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1.
Mol Neurobiol ; 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38349515

RESUMO

Parkinson's disease (PD) is a neurological disorder that affects dopaminergic neurons. The lack of understanding of the underlying molecular mechanisms of PD pathology makes treating it a challenge. Several pieces of evidence support the protective role of enriched environment (EE) and exercise on dopaminergic neurons. The specific aspect(s) of neuroprotection after exposure to EE have not been identified. Therefore, we have investigated the protective role of EE on dopamine dysregulation and subsequent downregulation of DJ1 protein using in vitro and in vivo models of PD. Our study for the first time demonstrated that DJ1 expression has a direct correlation with dopamine downregulation in PD models and exposure to EE has a significant impact on improving the behavioral changes in PD mice. This research provides evidence that exercise in EE has a positive effect on PD without interfering with the current line of therapy.

2.
Cancers (Basel) ; 16(3)2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38339230

RESUMO

Neurofibromatosis type 1 (NF1) is caused by mutations in the NF1 gene. The clinical presentation of NF1 includes diverse neurological issues in pediatric and adult patients, ranging from learning disabilities, motor skill issues, and attention deficit disorder, to increased risk of depression and dementia. Preclinical research suggests that abnormal neuronal signaling mediates spatial learning and attention issues in NF1; however, drugs that improve phenotypes in models show inconclusive results in clinical trials, highlighting the need for a better understanding of NF1 pathophysiology and broader therapeutic options. Most NF1 patients show abnormalities in their brain white matter (WM) and myelin, and links with NF1 neuropathophysiology have been suggested; however, no current data can clearly support or refute this idea. We reported that myelin-targeted Nf1 mutation impacts oligodendrocyte signaling, myelin ultrastructure, WM connectivity, and sensory-motor behaviors in mice; however, any impact on learning and memory remains unknown. Here, we adapted a voluntary running test-the complex wheel (CW; a wheel with unevenly spaced rungs)-to delineate fine motor skill learning curves following induction of an Nf1 mutation in pre-existing myelinating cells (pNf1 mice). We found that pNf1 mutant females experience delayed or impaired learning in the CW, while proper learning in pNf1 males is predominantly disrupted; these phenotypes add complexity to the gender-dependent learning differences in the mouse strain used. No broad differences in memory of acquired CW skills were detected in any gender, but gene-dose effects were observed at the studied time points. Finally, nitric oxide signaling regulation differentially impacted learning in wild type (WT)/pNf1, male/female mice. Our results provide evidence for fine motor skill learning issues upon induction of an Nf1 mutation in mature myelinating cells. Together with previous connectivity, cellular, and molecular analyses, these results diversify the potential treatments for neurological issues in NF1.

4.
Biol Sex Differ ; 14(1): 77, 2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-37919790

RESUMO

BACKGROUND: The prairie vole (Microtus ochrogaster) is a socially monogamous rodent that establishes an enduring pair bond after cohabitation, with (6 h) or without (24 h) mating. Previously, we reported that social interaction and mating increased cell proliferation and differentiation to neuronal fate in neurogenic niches in male voles. We hypothesized that neurogenesis may be a neural plasticity mechanism involved in mating-induced pair bond formation. Here, we evaluated the differentiation potential of neural progenitor cells (NPCs) isolated from the subventricular zone (SVZ) of both female and male adult voles as a function of sociosexual experience. Animals were assigned to one of the following groups: (1) control (Co), sexually naive female and male voles that had no contact with another vole of the opposite sex; (2) social exposure (SE), males and females exposed to olfactory, auditory, and visual stimuli from a vole of the opposite sex, but without physical contact; and (3) social cohabitation with mating (SCM), male and female voles copulating to induce pair bonding formation. Subsequently, the NPCs were isolated from the SVZ, maintained, and supplemented with growth factors to form neurospheres in vitro. RESULTS: Notably, we detected in SE and SCM voles, a higher proliferation of neurosphere-derived Nestin + cells, as well as an increase in mature neurons (MAP2 +) and a decrease in glial (GFAP +) differentiated cells with some sex differences. These data suggest that when voles are exposed to sociosexual experiences that induce pair bonding, undifferentiated cells of the SVZ acquire a commitment to a neuronal lineage, and the determined potential of the neurosphere is conserved despite adaptations under in vitro conditions. Finally, we repeated the culture to obtain neurospheres under treatments with different hormones and factors (brain-derived neurotrophic factor, estradiol, prolactin, oxytocin, and progesterone); the ability of SVZ-isolated cells to generate neurospheres and differentiate in vitro into neurons or glial lineages in response to hormones or factors is also dependent on sex and sociosexual context. CONCLUSION: Social interactions that promote pair bonding in voles change the properties of cells isolated from the SVZ. Thus, SE or SCM induces a bias in the differentiation potential in both sexes, while SE is sufficient to promote proliferation in SVZ-isolated cells from male brains. In females, proliferation increases when mating is performed. The next question is whether the rise in proliferation and neurogenesis of cells from the SVZ are plastic processes essential for establishing, enhancing, maintaining, or accelerating pair bond formation. Highlights 1. Sociosexual experiences that promote pair bonding (social exposure and social cohabitation with mating) induce changes in the properties of neural stem/progenitor cells isolated from the SVZ in adult prairie voles. 2. Social interactions lead to increased proliferation and induce a bias in the differentiation potential of SVZ-isolated cells in both male and female voles. 3. The differentiation potential of SVZ-isolated cells is conserved under in vitro conditions, suggesting a commitment to a neuronal lineage under a sociosexual context. 4. Hormonal and growth factors treatments (brain-derived neurotrophic factor, estradiol, prolactin, oxytocin, and progesterone) affect the generation and differentiation of neurospheres, with dependencies on sex and sociosexual context. 5. Proliferation and neurogenesis in the SVZ may play a crucial role in establishing, enhancing, maintaining, or accelerating pair bond formation.


In this study, researchers evaluated whether social interactions and copulation induce changes in the proliferation and differentiation of neural progenitor cells in adult male and female voles using an in vitro neurosphere formation assay. The following groups were assigned: control animals without any exposure to another vole outside their litter, another group with social exposure consisting of sensory exposure to a vole of the opposite sex and a third group with social cohabitation and copulation. Forty eight hours after social interactions, cells were isolated from the neurogenic niche subventricular zone (SVZ) and cultured to assess their self-renewal and proliferation abilities to form neurospheres. The results showed in the social interaction groups, a greater number and growth of neurospheres in both males and females. Differentiation capacity was assessed by immunodetection of MAP2 and GFAP to identify neurons or glia, respectively, arise from neurospheres, with an increase in neuronal fate in groups with social interaction. In the second part of the study, the researchers analyzed the effect of different hormone and growth factor treatments and found that the response in both proliferation and differentiation potential may vary depending on the sociosexual context or sex. This study suggests that social interactions leading to pair bond formation alter the properties of SVZ cells, whereby proliferation and neurogenesis may have an impact on the establishment and maintenance of pair bonding.


Assuntos
Células-Tronco Neurais , Caracteres Sexuais , Animais , Feminino , Masculino , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Ocitocina/metabolismo , Pradaria , Prolactina/metabolismo , Progesterona , Neurônios/metabolismo , Encéfalo/metabolismo , Células-Tronco Neurais/metabolismo , Arvicolinae/metabolismo , Proliferação de Células , Estradiol/metabolismo , Proteínas de Ligação a DNA/metabolismo
6.
Molecules ; 28(15)2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37570779

RESUMO

In this work, the structural, electronic, and optical stability properties of the chitosan monomer (M-Ch) and atomic silver complex are reported, as well as a unitary cell of a silver cluster in the gas phase and acetic acid. The generalized gradient approximation HSEh1PBE/def2-TZVPP50 results established the structures' anionic charge (Q = -1|e|) and the doublet state (M = 2). The high cohesive energy indicates structural stability, and the quantum-mechanical descriptors show a high polarity and low chemical reactivity. Also, the quantum-mechanical descriptors present a low work function that shows the structures are suitable for applications in light-emitting diodes. Finally, the electronic behavior observed by the |HOMO-LUMO| gap energy changes depending on the atomic silver incorporated into the complex.

7.
Diagnostics (Basel) ; 13(15)2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37568921

RESUMO

Patent ductus arteriosus (PDA) is frequent in preterm newborns, and its incidence is inversely associated with the degree of prematurity. The first choice of pharmacological treatment is ibuprofen. Several genes, including EPAS1, have been proposed as probable markers associated with a genetic predisposition for the development of PDA in preterm infants. EPAS 1 NG_016000.1:g.84131C>G or rs7557402 has been reported to be probably benign and associated with familial erythrocytosis by the Illumina Clinical Services Laboratory. Other variants of EPAS1 have been previously reported to be benign for familial erythrocytosis because they decrease gene function and are positive for familial erythrocytosis because the overexpression of EPAS1 is a key factor in uncontrolled erythrocyte proliferation. However, this could be inconvenient for ductal closure, since for this process to occur, cell proliferation, migration, and differentiation should take place, and a decrease in EPAS1 gene activity would negatively affect these processes. Single-nucleotide polymorphisms (SNPs) in EPAS1 and TFAP2B genes were searched with high-resolution melting and Sanger sequencing in blood samples of preterm infants with hemodynamically significant PDA treated with ibuprofen at the National Institute of Perinatology. The variant rs7557402, present in the EPAS1 gene eighth intron, was associated with a decreased response to treatment (p = 0.007, OR = 3.53). The SNP rs7557402 was associated with an increased risk of pharmacological treatment failure. A probable mechanism involved could be the decreased activity of the product of the EPAS1 gene.

8.
Glia ; 71(12): 2701-2719, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37382486

RESUMO

Evidence for myelin regulating higher-order brain function and disease is rapidly accumulating; however, defining cellular/molecular mechanisms remains challenging partially due to the dynamic brain physiology involving deep changes during development, aging, and in response to learning and disease. Furthermore, as the etiology of most neurological conditions remains obscure, most research models focus on mimicking symptoms, which limits understanding of their molecular onset and progression. Studying diseases caused by single gene mutations represents an opportunity to understand brain dys/function, including those regulated by myelin. Here, we discuss known and potential repercussions of abnormal central myelin on the neuropathophysiology of Neurofibromatosis Type 1 (NF1). Most patients with this monogenic disease present with neurological symptoms diverse in kind, severity, and onset/decline, including learning disabilities, autism spectrum disorders, attention deficit and hyperactivity disorder, motor coordination issues, and increased risk for depression and dementia. Coincidentally, most NF1 patients show diverse white matter/myelin abnormalities. Although myelin-behavior links were proposed decades ago, no solid data can prove or refute this idea yet. A recent upsurge in myelin biology understanding and research/therapeutic tools provides opportunities to address this debate. As precision medicine moves forward, an integrative understanding of all cell types disrupted in neurological conditions becomes a priority. Hence, this review aims to serve as a bridge between fundamental cellular/molecular myelin biology and clinical research in NF1.

9.
Cells ; 12(8)2023 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-37190101

RESUMO

Pluripotent stem cells (PSCs; embryonic stem cells and induced pluripotent stem cells) can recapitulate critical aspects of the early stages of embryonic development; therefore, they became a powerful tool for the in vitro study of molecular mechanisms that underlie blastocyst formation, implantation, the spectrum of pluripotency and the beginning of gastrulation, among other processes. Traditionally, PSCs were studied in 2D cultures or monolayers, without considering the spatial organization of a developing embryo. However, recent research demonstrated that PSCs can form 3D structures that simulate the blastocyst and gastrula stages and other events, such as amniotic cavity formation or somitogenesis. This breakthrough provides an unparalleled opportunity to study human embryogenesis by examining the interactions, cytoarchitecture and spatial organization among multiple cell lineages, which have long remained a mystery due to the limitations of studying in utero human embryos. In this review, we will provide an overview of how experimental embryology currently utilizes models such as blastoids, gastruloids and other 3D aggregates derived from PSCs to advance our understanding of the intricate processes involved in human embryo development.


Assuntos
Embrião de Mamíferos , Células-Tronco Pluripotentes , Gravidez , Feminino , Humanos , Desenvolvimento Embrionário , Linhagem da Célula , Blastocisto
10.
Nutrients ; 15(3)2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36771304

RESUMO

To evaluate the effectiveness of the healthy lifestyle promotion program for Yaquis (PREVISY) on insulin resistance in the short- and medium-term periods in adults who are overweight/obese and have an increased risk for diabetes. Using a translational research design, an intervention program was implemented in a sample of 93 Yaqui adult subjects. The effectiveness of PREVISY was evaluated by comparing the levels of Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and the Triglycerides-Glucose Index (TyG index) at 6 and 12 months using a paired t-test. Results: In the subjects who completed the program, a decrease in the HOMA-IR index (∆ = -0.91 and ∆ = -1.29, p ≤ 0.05) and the TyG index (∆ = -0.24 y ∆ = -0.20, p ≤ 0.05) was observed in the short- and medium-term period, respectively. Subjects with body weight loss ≥ 10% showed decreased levels of HOMA-IR (∆ = -3.32 and ∆ = -4.89, p ≤ 0.05) and the TyG index (∆ = -0.80 and ∆ = -0.60, p ≤ 0.05) at 6 and 12 months, respectively. A stronger benefit of the program was found in subjects with obesity (vs. overweight) and with high and very high risk of diabetes (vs. moderate risk) in IR markers (p ≤ 0.05). The PREVISY program demonstrated its effectiveness in the improvement of some markers of insulin resistance in Yaqui adults at risk of diabetes.


Assuntos
Diabetes Mellitus , Resistência à Insulina , Adulto , Humanos , Sobrepeso , México , Glicemia , Obesidade , Triglicerídeos , Glucose , Estilo de Vida
11.
Am J Med Genet A ; 188(6): 1915-1927, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35266292

RESUMO

RASopathies are a group of genetic disorders that are caused by genes that affect the canonical Ras/mitogen-activated protein kinase (MAPK) signaling pathway. Despite tremendous progress in understanding the molecular consequences of these genetic anomalies, little movement has been made in translating these findings to the clinic. This year, the seventh International RASopathies Symposium focused on expanding the research knowledge that we have gained over the years to enhance new discoveries in the field, ones that we hope can lead to effective therapeutic treatments. Indeed, for the first time, research efforts are finally being translated to the clinic, with compassionate use of Ras/MAPK pathway inhibitors for the treatment of RASopathies. This biannual meeting, organized by the RASopathies Network, brought together basic scientists, clinicians, clinician scientists, patients, advocates, and their families, as well as representatives from pharmaceutical companies and the National Institutes of Health. A history of RASopathy gene discovery, identification of new disease genes, and the latest research, both at the bench and in the clinic, were discussed.


Assuntos
Síndrome de Costello , Síndrome de Noonan , Síndrome de Costello/genética , Humanos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Síndrome de Noonan/genética , Transdução de Sinais , Proteínas ras/genética , Proteínas ras/metabolismo
12.
Sensors (Basel) ; 22(5)2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35271028

RESUMO

The present work describes the implementation of a prototype to characterize thermoelectric modules (TEM). The goal is to study the energy conversion by means of thermoelectric modules mounted on concrete structures. The proposed experimental system is used for the electrical characterization of a commercially available thermoelectric module TEC1-12710 to prove its operation while embedded in a concrete slab, typical of building constructions. In this case, the parameters that define thermal energy conversion into electrical energy are open-circuit voltage generation, loaded circuit voltage generation, and load current. A known external load is connected to the terminals of the TEM for the purpose of its electric characterization. An electrical heating element on the hot side and a thermoelectric cooler on the cold side produce a temperature difference on the concrete slab. This arrangement allows the emulation of a temperature gradient produced by sunlight over a concrete structure. The objective is to measure the resulting electrical energy produced by the combination of concrete slab and the thermoelectric module. By controlling the temperature difference between the sides of the thermoelectric module under test, it is possible to simulate the effect of the temperature gradient under different sunlight conditions. Two digital PI controllers regulate the temperature conditions, thus providing controlled conditions for the experiments.

13.
BMC Public Health ; 22(1): 308, 2022 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-35164732

RESUMO

BACKGROUND: The Yaquis are an Indigenous group who inhabit in the state of Sonora in northwestern Mexico. This group has experienced changes in their lifestyle, moving from a traditional lifestyle to a more modern one, resulting in an increase of obesity and its comorbidities. However, few studies have been done in this group. The aim of this study was to determine the prevalence of overweight, obesity and central obesity and to identify the factors associated with body mass index (BMI) in a representative sample of Indigenous Yaqui people from Sonora, Mexico. METHODS: A cross-sectional survey with multistage sampling was conducted among adults (N = 351) with residence in Yaqui traditional villages (Vícam, Pótam, Loma de Guamúchil, Loma de Bácum, Tórim, Ráhum, Huiribis or Belem). Anthropometric measurements were taken to diagnose overweight, obesity and central obesity. Food frequency and physical activity (PA) questionnaires designed for the Yaqui population were applied, as well as sociodemographic and clinical history questionnaires. The factors associated with BMI were assessed using multiple linear regression considering the complex design of the sampling. RESULTS: The prevalence of overweight, obesity and central obesity in the population were 36.5%, 35.0% and 76.0%, respectively. Having higher values of the modernization index (ß = 0.20, p = 0.049) was associated with a higher BMI, while having a higher consumption of a "prudent" dietary pattern (traditional dishes, fruits, vegetables and low-fat dairy) (ß = -0.58, p = 0.009) and performing a greater number of hours per week of vigorous PA (ß = -0.14, p = 0.017) were associated with a lower BMI. CONCLUSIONS: The prevalence of the studied abnormalities is high. The evidence presented in this study suggests that interventions are needed and more research is required to determine the appropriate components of such interventions, in order to meet the needs of the Yaqui people.


Assuntos
Obesidade Abdominal , Sobrepeso , Adulto , Índice de Massa Corporal , Estudos Transversais , Humanos , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Prevalência
14.
Front Bioeng Biotechnol ; 9: 773294, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34976970

RESUMO

Purpose: To evaluate long-term in vivo functionality of corneas regenerated using a cell-free, liquid hydrogel filler (LiQD Cornea) after deep corneal trauma in the feline model. Methods: Two healthy cats underwent 4 mm diameter stepwise 250/450 µm deep surgical corneal ablation with and without needle perforation. The filler comprising 10% (w/w) collagen-like peptide conjugated to polyethylene glycol (CLP-PEG) and 1% fibrinogen and crosslinked with 2% (w/w) 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM), was applied to the wound bed previously coated with thrombin (250 U/ml). In situ gelation occurred within 5 min, and a temporary tarsorrhaphy was performed. Eyes were examined weekly for 1 month, then monthly over 12 months. Outcome parameters included slit-lamp, Scheimpflug tomography, optical coherence tomography, confocal and specular microscopy, and immunohistochemistry studies. Results: The gelled filler was seamlessly incorporated, supporting smooth corneal re-epithelialization. Progressive in-growth of keratocytes and nerves into the filler corresponding to the mild haze observed faded with time. The regenerated neo-cornea remained stably integrated throughout the 12 months, without swelling, inflammation, infection, neovascularization, or rejection. The surrounding host stroma and endothelium remained normal at all times. Tomography confirmed restoration of a smooth surface curvature. Conclusion: Biointegration of this hydrogel filler allowed stable restoration of corneal shape and transparency in the feline model, with less inflammation and no neovascularization compared to previous reports in the minipig and rabbit models. It offers a promising alternative to cyanoacrylate glue and corneal transplantation for ulcerated and traumatized corneas in human patients.

15.
J Diabetes Res ; 2020: 6320402, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33062713

RESUMO

Type 2 diabetes (T2D) is a public health problem worldwide, and the main risk factor for its development is obesity. The Yaqui ethnic group of Sonora has serious obesity problems, resulting in an increased risk of T2D in its inhabitants. The objective of this study was to evaluate the effectiveness of a health promotion program on obesity parameters and cardiovascular risk factors in short- (6 months) and medium-term periods (12 months) in indigenous Yaquis of Sonora. The design is a translational clinical study of a single cohort with prepost intervention measurements in a sample of 93 subjects. The effectiveness of the program was evaluated by comparing obesity parameters, metabolic markers, and physical activity 6 and 12 months with those measured under basal conditions using a paired t-test or Wilcoxon rank-sum test. The short-term retention percentage was 58.0%. There was a decrease in body weight (Δ = -3.9 kg, p ≤ 0.05) and other obesity parameters, and an increase in physical activity and improvements in metabolic markers (p ≤ 0.05) was observed. Similar findings were obtained for the medium-term period; body weight loss was also -3.9 kg (p ≤ 0.05). The short and medium-term results of the program showed improvements in the obesity parameters and other cardiovascular risk factors of the participants. These results support the effectiveness of the program and its translation in this ethnic group.


Assuntos
Diabetes Mellitus Tipo 2/etnologia , Diabetes Mellitus Tipo 2/epidemiologia , Estilo de Vida , Obesidade/etnologia , Obesidade/epidemiologia , Pesquisa Translacional Biomédica/organização & administração , Adulto , Antropometria , Composição Corporal , Peso Corporal , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/etnologia , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Masculino , México/epidemiologia , México/etnologia , Pessoa de Meia-Idade , Obesidade/complicações , Grupos Populacionais , Projetos de Pesquisa , Risco , Fatores de Risco
16.
J Adv Res ; 25: 77-85, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32922976

RESUMO

Fractional-order chaotic oscillators (FOCOs) have been widely studied during the last decade, and some of them have been implemented on embedded hardware like field-programmable gate arrays, which is a good option for fast prototyping and verification of the desired behavior. However, the hardware resources are dependent on the length of the digital word that is used, and this can degrade the desired response due to the finite number of bits to perform computer arithmetic. In this manner, this paper shows the implementation of FOCOs using analog electronics to generate continuous-time chaotic behavior. Charef's method is applied to approximate the fractional-order derivatives as a ratio of two polynomials in the Laplace domain. For instance, two commensurate FOCOs are the cases of study herein, for which we show their dynamical analysis by evaluating their equilibrium points and eigenvalues that are used to estimate the minimum fractional-order that guarantees their chaotic behavior. We propose the use of first-order all-pass and low-pass filters to design the ratio of the polynomials that approximate the fractional-order. The filters are implemented using amplifiers and synthesized on a field-programmable analog array (FPAA) device. Experimental results are in good agreement with simulation results thus demonstrating the usefulness of FPAAs to generate continuous-time chaotic behavior, and to allow reprogramming of the parameters of the FOCOs.

17.
Proc Natl Acad Sci U S A ; 117(36): 22506-22513, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32839340

RESUMO

Neurofibromin gene (NF1) mutation causes neurofibromatosis type 1 (NF1), a disorder in which brain white matter deficits identified by neuroimaging are common, yet of unknown cellular etiology. In mice, Nf1 loss in adult oligodendrocytes causes myelin decompaction and increases oligodendrocyte nitric oxide (NO) levels. Nitric oxide synthase (NOS) inhibitors rescue this pathology. Whether oligodendrocyte pathology is sufficient to affect brain-wide structure and account for NF1 imaging findings is unknown. Here we show that Nf1 gene inactivation in adult oligodendrocytes (Plp-Nf1fl/+ mice) results in a motor coordination deficit. Magnetic resonance imaging in awake mice showed that fractional anisotropy is reduced in Plp-Nf1fl/+ corpus callosum and that interhemispheric functional connectivity in the motor cortex is also reduced, consistent with disrupted myelin integrity. Furthermore, NOS-specific inhibition rescued both measures. These results suggest that oligodendrocyte defects account for aspects of brain dysfunction in NF1 that can be identified by neuroimaging and ameliorated by NOS inhibition.


Assuntos
Encéfalo , Neurofibromina 1 , Óxido Nítrico Sintase/antagonistas & inibidores , Oligodendroglia/metabolismo , Animais , Encéfalo/citologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Deleção de Genes , Imageamento por Ressonância Magnética , Camundongos , Camundongos Endogâmicos C57BL , Bainha de Mielina/metabolismo , Neurofibromina 1/genética , Neurofibromina 1/metabolismo , Óxido Nítrico/metabolismo
18.
Rev Med Inst Mex Seguro Soc ; 58(3): 317-327, 2020 05 18.
Artigo em Espanhol | MEDLINE | ID: mdl-34002991

RESUMO

Currently, diabetes represents a serious health problem, due to the complications it entails and because of its high mortality rate. Type 2 diabetes mellitus (T2DM) is the most prevalent and it is characterized by insulin resistance. The objective was to analyze the available scientific literature on prevalence and factors associated to T2DM in indigenous population of Mexico. Searches for articles published between 1990 and 2019 in English and Spanish were carried out in 13 electronic databases. Combinations of eight keywords were used according to the MeSH vocabulary. To select the studies, it was used the JBI's Critical Appraisal Tools guide in Spanish for analytical prevalence studies. Out of 478, 12 cross-sectional studies reported T2DM prevalences from 12 indigenous groups located in Mexico: Huichol (0%), Mexican (0%), Tepehuano (0 and 0.83%), Mazateco (2.01%), Otomí (4.4%), Tojolabal (4.7%), Mixe (6.9%), Pima (6.9 and 9.0%), Zapoteco (8.7%), Maya (10.6%), Yaqui (18.3 and 14.8%) and Mixteco (19.0 and 26.2%). Factors associated with T2DM reported were being older, being female, less education level, presence of family history of T2DM, obesity, high blood pressure and increased waist-hip circumference. There is little evidence of the prevalence of T2DM in indigenous groups in Mexico. Studies found suggest a diversity of prevalences, ranging from lower to greater prevalences. Considering the risk factors associated with T2DM is essential to generate prevention strategies according to the context of each ethnic group, in order to improve the epidemiological landscape of diabetes in indigenous groups of Mexico.


Actualmente la diabetes representa un grave problema de salud por las complicaciones que conlleva y por su elevada tasa de mortalidad. La diabetes mellitus tipo 2 (DM2) es la más prevalente y se caracteriza por la resistencia a la insulina. El objetivo fue analizar la literatura científica disponible sobre la prevalencia y los factores asociados a DM2 en población indígena de México. Se buscaron artículos publicados entre 1990 y 2019 en inglés y español en 13 bases de datos electrónicas. Se utilizaron combinaciones de ocho palabras clave según el vocabulario MeSH. Para seleccionar los estudios se siguió la guía JBI's Critical Appraisal tools en español para estudios de prevalencia analíticos. De 478, 12 investigaciones con diseño trasversal mostraron prevalencias de DM2 de 12 grupos indígenas de México: huichol (0%), mexicanero (0%), tepehuano (0 y 0.83%), mazateco (2.01%), otomí (4.4%), tojolabal (4.7%), mixe (6.9%), pima (6.9 y 9.0%), zapoteco (8.7%), maya (10.6%), yaqui (18.3 y 14.8%) y mixteco (19.0 y 26.2%). Los factores asociados a DM2 fueron mayor edad, ser mujer, menor escolaridad, presencia de antecedentes familiares de diabetes, presentar obesidad, hipertensión arterial y una mayor circunferencia de cintura-cadera. Hay poca evidencia de la prevalencia de DM2 en grupos indígenas de México. Los estudios encontrados sugieren heterogeneidad en las prevalencias, desde muy bajas a muy altas. Considerar los factores de riesgo asociados a la DM2 es imprescindible para generar estrategias de prevención según el contexto de cada etnia, a fin de mejorar el panorama epidemiológico de la diabetes en grupos indígenas de México.


Assuntos
Diabetes Mellitus Tipo 2 , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Feminino , Humanos , México/epidemiologia , Grupos Populacionais , Prevalência , Fatores de Risco
19.
Rev. mex. cardiol ; 29(2): 90-97, Apr.-Jun. 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1020706

RESUMO

Abstract: Introduction: The hypertension (HT) is a public health problem worldwide. This disease is a risk factor for heart diseases and, cerebrovascular and renal failure, which are considered the main causes of mortality. Objective: This study aimed to describe factors associated with a previous diagnosis of HT in a group of Yaqui adults from Sonora, Mexico. Material and methods: We conducted a cross-sectional epidemiological study in which 108 individuals ≥ 18 years of age were included. HT was considered as prior diagnosis. In addition, anthropometric assessment, medical history and sociodemographic questionnaires were also applied. The sex- and age adjusted prevalence was estimated using the direct method of standardization using the studied sample as the standard population. The factors associated with previous diagnosis of HT were determined using multiple logistic regression analysis. Results: The sex- and age-adjusted prevalence of a previous diagnosis of HT was 12.0% (95% CI: 6.3-17.6) in the overall population. The age-adjusted prevalence in men was 7.1%, and it was 14.0% in women with no significant difference between genders. The independent factors associated with HT were increased waist circumference (cm) (OR: 1.07, 95% CI: 1.01-1.14) and a previous diagnosis of diabetes (OR: 4.14, 95% CI: 1.03-16.61). Conclusions: The prevalence of a previous diagnosis of HT was high, and it could be higher after confirmation of new diagnosis cases in the population. The identification of factors associated with HT may be useful for creating programs to prevent chronic diseases in this ethnic group.(AU)


Resumen: Introducción: La hipertensión arterial (HTA) es un problema de salud pública a nivel mundial. Esta enfermedad es un factor de riesgo para enfermedades del corazón, cerebrovasculares y falla renal, las cuales son consideradas entre las principales causas de mortalidad. Objetivo: Describir factores asociados con el diagnóstico previo de HTA en un grupo de adultos Yaquis de Sonora, México. Material y métodos: Llevamos a cabo un estudio epidemiológico con diseño transversal donde fueron estudiados 108 individuos ≥ 18 años de edad. La HTA fue considerada como diagnóstico previo, se hizo una evaluación antropométrica y se aplicaron cuestionarios de historial clínico y sociodemográficos. La prevalencia de HTA ajustada por edad y sexo se estimó por el método directo de estandarización utilizando la población estudiada como población estándar. Los factores asociados con el diagnóstico previo de HTA fueron obtenidos mediante análisis de regresión logística múltiple. Resultados: La prevalencia de diagnóstico previo de HTA fue 12.0% (IC 95%, 6.3-17.6) en la población total. La prevalencia ajustada por edad en hombres fue 7.1 y 14.0% en mujeres; sin diferencias significativas entre sexo. Los factores asociados de manera independiente con HTA fueron una mayor circunferencia de cintura (cm) (RM: 1.07; IC 95%, 1.01-1.14) y el diagnóstico previo de diabetes (RM: 4.14; IC 95%, 1.03-16.61). Conclusiones: La prevalencia de diagnóstico previo de HTA fue alta y podría incrementar con la confirmación de diagnóstico de casos nuevos en la población. La identificación de factores asociados con HTA puede servir para crear programas de prevención de enfermedades crónicas en este grupo étnico.(AU)


Assuntos
Humanos , Povos Indígenas , Hipertensão/diagnóstico , Estudos Epidemiológicos , Prevalência , Estudos Transversais , Diagnóstico Precoce , México
20.
Mamm Genome ; 29(1-2): 112-127, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29197979

RESUMO

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that remain a human health concern with newly discovered sources of contamination and ongoing bioaccumulation and biomagnification. Children exposed during early brain development are at highest risk of neurological deficits, but highly exposed adults reportedly have an increased risk of Parkinson's disease. Our previous studies found allelic differences in the aryl hydrocarbon receptor and cytochrome P450 1A2 (CYP1A2) affect sensitivity to developmental PCB exposure, resulting in cognitive deficits and motor dysfunction. High-affinity Ahr b Cyp1a2(-/-) mice were most sensitive compared with poor-affinity Ahr d Cyp1a2(-/-) and wild-type Ahr b Cyp1a2(+/+) mice. Our follow-up studies assessed biochemical, histological, and gene expression changes to identify the brain regions and pathways affected. We also measured PCB and metabolite levels in tissues to determine if genotype altered toxicokinetics. We found evidence of AHR-mediated toxicity with reduced thymus and spleen weights and significantly reduced thyroxine at P14 in PCB-exposed pups. In the brain, the greatest changes were seen in the cerebellum where a foliation defect was over-represented in Cyp1a2(-/-) mice. In contrast, we found no difference in tyrosine hydroxylase immunostaining in the striatum. Gene expression patterns varied across the three genotypes, but there was clear evidence of AHR activation. Distribution of parent PCB congeners also varied by genotype with strikingly high levels of PCB 77 in poor-affinity Ahr d Cyp1a2(-/-) while Ahr b Cyp1a2(+/+) mice effectively sequestered coplanar PCBs in the liver. Together, our data suggest that the AHR pathway plays a role in developmental PCB neurotoxicity, but we found little evidence that developmental exposure is a risk factor for Parkinson's disease.


Assuntos
Citocromo P-450 CYP1A2/genética , Fígado/efeitos dos fármacos , Doença de Parkinson Secundária/genética , Receptores de Hidrocarboneto Arílico/genética , Animais , Citocromo P-450 CYP1A2/metabolismo , Genótipo , Humanos , Fígado/patologia , Camundongos , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/patologia , Bifenilos Policlorados/metabolismo , Bifenilos Policlorados/toxicidade , Receptores de Hidrocarboneto Arílico/metabolismo , Fatores de Risco
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