RESUMO
BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a well established treatment for severe obesity and type 2 diabetes. Although the gut microbiota is linked to the efficacy of LSG, the underlying mechanisms remain elusive. The effect of LSG for morbid obesity on the gut microbiota and bile acids was assessed here. METHODS: Severely obese subjects who were candidates for LSG were included and followed until 6 months after surgery. The composition and abundance of the microbiota and bile acids in faeces were assessed by 16S ribosomal RNA sequencing, quantitative PCR and liquid chromatography-mass spectrometry. RESULTS: In total, 28 patients with a mean(s.d.) BMI of 44·2(6·6) kg/m2 were enrolled. These patients had achieved excess weight loss of 53·2(19·0) per cent and showed improvement in metabolic diseases by 6 months after LSG, accompanied by an alteration in the faecal microbial community. The increase in α-diversity and abundance of specific taxa, such as Rikenellaceae and Christensenellaceae, was strongly associated with reduced faecal bile acid levels. These changes had a significant positive association with excess weight loss and metabolic alterations. However, the total number of faecal bacteria was lower in patients before (mean(s.d.) 10·26(0·36) log10 cells per g faeces) and after (10·39(0·29) log10 cells per g faeces) operation than in healthy subjects (10·83(0·27) log10 cells per g faeces). CONCLUSION: LSG is associated with a reduction in faecal bile acids and greater abundance of specific bacterial taxa and α-diversity that may contribute to the metabolic changes.
ANTECEDENTES: La gastrectomía vertical laparoscópica (laparoscopic sleeve gastrectomy, LSG) es un tratamiento bien establecido para la obesidad grave y la diabetes tipo 2. Aunque la microbiota intestinal se ha vinculado con la eficacia de LSG, los mecanismos subyacentes siguen siendo poco conocidos. En este estudio se evaluó el efecto de LSG en la obesidad mórbida sobre la microbiota del intestino y de los ácidos biliares (bile acids, BA). MÉTODOS: Tras la aprobación del Comité ético y la obtención del consentimiento informado, los sujetos con obesidad grave que eran candidatos para LSG fueron incluidos en el estudio y seguidos durante 6 meses después de la operación. Se evaluaron la composición y abundancia de la microbiota y BA en las heces mediante secuenciación del gen 16S rRNA, PCR cuantitativa y cromatografía líquida-espectrometría de masas. RESULTADOS: En total, 28 pacientes con una mediana (rango) del IMC de 43,9 kg/m2 (35,0-61,9) fueron reclutados y a los 6 meses tras una LSG, consiguieron una pérdida del exceso de peso de 47,3% (20,7-95,1) y mejoría de las enfermedades metabólicas acompañada de una alteración en la comunidad microbiana fecal. El aumento en la diversidad α y abundancia de especies taxonómicas específicas como Rikenellaceae y Christensenellaceae, se asociaba fuertemente con niveles fecales reducidos de BA. Estos cambios se asociaban de manera positiva y significativa con la pérdida del exceso de peso y las alteraciones metabólicas. Sin embargo, el número total de bacterias fecales en los pacientes fue inferior al de los sujetos sanos (10,84 log10 células/g heces (9,46-11,35)) antes de la operación (10,26 log10 células/g heces (9,44-10,91)) y después de la misma (10,42 log10 células/g heces (9,57-10,96)). CONCLUSIÓN: LSG se asoció con menos BA fecal y mayor abundancia de especies bacterianas específicas y diversidad α lo que puede contribuir a los cambios metabólicos.
Assuntos
Ácidos e Sais Biliares/análise , Fezes/química , Gastrectomia/métodos , Laparoscopia/estatística & dados numéricos , Obesidade Mórbida/cirurgia , Adulto , Carga Bacteriana , Biodiversidade , Diabetes Mellitus Tipo 2/microbiologia , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Humanos , Concentração de Íons de Hidrogênio , Masculino , Obesidade Mórbida/microbiologia , RNA Ribossômico 16S/genéticaRESUMO
Fractures are medical conditions that compromise the athletic potential of horses and/or the safety of jockeys. Therefore, the reduction of fracture risk is an important horse and human welfare issue. The present study used molecular genetic approaches to determine the effect of genetic risk for fracture at four candidate SNPs spanning the myostatin (MSTN) gene on horse chromosome 18. Among the 3706 Japanese Thoroughbred racehorses, 1089 (29.4%) had experienced fractures in their athletic life, indicating the common occurrence of this injury in Thoroughbreds. In the case/control association study, fractures of the carpus (carpal bones and distal radius) were statistically associated with g.65809482T/C (P = 1.17 x 10-8 ), g.65868604G/T (P = 2.66 x 10-9 ), and g.66493737C/T (P = 6.41 x 10-8 ). In the retrospective cohort study using 1710 racehorses born in 2000, the relative risk (RR) was highest for male horses at g.65868604G/T, based on the dominant allele risk model (RR = 2.251, 95% confidence interval 1.407-3.604, P = 0.00041), and for female horses at g.65868604G/T, based on the recessive allele risk model (RR = 2.313, 95% confidence interval 1.380-3.877, P = 0.00163). Considering the association of these SNPs with racing performance traits such as speed, these genotypes may affect the occurrence of carpus fractures in Japanese Thoroughbred racehorses as a consequence of the non-genetic influence of the genotype on the distance and/or intensity of racing and training. The genetic information presented here may contribute to the development of strategic training programs and racing plans for racehorses that improve their health and welfare.
Assuntos
Fraturas Ósseas/genética , Fraturas Ósseas/veterinária , Cavalos/genética , Polimorfismo de Nucleotídeo Único , Animais , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Japão , Masculino , Estudos RetrospectivosRESUMO
BACKGROUND: According to the World Health Organization, an estimated 80% or more deaths in Pacific island countries, including Fiji, were related to non-communicable diseases (NCDs). Although competency-based approaches have been effective for developing healthcare workers' capabilities, there are only a few reports on competency scales of healthcare workers for NCD prevention. We aimed to develop a self-reported measurement scale on a potential component of competency in the healthcare staff engaged in the prevention and control of NCDs in Fiji. METHODS: There were 378 Ministry of Health and Medical Services staff members working on NCD prevention and control in Fiji included in this study, which was a cross-sectional survey of social factors, working situation factors, and competency. Exploratory factor analysis was conducted to assess potential competency components, whereas Cronbach's α coefficient and analysis of variance were used to assess the validity and reliability of the scale items, respectively. Multivariate regression analyses were conducted to analyze the respondents' factor scores relative to social status and work situations. RESULTS: The factor analysis revealed 16 items that identified competency in four work types: 1) work management, 2) monitoring and evaluation, 3) community partnership, and 4) community diagnosis. The monitoring and evaluation roles were related to ethnic background, community partnership was related to religion, and community diagnosis was related to academic qualifications. CONCLUSIONS: Based on the results, we developed a competency scale for the four work types. This scale can help healthcare workers engage in better management of residents with NCDs in Fiji.
Assuntos
Competência Clínica/normas , Doenças não Transmissíveis/prevenção & controle , Prática de Saúde Pública/normas , Autorrelato , Adulto , Análise Fatorial , Feminino , Fiji/epidemiologia , Inquéritos Epidemiológicos , Humanos , MasculinoRESUMO
A ferromagnetic sphere can support optical vortices in the form of whispering gallery modes and magnetic quasivortices in the form of magnetostatic modes with nontrivial spin textures. These vortices can be characterized by their orbital angular momenta. We experimentally investigate Brillouin scattering of photons in the whispering gallery modes by magnons in the magnetostatic modes, zeroing in on the exchange of the orbital angular momenta between the optical vortices and magnetic quasivortices. We find that the conservation of the orbital angular momentum results in different nonreciprocal behavior in the Brillouin light scattering. New avenues for chiral optics and optospintronics can be opened up by taking the orbital angular momenta as a new degree of freedom for cavity optomagnonics.
RESUMO
OBJECTIVE: Moderate mechanical stress generated by normal joint loading and movement is essential for the maintenance of healthy articular cartilage. However, the effects of reduced loading caused by the absence of weight bearing or joint motion on articular cartilage and subchondral bone is still poorly understood. We aimed to characterize morphological and metabolic responses of articular cartilage and subchondral bone to decreased mechanical stress in vivo. METHODS: Mice were subjected to periods of hindlimb unloading by tail suspension or external fixation of the knee joints. The articular surface was observed with digital microscope and the epiphyseal bone was assessed by micro-CT analysis. Articular cartilage and subchondral bone were further evaluated by histomorphometric, histochemical, and immunohistochemical analyses. RESULTS: The joint surface was intact, but thickness of both the total and uncalcified layer of articular cartilage were decreased both after joint unloading and immobilization. Subchondral bone atrophy with concomitant marrow expansion predisposed osteoclast activity at bone surface to invade into cartilaginous layer. Uncalcified cartilage showed decreased aggrecan content and increased aggrecanase expression. Alkaline phosphatase (ALP) activity was increased at uncalcified cartilage, whereas decreased at calcified cartilage. The distributions of hypertrophic chondrocyte markers remained unchanged. CONCLUSION: Thinning of articular cartilage induced by mechanical unloading may be mediated by metabolic changes in chondrocytes, including accelerated aggrecan catabolism and exquisitely modulated matrix mineralization, and cartilage matrix degradation and resorption by subchondral osteoclasts. Cartilage degeneration without chondrocyte hypertrophy under unloading condition indicate the possible existence of mechanism which is different from osteoarthritis pathogenesis.
Assuntos
Cartilagem Articular/patologia , Imobilização , Articulação do Joelho/fisiopatologia , Estresse Mecânico , Análise de Variância , Animais , Biópsia por Agulha , Cartilagem Articular/fisiopatologia , Condrócitos/ultraestrutura , Modelos Animais de Doenças , Imuno-Histoquímica , Articulação do Joelho/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Varredura/métodos , Osteoartrite/patologia , Osteoartrite/fisiopatologia , Distribuição Aleatória , Valores de Referência , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: A new electro-mechanical device for measuring the lateral stiffness of the skin is now available. It basically allows to recording the forces that the skin opposes to a lateral displacement (1-2 mm) of a pinching type movement. Preliminary assays of this device to various skin sites and an artificial substrate aimed at defining its major characteristics (sensitivity, reproducibility, variations according to skin site). METHODS: The calibration of the device (Khelometer® ) and assessment of its reproducibility were carried out through the use of elastometer substrates of various stiffness's. The device was then used, in vivo, at different skin sites (scalp, inner and outer forearms, cheeks) of 213 healthy Japanese women of various ages. The short-time effect of a hydrating regimen (7% glycerol) was recorded on the outer forearm. RESULTS: This new device offers an appreciable reproducibility in vitro and in vivo (coefficient of variation of 2-4% and 5-14%, respectively). Unlike other biophysical methods, the Khelometer® can be easily applied onto the human scalp that shows a higher stiffness than the two other skin sites, increasing with age and presence of alopecia. In all the three studied skin sites, the impact of age leads to significantly higher lateral skin stiffness (LSS, expressed as N/mm) values. The latter were found significantly different between the two sides of the forearms where the outer (sun-exposed) side showed statistically slightly higher LSS, than the unexposed inner side. LSS values found on cheeks (≈0.5 N/mm) were about four times lower than those of the scalp (≈2 N/mm) and about half those of forearms (≈1 N/mm). The effect of a 7% glycerol based formula was recorded 20 min post application onto the forearm, leading to a slight drop in LSS (approx. 15%) as compared to a vehicle-applied skin site. CONCLUSION: These preliminary studies clearly indicate that this new device, applicable to any skin site, offers appreciable assets such as sensitivity and reproducibility. Accordingly, it appears as a new approach in the non-invasive biophysical measurements of the skin surface, in both advanced and applied research investigations.
Assuntos
Fenômenos Biomecânicos/fisiologia , Testes de Dureza/instrumentação , Anormalidades da Pele/patologia , Pele/patologia , Adulto , Idoso , Envelhecimento/fisiologia , Povo Asiático , Crioprotetores/farmacologia , Elastômeros , Feminino , Antebraço/fisiologia , Glicerol/administração & dosagem , Glicerol/farmacologia , Humanos , Pessoa de Meia-Idade , Dados Preliminares , Reprodutibilidade dos Testes , Couro Cabeludo/fisiologia , Pele/efeitos dos fármacos , Fenômenos Fisiológicos da PeleRESUMO
We experimentally implement a system of cavity optomagnonics, where a sphere of ferromagnetic material supports whispering gallery modes (WGMs) for photons and the magnetostatic mode for magnons. We observe pronounced nonreciprocity and asymmetry in the sideband signals generated by the magnon-induced Brillouin scattering of light. The spin-orbit coupled nature of the WGM photons, their geometrical birefringence, and the time-reversal symmetry breaking in the magnon dynamics impose the angular-momentum selection rules in the scattering process and account for the observed phenomena. The unique features of the system may find interesting applications at the crossroad between quantum optics and spintronics.
RESUMO
Procaterol (PCR) is a beta-2-adrenergic bronchodilator widely used in Japanese racehorses for treating lower respiratory disease. The pharmacokinetics of PCR following single intravenous (0.5 µg/kg) and oral (2.0 µg/kg) administrations were investigated in six thoroughbred horses. Plasma and urine concentrations of PCR were measured using liquid chromatography-mass spectrometry. Plasma PCR concentration following intravenous administration showed a biphasic elimination pattern. The systemic clearance was 0.47 ± 0.16 L/h/kg, the steady-state volume of the distribution was 1.21 ± 0.23 L/kg, and the elimination half-life was 2.85 ± 1.35 h. Heart rate rapidly increased after intravenous administration and gradually decreased thereafter. A strong correlation between heart rate and plasma concentration of PCR was observed. Plasma concentrations of PCR after oral administration were not quantifiable in all horses. Urine concentrations of PCR following intravenous and oral administrations were quantified in all horses until 32 h after administration. Urine PCR concentrations were not significantly different on and after 24 h between intravenous and oral administrations. These results suggest that the bioavailability of orally administrated PCR in horses is very poor, and the drug was eliminated from the body slowly based on urinary concentrations. This report is the first study to demonstrate the pharmacokinetic character of PCR in thoroughbred horses.
Assuntos
Broncodilatadores/farmacocinética , Cavalos/sangue , Procaterol/farmacocinética , Administração Oral , Animais , Área Sob a Curva , Disponibilidade Biológica , Broncodilatadores/sangue , Broncodilatadores/urina , Feminino , Meia-Vida , Frequência Cardíaca/efeitos dos fármacos , Injeções Intravenosas/veterinária , Masculino , Procaterol/sangue , Procaterol/urinaAssuntos
Antineoplásicos/uso terapêutico , Mesilato de Imatinib/uso terapêutico , Neoplasias Hepáticas/secundário , Melanoma/tratamento farmacológico , Proteínas Proto-Oncogênicas c-kit/genética , Neoplasias Vulvares/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Sequência de Bases , Feminino , Humanos , Metástase Linfática , Melanoma/genética , Melanoma/secundário , Mucosa , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Deleção de Sequência , Neoplasias Vulvares/genética , Neoplasias Vulvares/patologiaRESUMO
BACKGROUND: Oral mucositis is one of the most common side-effects of 5-fluorouracil (5-FU)-based chemotherapy. The objective of this study was to evaluate the effects of irsogladine maleate (IM) on fluorouracil-induced oral mucositis through a double-blind, placebo controlled trial. PATIENTS AND METHODS: Patients (N = 66) were randomly assigned to receive either placebo or IM (4 mg/day for 14 consecutive days). The incidence and maximum severity of fluorouracil-induced oral mucositis and safety of the irsogladine dosing regimen were evaluated. RESULTS: A cohort of 33 patients received placebo and 33 patients received IM. The incidence of oral mucositis was significantly lower for IM than for placebo (27% versus 73%; P < 0.001 by chi-square test). Specific adverse events considered related to IM were not found. CONCLUSION: IM significantly reduced the incidence and maximum severity of oral mucositis in patients treated with 5-FU-chemotherapy.
Assuntos
Fluoruracila/administração & dosagem , Estomatite/tratamento farmacológico , Estomatite/patologia , Triazinas/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Método Duplo-Cego , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Fluoruracila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Placebos , Estomatite/induzido quimicamente , Resultado do TratamentoRESUMO
OBJECTIVE: To document perinatal outcomes following use of the 'Solomon technique' in the selective photocoagulation of placental anastomoses for severe twin-twin transfusion syndrome (TTTS). METHODS: Between January 2010 and July 2012, data were collected from 102 consecutive monochorionic twin pregnancies complicated by severe TTTS that underwent fetoscopic laser ablation at four different centers. We compared outcomes between subjects that underwent selective laser coagulation using the Solomon technique (cases) and those that underwent selective laser coagulation without this procedure (controls). RESULTS: Of the 102 pregnancies examined, 26 (25.5%) underwent the Solomon technique and 76 (74.5%) did not. Of the 204 fetuses, 139 (68.1%) survived up to 30 days of age. At least one twin survived in 82 (80.4%) pregnancies and both twins survived in 57 (55.9%) pregnancies. When compared with the control group, the Solomon-technique group had a significantly higher survival rate for both twins (84.6 vs 46.1%; P < 0.01) and a higher overall neonatal survival rate (45/52 (86.5%) vs 94/152 (61.8%); P < 0.01). Use of the Solomon technique remained independently associated with dual twin survival (adjusted odds ratio (aOR), 11.35 (95% CI, 3.11-53.14); P = 0.0007) and overall neonatal survival rate (aOR, 4.65 (95% CI, 1.59-13.62); P = 0.005) on multivariable analysis. There were no cases of recurrent TTTS or twin anemia-polycythemia sequence (TAPS) in the Solomon-technique group. CONCLUSIONS: Use of the Solomon technique following selective laser coagulation of placental anastomoses appears to improve twin survival and may reduce the risk of recurrent TTTS and TAPS. Our data support the idea of performing a randomized controlled trial to evaluate the effectiveness of the Solomon technique.
Assuntos
Transfusão Feto-Fetal/cirurgia , Fetoscopia/métodos , Fotocoagulação a Laser/métodos , Adulto , Anastomose Arteriovenosa/cirurgia , Feminino , Humanos , Placenta/irrigação sanguínea , Placenta/cirurgia , Policitemia/prevenção & controle , Poli-Hidrâmnios/prevenção & controle , Gravidez , Resultado da Gravidez , Gravidez de Gêmeos , Estudos Retrospectivos , Prevenção SecundáriaRESUMO
AIMS: To determine whether the carotenoid production improves stress tolerance of lactic acid bacteria, the cloned enterococcal carotenoid biosynthesis genes were expressed in Lactococcus lactis ssp. cremoris MG1363, and the survival rate of carotenoid-producing engineered MG1363 strain under stress condition was investigated. METHODS AND RESULTS: We cloned carotenoid biosynthesis genes from yellow-pigmented Enterococcus gilvus. The cloned genes consisted of crtN and crtM and its promoter region were inserted into the shuttle vector pRH100, and the resulting plasmid was named pRC. The cloned crtNM was expressed using pRC in noncarotenoid-producing L. lactis ssp. cremoris MG1363. The expression of crtNM led to the production of C30 carotenoid 4,4'-diaponeurosporene. After exposure to 32 mmol l(-1) H2 O2 , low pH (1.5, acidified with HCl), 20% bile acid and 12 mg ml(-1) lysozyme, the survival rates of the MG1363 strain harbouring pRC were 18.7-, 6.8-, 8.8- and 4.4-fold higher, respectively, than those of MG1363 strain harbouring the empty vector pRH100. CONCLUSIONS: The expression of carotenoid biosynthesis genes from Ent. gilvus improves the multistress tolerance of L. lactis. SIGNIFICANCE AND IMPACT OF THE STUDY: First report of the improvement of multistress tolerance of lactic acid bacteria by the introduction of genes for carotenoid production.
Assuntos
Carotenoides/biossíntese , Enterococcus/genética , Lactococcus lactis/genética , Sequência de Bases , Expressão Gênica , Genes Bacterianos , Lactococcus lactis/metabolismo , Viabilidade Microbiana , Dados de Sequência Molecular , Estresse Fisiológico , TriterpenosRESUMO
Seaweeds are some of the principal primary producers of marine environments, and they are important ecological elements of coastal ecosystems. The effects of harmful chemicals on seaweeds may adversely affect coastal ecosystems, hence we aimed to develop a new phytotoxicity test using the gametophytes of a common temperate kelp species, Undaria pinnatifida (KU-1630), for the widely used antifouling chemical substances Cybutryne, Diuron, Cu2+, and Zn2+. Toxicity to gametophytes of U. pinnatifida was assessed by comparing the relative growth rate (RGR) at the logarithmic growth phase. Fragmentation method, initial algal biomass, photon irradiance, and adhesive period were investigated for developing optimal test conditions. Cybutryne exposure tests were performed with seven replicates and control, the RGR ranging from 0.17 to 0.19, while mean 7-day EC50 and no observed effect concentration (NOEC) were 5.1 µg/L and 1.8 µg/L, respectively. The 7-day EC50 for other antifoulants was 14 µg/L for Diuron, 17 µg/L for Cu2+, and 1500 µg/L for Zn2+. This test method demonstrated high sensitivity and reproducibility, and it may be added to the routine methods used for toxicity evaluation of hazardous chemicals.
Assuntos
Incrustação Biológica , Alga Marinha , Undaria , Diurona/toxicidade , Ecossistema , Reprodutibilidade dos Testes , Incrustação Biológica/prevenção & controleRESUMO
Loss of proteostasis is a hallmark of aging and Alzheimer disease (AD). Here, we identify ß-hydroxybutyrate (ßHB), a ketone body, as a regulator of protein solubility in the aging brain. ßHB is a small molecule metabolite which primarily provides an oxidative substrate for ATP during hypoglycemic conditions, and also regulates other cellular processes through covalent and noncovalent protein interactions. We demonstrate ßHB-induced protein insolubility across in vitro, ex vivo, and in vivo mouse systems. This activity is shared by select structurally similar metabolites, is not dependent on covalent protein modification, pH, or solute load, and is observable in mouse brain in vivo after delivery of a ketone ester. Furthermore, this phenotype is selective for pathological proteins such as amyloid-ß, and exogenous ßHB ameliorates pathology in nematode models of amyloid-ß aggregation toxicity. We have generated a comprehensive atlas of the ßHB-induced protein insolublome ex vivo and in vivo using mass spectrometry proteomics, and have identified common protein domains within ßHB target sequences. Finally, we show enrichment of neurodegeneration-related proteins among ßHB targets and the clearance of these targets from mouse brain, likely via ßHB-induced autophagy. Overall, these data indicate a new metabolically regulated mechanism of proteostasis relevant to aging and AD.
RESUMO
We have performed angle-resolved photoemission spectroscopy on Pb(Bi(1-x)Sb(x))2Te4, which is a member of lead-based ternary tellurides and has been theoretically proposed as a candidate for a new class of three-dimensional topological insulators. In PbBi2Te4, we found a topological surface state with a hexagonally deformed Dirac-cone band dispersion, indicating that this material is a strong topological insulator with a single topological surface state at the Brillouin-zone center. Partial replacement of Bi with Sb causes a marked change in the Dirac carrier concentration, leading to the sign change of Dirac carriers from n type to p type. The Pb(Bi(1-x)Sb(x))2Te4 system with tunable Dirac carriers thus provides a new platform for investigating exotic topological phenomena.
RESUMO
We performed systematic spin- and angle-resolved photoemission spectroscopy of TlBi(S(1-x)Se(x))(2) which undergoes a topological phase transition at x ~ 0.5. In TlBiSe(2) (x = 1.0), we revealed a helical spin texture of Dirac-cone surface states with an intrinsic in-plane spin polarization of ~0.8. The spin polarization still survives in the gapped surface states at x > 0.5, although it gradually weakens upon approaching x = 0.5 and vanishes in the nontopological phase. No evidence for the out-of-plane spin polarization was found, irrespective of x and momentum. The present results unambiguously indicate the topological origin of the gapped Dirac surface states, and also impose a constraint on models to explain the origin of mass acquisition of Dirac fermions.
RESUMO
OBJECTIVES: Hepatocyte growth factor (HGF) is one of the most potent survival-promoting factors for motor neurons. Overexpression of neuronal HGF has been shown to result in the attenuation of neuronal cell death and progression of disease in a familial amyotrophic lateral sclerosis (ALS) transgenic mouse model. HGF might be beneficial for motor neuron survival and is a good candidate agent for the treatment of ALS. So far, studies of the skin of ALS have shown unique pathological and biochemical abnormalities. However, there has been no study of HGF in ALS skin. MATERIALS AND METHODS: We made a quantitative immunohistochemical study of the expression of HGF in the skin from 19 patients with sporadic ALS and 16 controls. RESULTS: Hepatocyte growth factor immunoreactivity was positive in the epidermis, some dermal blood vessels, and glands in patients with ALS. These findings became more conspicuous as ALS progressed. The optical density for HGF immunoreactivity of the nucleus and the cytoplasm in the epidermis in ALS was significantly higher (P < 0.001 and P < 0.001) than in controls. There was a significant positive relation (r = 0.53, P < 0.02 and r = 0.73, P < 0.001) between HGF immunoreactivity and duration of illness in the nucleus and the cytoplasm in the epidermis in patients with ALS. CONCLUSIONS: These findings suggest that changes in HGF in ALS skin are related to the disease process and that metabolic alterations of HGF may take place in the skin of patients with ALS.
Assuntos
Esclerose Lateral Amiotrófica/metabolismo , Fator de Crescimento de Hepatócito/metabolismo , Pele/metabolismo , Pele/patologia , Adulto , Idoso , Esclerose Lateral Amiotrófica/patologia , Progressão da Doença , Células Epidérmicas , Epiderme/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Activating mutation of KRAS and BRAF are focused on as potential prognostic and predictive biomarkers in patients with colorectal cancer (CRC) treated with anti-EGFR therapies. This study investigated the clinicopathological features and prognostic impact of KRAS/BRAF mutation in advanced and recurrent CRC patients. METHOD: Patients with advanced and recurrent CRC treated with systemic chemotherapy (n=229) were analysed for KRAS/BRAF genotypes by cycleave PCR. Prognostic factors associated with survival were identified by univariate and multivariate analyses using the Cox proportional hazards model. RESULTS: KRAS and BRAF mutations were present in 34.5% and 6.5% of patients, respectively. BRAF mutated tumours were more likely to develop on the right of the colon, and to be of the poorly differentiated adenocarcinoma or mucinous carcinoma, and peritoneal metastasis. The median overall survival (OS) for BRAF mutation-positive and KRAS 13 mutation-positive patients was 11.0 and 27.7 months, respectively, which was significantly worse than that for patients with wild-type (wt) KRAS and BRAF (40.6 months) (BRAF; HR=4.25, P<0.001, KRAS13; HR=2.03, P=0.024). After adjustment for significant features by multivariate Cox regression analysis, BRAF mutation was associated with poor OS (HR=4.23, P=0.019). CONCLUSION: Presence of mutated BRAF is one of the most powerful prognostic factors for advanced and recurrent CRC. The KRAS13 mutation showed a trend towards poor OS in patients with advanced and recurrent CRC.
Assuntos
Neoplasias Colorretais/genética , Proteínas Proto-Oncogênicas B-raf/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Genes ras , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , RecidivaRESUMO
BACKGROUND AND OBJECTIVE: Several studies have hypothesized that periodontal disease may increase the risk of pre-eclampsia. The correlation between the two diseases would probably be based on hypertension-related cytokine release in the local periodontal environment. The aim of this study was to evaluate the association between periodontal disease and pre-eclampsia, and the correlation of the two conditions with interleukin-6 (IL-6) and tumor necrosis factor-α(TNFα) mRNA expression. MATERIAL AND METHODS: A case-control analysis of 116 pregnant women, 58 with pre-eclampsia (cases) and 58 normotensive pregnant women (controls) was performed. In addition to collection of socio-demographic data and periodontal evaluation, peripheral blood samples were collected for laboratory analysis of IL-6 and TNFα mRNA expression by real-time PCR. RESULTS: There was an association between periodontitis and pre-eclampsia (adjusted odds ratio 3.73; 95% confidence interval 1.32-10.58). Increased TNFα mRNA expression was observed in pre-eclamptic women; however, there was no correlation between periodontitis and systemic cytokine expression. In the case group, systemic cytokine mRNA levels were similar in pregnant women with and without periodontitis (means±SD): 0.73±0.24 vs. 0.82±0.38 for TNFα and 1.31±1.49 vs. 1.09±0.74 for IL-6, respectively. CONCLUSION: Periodontitis was clinically related to pre-eclampsia; however, the supposed mechanism that correlates the two diseases, i.e. a systemic inflammatory process involving cytokines TNFα and IL-6 in the presence of periodontal disease, could not be confirmed in this study.
Assuntos
Doenças Periodontais/imunologia , Pré-Eclâmpsia/imunologia , Adulto , Estudos de Casos e Controles , Citocinas/análise , Índice de Placa Dentária , Feminino , Idade Gestacional , Hemorragia Gengival/imunologia , Humanos , Interleucina-6/análise , Perda da Inserção Periodontal/imunologia , Doenças Periodontais/sangue , Bolsa Periodontal/imunologia , Periodontite/sangue , Periodontite/imunologia , Pré-Eclâmpsia/sangue , Gravidez , Classe Social , Fator de Necrose Tumoral alfa/análise , Adulto JovemRESUMO
The dynamic behavior and kinetics of the structural transformation of supported bimetallic nanoparticle catalysts with synergistic functions in the oxidation process are fundamental issues to understand their unique catalytic properties as well as to regulate the catalytic capability of alloy nanoparticles. The phase separation and structural transformation of Pt(3)Sn/C and PtSn/C catalysts during the oxidation process were characterized by in situ time-resolved energy-dispersive XAFS (DXAFS) and quick XAFS (QXAFS) techniques, which are element-selective spectroscopies, at the Pt L(III)-edge and the Sn K-edge. The time-resolved XAFS techniques provided the kinetics of the change in structures and oxidation states of the bimetallic nanoparticles on carbon surfaces. The kinetic parameters and mechanisms for the oxidation of the Pt(3)Sn/C and PtSn/C catalysts were determined by time-resolved XAFS techniques. The oxidation of Pt to PtO in Pt(3)Sn/C proceeded via two successive processes, while the oxidation of Sn to SnO(2) in Pt(3)Sn/C proceeded as a one step process. The rate constant for the fast Pt oxidation, which was completed in 3 s at 573 K, was the same as that for the Sn oxidation, and the following slow Pt oxidation rate was one fifth of that for the first Pt oxidation process. The rate constant and activation energy for the Sn oxidation in PtSn/C were similar to those for the Sn oxidation in Pt(3)Sn/C. In the PtSn/C, however, it was hard for Pt oxidation to PtO to proceed at 573 K, where Pt oxidation was strongly affected by the quantity of Sn in the alloy nanoparticles due to swift segregation of SnO(2) nanoparticles/layers on the Pt nanoparticles. The mechanisms for the phase separation and structure transformation in the Pt(3)Sn/C and PtSn/C catalysts are also discussed on the basis of the structural kinetics of the catalysts themselves determined by the in situ time-resolved DXAFS and QXAFS.