pancreatic cancer. The human runt-related transcription factor 3 gene (RUNX3) is an important component of this pathway. RUNX3 locus 1p36 is commonly deleted in a variety of human cancers, including pancreatic cancer. Therefore, we examined genetic and epigenetic alterations of RUNX3 in human pancreatic cancer. Thirty-two patients with pancreatic cancer were investigated in this study. We examined the methylation status of RUNX3 promoter region, loss of heterozygosity (LOH) at 1p36, and conducted a mutation analysis. The results were compared with clinicopathological data. Promoter hypermethylation was detected in 20 (62.5%) of 32 pancreatic cancer tissues, confirmed by sequence of bisulphite-treated DNA. Loss of heterozygosity was detected in 11 (34.3%) of 32 pancreatic cancers. In comparison with clinicopathological data, hypermethylation showed a relation with a worse prognosis (P=0.0143). Hypermethylation and LOH appear to be common mechanisms for inactivation of RUNX3 in pancreatic cancer. Therefore, RUNX3 may be an important tumour suppressor gene related to pancreatic cancer.
Assuntos
Cromossomos Humanos Par 1 , Subunidade alfa 3 de Fator de Ligação ao Core/genética , Inativação Gênica , Neoplasias Pancreáticas/genética , Adulto , Idoso , Metilação de DNA , Análise Mutacional de DNA , Epigênese Genética , Feminino , Humanos , Perda de Heterozigosidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias Pancreáticas/metabolismo , Polimorfismo Conformacional de Fita Simples , Valor Preditivo dos Testes , Prognóstico , Regiões Promotoras Genéticas , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Análise de Sobrevida , Fator de Crescimento Transformador beta/metabolismoRESUMO
Ischemia/reperfusion (I/R) injury during small intestinal transplantation (SITx) frequently causes complications including dysmotility, inflammation and organ failure. Recent evidence indicates hydrogen inhalation eliminates toxic hydroxyl radicals. Syngeneic, orthotopic SITx was performed in Lewis rats with 3 h of cold ischemic time. Both donor and recipient received perioperative air or 2% hydrogen inhalation. SITx caused a delay in gastrointestinal transit and decreased jejunal circular muscle contractile activity 24 h after surgery. Hydrogen treatment resulted in significantly improved gastrointestinal transit, as well as jejunal smooth muscle contractility in response to bethanechol. The transplant induced upregulation in the inflammatory mediators CCL2, IL-1 beta, IL-6 and TNF-alpha were mitigated by hydrogen. Hydrogen significantly diminished lipid peroxidation compared to elevated tissue malondialdehyde levels in air-treated grafts demonstrating an antioxidant effect. Histopathological mucosal erosion and increased gut permeability indicated a breakdown in posttransplant mucosal barrier function which was significantly attenuated by hydrogen treatment. In recipient lung, hydrogen treatment also resulted in a significant abatement in inflammatory mRNA induction and reduced neutrophil recruitment. Hydrogen inhalation significantly ameliorates intestinal transplant injury and prevents remote organ inflammation via its antioxidant effects. Administration of perioperative hydrogen gas may be a potent and clinically applicable therapeutic strategy for intestinal I/R injury.