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1.
Pulmonology ; 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38309995

RESUMO

INTRODUCTION AND OBJECTIVES: Hypersensitivity pneumonitis (HP) is an interstitial lung disease with diverse clinical features that can present a fibrotic phenotype similar to idiopathic pulmonary fibrosis (IPF) in genetically predisposed individuals. While several single nucleotide polymorphisms (SNPs) have been associated with IPF, the genetic factors contributing to fibrotic HP (fHP) remain poorly understood. This study investigated the association of MUC5B and TOLLIP variants with susceptibility, clinical presentation and survival in Portuguese patients with fHP. MATERIAL AND METHODS: A case-control study was undertaken with 97 fHP patients and 112 controls. Six SNPs residing in the MUC5B and TOLLIP genes and their haplotypes were analyzed. Associations with risk, survival, and clinical, radiographic, and pathological features of fHP were probed through comparisons among patients and controls. RESULTS: MUC5B rs35705950 and three neighboring TOLLIP variants (rs3750920, rs111521887, and rs5743894) were associated with increased susceptibility to fHP. Minor allele frequencies were greater among fHP patients than in controls (40.7% vs 12.1%, P<0.0001; 52.6% vs 40.2%, P = 0.011; 22.7% vs 13.4%, P = 0.013; and 23.2% vs 12.9%, P = 0.006, respectively). Haplotypes formed by these variants were also linked to fHP susceptibility. Moreover, carriers of a specific haplotype (G-T-G-C) had a significant decrease in survival (adjusted hazard ratio 6.92, 95% CI 1.73-27.64, P = 0.006). Additional associations were found between TOLLIP rs111521887 and rs5743894 variants and decreased lung function at baseline, and the MUC5B SNP and radiographic features, further highlighting the influence of genetic factors in fHP. CONCLUSION: These findings suggest that TOLLIP and MUC5B variants and haplotypes may serve as valuable tools for risk assessment and prognosis in fibrotic hypersensitivity pneumonitis, potentially contributing to its patient stratification, and offer insights into the genetic factors influencing the clinical course of the condition.

3.
Pulmonology ; 2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36180353

RESUMO

INTRODUCTION: Malignant pleural effusion (MPE) is a common complication in advanced stages of malignancy and is associated with poor prognosis. Non-expandable lung (NEL) often occurs and its presence influences the MPE approach. Our main objective was to assess risk factors for malignant NEL. METHODS: Patients diagnosed with pathologically confirmed MPE between January 2012 and December 2018 in our institution were retrospectively analyzed. Demographic and clinical data of patients were reviewed and compared according to the presence or absence of NEL. A univariate and multivariate binary logistic regression analysis were used to determine predictors of the development of NEL. RESULTS: Of 365 patients included, 68 (18.6%) had NEL. After multivariate analysis, we found that loculated MPE (OR 8.63, 95%CI 4.30-17.33, p<0.001), complete hemithorax opacification (OR 2.81, 95%CI 1.17-6.76, p<0.021), lung cancer (OR 2.09, 95%CI 1.01-4.31, p=0.047) and higher effusion-serum LDH ratio (OR 1.09, 95%CI 1.00-1.17, p=0.039) were independent predictors of malignant NEL. There were no significant differences compared with expandable lung group regarding time from primary malignancy diagnosis to MPE diagnosis (3.0, IQR 0.0-75.8 vs 2.0, IQR 0.0-75.5 weeks, p=0.942) or MPE symptoms onset to MPE diagnosis (4.0, IQR 1.0-9.0 vs 3.0, IQR 1.0-9.0 weeks, p=0.497). Patients with NEL had a higher number of therapeutic pleural drainages (3.0, IQR 2.0-6.0 vs 2.0, IQR 1.0-3.0; p<0.001) and longer hospital stay (32.5, IQR 15.5-46.3 vs 21.0, IQR 11.0-36.0, p=0.007), measured in hospitalization days until the end of life, than patients with expandable lung. The rate of recurrence of pleural effusion was not significantly different between groups (p=0.291). Overall survival (OS) was 3.0 (95%CI, 2.3-3.7) months, regardless of lung expandability (p=0.923). CONCLUSION: Loculated MPE, complete hemithorax opacification, lung cancer and a higher effusion-serum LDH ratio were found to be independent predictors for NEL. These patients underwent thoracocenteses more frequently and had longer hospitalization days, although without significant impact in the OS.

4.
Pulmonology ; 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-34987020

RESUMO

INTRODUCTION: The diagnosis of airway obstruction can be made through FEV1/FVC ratio <0.7 or FEV1/VC ratio < lower limit of normality (LLN). Several authors advocate that FEV1/FEV6 ratio is an alternative to diagnosing obstructive ventilatory defect, while others have determined that the best cut-off for this ratio (best combined sensitivity and specificity) is 0.73. OBJECTIVE: To evaluate the non-inferiority of FEV1/FEV6 ratio < 0.73 when compared to FEV1/FVC ratio < 0.7 and FEV1/VC < LLN in diagnosing airway obstruction. METHODS: A retrospective analysis of the medical records from patients who underwent spirometry or plethysmography in a university central hospital from June 1st to December 31st, 2018 was carried out. Only medical records which included FEV1/FVC < 0.7 or FEV1/VC < LLN were selected, and these results were compared to FEV1/FEV6 ratio. RESULTS: A total of 526 patients with obstructive ventilatory defect were identified by one of the two ratios described. Of these, 95.1%, 87.4% and 88.6% were obstructive by FEV1/FVC, FEV1/VC, and FEV1/FEV6 ratio, respectively. The positive predictive value (PPV) of FEV1/FEV6 in relation to FEV1/FVC ratio was 99.6% (p < 0.001) with a diagnostic efficacy of 92.8%, whereas the PPV of FEV1/FEV6 in relation to FEV1/VC was 91.0% (p < 0.001) and diagnostic efficacy was 85.2%. Most false negatives, comparing FEV6 with the other two tests, were found in patients with FEV1 > 70% (mild obstruction) and in individuals aged >50 years. CONCLUSIONS: FEV1/FEV6 < 0.73 may be a good alternative ratio, as it is non-inferior to FEV1/VC and FEV1/FVC in diagnosing obstructive ventilatory defect.

5.
Poult Sci ; 100(2): 926-937, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33518146

RESUMO

Herein, we investigated the effect of Chlorella vulgaris as ingredient (10% of incorporation) in broiler diets, supplemented or not with 2 formulations of Carbohydrate-Active enZymes (CAZymes; Rovabio Excel AP and a mixture of recombinant CAZymes, composed by an exo-ß-glucosaminidase, an alginate lyase, a peptidoglycan N-acetylmuramic acid deacetylase and a lysozyme), on growth performance, meat quality, fatty acid composition, oxidative stability, and sensory traits. One hundred twenty 1-day-old Ross 308 male birds were randomly assigned to one of the 4 experimental diets (n = 30): corn-soybean meal-basal diet (control), basal diet with 10% C. vulgaris (CV), CV supplemented with 0.005% of a commercial CAZyme cocktail (Rovabio Excel AP), (CV + R), and CV supplemented with 0.01% of a 4-CAZyme mixture previously selected (CV + M) during the experimental period lasted from day 21 to day 35. Body weight gain and feed conversion rate of broilers were not affected by C. vulgaris but digesta viscosity increased more than 2-fold (P < 0.001) relative to the control. In addition, neither cooking loss, shear force, juiciness, flavor nor off-flavor was impaired by dietary treatments (P > 0.05). By contrast, the dietary C. vulgaris increased tenderness, yellowness (b∗) and total carotenoids in breast and thigh meats. However, no additional protective effect against lipid oxidation was observed in meat with the inclusion of microalga. Chlorella vulgaris, independently of CAZymes, had a minor impact on meat fatty acid composition but improved the proportion of some beneficial fatty acids. In summary, our data indicate a slight improvement of broiler meat quality and lipid nutritional value, without impairment of broilers' growth performance, thus supporting the usefulness of this microalga in poultry diets, up to this high level of incorporation. By contrast, the selected CAZyme mixtures used do not significantly improve the release of microalga nutrients in poultry diets, through the disruption of microalga cell wall, which warrants further research.


Assuntos
Galinhas , Chlorella vulgaris , Lipídeos/análise , Carne/normas , Amidoidrolases/metabolismo , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Metabolismo dos Carboidratos/efeitos dos fármacos , Dieta/veterinária , Suplementos Nutricionais , Endopeptidases/metabolismo , Hexosaminidases/metabolismo , Masculino , Carne/análise , Muramidase/metabolismo , Polissacarídeo-Liases/metabolismo
7.
Food Res Int ; 132: 109061, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32331671

RESUMO

Genotypes of bananas and plantains have been studied for biofortification purposes, mainly due to content of resistant starch (RS) and polyphenols. This study aims to identify banana and plantain genotypes with a high content of resistant starch, phenolic compounds and minerals, and to evaluate the impact of the ripening stage and domestic thermal processing to select superior genotypes with high levels of functional compounds. In this study, it was used bunches of bananas and plantain genotypes. The phenolic compounds profiles were determined by HPLC-DAD in pulps and peels. The resistant starch and the minerals (K, Na, Zn, Cu and Fe) were evaluated in pulps and peels of unripe fruit. The results of phenolic compounds were studied in three ripening stages, and after thermal processing (ripe stage) of two genotypes, which were most promising for biofortification studies. Resistant starch and minerals were analysed in the unripe fruits. The peel biomass showed the highest values of phenolic compounds and minerals. The total starch content in the pulp varied from 42.3% ('FC06-02') to 80.6% ('Pelipita'). Plantains and cooking bananas presented the highest contents of starch and resistant starch (stage 2 - green with yellow traces). The pulps of the dessert genotypes 'Khai' and 'Ouro da Mata', and cooking genotype 'Pacha Nadam' stood out due to their minerals high contents (P, K and Fe; Zn and Fe; Ca, Mg and Zn, respectively). The dessert bananas (e.g., 'Ney Poovan') and cooking bananas (e.g., 'Tiparot') had the highest concentrations of phenolic compounds, mainly in ripe fruit (stage 5 - yellow with green). In addition, the thermal processing of Musa spp. fruit led to increasing these secondary metabolites, mainly the cooking of fruit with peel by boiling, which should be preferred in domestic preparations.


Assuntos
Antioxidantes/análise , Culinária , Frutas/química , Musa/química , Valor Nutritivo , Plantago/química , Catequina/análise , Minerais/análise , Musa/genética , Fenóis/análise , Melhoramento Vegetal , Polifenóis/análise , Amido
8.
Rev. esp. anestesiol. reanim ; 66(9): 483-486, nov. 2019.
Artigo em Espanhol | IBECS | ID: ibc-187757

RESUMO

La prevalencia mundial de diabetes mellitus (DM) ha aumentado drásticamente en las últimas 2 décadas, y esto afecta al 10-15% de la población quirúrgica1. La metformina representa el pilar de la terapia antihiperglucémica para la DM tipo 2, que proporciona numerosos efectos beneficiosos. Sin embargo, un efecto adverso raro, pero grave, es el desarrollo de acidosis láctica asociada a metformina (MALA) con una alta tasa de mortalidad. Describimos un caso grave de MALA en el período postoperatorio, que culminó en un paro cardíaco. Por lo tanto, los anestesistas deben tener conocimientos y ser expertos en el cuidado de pacientes con diabetes, siendo imperativo centrarse en la evaluación preoperatoria, la optimización, el tratamiento preexistente durante el período de inanición y la identificación de pacientes medicados con metformina en situación de riesgo de desarrollar MALA


The worldwide prevalence of diabetes mellitus (DM) has risen dramatically over the past two decades and this affects 10-15% of the surgical population1. Metformin represents the mainstay of anti-hyperglycaemic therapy for type 2 DM, providing numerous beneficial effects. However, a rare but severe adverse effect is the development of metformin-associated lactic acidosis (MALA) with high mortality rate. We describe a severe case of MALA in the postoperative period that culminated in cardiac arrest. Whereby anaesthetists should be knowledgeable and skilled in the care of patients with diabetes being imperative to focus on preoperative assessment, optimisation, management of pre-existing treatment during the starvation period and identification of patients medicated with metformin at risk of developing MALA


Assuntos
Humanos , Feminino , Idoso , Acidose Láctica/induzido quimicamente , Metformina/efeitos adversos , Diabetes Mellitus Tipo 2/complicações , Procedimentos Cirúrgicos em Ginecologia/métodos , Complicações Intraoperatórias/epidemiologia , Monitorização Intraoperatória/métodos , Suspensão de Tratamento , Insuficiência Renal Crônica/complicações
9.
Rev Esp Anestesiol Reanim (Engl Ed) ; 66(9): 483-486, 2019 Nov.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31601432

RESUMO

The worldwide prevalence of diabetes mellitus (DM) has risen dramatically over the past two decades and this affects 10-15% of the surgical population1. Metformin represents the mainstay of anti-hyperglycaemic therapy for type 2 DM, providing numerous beneficial effects. However, a rare but severe adverse effect is the development of metformin-associated lactic acidosis (MALA) with high mortality rate. We describe a severe case of MALA in the postoperative period that culminated in cardiac arrest. Whereby anaesthetists should be knowledgeable and skilled in the care of patients with diabetes being imperative to focus on preoperative assessment, optimisation, management of pre-existing treatment during the starvation period and identification of patients medicated with metformin at risk of developing MALA.


Assuntos
Acidose Láctica/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversos , Complicações Pós-Operatórias/induzido quimicamente , Idoso , Anuria/etiologia , Feminino , Parada Cardíaca/etiologia , Humanos , Cuidados Pré-Operatórios/métodos
10.
Adv Food Nutr Res ; 89: 53-94, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31351530

RESUMO

Pork, one of the most consumed meats worldwide, has been facing major challenges regarding its low sensory quality and unhealthy image of fat. This chapter addresses current feeding strategies to ameliorate pork sensory attributes and nutritional quality by increasing intramuscular fat deposition and improving fatty acid composition, respectively. Dietary protein reduction, alone or combined with some components, contributes to satisfy consumer requirements and enhances the competitiveness of the meat industry with higher pork quality and lower production costs. In addition, feeding sources of n-3 polyunsaturated fatty acids to pigs, mainly from marine origin (rich in eicosapentaenoic and docosahexaenoic acids), increases their content in pork, thus improving the health value of its fatty acid profile. In the near future, the inclusion of microalgae and seaweeds in feed represents a promising approach for the maintenance and development of the livestock sector, as an environmental friendly alternative to balance food and feed industries.


Assuntos
Distribuição da Gordura Corporal , Dieta/veterinária , Músculo Esquelético/fisiologia , Valor Nutritivo , Carne de Porco/normas , Animais , Suínos
11.
Epidemiol Infect ; 146(10): 1293-1300, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29925445

RESUMO

Reducing the risk of human immunodeficiency virus type 1 (HIV-1) transmission is still a public health priority. The development of effective control strategies relies on the quantification of the effects of prophylactic and therapeutic measures in disease incidence. Although several assays can be used to estimate HIV incidence, these estimates are limited by the poor performance of these assays in distinguishing recent from long-standing infections. To address such limitation, we have developed an assay to titrate p24-specific IgG3 antibodies as a marker of recent infection. The assay is based on a recombinant p24 protein capable to detect total IgG antibodies in sera using a liquid micro array and enzyme-linked immunosorbent assay. Subsequently, the assay was optimised to detect and titrate anti-p24 IgG3 responses in a panel of sequential specimens from seroconverters over 24 months. The kinetics of p24-specific IgG3 titres revealed a transient peak in the 4 to 5-month period after seroconversion. It was followed by a sharp decline, allowing infections with less than 6 months to be distinguished from older ones. The developed assay exhibited a mean duration of recent infection of 144 days and a false-recent rate of ca. 14%. Our findings show that HIV-1 p24-specific IgG3 titres can be used as a tool to evaluate HIV incidence in serosurveys and to monitor the efficacy of vaccines and other transmission control strategies.


Assuntos
Anticorpos Antivirais/sangue , Proteína do Núcleo p24 do HIV/imunologia , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , HIV-1/imunologia , Imunoglobulina G/sangue , Biomarcadores/sangue , Ensaio de Imunoadsorção Enzimática , Humanos , Incidência , Cinética , Soroconversão , Estudos Soroepidemiológicos , Fatores de Tempo
12.
J Laryngol Otol ; 132(7): 651-656, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29893657

RESUMO

OBJECTIVES: To analyse publication and citations trends of case reports within otolaryngology - head and neck surgery literature, with specific attention to the most-cited reports.Study designDatabase query. METHODS: Web of Science was searched for article type 'case reports' published in the leading otolaryngology - head and neck surgery journals since 1945. Variables including publication dates, citation dates and numbers, author, author number, and others were recorded and analysed for trends. The reports with the most citations (classics) were further studied. RESULTS: Of nearly 67 000 published articles in leading otolaryngology - head and neck surgery journals, the overall number of case reports as a percentage of the total has substantially decreased over time. A total of 110 case report classics were identified for which citations have increased. CONCLUSION: Although the case report may not be worthy of its tarnished record, declining trends in publication suggest a limited future for this valuable research and educational resource.


Assuntos
Bibliometria , Prontuários Médicos , Otolaringologia/tendências , Procedimentos Cirúrgicos Otorrinolaringológicos , Humanos
13.
Physiol Int ; 105(1): 76-85, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29602293

RESUMO

Experimental studies in animal models have described the benefits of physical exercise (PE) to kidney diseases associated with hypertension. Land- and water-based exercises induce different responses in renal function. Our aim was to evaluate the renal alterations induced by different environments of PE in spontaneously hypertensive rats (SHRs). The SHRs were divided into sedentary (S), swimming exercise (SE), and running exercise (RE) groups, and were trained for 8 weeks under similar intensities (60 min/day). Arterial pressure (AP) and heart rate (HR) were recorded. The renal function was evaluated through urinary volume at each week of training; sodium and potassium excretions, plasma and urinary osmolarities, glomerular filtration rate (GFR), levels of proteinuria, and renal damage were determined. SE and RE rats presented reduced mean AP, systolic blood pressure, and HR in comparison with S group. SE and RE rats showed higher urine osmolarity compared with S. SE rats showed higher free water clearance (P < 0.01), lower urinary density (P < 0.0001), and increased weekly urine volume (P < 0.05) in comparison with RE and S groups. GFR was increased in both SE and RE rats. The proteinuria of SE (7.0 ± 0.8 mg/24 h) rats was decreased at the 8th week of the PE in comparison with RE (9.6 ± 0.8 mg/24 h) and S (9.8 ± 0.5 mg/24 h) groups. The glomerulosclerosis was reduced in SE rats (P < 0.02). SE produced different response in renal function in comparison with RE, in which only swimming-trained rats had better profile for proteinuria and glomerulosclerosis.


Assuntos
Terapia por Exercício/métodos , Glomerulonefrite/prevenção & controle , Hipertensão/terapia , Rim/fisiopatologia , Proteinúria/prevenção & controle , Corrida , Natação , Animais , Pressão Sanguínea , Modelos Animais de Doenças , Taxa de Filtração Glomerular , Glomerulonefrite/etiologia , Glomerulonefrite/patologia , Glomerulonefrite/fisiopatologia , Frequência Cardíaca , Hipertensão/complicações , Hipertensão/fisiopatologia , Rim/patologia , Masculino , Proteinúria/etiologia , Proteinúria/patologia , Proteinúria/fisiopatologia , Ratos Endogâmicos SHR , Fatores de Tempo
14.
Animal ; 11(11): 2094-2102, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28462759

RESUMO

The present study aims to assess the effects of pig's genotype (lean v. fatty) and dietary protein level (control v. reduced) on intramuscular fat (IMF) content, fatty acid composition and fibre profile of psoas major, a representative red muscle in pig's carcass scarcely studied relative to white longissimus lumborum. The experiment was conducted on 40 intact male pigs (20 Alentejana purebred and 20 Large White×Landrace×Pietrain crossbred) from 60 to 93 kg of live weight. Pigs were divided and allocated to four dietary groups: control protein diet equilibrated for lysine (17.5% of CP and 0.7% of lysine) and reduced protein diet (RPD) not equilibrated for lysine (13.1% of crude protein and 0.4% of lysine) within a 2×2 factorial arrangement (two genotypes and two diets). Alentejana purebred had higher IMF content (15.7%) and monounsaturated fatty acids (MUFA) (8.9%), whereas crossbred pigs had higher PM weight (46.3%) and polyunsaturated fatty acids (PUFA) (20.1%). The genotype also affected colour with higher lightness (15.1%) and yellowness (33.8%) and lower redness (9.9%) scores in crossbred pigs. In line with this, fatty pigs displayed more oxidative fibres (29.5%), whilst lean pigs had more glycolytic (54.4%). Relative to fatty acids, RPD increased MUFA (5.2%) and SFA (3.2%) but decreased PUFA (14.8%). Ultimately, RPD increased IMF content (15.7%) in the red muscle under study, with no impact on glycolytic to oxidative fibre type transformation.


Assuntos
Tecido Adiposo/metabolismo , Criação de Animais Domésticos , Dieta com Restrição de Proteínas/veterinária , Músculos Psoas/metabolismo , Sus scrofa/metabolismo , Animais , Genótipo , Masculino , Distribuição Aleatória , Sus scrofa/genética
15.
Brain Struct Funct ; 222(6): 2547-2558, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28283747

RESUMO

The pedunculopontine nucleus (PPN) has been proposed as target for deep brain stimulation (DBS) in patients with postural instability and gait disorders due to its involvement in muscle tonus adjustments and control of locomotion. However, it is a deep-seated brainstem nucleus without clear imaging or electrophysiological markers. Some studies suggested that diffusion tensor imaging (DTI) may help guiding electrode placement in the PPN by showing the surrounding fiber bundles, but none have provided a direct histological correlation. We investigated DTI fractional anisotropy (FA) maps from in vivo and in situ post-mortem magnetic resonance images (MRI) compared to histological evaluations for improving PPN targeting in humans. A post-mortem brain was scanned in a clinical 3T MR system in situ. Thereafter, the brain was processed with a special method ideally suited for cytoarchitectonic analyses. Also, nine volunteers had in vivo brain scanning using the same MRI protocol. Images from volunteers were compared to those obtained in the post-mortem study. FA values of the volunteers were obtained from PPN, inferior colliculus, cerebellar crossing fibers and medial lemniscus using histological data and atlas information. FA values in the PPN were significantly lower than in the surrounding white matter region and higher than in areas with predominantly gray matter. In Nissl-stained histologic sections, the PPN extended for more than 10 mm in the rostro-caudal axis being closely attached to the lateral parabrachial nucleus. Our DTI analyses and the spatial correlation with histological findings proposed a location for PPN that matched the position assigned to this nucleus in the literature. Coregistration of neuroimaging and cytoarchitectonic features can add value to help establishing functional architectonics of the PPN and facilitate neurosurgical targeting of this extended nucleus.


Assuntos
Imagem de Tensor de Difusão/métodos , Imageamento por Ressonância Magnética/métodos , Núcleo Tegmental Pedunculopontino/diagnóstico por imagem , Núcleo Tegmental Pedunculopontino/patologia , Adulto , Idoso , Pontos de Referência Anatômicos , Anisotropia , Autopsia , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Adulto Jovem
16.
Hum Exp Toxicol ; 36(1): 33-41, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26944940

RESUMO

Pentavalent antimonial (Sb5+) drugs such as meglumine antimoniate (MA) are the mainstay treatment of leishmaniases in developing countries. The effects of these compounds on drug-metabolizing enzymes have not been characterized and their potential pharmacokinetic interactions with other drugs are therefore unknown. The present study investigated whether treatment with MA (300 mg Sb5+/kg body weight/day, subcutaneously) for 24 days affected the activities of cytochrome P450 (CYP)1A (ethoxyresorufin- O-deethylase), CYP2A5 (coumarin 7-hydroxylase), CYP2E1 ( p-nitrophenol-hydroxylase), CYP2B9/10 (benzyloxy-resorufin- O-debenzylase), or CYP3A11 (erythromycin- N-demethylase) in the livers of Swiss Webster (SW) and DBA-2 male and female mice. The results showed that CYP2A5-, CYP2E1-, and CYP3A11-catalyzed reactions were unaffected by MA treatment. A decrease in CYP2B9/10 activity was noted in DBA-2 females (but not males) and was not observed in SW males or females. However, repeated MA administration reduced mouse liver CYP1A activity. CYP1A2 messenger RNA (mRNA) levels were not affected by MA and in vitro exposure of mouse liver microsomes to Sb3+ and Sb5+ did not reduce CYP1A activity. These findings suggested that in vivo treatment with Sb5+ drugs depressed CYP1A activity, without downregulating CYP1A2 mRNA expression. Since in vitro treatment of liver microsomes failed to inhibit CYP1A activity, this effect may require intact cells.

17.
Transl Psychiatry ; 6(10): e918, 2016 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-27754481

RESUMO

The kynurenine pathway of tryptophan metabolism has an important role in mediating the behavioral effects of inflammation, which has implications in understanding neuropsychiatric comorbidity and for the development of novel therapies. Inhibition of the rate-limiting enzyme, indoleamine 2,3-dioxygenase (IDO), prevents the development of many of these inflammation-induced preclinical behaviors. However, dysregulation in the balance of downstream metabolism, where neuroactive kynurenines are generated, is hypothesized to be a functionally important pathogenic feature of inflammation-induced depression. Here we utilized two novel transgenic mouse strains to directly test the hypothesis that neurotoxic kynurenine metabolism causes depressive-like behavior following peripheral immune activation. Wild-type (WT) or kynurenine 3-monooxygenase (KMO)-deficient (KMO-/-) mice were administered either lipopolysaccharide (LPS, 0.5 mg kg-1) or saline intraperitoneally. Depressive-like behavior was measured across multiple domains 24 h after immune challenge. LPS precipitated a robust depressive-like phenotype, but KMO-/- mice were specifically protected from LPS-induced immobility in the tail suspension test (TST) and reduced spontaneous alternations in the Y-maze. Direct administration of 3-hydroxykynurenine, the metabolic product of KMO, caused a dose-dependent increase in depressive-like behaviors. Mice with targeted deletion of 3-hydroxyanthranilic acid dioxygenase (HAAO), the enzyme that generates quinolinic acid, were similarly challenged with LPS. Similar to KMO-/- mice, LPS failed to increase immobility during the TST. Whereas kynurenine metabolism was generally increased in behaviorally salient brain regions, a distinct shift toward KMO-dependent kynurenine metabolism occurred in the dorsal hippocampus in response to LPS. Together, these results demonstrate that KMO is a pivotal mediator of hippocampal-dependent depressive-like behaviors induced by peripheral LPS challenge.


Assuntos
Depressão/induzido quimicamente , Depressão/imunologia , Hipocampo/efeitos dos fármacos , Hipocampo/imunologia , Inflamação/imunologia , Quinurenina 3-Mono-Oxigenase/deficiência , Cinurenina/farmacocinética , Cinurenina/toxicidade , Animais , Feminino , Lipopolissacarídeos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Atividade Motora/efeitos dos fármacos , Oxirredutases/deficiência
18.
J Laryngol Otol ; 129(5): 489-93, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25825362

RESUMO

OBJECTIVE: This study aimed to evaluate the changes in impact factors of otorhinolaryngology journals over the past 15 years. METHOD: Using the online edition of Journal Citation Reports, standard (2-year) and 5-year impact factors were calculated for the leading 15 journals. RESULTS: The results were compared with the impact factors for 1998. The average standard impact factor and 5-year impact factor increased by 2.72 and 2.05 fold respectively when compared with 1998. The average 2012 standard impact factor and 5-year impact factor were 1.82 and 1.99 respectively, reflecting a 9.3 per cent difference. The average 1998 standard impact factor and 5-year impact factor were 0.67 and 0.97 respectively, reflecting a 44.8 per cent difference. The Journal of the Association for Research in Otolaryngology had the highest standard and five-year impact factors. CONCLUSION: These data may indicate changing clinical and research interests within our field, as well as increased speed and ease with which the internet has allowed citation. As a result, five-year intervals may no longer be necessary to adequately gauge journal impact.


Assuntos
Fator de Impacto de Revistas , Otolaringologia/tendências , Publicações Periódicas como Assunto/tendências , Seguimentos , Humanos
19.
Int J Sports Med ; 35(14): 1155-60, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25144438

RESUMO

The aim of this study was to evaluate the effects of a single partial-body cryotherapy bout between training sessions on strength recovery. 12 young men (23.9±5.9 years) were randomly exposed to 2 different conditions separated by 7 days: 1) Partial-body cryotherapy (subjects were exposed to 3 min of partial-body cryotherapy at - 110 °C between 2 high-intensity training sessions); 2) Control (subjects were not exposed to partial-body cryotherapy between 2 high-intensity training sessions). Subjects were exposed to partial-body cryotherapy after the first training session. The 2 knee extension high-intensity training sessions were separated by a 40-min rest interval. Knee extension training consisted of 6 sets of 10 repetitions at 60°.s(-1) for concentric actions and 6 sets of 10 at 180.s(-1) for eccentric actions. The decrease in eccentric peak torque and total work was significantly (p<0.05) less after partial-body cryotherapy (5.6 and 2%, respectively) when compared to control (16 and 11.6%, respectively). However, the decrease in concentric peak torque and total work was not different (p>0.05) between partial-body cryotherapy (9.4 and 6.5%, respectively) and control (7.5 and 5.2%, respectively). These results indicate that the use of partial-body cryotherapy between-training sessions can enhance eccentric muscle performance recovery.


Assuntos
Crioterapia , Força Muscular/fisiologia , Músculo Esquelético/fisiologia , Treinamento Resistido , Adulto , Humanos , Joelho/fisiologia , Masculino , Torque , Adulto Jovem
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