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OBJECTIVE: We aimed to investigate mechano-sensitivity at the afferent nerve fibers projecting to degenerated intervertebral disc (IVD) and nociceptive behaviour in a rat model of low back pain (LBP). DESIGN: Animal model with LBP was established by lumbar 4/5 IVD puncture and nucleus pulposus aspiration. In vivo single nerve recordings (n = 121) were introduced to measure discharge frequency at the afferent nerve fiber innervating the IVD during mechanical stimulations (von Frey filament or intradiscal pressure). Nerve growth factor (NGF) expression levels in the IVD (n = 20) were assessed by Western blot. LBP-related behaviour (n = 22) was assessed by measuring changes in rearing, mechanical paw-withdrawal threshold, and dynamic weight bearing in a freely walking rat. Inhibitory effect of morphine on the neuronal excitability (n = 19) and painful behaviour (n = 28) was also assessed. RESULTS: Compared to those with sham or naïve IVD, animal group with degenerated IVD displayed the sensitized neuronal responses and painful behaviour, with hyperexcitability of the afferent nerve fibers in any range of mechanical stimulations (von Frey filament stimulation; 1, 2, and 26 g; intradiscal pressure, 1,500-3,000 mm Hg), strong upregulation of NGF (200-250 % increase), and LBP-like behaviour such as failure of rearing, front limbs-dependent walking pattern, and hypersensitivity in hind-paws. However, the neuronal hyperexcitability and pain behaviour were attenuated after local (30 µM) or systemic (3 mg kg-1) morphine administration. CONCLUSIONS: Our study suggests that enhanced mechano-sensitivity at the afferent nerve fiber innervating degenerated IVD is deeply correlated with LBP development, which supports the hypothesis that hyperexcited responses at the nerve fibers represent a decisive source of LBP.
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Degeneração do Disco Intervertebral/complicações , Disco Intervertebral/inervação , Dor Lombar/etiologia , Fibras Nervosas/metabolismo , Fator de Crescimento Neural/biossíntese , Neurônios Aferentes/metabolismo , Nociceptividade/fisiologia , Animais , Western Blotting , Modelos Animais de Doenças , Degeneração do Disco Intervertebral/diagnóstico , Dor Lombar/diagnóstico , Dor Lombar/fisiopatologia , Vértebras Lombares , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Recurrence of pancreatic cancer after primary pancreatectomy occurs in the vast majority of patients. The role of surgical treatment for recurrent pancreatic cancer is not well established. METHODS: Patients who underwent primary pancreatectomy with curative intent from 2000 to 2014 at a single large-volume centre were evaluated retrospectively. CT or PET was used to select patients with an isolated recurrence. The clinicopathological features and survival outcomes were compared according to treatment modalities. RESULTS: Of the 1610 patients with pancreatic cancer who underwent resection, 1346 (83·6 per cent) were diagnosed with recurrent pancreatic cancer. Recurrence was locoregional in 366 patients (27·2 per cent), distant multifocal in 251 (18·6 per cent), distant isolated in 188 (14·0 per cent), locoregional plus distant in 153 (11·4 per cent) and peritoneal seeding in 388 (28·8 per cent). Of the 1346 patients with recurrence, 197 (14·6 per cent) had isolated recurrence; of these, 48 (24·4 per cent of all isolated recurrences; 3·6 per cent of all recurrences) underwent resection. Median survival of the 197 patients after diagnosis of isolated recurrence was 14·7 months; it was longer in patients who underwent surgical resection than among those treated non-surgically (23·5 versus 12·0 months; P = 0·014). Multivariable analysis showed that chemotherapy and resection for recurrence were associated with better prognosis. Median survival after recurrence was longest in the 23 patients with isolated pulmonary recurrence (33·3 months). Survival after recurrence was better in patients who underwent resection of isolated recurrence in the remnant pancreas (median 28·0 versus 12·0 months, P = 0·010) and lung (median 36·5 versus 9·5 months; P = 0·010) than in those who did not undergo resection. CONCLUSION: Surgical resection may be considered an option for treatment of patients with isolated recurrent pancreatic cancer.
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Adenocarcinoma/terapia , Recidiva Local de Neoplasia/terapia , Neoplasias Pancreáticas/terapia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/mortalidade , Pancreatectomia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/mortalidade , Tomografia por Emissão de Pósitrons , Reoperação , Estudos Retrospectivos , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
OBJECTIVES: To determine differences in arch forms derived from the root apices locations between individuals with <2 mm maxillary crowding and controls. SETTING AND SAMPLE POPULATION: The Department of Orthodontics, Pusan National University. Cone-beam computed tomography (CBCT) images of 102 patients in the control group and 95 patients in the crowding group. MATERIALS AND METHODS: X, Y and Z coordinates of the tip of the crowns and the apex of the root of the maxillary teeth (except second molars) were determined on the CBCT images. The acquired three-dimensional (3D) coordinates were converted into two-dimensional (2D) coordinates via projection on the palatal plane, and the Procrustes analysis was employed to process the converted 2D coordinates. The mean shape of the arch form derived from the location of the tip of the crowns and the apex of the root was compared between groups using the statistical shape analysis. RESULTS: There was a statistically significant difference (P = .046) between the groups for the mean shape of the root apex arch form, but the difference was small and clinically irrelevant as it is minor compared to the degree of crowding. CONCLUSIONS: Maxillary arch from at the level of the maxillary apices only shows minor differences between crowded and non-crowded dentitions.
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Tomografia Computadorizada de Feixe Cônico , Má Oclusão/diagnóstico por imagem , Má Oclusão/patologia , Maxila/diagnóstico por imagem , Maxila/patologia , Raiz Dentária/diagnóstico por imagem , Raiz Dentária/patologia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND: Severe damage to the tooth, periodontal ligament, and pulpal tissue often occurs with intrusive luxation, and outcomes are quite unpredictable because of the variable ways in which the injury may occur, which influences both the choice of treatment and prognosis. CASE REPORT: This case presents a novel method for the management of an intruded permanent maxillary central incisor with an immature apex. At first, watchful waiting for spontaneous re-eruption was the chosen treatment option. A palatal gingivectomy was performed and endodontic access was established, following which, an intracanal medicament of calcium hydroxide was applied. A root canal treatment was completed, and apexification with mineral trioxide aggregate was performed. Re-eruption failed to reach completion, so complete repositioning was performed with the aid of orthodontics for two months. CONCLUSION: The present case illustrates the partial re-eruption of a severely intruded immature permanent tooth with the use of interim medication in the root canal. This case also shows complete re-eruption with the aid of timely orthodontic repositioning after apexification.
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Incisivo/lesões , Avulsão Dentária/terapia , Apexificação , Criança , Dentição Permanente , Feminino , Humanos , Incisivo/diagnóstico por imagem , Maxila , Ortodontia Corretiva , Tratamento do Canal Radicular , Avulsão Dentária/diagnóstico por imagem , Erupção DentáriaRESUMO
PURPOSE OF INVESTIGATION: The authors investigated the expression patterns of interleukin (IL)-lß and tumor necrosis factor (TNF)-α, cytokines associated with peritoneal inflammatory reactions, and of B cell leukemia lymphoma (Bcl)-6 and B lymphocyte inducer of maturation program (Blimp)-1, transcriptional factors associated with immunoglobulin (Ig) production; the concentrations of Igs, and their correlation, in patients with and without endometriosis. MATERIALS AND METHODS: The authors analyzed the peritoneal fluid of 98 patients, 46 with endometriosis, and 52 with benign tumors. RESULTS: IL-1 and TNF-α mRNAs and IgG and IgA concentrations were higher in the endometriosis group, but the differences were not statistically significant. However, Bcl-6 mRNA level was significantly lower and Blimp-1 mRNA level was significantly higher in the endometriosis group with significant correlations among transcriptional factors, Igs, and cytokines (p < 0.05). CONCLUSION: Peritoneal immune responses in patients with endometriosis may be due to increased IgG and IgA concentrations, as well as to changes in expression of proinflammatory cytokines and transcriptional factors.
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Líquido Ascítico/metabolismo , Proteínas de Ligação a DNA/metabolismo , Endometriose/metabolismo , Proteínas Repressoras/metabolismo , Adulto , Citocinas , Endometriose/imunologia , Feminino , Humanos , Imunoglobulina A/metabolismo , Imunoglobulina G/metabolismo , Interleucina-1beta/metabolismo , Masculino , Pessoa de Meia-Idade , Cavidade Peritoneal , Peritônio/imunologia , Fator 1 de Ligação ao Domínio I Regulador Positivo , Proteínas Proto-Oncogênicas c-bcl-6 , Fator de Necrose Tumoral alfa/metabolismoRESUMO
This study was conducted to determine the effects of feeding by-product feed (BF)-based silage on the performance, blood metabolite parameters, and carcass characteristics of Hanwoo steers. The BF-based silage was composed of 50% spent mushroom substrate, 21% recycled poultry bedding, 15% cut ryegrass straw, 10.8% rice bran, 2% molasses, 0.6% bentonite, and 0.6% microbial additive (on a wet basis), and ensiled for over 5 d. Fifteen steers were allocated to three diets during the growing and fattening periods (3.1 and 9.8 months, respectively): a control diet (concentrate mix and free access to rice straw), a 50% BF-based silage diet (control diet+50% of maximum BF-based silage intake), and a 100% BF-based silage diet (the same amount of concentrate mix and ad libitum BF-based silage). The BF-based silage was fed during the growing and fattening periods, and was replaced with larger particles of rice straw during the finishing period. After 19.6 months of the whole period all the steers were slaughtered. Compared with feeding rice straw, feeding BF-based silage tended (p = 0.10) to increase the average daily gain (27%) and feed efficiency (18%) of the growing steers, caused by increased voluntary feed intake. Feeding BF-based silage had little effect on serum constituents, electrolytes, enzymes, or the blood cell profiles of fattening steers, except for low serum Ca and high blood urea concentrations (p<0.05). Feeding BF-based silage did not affect cold carcass weight, yield traits such as back fat thickness, longissimus muscle area, yield index or yield grade, or quality traits such as meat color, fat color, texture, maturity, marbling score, or quality grade. However, it improved good quality grade (1(+) and 1(++)) appearance rates (60% for the control group vs 100% for the BF-based silage-fed groups). In conclusion, cheap BF-based silage could be successfully used as a good quality roughage source for beef cattle.
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This study was conducted to determine the effects of feeding a trace minerals-fortified microbial culture (TMC) on the performance and carcass characteristics of late-fattening Hanwoo steers. A mixture of microbes (0.6% [v/w] of Enterobacter sp., Bacillus sp., Lactobacillus sp., and Saccharomyces sp.) was cultured with 99% feedstuff for ensiling and 0.4% trace minerals (zinc, selenium, copper, and cobalt). Sixteen late-fattening steers (mean age, 21.8 months) were allocated to two diets: a control diet (concentrate mix and rice straw) and a treated diet (control diet+3.3% TMC). At a mean age of 31.1 months, all the steers were slaughtered. The addition of TMC to the diet did not affect the average daily weight gain of the late fattening steers, compared with that of control steers. Moreover, consuming the TMC-supplemented diet did not affect cold carcass weight, yield traits such as back fat thickness, longissimus muscle area, yield index or yield grade, or quality traits such as meat color, fat color, texture, maturity, marbling score, or quality grade. However, consumption of a TMC-supplemented diet increased the concentrations of zinc, selenium, and sulfur (p<0.05) in the longissimus muscle. With respect to amino acids, animals consuming TMC showed increased (p<0.05) concentrations of lysine, leucine, and valine among essential amino acids and a decreased (p<0.05) concentration of proline among non-essential amino acids. In conclusion, the consumption of a TMC-supplemented diet during the late-fattening period elevated the concentrations of certain trace minerals and essential amino acids in the longissimus muscle, without any deleterious effects on performance and other carcass characteristics of Hanwoo steers.
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BACKGROUND: 4-1BB, a member of the TNF receptor superfamily, has a role in various inflammatory pathologies through its interaction with 4-1BB ligand. We previously demonstrated that it participates in initiating and promoting obesity-induced adipose inflammation in a rodent model. OBJECTIVE: In this study, we examined whether 4-1BB is related to obesity-induced adipose inflammation and metabolic parameters in humans. METHODS: A total of 50 subjects, 25 obese (body mass index (BMI)≥25 kg m(-2)) and 25 lean (BMI<23 kg m(-2)) participated in the study. The levels of 4-1BB transcripts and soluble 4-1BB protein (s4-1BB) in subcutaneous adipose tissue were measured by quantitative real-time PCR and enzyme-linked immunosorbent assay, respectively. Inflammatory and metabolic parameters were measured by enzymatic analysis and immunoassay. RESULTS: Obese subjects had higher levels of both 4-1BB transcripts and s4-1BB protein in subcutaneous adipose tissue than lean controls, and the levels were correlated with BMI and the expression of inflammatory markers, as well as with serum metabolic parameters. Moreover, s4-1BB was released from human adipocytes, and elicited chemotactic responses from human monocytes/T cells as well as enhancing their inflammatory activity, indicating that it may promote human adipose inflammation. DISCUSSION: Our data demonstrate that elevated levels of 4-1BB transcripts and s4-1BB in adipose tissue are closely associated with obesity-induced inflammation and metabolic dysregulation. They suggest that both 4-1BB transcripts and s4-1BB could serve as novel biomarkers and/or therapeutic targets for obesity-induced inflammation and metabolic syndrome in humans.
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Ligante 4-1BB/metabolismo , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Inflamação/metabolismo , Obesidade/metabolismo , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo , Tecido Adiposo/imunologia , Índice de Massa Corporal , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Inflamação/imunologia , Masculino , Obesidade/imunologia , Obesidade/fisiopatologia , Reação em Cadeia da Polimerase em Tempo Real , SolubilidadeRESUMO
A novel scheme for the focusing of high-energy leptons in future linear colliders was proposed in 2001 [P. Raimondi and A. Seryi, Phys. Rev. Lett. 86, 3779 (2001)]. This scheme has many advantageous properties over previously studied focusing schemes, including being significantly shorter for a given energy and having a significantly better energy bandwidth. Experimental results from the ATF2 accelerator at KEK are presented that validate the operating principle of such a scheme by demonstrating the demagnification of a 1.3 GeV electron beam down to below 65 nm in height using an energy-scaled version of the compact focusing optics designed for the ILC collider.
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OBJECTIVES: To identify susceptibility genes underlying degenerative bony changes of the temporomandibular joint (TMJ). MATERIALS AND METHODS: Bony changes of the TMJ condylar head were diagnosed by examination of panoramic radiographs and/or magnetic resonance images and/or computed tomography images. We conducted a genome-wide association study (GWAS) of 146 cases with TMJ degeneration and 374 controls from East Asian populations using an Illumina HumanOmniExpress BeadChip. After rigorous quality-control filtering, approximately 550,000 single nucleotide polymorphisms (SNPs) were used for tests of associations with disease status. RESULTS: Forty-one SNPs at 22 independent loci showed association signals at P < 1 × 10(-4). The SNP rs878962, which maps on an intron of TSPAN9 on chromosome 12, showed the strongest association (combined OR = 1.89, 95% confidence interval = 1.43-2.50, P = 8.1 × 10(-6)). According to in silico predictions of the 41 SNPs, two intronic SNPs of APOL3 (rs80575) and MRC2 (rs2460300) may fall within regulatory elements and affect DNA-protein interactions. We could not replicate SNPs located on genes that have been reported to be associated with temporomandibular disorder or temporomandibular osteoarthritis in previous studies at P < 1 × 10(-4). CONCLUSIONS: Our GWAS identified 22 independent loci showing suggestive association signals with degenerative bony changes of the TMJ. These loci provide good candidates for future follow-up studies.
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Estudo de Associação Genômica Ampla , Transtornos da Articulação Temporomandibular/genética , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Adulto JovemRESUMO
OBJECTIVES: This study aimed to determine the viability of using axial cervical vertebrae (ACV) as biological indicators of skeletal maturation and to build models that estimate ossification level with improved explanatory power over models based only on chronological age. MATERIALS AND METHODS: The study population comprised 74 female and 47 male patients with available hand-wrist radiographs and cone-beam computed tomography images. Generalized Procrustes analysis was used to analyze the shape, size, and form of the ACV regions of interest. The variabilities of these factors were analyzed by principal component analysis. Skeletal maturation was then estimated using a multiple regression model. RESULTS: Separate models were developed for male and female participants. For the female estimation model, the adjusted R(2) explained 84.8% of the variability of the Sempé maturation level (SML), representing a 7.9% increase in SML explanatory power over that using chronological age alone (76.9%). For the male estimation model, the adjusted R(2) was over 90%, representing a 1.7% increase relative to the reference model. CONCLUSIONS: The simplest possible ACV morphometric information provided a statistically significant explanation of the portion of skeletal-maturation variability not dependent on chronological age. These results verify that ACV is a strong biological indicator of ossification status.
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Determinação da Idade pelo Esqueleto/estatística & dados numéricos , Vértebras Cervicais/crescimento & desenvolvimento , Osteogênese/fisiologia , Adolescente , Fatores Etários , Pontos de Referência Anatômicos/diagnóstico por imagem , Vértebra Cervical Áxis/diagnóstico por imagem , Ossos do Carpo/diagnóstico por imagem , Ossos do Carpo/crescimento & desenvolvimento , Atlas Cervical/diagnóstico por imagem , Vértebras Cervicais/diagnóstico por imagem , Criança , Tomografia Computadorizada de Feixe Cônico/métodos , Feminino , Forame Magno/diagnóstico por imagem , Ossos da Mão/diagnóstico por imagem , Ossos da Mão/crescimento & desenvolvimento , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Modelos Estatísticos , Análise de Componente Principal , Análise de Regressão , Fatores SexuaisRESUMO
This study was conducted to evaluate the ensiling characteristics and the in situ degradability of a by-product feed (BF)-based silage. Before ensilation, the BF-based mixture was composed of 50% spent mushroom substrate, 21% recycled poultry bedding, 15% ryegrass straw, 10.8% rice bran, 2% molasses, 0.6% bentonite, and 0.6% microbial inoculant on a wet basis and ensiled for up to 4 weeks. The BF-based silage contained on average 39.3% moisture, 13.4% crude protein (CP), and 52.2% neutral detergent fiber (NDF), 49% total digestible nutrient, and 37.8% physically effective NDF1.18 on a dry matter (DM) basis. Ensiling the BF-based silage for up to 4 weeks affected (p<0.01) the chemical composition to a small extent, increased (p<0.05) the lactic acid and NH3-N content, and decreased (p<0.05) both the total bacterial and lactic acid bacterial counts from 10(9) to 10(8) cfu/g when compared to that before ensiling. These parameters indicated that the silage was fermented and stored well during the 4-week ensiling period. Compared with rice or ryegrass straws, the BF-based silage had a higher (p<0.05) water-soluble and filterable fraction, a lower insoluble degradable DM and CP fraction (p<0.05), a lower digestible NDF (p<0.05) fraction, a higher (p<0.05) DM and CP disappearance and degradability rate, and a lower (p<0.05) NDF disappearance and degradability rate. These results indicated that cheap, good-quality BF-based roughage could be produced by ensiling SMS, RPB, rice bran, and a minimal amount of straw.
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BACKGROUND: γ-Glutamyl hydrolase (GGH) regulates intracellular folate and antifolates for optimal nucleotide biosynthesis and antifolate-induced cytotoxicity, respectively. The modulation of GGH may therefore affect chemosensitivity of cancer cells, and exogenous folate levels may further modify this effect. METHODS: We generated a novel model of GGH modulation in human HCT116 and MDA-MB-435 cancer cells and investigated the effect of GGH modulation on chemosensitivity to 5-fluorouracil (5FU) and methotrexate (MTX) at different folate concentrations in vitro and in vivo. RESULTS: Overexpression of GGH significantly decreased chemosensitivity of MDA-MB-435 cells to 5FU and MTX at all folate concentrations as expected. In contrast, in HCT116 cells this predicted effect was observed only at very high folate concentration, and as the folate concentration decreased this effect became null or paradoxically increased. This in vitro observation was confirmed in vivo. Inhibition of GGH significantly increased chemosensitivity of both cancer cells to 5FU at all folate concentrations. Unexpectedly, GGH inhibition significantly decreased chemosensitivity of both cancer cells to MTX at all folate concentrations. In both GGH modulation systems and cell lines, the magnitude of chemosensitivity effect incrementally increased as folate concentration increased. CONCLUSION: Modulation of GGH affects chemosensitivity of cancer cells to 5FU and MTX, and exogenous folate levels can further modify the effects.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias do Colo/tratamento farmacológico , Fluoruracila/farmacologia , Ácido Fólico/farmacologia , Metotrexato/farmacologia , gama-Glutamil Hidrolase/antagonistas & inibidores , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/enzimologia , Animais , Neoplasias da Mama/enzimologia , Linhagem Celular Tumoral , Neoplasias do Colo/enzimologia , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Fluoruracila/administração & dosagem , Ácido Fólico/administração & dosagem , Células HCT116 , Humanos , Masculino , Metotrexato/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Transfecção , Ensaios Antitumorais Modelo de Xenoenxerto , gama-Glutamil Hidrolase/genética , gama-Glutamil Hidrolase/metabolismoRESUMO
BACKGROUND: High multivitamin (10-fold AIN-93G, HV) diets fed during pregnancy to Wistar rats increase characteristics of metabolic syndrome in offspring when weaned to the recommended vitamin (RV) diet. OBJECTIVE: To determine whether the effects of HV gestational diets on obesogenic phenotypes in the offspring arise as a consequence of altered hypothalamic control of feeding behavior and if their increased food intake could be prevented by feeding them HV or high folate (10-fold folate, HFol) diets. METHODS: Male offspring of dams fed HV diet during pregnancy weaned to RV, HV or HFol diets were compared with those born to RV dams and weaned to RV diet for 29 weeks. Food intake over 72 h and body weight were measured bi-weekly and weekly, respectively. Glucose response to a glucose load was measured at 18 weeks post weaning. Hypothalamic gene expression of feeding-related neuropeptides including neuropeptide Y, pro-opiomelanocortin (POMC), insulin receptor, leptin receptor, brain-derived neurotrophic factor (BDNF), receptors for dopamine (DopaR1/2/5) and serotonin (SeroR1A/2A/2C), as well as global DNA methylation and brain and plasma folate concentrations were measured at 29 weeks post weaning. RESULTS: HV or HFol pup diets increased brain and plasma folate concentrations and prevented the increase in food intake (5%, P=0.03), body weight (8%, P=0.0006) and glucose response to a glucose load (36%, P=0.02) found in those fed the RV diet. Expression of anorexigenic POMC (P=0.004) and BDNF (P=0.02) was higher, and DopaR1 was lower (P=0.06) in pups fed the HV diet. The HFol pup diet partially brought BDNF to the control level (P=0.02) and lowered SeroR2A (P=0.008). Expression of other genes was unaffected. Global DNA methylation was similar among the diet groups. CONCLUSION: The obesogenic phenotype in offspring from HV-fed dams is prevented by feeding HV or HFol pup diets, possibly due to post-weaning modulation of food intake regulatory mechanisms.
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Ingestão de Alimentos/genética , Ácido Fólico/farmacologia , Hipotálamo/metabolismo , Síndrome Metabólica/metabolismo , Obesidade/metabolismo , Vitaminas/farmacologia , Animais , Animais Recém-Nascidos , Biomarcadores/metabolismo , Peso Corporal , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Comportamento Alimentar , Feminino , Ácido Fólico/administração & dosagem , Ácido Fólico/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Masculino , Fenômenos Fisiológicos da Nutrição Materna/genética , Síndrome Metabólica/etiologia , Síndrome Metabólica/genética , Obesidade/etiologia , Obesidade/genética , Fenótipo , Pró-Opiomelanocortina/metabolismo , Ratos , Ratos Wistar , Receptor de Insulina/metabolismo , Receptores Dopaminérgicos/metabolismo , Receptores para Leptina/metabolismo , Receptores de Serotonina , Vitaminas/administração & dosagem , DesmameRESUMO
OBJECTIVE: Changes in respiratory parameters and pulmonary function tests were evaluated after shoulder arthroscopic surgery with brachial plexus block (BPB). The purpose of this study was to identify the mechanism of respiratory dysfunction after this type of surgery. METHODS: Patients undergoing arthroscopic rotator cuff repair under general anesthesia (GA) with BPB were enrolled in the arthroscopy group (n = 30) while those undergoing open reduction of a clavicle or humerus fracture under GA were enrolled in the control group (n = 30). Forced vital capacity (FVC) and forced expiratory volume 1 s (FEV(1)) were measured at the outpatient clinic stage (#1) before (#2) and 20 min after BPB (#3) and 1 h after extubation (#4). Respiratory variable measurements along with the cuff leak test were performed 5 min after surgical positioning (T1) and at the start of skin closure (T2). Respiratory discomfort was evaluated after extubation. The upper airway diameters and soft tissue depth of chest wall were also measured by ultrasonography at stages #3 and #4. RESULTS: Static compliance decreased significantly at T2 in the arthroscopy group (50 ± 11 at T1 vs. 44 ± 9 ml/cm H(2)O at T2, p =0.035) but not in the control group. The incidence of positive cuff leak tests at T2 was significantly higher in the arthroscopy group than in the control group (47% in the arthroscopy group vs. 17% in controls, p =0.010). While FEV(1) and FVC remained stable at stages #1 and #2, FVC and FEV(1) decreased at stages #3 and #4 only in the arthroscopy group (FVC in arthroscopy group, #2: 3.26 ± 0.77 l; #3: 2.55 ± 0.63 l, p =0.015 vs. #2; #4: 2.66 ± 0.41 l, p =0.040 vs. #2). The subglottic diameter decreased at #4 in the arthroscopy group, while no changes occurred in the control group (0.70 ± 0.21 cm vs. 0.85 ± 0.23 cm in the arthroscopy and control groups, respectively, p =0.011). Depth of skin to pleura increased at both intercostal spaces 1-2 and 3-4 in the arthroscopy group. There were three cases of hypoxia (S(p)O(2) < 95%) with room air in the arthroscopy group while none occurred in the controls. CONCLUSION: Shoulder arthroscopic surgery under GA with BPB induced both restrictive and obstructive pathologies. It is important to maintain a high level of awareness for the potential negative respiratory effects of this surgery especially for subjects with pre-existing cardiopulmonary disease. The measurements in this study would be useful to monitor the risk of respiratory dysfunction in these patients.
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Anestesia Geral , Artroscopia/métodos , Plexo Braquial , Bloqueio Nervoso , Complicações Pós-Operatórias/terapia , Doenças Respiratórias/terapia , Ombro/cirurgia , Idoso , Extravasamento de Materiais Terapêuticos e Diagnósticos , Feminino , Volume Expiratório Forçado , Humanos , Intubação Intratraqueal , Complacência Pulmonar , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/fisiopatologia , Troca Gasosa Pulmonar/fisiologia , Testes de Função Respiratória , Mecânica Respiratória , Doenças Respiratórias/etiologia , Doenças Respiratórias/fisiopatologia , Manguito Rotador/cirurgia , Capacidade VitalRESUMO
BACKGROUND AND OBJECTIVES: Sinomenine is an alkaloid compound and a prominent anti-inflammatory agent found in the root of the climbing plant Sinomenium acutum. However, its effects on the mechanism of human mast cell line (HMC)-1-mediated inflammation remained unknown. MATERIALS AND METHODS: To provide insight into the biological effects of sinomenine, we examined its influence on the pro-inflammatory cytokine production in HMC-1 cells stimulated by phorbol 12-myristate-13-acetate (PMA) plus A23187 by evaluating the stimulated cells in the presence or absence of sinomenine. In the present study, the pro-inflammatory cytokine production was measured using ELISA, Reverse Transcription-polymerase chain reaction (RT-PCR) and nuclear factor (NF)-kappaB, mitogen-activated protein kinases (MAPKs) pathway activation, as determined by Western blot analysis. Also, cyclooxygenase (COX)-2 expression was measured through Western blot and RT-PCR analysis. RESULTS: Sinomenine inhibited the pro-inflammatory cytokine production induced by PMA plus A23187 in a dose-dependent manner. Furthermore, sinomenine inhibited the phosphorylations of extracellular signal-regulated kinase (ERK) and p38 MAPKs as well as the translocation of NF-kappaB p65 through reduced IkappaBalpha degradation. In addition, sinomenine suppressed COX-2 protein and mRNA expression dose-dependently. CONCLUSIONS: Taken together, the results of this study indicate that the anti-inflammatory effects of sinomenine may occur via the inhibition of pro-inflammatory cytokine and COX-2 production through the inhibition of MAPKs and NF-kappaB pathway activation by PMA plus A23187 stimulation in HMC-1 cells.
Assuntos
Anti-Inflamatórios/farmacologia , Calcimicina/farmacologia , Mediadores da Inflamação/antagonistas & inibidores , Morfinanos/farmacologia , Acetato de Tetradecanoilforbol/farmacologia , Células Cultivadas , Ciclo-Oxigenase 2/biossíntese , Ciclo-Oxigenase 2/genética , Humanos , Mediadores da Inflamação/metabolismo , NF-kappa B/metabolismo , FosforilaçãoRESUMO
Traces of long-lived fallout-derived radioisotopes ((134)Cs and (137)Cs) were found in wet and dry deposition samples collected from the west and east coasts of South Korea from March to May 2011 following the release of radionuclides from the damaged nuclear power plants in Fukushima, Japan. The analysis of air mass back trajectory and atmospheric pressure systems indicated that the Fukushima-derived radiocaesium had predominantly reached South Korea from the west by surface westerlies from 11 March to 5 April; however, after 6 April, air masses arrived from Japan directly due to a high pressure system that developed to the east of Japan. Spatial variation of deposition fluxes of radiocaesium in South Korea was partly attributed to the presence of local longitudinal orography.
Assuntos
Radioisótopos de Césio/análise , Acidente Nuclear de Fukushima , Cinza Radioativa , Japão , Conceitos Meteorológicos , República da Coreia , Poluentes Radioativos do Solo/análise , Poluentes Radioativos da Água/análiseRESUMO
This study evaluated the effect of dietary supplementation of microbially-fermented spent mushroom substrates (MFSMS) on weight gain, carcass characteristics, and economic efficiency of Hanwoo steers. Highly cellulolytic bacteria (Enterobacter spp. and Bacillus spp.) isolated from spent mushroom substrates (SMS) stacks were inoculated (1% v/v) into the SMS, which was anaerobically fermented and fed to the steers for 12.6 months during the growing and fattening periods. Growing Hanwoo steers were assigned to the control group without supplementation of Microbially-fermented SMS (MFSMS), to a treatment group with 50% of MFSMS (1/2 of the ad libitum group), and to a treatment group with ad libitum access to SMS (the ad libitum group). All the groups were fed the formulated feed and rice straw. The voluntary intake (DM basis) of MFSMS was 1.6 kg/d during the growing period and 1.4 kg/d during the fattening period. The voluntary rice straw intake decreased by 6 to 11%, but the total voluntary DMI increased by 7 to 15% with MFSMS fed. The increased DMI with MFSMS supplementation resulted in a tendency of increased (p = 0.055) live weight gain by 8 to 12% compared with the control group. At slaughtering, the supplementation of MFSMS increased (p<0.05) the ribeye area by an average of 10 cm(2). In conclusion, feeding MFSMS improved growth performance and carcass traits of Hanwoo steers and could successfully replace a part of conventional roughage such as rice straw commonly used in Asian countries.
RESUMO
Ideal cancer gene therapies should have high tumor specificity and efficacy, and allow systemic administration to target metastases. We recently developed a bi-directional, two-step transcriptional amplification (TSTA) system driven by the tumor-specific Survivin promoter (pSurv) to amplify the correlated expression of both the reporter gene firefly luciferase (FL) and therapeutic gene tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Here, we compare the specificity and potency of an adenovirus carrying this system (Ad-pSurv-TSTA-TRAIL-FL) to a nonspecific vector (Ad-pCMV-FL) in an orthotopic hepatocellular carcinoma (HCC) rat model after systemic administration. At 24 h after injection of Ad-pCMV-FL, bioluminescence imaging revealed a trend (P=0.30) towards greater FL expression in liver versus tumor. In striking contrast, Ad-pSurv-TSTA-TRAIL-FL showed increased FL activity within the tumor compared with the liver (P<0.01), a strong trend towards reduced liver expression compared with Ad-pCMV-FL (P=0.07), and importantly, similar FL levels within tumor compared with Ad-pCMV-FL (P=0.32). Hence, this vector shows potent, tumor-specific transgene expression even after extensive liver transduction and may be of significant value in avoiding hepatotoxicity in HCC patients. Future studies will explore the benefits of tumor-specific TRAIL expression in this model, the potential to target metastases and the extension of this vector for the treatment of other Survivin-positive tumors is warranted.
Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Proteínas Associadas aos Microtúbulos/genética , Ligante Indutor de Apoptose Relacionado a TNF/genética , Adenoviridae/genética , Animais , Expressão Gênica , Marcação de Genes , Genes Reporter , Vetores Genéticos , Luciferases de Vaga-Lume/genética , Luciferases de Vaga-Lume/metabolismo , Regiões Promotoras Genéticas , Ratos , Sensibilidade e Especificidade , Survivina , TransgenesRESUMO
A new insect member of the signal transducer and activator of transcription (STAT) family of transcription factors, Hyphantria cunea STAT (HcSTAT), was cloned from the lepidopteran H. cunea. The domain involved in DNA interaction and the Src homology 2 (SH2) domain were well conserved. During all developmental stages, the gene was expressed at a low level in the haemocytes, fat body cells, midgut, epidermis and Malpighian tubules. The haemocytes and Malpighian tubules showed transcriptional activation of HcSTAT upon Gram-negative and Gram-positive bacterial challenges. These challenges increased the induction and nuclear translocation of the HcSTAT protein that recognizes a STAT target site in H. cunea haemocytes. In vivo treatment with sodium orthovanadate translocated HcSTAT to the haemocyte nucleus. This study shows the involvement of the haemocyte Janus kinase/STAT pathway after microbial infection in lepidopteran insects.