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1.
Xenobiotica ; 53(4): 309-319, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37476967

RESUMO

Personal care products, such as UV filters, are frequently present in aquatic ecosystems, but studies on their impact on marine organisms are still scarce. Here we addressed the effects of benzophenone-3 (BP-3) on the antioxidant status of Perna perna mussels exposed to concentrations of 0.1 and 3 µg.L-1 for 72 h and 7 days. Glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), glucose-6-phosphate dehydrogenase (G6PDH) activity and lipoperoxidation (MDA) were evaluated in the gills. A significant reduction (p < 0.05) in the activity of G6PDH and GPx was observed after exposure for 7 days to 0.1 µg.L-1. However, no significant differences were observed in GST activity and MDA levels, independently of the exposure time. Principal component analysis (PCA) showed an association of BP-3 highest concentration with GR and MDA at 72 h and only with GR at 7 days of exposure. Similarly, the integrated biomarker response (IBR) demonstrated GR and MDA alterations. In conclusion, environmentally relevant concentrations of BP-3 altered antioxidant and auxiliary enzymes, which could cause long-term damage to P.perna mussels. The need to implement more efficient techniques in wastewater treatment systems is pointed out, especially in summer, when UV filters are used more frequently and abundantly.


Assuntos
Perna (Organismo) , Poluentes Químicos da Água , Animais , Antioxidantes , Perna (Organismo)/fisiologia , Ecossistema , Catalase , Glutationa Transferase , Glutationa Redutase/farmacologia , Glutationa Peroxidase/farmacologia , Poluentes Químicos da Água/toxicidade , Biomarcadores
2.
Animals (Basel) ; 12(18)2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36139178

RESUMO

High ambient temperatures and relative humidity affect the behavior and physiology of the animal. This study investigated the influence of different heat-stress-reducing systems on the physiological, behavioral, and preferential responses of Holstein and Jersey cows and heifers on pasture. Experimental treatments were: (1) three heat-stress-reducing systems (sprinklers + artificial shade; showers + artificial shade; and artificial shade); (2) two breeds (Holstein and Jersey); and (3) two physiological stages (lactating cows and pubertal heifers). Physiological and behavioral responses to treatments were measured every 30 min on collection days. The frequency and duration of the use of the systems were recorded continuously 24 h/day for 3 days in each period. The air temperature and the relative humidity were 26 ± 4.1 °C and 74 ± 11.3%, respectively. The experimental treatments affected (p = 0.0354) standing idle, grazing behavior (p = 0.0435), and the frequency and duration of use of the systems by the animals (p < 0.0001). For all treatments, the respiratory rate and the coat surface temperature were highly and significantly correlated (p < 0.05) with the temperature and humidity index. In conclusion, under ambient conditions, dairy cows preferred using sprinklers or showers over artificial shade. These systems were more efficient at reducing the heat load and led to better behavioral and physiological responses.

3.
Sci Rep ; 12(1): 15570, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36114222

RESUMO

The aim of this study was to cross-sectionally explore the association of obesity with spinal posture and mobility, commonly associated with musculoskeletal problems, by comparing the spinal parameters between 90 obese and 109 normal-weight children and adolescents. A non-invasive electromechanical device, the Idiag M360 (Idiag, Fehraltorf, Switzerland), was used to measure the spinal parameters. An age-and-sex-adjusted two-way analysis of variance (ANOVA) was used to determine postural and mobility differences between the two groups. Children and adolescents with obesity had significantly greater thoracic kyphosis [difference between groups (Δ) = 13.00, 95% CI 10.10-15.80, p < 0.0001] and thoracic extension (Δ = 6.50, 95% CI 2.90-11.60, p = 0.005), as well as smaller mobility in thoracic flexion (Δ = 5.00, 95% CI 1.20-8.80, p = 0.01), thoracic lateral flexion (Δ = 17.70, 95% CI 11.60-23.80, p < 0.0001), lumbar flexion (Δ = 12.10, 95% CI 8.70-15.50, p < 0.0001), lumbar extension (Δ = 7.10, 95% CI 3.10-12.20, p = 0.003) and lumbar lateral flexion (Δ = 9.10, 95% CI 5.50-12.80, p < 0.0001) compared to the normal-weight children and adolescents. These findings provide important information about the characteristics of the spine in children and adolescents with obesity and unique insights into obesity-related mechanical challenges that the spine has to withstand and strategies designed to improve spinal mobility in this young population.


Assuntos
Cifose , Obesidade Infantil , Adolescente , Criança , Humanos , Região Lombossacral , Postura , Coluna Vertebral
4.
Animals (Basel) ; 11(5)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065215

RESUMO

This study aimed to evaluate the effects of annatto seeds, linseed oil and their combination on DMI, apparent total tract digestibility, antioxidant capacity and milk composition of dairy cows. Four lactating Holstein cows (120 ± 43 days in milk; 15.98 ± 2.02 kg of milk/day, mean ± SD) were allocated in a 4 × 4 Latin square with a 2 × 2 factorial arrangement (with or without annatto seeds at 15 g/kg of dry matter (DM); with or without linseed oil at 30 g/kg of DM) and provided four different diets: control (no annatto seeds or linseed oil); annatto seeds (15 g/kg of DM); linseed oil (30 g/kg of DM); and a combination of both annatto seeds and linseed oil. Annatto seeds reduced DM intake, and milk yield, protein and lactose, but increased content of fat, total solids and short chain fatty acid, with no effect on total antioxidant capacity of milk. Linseed oil supplementation decreased medium chain fatty acid proportion and n-6/n-3 ratio, conversely it increased long chain fatty acids and n-3 fatty acid content of milk, ether extract intake and total-tract digestibility. Thus, linseed oil supplementation in dairy cow diets improved the milk FA profile but decreased milk fat concentration, whereas annatto seeds did not influence antioxidant capacity and depressed feed intake and milk yield.

6.
BMC Endocr Disord ; 18(1): 96, 2018 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-30587244

RESUMO

BACKGROUND: Growth hormone (GH) is a heterogeneous protein composed of several molecular isoforms, the most abundant ones being the 22 kDa- and 20 kDa-GH. Exercise-induced secretion of GH isoforms has been extensively investigated in normal-weight individuals due to antidoping purposes, particularly recombinant human GH (rhGH) abuse. On the other hand, the evaluation of exercise-induced responses in GH isoforms has never been performed in obese subjects. METHODS: The acute effects of whole body vibration (WBV) or maximal voluntary contraction (MVC) alone and the combination of MVC with WBV (MVC + WBV) on circulating levels of 22 kDa- and 20 kDa-GH were evaluated in 8 obese male adolescents [mean age ± SD: 17.1 ± 3.3 yrs.; weight: 107.4 ± 17.8 kg; body mass index (BMI): 36.5 ± 6.6 kg/m2; BMI standard deviation score (SDS): 3.1 ± 0.6]. RESULTS: MVC (alone or combined with WBV) significantly stimulated 22 kDa- and 20 kDa-GH secretion, while WBV alone was ineffective. In particular, 22 kDa- and 20 kDa-GH peaks were significantly higher after MVC + WBV and MVC than WBV. In addition, 22 kDa-GH (but not 20 kDa-GH) peak was significantly higher after MVC + WBV than MVC. Importantly, the ratio of circulating levels of 22 kDa- to 20 kDa-GH was constant throughout the time window of evaluation after exercise and similar among the three different protocols of exercise. CONCLUSIONS: The results of the present study confirm the ability of MVC, alone and in combination with WBV, to stimulate both 22 kDa- and 20 kDa-GH secretion in obese patients, these responses being related to the exercise workload. Since the ratio of 22 kDa- to 20 kDa-GH is constant after exercise and independent from the protocols of exercise as in normal-weight subjects, hyposomatotropism in obesity does not seem to depend on an unbalance of circulating GH isoforms. Since the present study was carried out in a small cohort of obese sedentary adolescents, these preliminary results should be confirmed in further future studies enrolling overweight/obese subjects with a wider age range.


Assuntos
Hormônio do Crescimento Humano/sangue , Contração Muscular/fisiologia , Obesidade/sangue , Vibração , Adolescente , Índice de Massa Corporal , Peso Corporal , Exercício Físico/fisiologia , Humanos , Masculino , Obesidade/fisiopatologia , Isoformas de Proteínas/sangue , Comportamento Sedentário , Adulto Jovem
7.
An Acad Bras Cienc ; 90(4): 3839-3852, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30427395

RESUMO

Our objective was to quantify the relationship between seasons of the year, milk production, and milk composition of a dairy farm based on data for 48 consecutive months, using multivariate statistical analyses. The dataset contained information on productive indexes and milk composition from the bulk tank milk, which was measured from milk samples, collected monthly and used to determine the total dry extract and defatted dry extract, lactose, fat, protein, somatic cell count, and total bacterial count. Seasons of the year and milk production/hectare were also considered. Factor, cluster, and discriminant analysis were used to study the relationships between the above-mentioned variables. A positive relationship was noted between season and total dry extract, defatted dry extract, milk fat, and protein, with higher values being observed in winter and spring. Similarly, a positive relationship was noted between season and milk production/hectare, lactose content, with an increase in milk production and lactose content in winter and spring, which was negatively related to the somatic cell count and total bacterial count. Milk production and composition varied mainly with seasons. Multivariate analyses facilitated a better understanding of the relationship between milk production and composition on this dairy farm.


Assuntos
Lactação/fisiologia , Leite/química , Estações do Ano , Animais , Brasil , Bovinos , Contagem de Células/veterinária , Feminino , Proteínas do Leite/análise , Análise Multivariada
8.
Growth Horm IGF Res ; 42-43: 22-27, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30075349

RESUMO

BACKGROUND: The anabolic, lipolytic and anti-inflammatory effects of exercise-stimulated GH secretion could be usefully exploited in the multidisciplinary rehabilitative programs of obese patients, who are reported to suffer from hyposomatotropism. To date, evaluation of GH responses to whole body vibration (WBV) in combination with maximal voluntary contractions (MVC) has been performed in normal-weight subjects, but not obese patients. Thus, aim of the present study was to investigate the effects of WBV and MVC, alone and combined, on GH responsiveness in obese subjects. METHODS: The acute effects of WBV or MVC alone and the combination of MVC with WBV (MVC + WBV) on serum GH, cortisol and IGF-I and blood lactate (LA) levels were evaluated in 8 obese male adolescents [mean age ±â€¯SD: 17.1 ±â€¯3.3 yrs.; weight: 107.4 ±â€¯17.8 kg; body mass index (BMI): 36.5 ±â€¯6.6 kg/m2; BMI standard deviation score (SDS): 3.1 ±â€¯0.6]. RESULTS: WBV and MVC (alone or combined) significantly stimulated GH secretion. In particular, GH peaks and net areas under the curve (nAUCs) were significantly higher after MVC + WBV and MVC than WBV, without any difference between MVC + WBV and MVC groups; anyway, an additive effect on GH levels immediately after the execution of MVC + WBV test was found in comparison with MVC test. LA peaks significantly increased after each exercise (vs. basal condition), being significantly higher after MVC + WBV and MVC than WBV, without any difference between MVC + WBV and MVC groups. Peak LA values were significantly correlated with GH peaks and nAUCs. In contrast to the unchanged IGF-I levels, MVC + WBV and MVC (but not WBV) significantly stimulated cortisol secretion. CONCLUSIONS: The results of the present study confirm the ability of MVC and WBV to stimulate GH secretion in obese patients. Rehabilitative programs combining different types of exercise eliciting a potent GH response seem to be important to counteract the hyposomatotropism of obese patients. Due to its limited stress upon joints without provoking an excessive fatigue, WBV could be usefully employed in the initial stages of a weight loss program alone or in combination with more potent GH releasing stimuli, such as MVC.


Assuntos
Exercício Físico/fisiologia , Hormônio do Crescimento Humano/metabolismo , Contração Muscular/fisiologia , Músculo Esquelético/fisiologia , Obesidade/fisiopatologia , Adolescente , Índice de Massa Corporal , Humanos , Hidrocortisona/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Músculo Esquelético/citologia , Vibração
9.
J Neurovirol ; 24(5): 656-659, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29995288

RESUMO

A previously healthy 6-year-old boy was admitted to hospital with hypotonia and hyposthenia of lower limbs. Electromyography and slow motor nerve conduction velocity test identified a lower limb acute motor axonal neuropathy. Brain and spinal cord magnetic resonance imaging demonstrated multifocal cortical gray matter lesions in both cerebral hemispheres consistent with gray matter acute disseminated encephalitis otherwise with viral/Mycoplasma pneumoniae encephalitis, and signs of involvement of anterior nerve roots of the cauda equina consistent with Guillain-Barré syndrome. The patient resulted negative to routinely bacterial and viral investigations but positive to human parechovirus that sequence analyses confirmed as type 6. Intravenous immunoglobulins and methylprednisolone treatment were administered but did not relieve the symptoms of Guillain-Barré syndrome. The disease improved gradually over the next 3-month follow-up with a complete remission of both central and peripheral nervous system symptoms.


Assuntos
Síndrome de Guillain-Barré/virologia , Infecções por Picornaviridae/imunologia , Criança , Humanos , Masculino , Parechovirus
10.
Eur J Neurol ; 25(6): 833-840, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29489040

RESUMO

BACKGROUND AND PURPOSE: Ataxia-telangiectasia (A-T) is a rare neurodegenerative disease, due to A-T mutated (ATM) gene mutations, which typically presents with signs of progressive neurological dysfunction, cerebellar ataxia and uncoordinated movements. A-T severely affects patients' quality of life. Successful treatment options are still not available. The aim of this multicenter study, performed with a blind evaluation procedure, was to define the minimal effective dosage of oral betamethasone, thus preventing the occurrence of side effects. METHODS: Nine A-T patients were enrolled to receive betamethasone at increasing dosages of 0.001, 0.005 and 0.01 mg/kg/day. Neurological assessment and the evaluation of quality of life were performed through the Scale for the Assessment and Rating of Ataxia and the Italian version of the Childhood Health Assessment Questionnaire (CHAQ) at each time-point. The drug safety profile was evaluated. Patients were categorized as responders, partial responders and non-responders. RESULTS: Four of nine patients had a benefit at a dose of 0.005 mg/kg/day of oral betamethasone. Using the higher dosage, only one additional patient had a positive response. Conversely, a daily dose of 0.001 mg/kg was ineffective. A correlation between the serum adrenocorticotropic hormone levels and the clinical response was observed. Five of 30 CHAQ items improved in four patients. CONCLUSIONS: These data suggest that a short-term betamethasone oral treatment, at a daily dosage of 0.005 mg/kg, is effective in some patients. Pre-existing risk factors for side effects should be taken into account before therapy.


Assuntos
Ataxia Telangiectasia/tratamento farmacológico , Betametasona/administração & dosagem , Glucocorticoides/administração & dosagem , Adolescente , Betametasona/uso terapêutico , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Glucocorticoides/uso terapêutico , Humanos , Masculino , Fenótipo , Qualidade de Vida , Resultado do Tratamento , Adulto Jovem
11.
Ecology ; 98(11): 2979, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28857166

RESUMO

Our understanding of mammal ecology has always been hindered by the difficulties of observing species in closed tropical forests. Camera trapping has become a major advance for monitoring terrestrial mammals in biodiversity rich ecosystems. Here we compiled one of the largest datasets of inventories of terrestrial mammal communities for the Neotropical region based on camera trapping studies. The dataset comprises 170 surveys of medium to large terrestrial mammals using camera traps conducted in 144 areas by 74 studies, covering six vegetation types of tropical and subtropical Atlantic Forest of South America (Brazil and Argentina), and present data on species composition and richness. The complete dataset comprises 53,438 independent records of 83 species of mammals, includes 10 species of marsupials, 15 rodents, 20 carnivores, eight ungulates and six armadillos. Species richness averaged 13 species (±6.07 SD) per site. Only six species occurred in more than 50% of the sites: the domestic dog Canis familiaris, crab-eating fox Cerdocyon thous, tayra Eira barbara, south American coati Nasua nasua, crab-eating raccoon Procyon cancrivorus and the nine-banded armadillo Dasypus novemcinctus. The information contained in this dataset can be used to understand macroecological patterns of biodiversity, community, and population structure, but also to evaluate the ecological consequences of fragmentation, defaunation, and trophic interactions.


Assuntos
Biodiversidade , Florestas , Mamíferos/fisiologia , Animais , Argentina , Brasil , Cães , Ecossistema
12.
Eur J Vasc Endovasc Surg ; 53(6): 793-801, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28341530

RESUMO

OBJECTIVES: To analyse the results and review the literature about thoracic aortic endovascular repair (TEVAR) for type B acute aortic dissection (TBAAD) complicated by descending thoracic aortic aneurysm (DTA) in the hyperacute or acute phases. METHODS: This was a multicentre, observational descriptive study. Inclusion criteria were TBAAD with a DTA of ≥50 mm, TBAAD on an already known aneurysmal descending thoracic aorta, and TBAAD presenting with an enlarged aorta with a total diameter <50 mm, but with >50% diameter increase compared with a previous computed tomography angiography (CTA) showing a non-dissected aorta with normal sizing. Primary endpoints were early and long-term survival, freedom from TEVAR and aortic related mortality (ARM), and freedom from re-intervention. RESULTS: Twenty-two patients were included in the analysis. The mean aortic diameter was 66 ± 26 mm (range 42-130; IQR 51-64). The in hospital TEVAR related mortality was 14% (n = 3). The mean radiological follow-up was 56 ± 45 months (range 6-149; IQR 12-82), and the follow-up index 0.97 ± 0.1. All surviving patients were available for follow-up. During follow-up the cumulative mortality was 26% (n = 5) and TEVAR related mortality was 5% (n = 1). Overall the estimate of survival was 82% (95%CI: 61.5-93) at 1 year, and 64% at 5 years. Ongoing primary clinical success was 79% (re-intervention n = 4). Freedom from aortic related mortality was 86% (95%CI: 66-95) at 1 and 5 year, while freedom from re-intervention was 95% (95%CI: 75.5-95) at 1 year, and 77% (95%CI: 50-92) at 5 years. CONCLUSIONS: In our experience, DTA is a frequent complication from the very beginning of the clinical onset of TBAAD. In this high-risk cohort, TEVAR showed satisfactory results, better than those predicted by the risk score for open repair, with favourable stability of the aortic diameter and no aortic related adverse events during follow-up.


Assuntos
Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Implante de Prótese Vascular , Procedimentos Endovasculares , Doença Aguda , Idoso , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/mortalidade , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/mortalidade , Aortografia/métodos , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Angiografia por Tomografia Computadorizada , Intervalo Livre de Doença , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Itália , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
13.
J Endocrinol Invest ; 40(2): 217-226, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27639403

RESUMO

PURPOSE: To investigate the effects of a 3-week weight-management program entailing moderate energy restriction, nutritional education, psychological counseling and three different exercise training (a: low intensity, LI: 40 % V'O2max; b: high intensity, HI: 70 % V'O2max; c: high-intensity interval training, HIIT), on body composition, energy expenditure and fat oxidation rate in obese adolescents. METHODS: Thirty obese adolescents (age: 15-17 years, BMI: 37.5 kg m-2) participated in this study. Before starting (week 0, W0) and at the end of the weight-management program (week 3, W3), body composition was assessed by an impedancemeter; basal metabolic rate (BMR), energy expenditure and substrate oxidation rate were measured during exercise and post-exercise recovery by indirect calorimetry. RESULTS: At W3, body mass (BM) and fat mass (FM) decreased significantly in all groups, the decreases being significantly greater in the LI than in the HI and HIIT subgroups (BM: -8.4 ± 1.5 vs -6.3 ± 1.9 vs -4.9 ± 1.3 kg and FM: -4.2 ± 1.9 vs -2.8 ± 1.2 vs -2.3 ± 1.4 kg, p < 0.05, respectively). V'O2peak, expressed in relative values, changed significantly only in the HI and HIIT groups by 0.009 ± 0.005 and 0.007 ± 0.004 L kg FFM-1 min-1 (p < 0.05). Furthermore, the HI and HIIT subgroups exhibited a greater absolute rate of fat oxidation between 50 and 70 % V'O2peak at W3. No significant changes were observed at W3 in BMR, energy expenditure during exercise and post-exercise recovery. CONCLUSION: A 3-week weight-management program induced a greater decrease in BM and FM in the LI than in the HI and HIIT subgroups, and greater increase in V'O2peak and fat oxidation rate in the HI and HIIT than in the LI subgroup.


Assuntos
Tecido Adiposo/metabolismo , Metabolismo Energético , Exercício Físico , Treinamento Intervalado de Alta Intensidade/métodos , Metabolismo dos Lipídeos , Obesidade/fisiopatologia , Adolescente , Metabolismo Basal , Biomarcadores/análise , Composição Corporal , Feminino , Seguimentos , Humanos , Masculino , Oxirredução , Consumo de Oxigênio , Prognóstico
14.
Orthod Craniofac Res ; 19(1): 46-53, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26428540

RESUMO

OBJECTIVES: Literature is poor of data about the occlusion in children affected by neurofibromatosis type 1 (NF1). This case-control study investigated the occlusal traits in a group of children with NF1. SETTING AND SAMPLE POPULATION: A hundred and fifteen children with NF1 were enrolled; non-NF1 controls were sequentially selected among subjects referred to the Pediatric Dentistry Department. MATERIAL AND METHODS: All patients underwent a clinical dental examination and a panoramic radiography. The following orthodontic variables were considered: molar relationship, overjet, overbite, cross-bite, scissor bite, and crowding/spacing. RESULTS: Class III molar relationship resulted significantly (p = 0.01) more common in children with NF1 than in the control group as well as the unilateral posterior cross-bite (p = 0.0017). Forty-three children with NF1 (37.3%) showed radiographic abnormalities; in one case, a plexiform neurofibroma was detected. CONCLUSIONS: An early orthodontic evaluation might be planned in the management of children with NF1 to prevent or decrease the need for extensive orthodontic interventions.


Assuntos
Neurofibromatose 1 , Estudos de Casos e Controles , Criança , Humanos , Má Oclusão , Sobremordida
15.
Rev Med Suisse ; 11(475): 1122, 1124-6, 2015 May 20.
Artigo em Francês | MEDLINE | ID: mdl-26152087

RESUMO

Colorectal and gastric cancers are the fourth and third leading causes of cancer death world-wide. Unfortunately, gastric cancer is usually diagnosed at an advanced stage after becoming metastatic in distant sites, so that palliative therapy is the mainstay of treatment. Major progress in the understanding of the biology, the development of valid biomarkers and molecular targeted drugs have improved the treatment options and prognosis of both cancers significantly in the last years. Here, we review the current standards of care for patients with advanced and metastatic colorectal and gastric cancer and outline the perspectives for the future.


Assuntos
Adenocarcinoma/terapia , Neoplasias Colorretais/terapia , Neoplasias Gástricas/terapia , Terapias em Estudo/tendências , Adenocarcinoma/patologia , Neoplasias Colorretais/patologia , Progressão da Doença , Humanos , Comunicação Interdisciplinar , Metástase Neoplásica , Seleção de Pacientes , Neoplasias Gástricas/patologia
16.
J Physiol ; 593(18): 4181-99, 2015 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26096614

RESUMO

KEY POINTS: Loss-of-function mutations of the skeletal muscle ClC-1 channel cause myotonia congenita with variable phenotypes. Using patch clamp we show that F484L, located in the conducting pore, probably induces mild dominant myotonia by right-shifting the slow gating of ClC-1 channel, without exerting a dominant-negative effect on the wild-type (WT) subunit. Molecular dynamics simulations suggest that F484L affects the slow gate by increasing the frequency and the stability of H-bond formation between E232 in helix F and Y578 in helix R. Three other myotonic ClC-1 mutations are shown to produce distinct effects on channel function: L198P shifts the slow gate to positive potentials, V640G reduces channel activity, while L628P displays a WT-like behaviour (electrophysiology data only). Our results provide novel insight into the molecular mechanisms underlying normal and altered ClC-1 function. ABSTRACT: Myotonia congenita is an inherited disease caused by loss-of-function mutations of the skeletal muscle ClC-1 chloride channel, characterized by impaired muscle relaxation after contraction and stiffness. In the present study, we provided an in-depth characterization of F484L, a mutation previously identified in dominant myotonia, in order to define the genotype-phenotype correlation, and to elucidate the contribution of this pore residue to the mechanisms of ClC-1 gating. Patch-clamp recordings showed that F484L reduced chloride currents at every tested potential and dramatically right-shifted the voltage dependence of slow gating, thus contributing to the mild clinical phenotype of affected heterozygote carriers. Unlike dominant mutations located at the dimer interface, no dominant-negative effect was observed when F484L mutant subunits were co-expressed with wild type. Molecular dynamics simulations further revealed that F484L affected the slow gate by increasing the frequency and stability of the H-bond formation between the pore residue E232 and the R helix residue Y578. In addition, using patch-clamp electrophysiology, we characterized three other myotonic ClC-1 mutations. We proved that the dominant L198P mutation in the channel pore also right-shifted the voltage dependence of slow gating, recapitulating mild myotonia. The recessive V640G mutant drastically reduced channel function, which probably accounts for myotonia. In contrast, the recessive L628P mutant produced currents very similar to wild type, suggesting that the occurrence of the compound truncating mutation (Q812X) or other muscle-specific mechanisms accounted for the severe symptoms observed in this family. Our results provide novel insight into the molecular mechanisms underlying normal and altered ClC-1 function.


Assuntos
Canais de Cloreto/genética , Mutação/genética , Miotonia Congênita/genética , Adulto , Idoso , Criança , Feminino , Estudos de Associação Genética/métodos , Heterozigoto , Humanos , Ativação do Canal Iônico/genética , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Adulto Jovem
17.
Pharm Biol ; 53(2): 242-50, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25420516

RESUMO

CONTEXT: Psidium cattleianum Sabine (Myrtacea) is rich in vitamin C and phenolic compounds, including epicatechin and gallic acid as the main components. OBJECTIVE: To evaluate the antifungal and antioxidant capacity in vitro of the essential oil of araçá (EOA). The acute toxicity of the EOA also was evaluated in mice. MATERIALS AND METHODS: The leaves of the P. cattleianum were extracted by steam distillation. The antioxidant capacity was evaluated by in vitro tests [1,1-diphenyl-2-picryl-hydrazyl (DPPH), 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonate) (ABTS), ferric ion reducing antioxidant power (FRAP), linoleic acid oxidation, thiobarbituric acid reactive species (TBARS)], and ex vivo analysis [TBARS, δ-aminulevunilate dehydratase (δ-Ala-D) and catalase activity, non-protein thiols (NPSH), and ascorbic acid levels]. The toxicity was studied in mice by a single oral administration of EOA; and the antifungal activity was performed with five strains of fungi. RESULTS: The EOA exhibited antioxidant activity in the FRAP assay and reduced lipid peroxidation in the cortex (Imax = 32.90 ± 2.62%), hippocampus (IC50 = 48.00 ± 3.00 µg/ml and Imax = 32.90 ± 2.62%), and cerebellum (Imax = 45.40 ± 14.04%) of mice. Acute administration of the EOA by the oral route did not cause toxicological effects in mice (LD50 > 500 µg/ml). The EOA also showed antifungal activity through of the determination minimum inhibitory concentration (MIC) values ranging from 41.67 ± 18.04 to 166.70 ± 72.17 µg/ml for tested strains. CONCLUSION: The results of present study indicate that EOA possess antioxidant properties, antifungal and not cause toxicity at tested doses.


Assuntos
Antifúngicos/farmacologia , Antioxidantes/farmacologia , Óleos Voláteis/isolamento & purificação , Psidium/química , Animais , Antifúngicos/química , Antifúngicos/isolamento & purificação , Antifúngicos/toxicidade , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/toxicidade , Compostos de Bifenilo/química , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Candida/efeitos dos fármacos , Relação Dose-Resposta a Droga , Radicais Livres/química , Rim/efeitos dos fármacos , Rim/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Óleos Voláteis/toxicidade , Picratos/química , Folhas de Planta/química , Testes de Toxicidade Aguda , Trichosporon/efeitos dos fármacos
18.
J Med Food ; 13(2): 336-42, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20170358

RESUMO

The aim of this study was to carry out pharmacological screening in order to evaluate the potential effects of lyophilized fruits of different cultivars of Vaccinium ashei Reade (Family Ericaceae) berries, commonly known as rabbiteye blueberries, on nociception. This was achieved using the formalin, hot plate, tail-flick, and writhing tests in mice. During this experiment the mice consumed approximately 3.2-6.4 mg/kg/day (p.o.) of the anthocyanins. The extract was administered for 21 days or 60 minutes before test. Morphine and diclofenac (10 mg/kg, p.o.) as the standard drug (positive control) and water (via oral gavage) as the negative control were administered before all tests. The blueberry extract produced a significant decrease in constrictions induced by acetic acid and caused graded inhibition of the second phase of formalin-induced pain. Moreover, in both the hot plate and tail-flick tests, it significantly increased the threshold. These data suggest that the extract from V. ashei produced antinociceptive effects, as demonstrated in the experimental models of nociception in mice. Additional experiments are necessary in order to clarify the true target for the antinociceptive effects of rabbiteye blueberry extract.


Assuntos
Analgésicos/uso terapêutico , Antocianinas/uso terapêutico , Mirtilos Azuis (Planta)/química , Dor/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Ácido Acético , Analgésicos/farmacologia , Animais , Antocianinas/farmacologia , Diclofenaco/farmacologia , Diclofenaco/uso terapêutico , Modelos Animais de Doenças , Formaldeído , Frutas , Temperatura Alta , Masculino , Camundongos , Morfina/farmacologia , Morfina/uso terapêutico , Contração Muscular , Dor/etiologia , Limiar da Dor/efeitos dos fármacos , Extratos Vegetais/farmacologia
19.
Pediatr Med Chir ; 29(4): 206-11, 2007.
Artigo em Italiano | MEDLINE | ID: mdl-17715604

RESUMO

The Authors present the CT and MR findings in three patients with Krabbe disease: early infantile, late infantile and juvenile. Three children, 5 and 9 months old respectively with Krabbe disease, were studied with CT and MR. the children presented with spasticity and signs of peripheral neuropathy, blindness and no interaction with the environment. In all patient CT revealed nonenhancing discrete dense lesions, simmetrically distribuited in the posterior limb of the internal capsule and posterior thalami and focal hypodensities of the midcerebellar peduncles and dentate nuclei, with mild cerebral atrophy. In one patients CT demonstrated bilateral calcifications of paraventricular white matter. Mr, in all, showed a generalized increase in T2 values of the periventricular white matter. The thalami and adjacents regions had markedly shortened T1 and slightly shortenede T2. The cerebellum and the brainstem appeared mottled with scattered areas of increased T2. MR confirmed the cerebral atrophy. In conclusion CT and MR findings in Krabbe disease (early infantile and late infantile) are usually not specific. However when they are both performed at the onset of neurological symptoms they can alert clinicians to the possibility of Krabbe disease.


Assuntos
Leucodistrofia de Células Globoides/diagnóstico , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Fatores Etários , Humanos , Lactente
20.
Neuropediatrics ; 34(3): 165-7, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12910443

RESUMO

Ataxia-telangiectasia, a genetic disease caused by the homozygous mutation of the ATM gene, is frequently associated to a deficit of humoral and cellular immune functions. A decreased thymic output and skewed T cell and B cell receptor repertoires have been recently described in children over 7 years of age and in adults with this disease and have been proposed as a possible explanation for the immunodeficiency. To understand whether T cell defects arise early in life as a consequence of ATM gene mutations, we analysed the extent of thymic function by measuring the number of naïve T cells and by studying the heterogeneity of T cells by means of heteroduplex analysis, in two children less than 2 years old with a remarkable reduction of T cell count. We found that the thymic output is decreased in babies with ataxia-telangiectasia if compared with that observed in age-matched normal babies. The low production of new T cells is associated to a reduction of the diversity of alpha/beta, but not gamma/delta, T lymphocytes. Our data indicate that ATM mutation limits the generation of a wide alpha/beta T cell repertoire and this feature can be responsible for the immunodeficiency observed in ataxia-telangiectasia babies.


Assuntos
Ataxia Telangiectasia/genética , Ataxia Telangiectasia/fisiopatologia , Rearranjo Gênico da Cadeia alfa dos Receptores de Antígenos dos Linfócitos T/genética , Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T/genética , Rearranjo Gênico da Cadeia delta dos Receptores de Antígenos dos Linfócitos T/genética , Rearranjo Gênico da Cadeia gama dos Receptores de Antígenos dos Linfócitos T/genética , Heterogeneidade Genética , Timo/imunologia , Timo/fisiopatologia , Adolescente , Adulto , Ataxia Telangiectasia/imunologia , Rearranjo Gênico da Cadeia alfa dos Receptores de Antígenos dos Linfócitos T/imunologia , Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T/imunologia , Rearranjo Gênico da Cadeia delta dos Receptores de Antígenos dos Linfócitos T/imunologia , Rearranjo Gênico da Cadeia gama dos Receptores de Antígenos dos Linfócitos T/imunologia , Humanos , Lactente , Mutação Puntual/genética , Reação em Cadeia da Polimerase
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