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1.
Nat Commun ; 11(1): 4904, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32994391

RESUMO

Mammalian frugivores are critical seed dispersers, but many are under threat of extinction. Futhermore, the impact of past and future defaunation on plant assemblages has yet to be quantified at the global scale. Here, we integrate palm and mammalian frugivore trait and occurrence data and reveal a global positive relationship between fruit size and frugivore body size. Global variation in fruit size is better explained by present-day frugivore assemblages than by Late Pleistocene assemblages, suggesting ecological and evolutionary reorganization after end-Pleistocene extinctions, except in the Neotropics, where some large-fruited palm species may have outlived their main seed dispersers by thousands of years. Our simulations of frugivore extinction over the next 100 years suggest that the impact of defaunation will be highest in the Old World tropics, and an up to 4% assemblage-level decrease in fruit size would be required to maintain the global body size-fruit size relationship. Overall, our results suggest that while some palm species may be able to keep pace with future defaunation through evolutionary changes in fruit size, large-fruited species may be especially vulnerable to continued defaunation.


Assuntos
Arecaceae/fisiologia , Coevolução Biológica , Conservação dos Recursos Naturais , Frutas/anatomia & histologia , Mamíferos/fisiologia , Animais , Arecaceae/anatomia & histologia , Tamanho Corporal/genética , Conjuntos de Dados como Assunto , Extinção Biológica , Frutas/genética , Herbivoria/fisiologia , Mamíferos/anatomia & histologia , Tamanho do Órgão/genética , Locos de Características Quantitativas , Dispersão de Sementes/fisiologia
2.
Korean J Parasitol ; 58(4): 461-466, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32871641

RESUMO

Toxoplasma gondii is an obligate intracellular protozoan parasite that can invade various organs in the host body, including the central nervous system. Chronic intracranial T. gondii is known to be associated with neuroprotection against neurodegenerative diseases through interaction with host brain cells in various ways. The present study investigated the neuroprotective effects of chronic T. gondii infection in mice with cerebral ischemia experimentally produced by middle cerebral artery occlusion (MCAO) surgery. The neurobehavioral effects of cerebral ischemia were assessed by measurement of Garcia score and Rotarod behavior tests. The volume of brain ischemia was measured by triphenyltetrazolium chloride staining. The expression levels of related genes and proteins were determined. After cerebral ischemia, corrected infarction volume was significantly reduced in T. gondii infected mice, and their neurobehavioral function was significantly better than that of the uninfection control group. Chronic T. gondii infection induced the expression of hypoxia-inducible factor 1-alpha (HIF-1α) in the brain before MCAO. T. gondii infection also increased the expression of vascular endothelial growth factor after the cerebral ischemia. It is suggested that chronic intracerebral infection of T. gondii may be a potential preconditioning strategy to reduce neural deficits associated with cerebral ischemia and induce brain ischemic tolerance through the regulation of HIF-1α expression.


Assuntos
Isquemia Encefálica/prevenção & controle , Encéfalo/parasitologia , Interações Hospedeiro-Parasita , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neuroproteção , Toxoplasma/fisiologia , Toxoplasmose/fisiopatologia , Animais , Encéfalo/citologia , Encéfalo/metabolismo , Encéfalo/patologia , Isquemia Encefálica/parasitologia , Isquemia Encefálica/patologia , Modelos Animais de Doenças , Expressão Gênica , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Camundongos Endogâmicos ICR , Tamanho do Órgão , Toxoplasmose/metabolismo , Toxoplasmose/patologia
3.
Ecotoxicol Environ Saf ; 203: 110974, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888622

RESUMO

Ammonia (NH3), an environmental pollutant, poses a serious threat to human and avian health. Although previous studies have showed that NH3 caused kidney injury, the molecular mechanisms of nephrotoxicity induced by NH3 remain unclear. To explore the mechanisms of NH3 nephrotoxicity, a total of 36 broiler chicks at one day of age were exposed to NH3. After 42 days of exposure, blood samples were collected to determine creatinine and uric acid; and kidney samples were weighted and then collected to detect ultrastructural changes, oxidative stress parameters, ATPases, necroptosis- and mitochondrial dynamics-related genes. The results showed that chickens exposed to NH3 showed lower relative kidney weight and an increase concentration in serum creatinine and uric acid. NH3 exposure caused nephrocyte necrosis and increased the expression of necroptosis-related genes (TNF-α, RIPK1, RIPK3, MLKL, and JNK). Besides, the activities of antioxidant systems (SOD, CAT, GSH-Px, and T-AOC) were reduced, whereas the concentrations of H2O2 and MDA were elevated. Lower activities of ATPases were obtained in NH3 treatment groups. Furthermore, the mitochondrial fission-related genes drp1 and mff were activated, and mitochondrial fusion-related genes opa1, mfn1 and mfn2 were suppressed after NH3 exposure. Based on the above results, we conclude that NH3 caused-oxidative stress and mitochondrial dysfunction mediated nephrocyte necroptosis in chickens. This study may provide new insight into NH3 nephrotoxicity.


Assuntos
Amônia/toxicidade , Poluentes Ambientais/toxicidade , Rim/efeitos dos fármacos , Dinâmica Mitocondrial/efeitos dos fármacos , Necroptose/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Galinhas , Expressão Gênica/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/metabolismo , Rim/ultraestrutura , Testes de Função Renal , Dinâmica Mitocondrial/genética , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/genética
4.
Niger J Clin Pract ; 23(9): 1243-1247, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32913163

RESUMO

Aim: This study aimed to determine the effects of strabismus surgery on choroidal thickness in paediatric patients with Spectral Domain-Optical Coherence Tomography (SD-OCT). Material and Methods: Sixty eyes of 60 children with esotropia were included. The mean age was 9.5 ± 3.1 years. The choroidal thickness was measured using SD-OCT, which was performed before the surgery and 1 week, 1 month and 3 months postoperatively. At the same time, the patients' visual acuity was evaluated. Results: There were no statistically significant differences between the preoperative and postoperative values in terms of the visual acuity (P > 0.05). When compared to the preoperative values, decreases were found in the choroidal thicknesses in all of the areas measured during the first week evaluation (P < 0.05). In the postoperative first month, significant decreases were also found in the choroidal thicknesses in all the areas measured (P < 0.05); however, in the postoperative third month, there were no changes in any of the areas (P > 0.05). Conclusions: We observed that there was a significant decrease in the choroidal thickness during the early postoperative period and no significant change in the late postoperative period in paediatric patients of double horizontal muscle surgery. Moreover, these early changes in the choroid in paediatric patients show that it does not cause a functional loss.


Assuntos
Corioide/diagnóstico por imagem , Corioide/patologia , Músculos Oculomotores/cirurgia , Procedimentos Cirúrgicos Oftalmológicos/efeitos adversos , Estrabismo/cirurgia , Tomografia de Coerência Óptica/instrumentação , Adolescente , Criança , Corioide/anatomia & histologia , Feminino , Humanos , Masculino , Tamanho do Órgão , Período Pós-Operatório , Tomografia de Coerência Óptica/métodos , Resultado do Tratamento , Acuidade Visual/fisiologia
5.
PLoS One ; 15(8): e0236641, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32776986

RESUMO

Alcohol Use Disorder (AUD) has been associated with abnormalities in hippocampal volumes, but these relationships have not been fully explored with respect to sub-regional volumes, nor in association with individual characteristics such as age, gender differences, drinking history, and memory. The present study examined the impact of those variables in relation to hippocampal subfield volumes in abstinent men and women with a history of AUD. Using Magnetic Resonance Imaging at 3 Tesla, we obtained brain images from 67 participants with AUD (31 women) and 64 nonalcoholic control (NC) participants (31 women). The average duration of the most recent period of sobriety for AUD participants was 7.1 years. We used Freesurfer 6.0 to segment the hippocampus into 12 regions. These were imputed into statistical models to examine the relationships of brain volume with AUD group, age, gender, memory, and drinking history. Interactions with gender and age were of particular interest. Compared to the NC group, the AUD group had approximately 5% smaller subiculum, CA1, molecular layer, and hippocampal tail regions. Age was negatively associated with volumes for the AUD group in the subiculum and the hippocampal tail, but no significant interactions with gender were identified. The relationships for delayed and immediate memory with hippocampal tail volume differed for AUD and NC groups: Higher scores on tests of immediate and delayed memory were associated with smaller volumes in the AUD group, but larger volumes in the NC group. Length of sobriety was associated with decreasing CA1 volume in women (0.19% per year) and increasing volume size in men (0.38% per year). The course of abstinence on CA1 volume differed for men and women, and the differential relationships of subfield volumes to age and memory could indicate a distinction in the impact of AUD on functions of the hippocampal tail. These findings confirm and extend evidence that AUD, age, gender, memory, and abstinence differentially impact volumes of component parts of the hippocampus.


Assuntos
Abstinência de Álcool , Alcoolismo/patologia , Hipocampo/patologia , Adulto , Idoso , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Memória , Pessoa de Meia-Idade , Tamanho do Órgão
6.
PLoS Biol ; 18(8): e3000764, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32780733

RESUMO

Tissue vibrations in the larynx produce most sounds that comprise vocal communication in mammals. Larynx morphology is thus predicted to be a key target for selection, particularly in species with highly developed vocal communication systems. Here, we present a novel database of digitally modeled scanned larynges from 55 different mammalian species, representing a wide range of body sizes in the primate and carnivoran orders. Using phylogenetic comparative methods, we demonstrate that the primate larynx has evolved more rapidly than the carnivoran larynx, resulting in a pattern of larger size and increased deviation from expected allometry with body size. These results imply fundamental differences between primates and carnivorans in the balance of selective forces that constrain larynx size and highlight an evolutionary flexibility in primates that may help explain why we have developed complex and diverse uses of the vocal organ for communication.


Assuntos
Canidae/fisiologia , Felidae/fisiologia , Herpestidae/fisiologia , Laringe/fisiologia , Primatas/fisiologia , Vocalização Animal/fisiologia , Animais , Evolução Biológica , Tamanho Corporal , Canidae/anatomia & histologia , Canidae/classificação , Felidae/anatomia & histologia , Felidae/classificação , Feminino , Herpestidae/anatomia & histologia , Herpestidae/classificação , Laringe/anatomia & histologia , Masculino , Mamíferos , Tamanho do Órgão , Filogenia , Primatas/anatomia & histologia , Primatas/classificação , Caracteres Sexuais , Fatores Sexuais , Som
7.
Yakugaku Zasshi ; 140(8): 1051-1061, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32741863

RESUMO

It has been reported that medium-chain triglyceride (MCT) have various physiological functions, such as anti-obesity and hypolipidemic effects. They can also elicit increased disaccharidase activity and intestinal cell proliferation. However, a meta-analysis of randomized controlled trials, comparing the effects of MCT on weight loss and body composition, detected commercial bias. Additional research on the physiological functions is needed in order to have conclusive evidence. Thus, we sought to evaluate the various functions of MCT by conducting a feeding study in rats. Rats fed a diet containing 15% (w/w) MCT, had significantly lower visceral fat weight, plasma and liver lipid concentrations; they had significantly higher intestinal maltase and glucoamylase activities; and they had a greater number of Ki-67 positive cells/crypt, compared to the rats fed a diet containing 15% (w/w) lard. The effects of a diet containing 5% (w/w) MCT was observed only for plasma cholesterol levels and the number of Ki-67 positive cells/crypt; in which some results were found to be inconsistent with previous reports. These results indicate that physiological functions of MCT are numerous and need to be confirmed by additional research.


Assuntos
Glucana 1,4-alfa-Glucosidase/metabolismo , Intestino Delgado/enzimologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Triglicerídeos/administração & dosagem , Triglicerídeos/farmacologia , alfa-Glucosidases/metabolismo , Animais , Fármacos Antiobesidade , Proliferação de Células/efeitos dos fármacos , Dieta , Hipolipemiantes , Intestino Delgado/citologia , Gordura Intra-Abdominal , Antígeno Ki-67/metabolismo , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos Sprague-Dawley , Triglicerídeos/química
8.
Life Sci ; 258: 118195, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32781073

RESUMO

AIMS: The estrogen-ERα axis participates in osteoblast maturation. This study was designed to further evaluated the roles of the estrogen-ERα axis in bone healing and the possible mechanisms. MAIN METHODS: Female ICR mice were created a metaphyseal bone defect in the left femurs and administered with methylpiperidinopyrazole (MPP), an inhibitor of ERα. Bone healing was evaluated using micro-computed tomography. Colocalization of ERα with alkaline phosphatase (ALP) and ERα translocation to mitochondria were determined. Levels of ERα, ERß, PECAM-1, VEGF, and ß-actin were immunodetected. Expression of chromosomal Runx2, ALP, and osteocalcin mRNAs and mitochondrial cytochrome c oxidase (COX) I and COXII mRNAs were quantified. Angiogenesis was measured with immunohistochemistry. KEY FINDINGS: Following surgery, the bone mass was time-dependently augmented in the bone-defect area. Simultaneously, levels of ERα were specifically upregulated and positively correlated with bone healing. Administration of MPP to mice consistently decreased levels of ERα and bone healing. As to the mechanisms, osteogenesis was enhanced in bone healing, but MPP attenuated osteoblast maturation. In parallel, expressions of osteogenesis-related ALP, Runx2, and osteocalcin mRNAs were induced in the injured zone. Treatment with MPP led to significant inhibition of the alp, runx2, and osteocalcin gene expressions. Remarkably, administration of MPP lessened translocation of ERα to mitochondria and expressions of mitochondrial energy production-related coxI and coxII genes. Furthermore, exposure to MPP decreased levels of PECAM-1 and VEGF in the bone-defect area. SIGNIFICANCE: The present study showed the contributions of the estrogen-ERα axis to bone healing through stimulation of energy production, osteoblast maturation, and angiogenesis.


Assuntos
Regeneração Óssea , Diferenciação Celular , Metabolismo Energético , Receptor alfa de Estrogênio/metabolismo , Neovascularização Fisiológica , Osteoblastos/citologia , Transdução de Sinais , Fosfatase Alcalina/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Regeneração Óssea/efeitos dos fármacos , Calo Ósseo/efeitos dos fármacos , Calo Ósseo/patologia , Diferenciação Celular/efeitos dos fármacos , Cromossomos de Mamíferos/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Metabolismo Energético/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Camundongos Endogâmicos ICR , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteocalcina/metabolismo , Osteogênese/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Pirazóis/administração & dosagem , Pirazóis/farmacologia , Regulação para Cima/efeitos dos fármacos , Cicatrização/efeitos dos fármacos
9.
PLoS One ; 15(8): e0235609, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32776940

RESUMO

Soccer is the most popular sport in the world and, since it is a contact sport, players are at risk for head injury, including concussion. Here, we proposed to investigate the association of heading and concussion with macroscopic brain structure among adult amateur soccer players. For this study, 375 amateur soccer players (median age 23 years) completed HeadCount-12m to estimate heading over the 12 months prior to MRI and lifetime concussion. T1-weighted 3D magnetization prepared rapid acquisition gradient echo (MP-RAGE) MRI was performed at 3 Tesla. Parcellation was performed using Freesurfer to extract regional gray and white matter volumes as well as regional cortical thickness and total intracranial volume. Regional cortical brain volumes were normalized by total intracranial volume. We categorized heading into quartiles and concussion as 0, 1 or 2 or more. Generalized linear regressions were used to test the association of heading or concussion with each brain morphometry metric, including age and sex, as covariates. Neither heading nor concussion were associated with reduced brain volume or cortical thickness. We observed that greater heading was associated with greater gray matter volume in the left inferior parietal area, which may reflect effects related to training.


Assuntos
Traumatismos em Atletas/diagnóstico por imagem , Concussão Encefálica/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Futebol , Adulto , Encéfalo/anatomia & histologia , Concussão Encefálica/etiologia , Córtex Cerebral/anatomia & histologia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Tamanho do Órgão
10.
Nat Commun ; 11(1): 4016, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32782260

RESUMO

Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson's disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders.


Assuntos
Encefalopatias/genética , Encefalopatias/patologia , Tronco Encefálico/anatomia & histologia , Encefalopatias/diagnóstico por imagem , Encefalopatias/metabolismo , Tronco Encefálico/diagnóstico por imagem , Tronco Encefálico/metabolismo , Tronco Encefálico/patologia , Homologia de Genes , Loci Gênicos , Estudo de Associação Genômica Ampla , Humanos , Imagem por Ressonância Magnética , Herança Multifatorial , Tamanho do Órgão/genética
11.
Int J Nanomedicine ; 15: 4763-4778, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32753865

RESUMO

Introduction: Methotrexate exhibits poor cutaneous bioavailability and systemic side effects on topical administration, so there is an unmet need for a novel carrier and its optimized therapy. Methotrexate-loaded nanostructured lipid carriers (MTXNLCs) were formulated and characterized to determine in vitro drug release and evaluate the role of MTXNLC gel in the topical treatment of psoriasis. Methods: A solvent diffusion technique was employed to prepare MTXNLCs, which was optimized using 32 full factorial designs. The mean diameter and surface morphology of MTXNLCs was evaluated. The crystallinity of lyophilized MTXNLCs was characterized by differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD). MTXNLCs were integrated in 1% w/w Carbopol 934 P gel base, and in vitro skin deposition studies in human cadaver skin (HCS) were carried out. Results: The optimized MTXNLCs were rod-shaped, with an average particle size of 253 ± 8.65 nm, a zeta potential of -26.4±0.86 mV, and EE of 54.00±1.49%. DSC and XRD data confirmed the formation of NLCs. Significantly higher deposition of MTX was found in HCS from MTXNLC gel (71.52 ±1.13%) as compared to MTX plain gel (38.48±0.96%). In vivo studies demonstrated significant improvement in therapeutic response and reduction in local side effects with MTXNLCs-loaded gel in the topical treatment of psoriasis. Anti-psoriatic efficacy of MTXNLCs 100 ug/cm2 compared with plain MTX gel was evaluated using imiquimod (IMQ)-induced psoriasis in BALB/c mice. The topical application of MTXNLCs to the mouse ear resulted in a significant reduction of psoriatic area and severity index, oxidative stress, inflammatory cytokines like TNF-α, IL-1ß, and IL-6 and IMQ-induced histopathological alterations in mouse ear samples. Conclusion: Developed formulation of MTXNLC gel demonstrated better anti-psoriatic activity and also displayed prolonged and sustained release effect, which shows that it can be a promising alternative to existing MTX formulation for the treatment of psoriasis.


Assuntos
Composição de Medicamentos , Géis/química , Imiquimode/uso terapêutico , Inflamação/tratamento farmacológico , Lipídeos/química , Metotrexato/uso terapêutico , Nanoestruturas/química , Psoríase/tratamento farmacológico , Administração Cutânea , Administração Tópica , Animais , Catalase/metabolismo , Citocinas/metabolismo , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Glutationa/metabolismo , Humanos , Inflamação/patologia , Malondialdeído/metabolismo , Camundongos Endogâmicos BALB C , Nanoestruturas/ultraestrutura , Tamanho do Órgão , Superóxido Dismutase/metabolismo
12.
Nat Commun ; 11(1): 4040, 2020 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-32788583

RESUMO

Children from lower income backgrounds tend to have poorer memory and language abilities than their wealthier peers. It has been proposed that these cognitive gaps reflect the effects of income-related stress on hippocampal structure, but the empirical evidence for this relationship has not been clear. Here, we examine how family income gaps in cognition relate to the anterior hippocampus, given its high sensitivity to stress, versus the posterior hippocampus. We find that anterior (but not posterior) hippocampal volumes positively correlate with family income up to an annual income of ~$75,000. Income-related differences in the anterior (but not posterior) hippocampus also predicted the strength of the gaps in memory and language. These findings add anatomical specificity to current theories by suggesting a stronger relationship between family income and anterior than posterior hippocampal volumes and offer a potential mechanism through which children from different income homes differ cognitively.


Assuntos
Cognição/fisiologia , Hipocampo/anatomia & histologia , Renda , Adolescente , Criança , Pré-Escolar , Família , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Modelos Lineares , Masculino , Memória/fisiologia , Grupos Minoritários , Tamanho do Órgão , Análise e Desempenho de Tarefas , Vocabulário , Adulto Jovem
13.
J Environ Pathol Toxicol Oncol ; 39(2): 137-147, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32749123

RESUMO

Lung carcinogenesis is one of the main sources of cancer-related mortality globally and it is estimated that nearly 1 million people die from it every year. The 5-year survival rate of lung carcinogenesis is reported at just 15%. The aim of the current research was to investigate the immunomodulatory effect of eriocitrin against benzo(a)pyrene [B(a) P]-induced lung tumorigenesis in Swiss albino mice. The lung sarcoma was provoked through oral gavage of B(a)P (50 mg/kg body weight) two times/week for four weeks. CEA, lung weight, lipid peroxidation (LPO), body weight, immuno-globulin (IgG, IgA, and IgM), tumor incidence, serum marker enzymes (LDH, AHH, λ-GT, and 5'-NTs), hematological counts (leucocytes, lymphocytes, neutrophils, absolute numbers of lymphocytes and neutrophils), antioxidants (SOD and CAT), inflammatory modulators (IL-1ß, IL-6, and TNF-α), immune complexes (avidity index, phagocyte index, NBT reduction, and SIC) and histopathological changes were analyzed. Moreover, the status of apoptosis proteins (Bax, caspase-9, and caspase-3) and cell proliferative protein (cyclin D1 and cyclin A) expression was determined by Western blot and PCNA by immunohistochemical analysis. B(a)P-challenged cancer-bearing mice exhibited augmented levels of lipid peroxidation, tumor incidence, lung weight, CEA, serum marker enzymes, IgA, SIC, cell proliferative markers, and inflammatory cytokines with concurrent decrease in body weight, antioxidant levels, hematological counts, immunoglobulins, immune complexes, and apoptotic protein expression. The eriocitrin treatments caused significant reversion of all these marker to previous levels. Overall, the results propose the immunomodulatory prospective of eriocitrin against B(a) P-induced lung carcinogenesis on Swiss albino mice.


Assuntos
Flavanonas/farmacologia , Fatores Imunológicos/farmacologia , Neoplasias Pulmonares/prevenção & controle , Animais , Anticarcinógenos/farmacologia , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Benzo(a)pireno/toxicidade , Peso Corporal/efeitos dos fármacos , Citocinas/metabolismo , Imunoglobulinas/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos C57BL , Tamanho do Órgão/efeitos dos fármacos , Fagócitos/efeitos dos fármacos
14.
J Comput Assist Tomogr ; 44(4): 533-539, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32697523

RESUMO

PURPOSE: The purpose of this study was to investigate the differences of gray matter volume (GMV) alteration patterns between hemodialysis with restless legs syndrome (HD-RLS) and hemodialysis without restless legs syndrome (HD-nRLS) patients using voxel-based morphometry. METHODS: Twenty-three HD-RLS patients, 27 HD-nRLS patients, and 27 age-, sex-, and education-matched healthy controls were included in this study. One-way analysis of covariance and post hoc analyses were used to assess differences in GMV, demographics, and clinical data among the 3 groups. Pearson correlation analysis was conducted between altered GMV in the HD-RLS group and clinical data. RESULTS: Compared with HD-nRLS patients, HD-RLS patients showed decreased GMV in the left primary motor cortex (false discovery rate corrected, P < 0.05). Compared with the healthy controls, both HD subgroups (ie, those with and without RLS) exhibited consistent GMV changes, including decreased GMV in the bilateral anterior cingulate and paracingulate gyrus and left middle temporal gyrus (false discovery rate corrected, P < 0.05). The GMV values in the left precentral gyrus were negatively correlated with the RLS rating scores (r = 0.2138, P = 0.0263). CONCLUSIONS: This abnormal decreased GMV in the sensorimotor cortex provides evidence for a sensory processing disorder in RLS that may be involved in the pathogenesis of RLS in HD patients.


Assuntos
Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Diálise Renal/efeitos adversos , Síndrome das Pernas Inquietas/diagnóstico por imagem , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Motor/diagnóstico por imagem , Córtex Motor/patologia , Tamanho do Órgão , Síndrome das Pernas Inquietas/complicações
15.
PLoS One ; 15(7): e0235621, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32678824

RESUMO

PURPOSE: This observational case series was to determine long term optic disc changes in eyes with large cup to disc ratio (CDR) and compare the changes induced by myopic shift during childhood with normal control eyes. METHODS: Children under 15 years of age who developed myopia with serial optic disc photographs and spectral domain (SD)-optical coherence tomography (OCT) images with a minimal interval of three years were evaluated. Children with average CDR ≥ 0.6 on SD-OCT were classified as having large CDR. The ratios of vertical disc diameter (VDD), horizontal disc diameter (HDD), and maximum peripapillary atrophy (PPA) width (PPW) were measured to quantify morphologic changes of optic discs and SD-OCT parameters, such as peripapillary retinal nerve fiber layer (RNFL) thickness and macular ganglion cell and inner plexiform layer (GCIPL) thickness were measured. RESULTS: Of the 82 eyes (82 patients) analyzed, 42 eyes had large CDR and 40 eyes were normal controls. The mean age and refractive error at initial examination were not different between groups (P = 0.33, P = 0.76, respectively). The changes in HDD/VDD and PPW/VDD ratios during follow-up showed no significant difference among the groups (P = 0.45, P = 0.62, respectively). No statistical significance was found in changes in RNFL and GCIPL thickness between the two groups (P = 0.74, P = 0.79, respectively). CONCLUSIONS: Children with enlarged CDR showed changes in optic disc morphology and RNFL/GCIPL thickness similar to normal children during myopic shift.


Assuntos
Miopia/diagnóstico por imagem , Miopia/patologia , Disco Óptico/diagnóstico por imagem , Disco Óptico/patologia , Tomografia de Coerência Óptica , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Tamanho do Órgão , Fatores de Tempo
16.
Toxicol Lett ; 332: 222-234, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32679240

RESUMO

The relative toxicity of three legacy and six emerging brominated flame retardants* was studied in the male Harlan Sprague Dawley rat. The hepatocellular and thyroid toxicity of each flame retardant was evaluated following five-day exposure to each of the nine flame retardants (oral gavage in corn oil) at 0.1-1000 µmol/kg body weight per day. Histopathology and transcriptomic analysis were performed on the left liver lobe. Centrilobular hypertrophy of hepatocytes and increases in liver weight were seen following exposure to two legacy (PBDE-47, HBCD) and to one emerging flame retardant (HCDBCO). Total thyroxine (TT4) concentrations were reduced to the greatest extent after PBDE-47 exposure. The PBDE-47, decaBDE, and HBCD liver transcriptomes were characterized by upregulation of liver disease-related and/or metabolic transcripts. Fewer liver disease or metabolic transcript changes were detected for the other flame retardants studied (TBB, TBPH, TBBPA-DBPE, BTBPE, DBDPE, or HCDBCO). PBDE-47 exhibited the most disruption of hepatocellular toxic endpoints, with the Nrf2 antioxidant pathway transcripts upregulated to the greatest extent, although some activation of this pathway also occurred after decaBDE, HBCD, TBB, and HCBCO exposure. These studies provide information that can be used for prioritizing the need for more in-depth brominated flame retardant toxicity studies.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/patologia , Retardadores de Chama/toxicidade , Hidrocarbonetos Bromados/toxicidade , Fígado/metabolismo , Transcriptoma/efeitos dos fármacos , Animais , Tamanho Celular/efeitos dos fármacos , Monitoramento Ambiental , Hepatócitos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Doenças da Glândula Tireoide/induzido quimicamente , Doenças da Glândula Tireoide/patologia , Tiroxina/metabolismo , Toxicogenética
17.
J Environ Sci Health B ; 55(9): 803-812, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32602772

RESUMO

Organophosphorus pesticides induce gender-specific developmental neurotoxicity after birth, especially in adolescents and adults. However, whether and when the selectivity occurs in fetus remains unclear. In this study, we analyzed chlorpyrifos (CPF)-induced neurotoxicity in the early fetal brains of male and female mice. The gestational dams were administered 0, 1, 3, and 5 mg/(kg.d) CPF during gestational days (GD)7-11, and brains from the fetuses were isolated and analyzed on GD12. Fetal gender was identified by PCR technique based on male-specific Sry gene and Myog control gene. The body weight and head weight, the activity of acetylcholinesterase (AChE), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and the content of malondialdehyde (MDA), as well as the oxidative stress-related gene expression were examined. Our results showed that CPF pretreatment induced AChE inhibition in GD12 fetal brain. CPF treatment activated SOD and GPX but not CAT and MDA. For oxidative stress-related gene expression, CPF pretreatment increased mRNA expression of Sod1, Cat, Gpx1, and Gpx2 in the fetal brain on GD12. The statistical analysis did not show gender-selective CPF-induced toxicity. Moreover, our results showed that although the gestational exposure to CPF could elicit abnormalities in the early fetal brain, the toxicity observed was not gender-specific.


Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/embriologia , Clorpirifos/toxicidade , Inseticidas/toxicidade , Acetilcolinesterase/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Encéfalo/metabolismo , Catalase/genética , Catalase/metabolismo , Inibidores da Colinesterase/toxicidade , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Camundongos Endogâmicos ICR , Síndromes Neurotóxicas/etiologia , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Fatores Sexuais , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Testes de Toxicidade/métodos
18.
Chem Biol Interact ; 328: 109197, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32710900

RESUMO

The present study was undertaken to assess the effect of imatinib mesylate; a tyrosine kinase inhibitor and a well-known anticancer with numerous medical benefits on blood sugar levels, insulin, and glucagon secretion in an experimental model of STZ-induced diabetes mellitus. Type 1 diabetes mellitus (T1DM) was induced by a single I.P. injection of Streptozotocin (STZ) (50 mg/kg) in male Sprague-Dawley rats. Daily oral imatinib (10 mg/kg) and (20 mg/kg) for 4 weeks induced a significant attenuation in signs of DM in rats reflected in their assessed lab values. Biomarkers of cell injury, tissue necrosis, and apoptosis; caspase-3 were significantly reduced with imatinib treatment. Furthermore, pancreatic antioxidants defenses of which; superoxide dismutase (SOD) and catalase activities, reduced glutathione (GSH) concentration, and total antioxidant capacity have significantly improved with a simultaneous reduction in malondialdehyde (MDA) content. Histopathologically, imatinib treatment was associated with a minimal pancreatic injury and marked restoration of insulin content in ß-cells. Moreover, imatinib treatment revealed a significant reduction in the infiltration of macrophages in ß-cells. Imatinib's ameliorative impact on DM may be attributed to it's mediated protection and preservation of pancreatic ß-cells function and the improvement in serum insulin levels and hence the improvement of blood glucose and overall glycemic control.


Assuntos
Diabetes Mellitus Experimental/patologia , Mesilato de Imatinib/farmacologia , Células Secretoras de Insulina/metabolismo , Administração Oral , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Antioxidantes/metabolismo , Biomarcadores/sangue , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Caspase 3/metabolismo , Catalase/metabolismo , Diabetes Mellitus Experimental/sangue , Modelos Animais de Doenças , Glucagon/sangue , Glutationa/metabolismo , Insulina/sangue , Células Secretoras de Insulina/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Estreptozocina , Superóxido Dismutase/metabolismo
19.
PLoS One ; 15(7): e0236490, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32716921

RESUMO

Individuals with spinal cord injury develop cardiovascular disease more than age-matched, non-injured cohorts. However, progression of systolic and diastolic dysfunction into cardiovascular disease after spinal cord injury is not well described. We sought to investigate the relationship between systolic and diastolic function in chronic spinal cord injury to describe how biological sex, level, severity, and duration of injury correlate with structural changes in the left ventricle. Individuals with chronic spinal cord injury participated in this study (n = 70). Registered diagnostic cardiac sonographers used cardiac ultrasound to measure dimensions, mass, and systolic and diastolic function of the left ventricle. We found no significant relationship to severity or duration of injury with left ventricle measurements, systolic function outcome, or diastolic function outcome. Moreover, nearly all outcomes measured were within the American Society of Echocardiography-defined healthy range. Similar to non-injured individuals, when indexed by body surface area (BSA) left ventricle mass [-14 (5) g/m2, p < .01], end diastolic volume [-6 (3) mL/m2, p < .05], and end systolic volume [-4 (1) mL/m2, p < .01] were significantly decreased in women compared with men. Likewise, diastolic function outcomes significantly worsened with age: E-wave velocity [-5 (2), p < .01], E/A ratio [-0.23 (0.08), p < .01], and e' velocity [lateral: -1.5 (0.3) cm/s, p < .001; septal: -0.9 (0.2), p < .001] decreased with age while A-wave velocity [5 (1) cm/s, p < .001] and isovolumic relaxation time [6 (3) ms, p < .05] increased with age. Women demonstrated significantly decreased cardiac size and volumes compared with men, but there was no biological relationship to dysfunction. Moreover, individuals were within the range of ASE-defined healthy values with no evidence of systolic or diastolic function and no meaningful relationship to level, severity, or duration of injury. Decreases to left ventricular dimensions and mass seen in spinal cord injury may result from adaptation rather than maladaptive myocardial remodeling, and increased incidence of cardiovascular disease may be related to modifiable risk factors.


Assuntos
Diástole/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Sístole/fisiologia , Adulto , Pressão Sanguínea , Feminino , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Análise Multivariada , Tamanho do Órgão
20.
PLoS One ; 15(7): e0236473, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32716979

RESUMO

Cerebral white-matter hyperintensities (WMHs) on MRI is associated with reduced compliance of the cerebral arterioles. We hypothesized that an echocardiography index for left ventricular (LV) diastolic function, E/e', might reflect the cerebral arteriolar compliance and evaluated the association between E/e' and long-term progression rate of the cerebral WMH volume. This retrospective study included individuals who were ≥ 50 years of age, with a preserved LV ejection fraction (≥ 50%) and neurological function status (modified Rankin scale score ≤1), and underwent initial and follow-up MRI evaluations within intervals of 34-45 months. Baseline clinical, laboratory, and echocardiography markers such as ejection fraction, LV mass index, and E/e' were obtained. WMH volume progression rate between the baseline and follow-up MRIs was designated as the outcome factor. 392 individuals (57.1% men; mean age: 66.7±8.4 years) were followed-up for 38.2±3.4 months. The mean WMH volume progression rate was 1.35±2.65 mL/year. The log-transformed value of WMH volume progression rate was linearly associated with the log-transformed E/e' (B coefficient = 0.365; 95% confidence interval [CI] 0.180-0.551; P = 0.001), along with the log-transformed values of baseline WMH volume (B = 0.142; 95% CI 0.106-0.179; P<0.001) and glomerular filtration rate (B = -0.182; 95% CI -0.321-0.044; P = 0.010). Additionally, a subgroup with an E/e' ≥15 exhibited a significantly higher WMH progression rate compared to the subgroups with lower E/e' values (P<0.001), especially in the lower quartiles (quartiles 1 and 2) of the baseline WMH volume. We concluded that echocardiographic marker E/e' is associated with the long-term progression rate of cerebral WMHs in population with preserved LV systolic function.


Assuntos
Progressão da Doença , Ecocardiografia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Tamanho do Órgão
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