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1.
Brain ; 146(12): 5000-5014, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37769648

RESUMO

Although neuromelanin is a dark pigment characteristic of dopaminergic neurons in the human substantia nigra pars compacta, its potential role in the pathogenesis of Parkinson's disease (PD) has often been neglected since most commonly used laboratory animals lack neuromelanin. Here we took advantage of adeno-associated viral vectors encoding the human tyrosinase gene for triggering a time-dependent neuromelanin accumulation within substantia nigra pars compacta dopaminergic neurons in macaques up to similar levels of pigmentation as observed in elderly humans. Furthermore, neuromelanin accumulation induced an endogenous synucleinopathy mimicking intracellular inclusions typically observed in PD together with a progressive degeneration of neuromelanin-expressing dopaminergic neurons. Moreover, Lewy body-like intracellular inclusions were observed in cortical areas of the frontal lobe receiving dopaminergic innervation, supporting a circuit-specific anterograde spread of endogenous synucleinopathy by permissive trans-synaptic templating. In summary, the conducted strategy resulted in the development and characterization of a new macaque model of PD matching the known neuropathology of this disorder with unprecedented accuracy. Most importantly, evidence is provided showing that intracellular aggregation of endogenous α-synuclein is triggered by neuromelanin accumulation, therefore any therapeutic approach intended to decrease neuromelanin levels may provide appealing choices for the successful implementation of novel PD therapeutics.


Assuntos
Doença de Parkinson , Sinucleinopatias , Animais , Humanos , Idoso , Sinucleinopatias/patologia , Substância Negra/metabolismo , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Doença de Parkinson/patologia , Primatas/metabolismo
2.
Int J Mol Sci ; 22(12)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203739

RESUMO

It is without any doubt that precision medicine therapeutic strategies targeting neurodegenerative disorders are currently witnessing the spectacular rise of newly designed approaches based on the use of viral vectors as Trojan horses for the controlled release of a given genetic payload. Among the different types of viral vectors, adeno-associated viruses (AAVs) rank as the ones most commonly used for the purposes of either disease modeling or for therapeutic strategies. Here, we reviewed the current literature dealing with the use of AAVs within the field of Parkinson's disease with the aim to provide neuroscientists with the advice and background required when facing a choice on which AAV might be best suited for addressing a given experimental challenge. Accordingly, here we will be summarizing some insights on different AAV serotypes, and which would be the most appropriate AAV delivery route. Next, the use of AAVs for modeling synucleinopathies is highlighted, providing potential readers with a landscape view of ongoing pre-clinical and clinical initiatives pushing forward AAV-based therapeutic approaches for Parkinson's disease and related synucleinopathies.


Assuntos
Pesquisa Biomédica , Dependovirus/genética , Vetores Genéticos/uso terapêutico , Doença de Parkinson/genética , Animais , Modelos Animais de Doenças , Técnicas de Transferência de Genes , Humanos
3.
Int J Mol Sci ; 22(9)2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34062940

RESUMO

Mutations in the GBA1 gene coding for glucocerebrosidase (GCase) are the main genetic risk factor for Parkinson's disease (PD). Indeed, identifying reduced GCase activity as a common feature underlying the typical neuropathological signatures of PD-even when considering idiopathic forms of PD-has recently paved the way for designing novel strategies focused on enhancing GCase activity to reduce alpha-synuclein burden and preventing dopaminergic cell death. Here we have performed bilateral injections of a viral vector coding for the mutated form of alpha-synuclein (rAAV9-SynA53T) for disease modeling purposes, both in mice as well as in nonhuman primates (NHPs), further inducing a progressive neuronal death in the substantia nigra pars compacta (SNpc). Next, another vector coding for the GBA1 gene (rAAV9-GBA1) was unilaterally delivered in the SNpc of mice and NHPs one month after the initial insult, together with the contralateral delivery of an empty/null rAAV9 for control purposes. Obtained results showed that GCase enhancement reduced alpha-synuclein burden, leading to improved survival of dopaminergic neurons. Data reported here support using GCase gene therapy as a disease-modifying treatment for PD and related synucleinopathies, including idiopathic forms of these disorders.


Assuntos
Neurônios Dopaminérgicos/metabolismo , Terapia Genética , Glucosilceramidase/genética , Doença de Parkinson/terapia , alfa-Sinucleína/genética , Animais , Dopamina/genética , Neurônios Dopaminérgicos/patologia , Vetores Genéticos/uso terapêutico , Humanos , Macaca/genética , Mesencéfalo/metabolismo , Mesencéfalo/patologia , Camundongos , Mutação/genética , Neuroproteção/genética , Doença de Parkinson/genética , Doença de Parkinson/patologia , Substância Negra/metabolismo , Substância Negra/patologia
5.
Acta Neurochir (Wien) ; 159(8): 1571-1576, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28526902

RESUMO

Retroclival epidural haematoma (REDH) has been reported infrequently. It is a rare entity which is probably underdiagnosed. It is most commonly seen in the paediatric population and is generally associated with high-velocity injuries. We report three cases of paediatric patients diagnosed with REDHs: two of them secondary to high-energy trauma related to a motor-vehicle accident and the other a low-energy trauma after a slip while playing football. All three patients were managed conservatively by cervical immobilisation with favourable outcome. REDH is probably underdiagnosed by computed tomography scan. When the suspicion is high, sagittal reconstructions or magnetic resonance imaging should be considered to confirm the diagnosis. Usually, it is related to hyperflexion or hyperextension cervical injuries secondary to motor vehicle accident. However, it can also be observed in milder injuries.


Assuntos
Hematoma Epidural Craniano/diagnóstico por imagem , Acidentes de Trânsito , Traumatismos em Atletas , Criança , Hematoma Epidural Craniano/etiologia , Hematoma Epidural Craniano/terapia , Humanos , Imageamento por Ressonância Magnética , Masculino , Tomografia Computadorizada por Raios X/métodos
6.
Neurocirugia (Astur) ; 26(5): 251-5, 2015.
Artigo em Espanhol | MEDLINE | ID: mdl-25579309

RESUMO

We report the case of a 32-year-old patient complaining of chronic low back pain radiating to his left thigh. His MRI showed a lytic L1 vertebral body injury. A transpedicular biopsy confirmed the diagnosis of giant cell tumor. He underwent a L1 vertebrectomy and vertebral body replacement with a titanium cylinder using anterior approach, followed by the removal of the L1 posterior arch and the placement of pedicle screws through a posterior approach. The giant cell tumor is a rare benign primary bone tumor that can be locally aggressive and can potentially spread to other areas, usually to the lungs. Although it most frequently affects long bones, approximately 10% of tumors are located in the spine. To minimise the risk of recurrence, the elective management option is surgery.


Assuntos
Tumores de Células Gigantes/diagnóstico , Dor Lombar/etiologia , Neoplasias da Coluna Vertebral/diagnóstico , Adulto , Tumores de Células Gigantes/cirurgia , Humanos , Vértebras Lombares/cirurgia , Masculino , Neoplasias da Coluna Vertebral/cirurgia
7.
Exp Parasitol ; 145 Suppl: S28-33, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25014111

RESUMO

Free-living amoebae (FLA) are protozoa that are widely distributed in nature. They are important in the cycling of nutrients in aquatic food chains, but their distribution in natural aquatic environments is not well known. We conducted a survey to determine the presence and distribution of FLA and their relation to some physicochemical parameters in streams of the Mexico Basin in Central Mexico. Thirty-two sites from 18 streams were sampled. Samples were centrifuged and cultured onto NNA-media to isolate amoebae. Identifications were based on morphology. The pathogenicity of Acanthamoeba isolates was tested. Oxygen saturation, temperature, pH, specific conductance, water flow, dissolved reactive phosphorus, nitrites, nitrates, ammonia, dissolved inorganic nitrogen and coliforms were determined. One hundred-and-twenty FLA representing 18 genera were identified. The most frequent genera were Vannella, Rosculus and Acanthamoeba. The frequency of potentially pathogenic FLA was low and only 3 Acanthamoeba isolates were invasive in mice. The highest species richness of FLA was found in streams located into agriculture activity areas and those close to small villages that discharge wastewater into them. Water temperatures were always below 17°C. Oxygen saturation and pH were within the limits for the growth of most FLA. The presence of Acanthamoeba and Naegleria was low; nevertheless, they include potentially pathogenic species and can act as vectors and reservoirs for microbial pathogens and can produce human infections.


Assuntos
Amoeba/fisiologia , Rios/parasitologia , Amoeba/isolamento & purificação , Amoeba/patogenicidade , Animais , Carga Bacteriana , Biodiversidade , Enterobacteriaceae/crescimento & desenvolvimento , México , Camundongos , Rios/química , Rios/microbiologia , Estações do Ano , Temperatura , Virulência
8.
Plants (Basel) ; 13(11)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38891312

RESUMO

Macrophytes and cladocerans represent the main antagonistic groups that regulate phytoplankton biomass; however, the mechanism behind this interaction is unclear. In laboratory conditions, we separately evaluated the effects of three submerged macrophytes (Ceratophyllum demersum, Myriophyllum aquaticum, and Stuckenia pectinata), as well as their exudates, and plant-associated microbiota (POM < 25 µm) + exudates on the population growth of Daphnia cf. pulex and Simocephalus cf. mixtus. Living Ceratophyllum, exudates, and POM < 25 µm + exudates exhibited the most robust positive effects on Simocephalus density and the rate of population increase (r). Subsequently, we examined the effects of Ceratophyllum on the filtration and feeding rates of Simocephalus and Daphnia, revealing significant (p < 0.001) promotion of filtration and feeding in Simocephalus but not in Daphnia. To elucidate the specific effects of this macrophyte on Simocephalus demography, we assessed selected life table variables across the same treatments. The treatments involving exudates and living Ceratophyllum resulted in approximately 40% longer survivorship and significantly (p < 0.01) enhanced fecundity. Our findings indicate that exudates from submerged macrophytes positively influence Simocephalus demography by increasing filtration rates, survivorship, and fecundity. This synergy suggests a substantial impact on phytoplankton abundance.

9.
Diagnostics (Basel) ; 13(22)2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37998576

RESUMO

Breast cancer is a significant health concern for women, emphasizing the need for early detection. This research focuses on developing a computer system for asymmetry detection in mammographic images, employing two critical approaches: Dynamic Time Warping (DTW) for shape analysis and the Growing Seed Region (GSR) method for breast skin segmentation. The methodology involves processing mammograms in DICOM format. In the morphological study, a centroid-based mask is computed using extracted images from DICOM files. Distances between the centroid and the breast perimeter are then calculated to assess similarity through Dynamic Time Warping analysis. For skin thickness asymmetry identification, a seed is initially set on skin pixels and expanded based on intensity and depth similarities. The DTW analysis achieves an accuracy of 83%, correctly identifying 23 possible asymmetry cases out of 20 ground truth cases. The GRS method is validated using Average Symmetric Surface Distance and Relative Volumetric metrics, yielding similarities of 90.47% and 66.66%, respectively, for asymmetry cases compared to 182 ground truth segmented images, successfully identifying 35 patients with potential skin asymmetry. Additionally, a Graphical User Interface is designed to facilitate the insertion of DICOM files and provide visual representations of asymmetrical findings for validation and accessibility by physicians.

10.
Biomedicines ; 10(4)2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35453499

RESUMO

It is without doubt that the gene therapy field is currently in the spotlight for the development of new therapeutics targeting unmet medical needs. Thus, considering the gene therapy scenario, neurological diseases in general and neurodegenerative disorders in particular are emerging as the most appealing choices for new therapeutic arrivals intended to slow down, stop, or even revert the natural progressive course that characterizes most of these devastating neurodegenerative processes. Since an extensive coverage of all available literature is not feasible in practical terms, here emphasis was made in providing some advice to beginners in the field with a narrow focus on elucidating the best delivery route available for fulfilling any given AAV-based therapeutic approach. Furthermore, it is worth nothing that the number of ongoing clinical trials is increasing at a breath-taking speed. Accordingly, a landscape view of preclinical and clinical initiatives is also provided here in an attempt to best illustrate what is ongoing in this quickly expanding field.

11.
J Environ Biol ; 32(4): 463-71, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22315825

RESUMO

This study provides valuable information on the ultrastructure and environmental conditions of the Trachelomonas Ehr. (Euglenophyceae) genus in the Guadalupe Dam, a eutrophic reservoir located in the suburbs of Mexico City, which receives a considerable volume of wastewaters. Specimens were collected at surface level between November 2005 and May 2006. Using LM and SEM twelve taxa from phytoplankton were identified of which, 9 are new records for Mexico. The reservoir is warm monomictic, with basic pH values (7.4-10.1), a high concentration of chlorophyll a(18-101 microg l(-1), a permanent anoxic bottom, specific conductivity (K25) of 205 to 290 microS cm(-1), N-NO3, 0.19-1.2 mg l(-1) and P-PO4 0.22-1.6 mg l(-1). Water temperature was 15.6-23.0 degrees C. Most of the Trachelomonas species were found during the dry season, when concentrations of organic matter, nitrogen and phosphorus as well as the temperature were the highest. Higher species richness was also associated with the warmer months. This research contributes to increase our knowledge on Trachelomonas in Mexico and constitutes the first detailed description of lorica ultrastructure of 12 taxa that grow in a body of water with high concentration of nutrients and a moderate amount of mineral contents.


Assuntos
Euglênidos/classificação , Abastecimento de Água , Euglênidos/ultraestrutura , México
12.
J Environ Biol ; 32(4): 497-503, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22315829

RESUMO

Taxonomical composition and abundance of the planktonic ciliate assemblage in a Lake Tezozomoc, a hypertrophic pond located into an urban park in Mexico City, was investigated along the rainy season (May to October). The aims of the study were to know the main trophic roles and ecological significance of ciliates in a highly productive environment. A low number of taxa (27) and a wide abundance fluctuation (104-387 cil ml(-1)) were found. The most abundant species (up to 162 cil ml(-1)) was Halteria grandinella, an oligotrich ciliate that graze on bacteria and picoplankton, but also several big body sized species that feed on pico and nanoplankton were abundant. Sudden temporal changes in species dominance occurred. Ciliate biomass was very high and fluctuated widely (1.6-88 10(6) microm(3) ml(-1)) being dominated by the >50 microm size fraction that mainly included the pico and nanoplankton feeders. Ciliates are a very important component in the plankton of hypertrophic lakes and their main control factor seems to be the grazing by big-body size Daphnia species.


Assuntos
Cilióforos , Ecossistema , Plâncton/fisiologia , Lagoas , Animais , Fatores de Tempo
13.
Spinal Cord Ser Cases ; 7(1): 43, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-34035212

RESUMO

INTRODUCTION: Traumatic upper cervical spine injuries are frequently associated with high-energy trauma. The potential injuries to vital organs associated to a possible neurological damage marks the severity of this pathology. The neurological structures can be affected by a primary injury, spinal cord, cranial nerves and spinal nerves; or secondary to a vascular compromise, mainly the vertebral arteries. The dislocation of the atlantoaxial joint causes an unstable cervical spine that could be often associated with fracture of the Atlas and Axis. Evidently, these have a high morbimortality rate. CASE PRESENTATION: A young woman who suffered a severe polytrauma secondary to a motor vehicle collision was diagnosed with a sagittal plane atlantoaxial joint dislocation associated with a type III odontoid fracture, despite an adequate initial polytrauma management, the neurological damage was too critical, ultimately the decease of the patient. DISCUSSION: The atlantoaxial joint dislocation is a rare condition of the upper cervical spine and is usually secondary to a high-energy traumatism. The disruption of the atlantoaxial ligaments originates the considered most unstable cervical spine lesion and with the highest mortality. Attributable to the kinetic the bone fracture of the Atlas and Axis are commonly related, specially the odontoid process. Early immobilization followed by surgical decompression and stabilization is primordial. Typically, these injuries have an ominous prognosis, that is aggravated if added a polytrauma affecting adjacent neurological structures and other vital organs.


Assuntos
Articulação Atlantoaxial , Fraturas Ósseas , Luxações Articulares , Processo Odontoide , Fraturas da Coluna Vertebral , Articulação Atlantoaxial/diagnóstico por imagem , Feminino , Humanos , Processo Odontoide/diagnóstico por imagem , Fraturas da Coluna Vertebral/complicações , Fraturas da Coluna Vertebral/diagnóstico por imagem
14.
PeerJ ; 8: e8416, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32030323

RESUMO

BACKGROUND: In Mexico, species of four families of free-living calanoid copepods have been recorded as inhabitants of several freshwater systems. These families are Centropagidae, Temoridae, Pseudodiaptomidae and Diaptomidae. The genera Leptodiaptomus and Mastigodiaptomus are the most speciose diaptomid genera in Mexico, and they inhabit natural and artificial lakes, ephemeral ponds, springs, and caverns. Leptodiaptomus is considered as an endemic Nearctic genus, whereas Mastigodiaptomus is a widely distributed Neotropical genus in the southern USA, Mexico, the Caribbean Islands and Central America. Based on new and recent evidence, Mastigodiaptomus diversity has been underestimated: six species of the genus were known before 2000. In this work three new Mastigodiaptomus species have been described from different regions of Mexico by using integrative taxonomy. We also gave amended diagnosis of M. nesus Bowman (1986) and M. patzcuarensis s. str. (Kiefer, 1938). METHODS: In this work, the taxonomic status of the species was clarified using modern, integrative method based on the COI gene as a DNA marker, plus micro-structural analysis (based on SEM and ligth microscopy). RESULTS: Three new species of Mastigodiaptomus were described based on genetic and morphological analyses: M. alexei sp. n., M. ha sp. n. and M. cihuatlan sp. n. Also amended description of M. nesus, morphological variation of M. patzcuarensis s. str., and a comparison of them with all known sequences within the genus are provided. These new findings show that in Mastigodiaptomus differences in several cuticular microstructures of several appendages (such as the antennules, the fifth legs, or the urosomites of these copepods) agree with the interspecific genetic divergence >3% observed in sequences of the COI gene, and the integration of this information is a powerful tool in species delineation.

15.
J Med Food ; 23(3): 297-304, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31747348

RESUMO

Excess of visceral adipose tissue (VAT) characteristic of obesity leads to a proinflammatory state disrupting the insulin signaling pathway, triggering insulin resistance (IR) and inflammation, the main processes contributing to obesity comorbidities. Ursolic acid (UA), a pentacyclic triterpenoid occurring in a variety of plant foods, exhibits anti-inflammatory properties. The aim of this study was to evaluate UA effects on IR, hyperinsulinemia, and inflammation in experimental diet-induced obesity. Forty male Wistar rats were randomly assigned to eight groups (n = 5). One group was used for time 0. Three groups were labeled as OBE (control): receiving high-fat diet (HFD; fat content 45.24% of energy) during 3, 6, or 9 weeks; three groups UA-PREV: exposed to simultaneous HFD and UA during 3, 6, or 9 weeks to evaluate UA preventive effects; one group UA-REV: receiving HFD for 6 weeks, followed by simultaneous HFD and UA for three additional weeks to analyze UA reversal effects. Measurements were performed after 3, 6, or 9 weeks of treatment. Adiposity was calculated by weighing VAT after sacrifice. Serum markers were quantified through colorimetric and enzyme-linked immunosorbent assay methods. VAT adipokines RNAm expression was evaluated by quantitative reverse transcriptase-polymerase chain reaction. Data were analyzed by Kruskal-Wallis and Mann-Whitney U tests. UA significantly decreased adiposity, IR, hyperinsulinemia, triacylglycerides, and cholesterol levels, and also VAT mRNA expression of MCP-1 (monocyte chemoattractant protein-1), IL (interleukin)-1ß and IL-6, concomitantly increasing adiponectin levels. UA metabolic effects demonstrated in this study support its potential therapeutic utility to improve IR, hyperinsulinemia, and inflammation observed in obesity and diabetes.


Assuntos
Adipocinas/genética , Hiperinsulinismo/tratamento farmacológico , Resistência à Insulina , Obesidade/tratamento farmacológico , Triterpenos/administração & dosagem , Adipocinas/metabolismo , Animais , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Dieta Hiperlipídica/efeitos adversos , Humanos , Hiperinsulinismo/etiologia , Hiperinsulinismo/genética , Hiperinsulinismo/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Obesidade/etiologia , Obesidade/genética , Obesidade/metabolismo , Ratos , Ratos Wistar , Ácido Ursólico
16.
Med Chem ; 13(8): 727-733, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28934926

RESUMO

BACKGROUND: 3,3'-Diindolylmethane (DIM) is a condensation product of indole-3-carbinol, a glucosinolate naturally occurring in Brassica genus vegetables. The antiinflammatory properties of DIM through the inhibition of NF-κB, as well as its ameliorating effects on glucose tolerance and hyperglicemic states, have been described. A subclinical proinflammatory profile resultant from the interaction of adipocytes and macrophages has been reported in obesity, affecting the insulin signaling pathway, contributing to insulin resistance. OBJECTIVE: The aim of this study was to evaluate the effect of DIM on proinflammatory cytokines and phosphorylation of IRS-1 pY612 and Akt-1/PKB pT308 in an obesity-induced inflammation model. METHODS: Differentiated 3T3-L1 adipocytes were co-cultured with RAW 264.7 macrophages and exposed to 20 µM, 40 µM and 60 µM DIM for 24 h followed by 100 nM insulin for 20 min. MCP-1, IL-6 and TNFα were quantified in the supernatant through individual ELISAs. Adipocyte lysates were used to determine the relative expression of the proinflammatory mediators by qPCR, and the phosphorylation of IRS-1 pY612 and Akt-1/PKB pT308 proteins by western blot analysis. RESULTS: DIM significantly (p<0.05) reduced the production and mRNA expression of MCP-1, IL-6, and TNFα in a DIM concentration dependent manner, concomitantly increasing the abundance of IRS-1 pY612 and Akt-1/PKB pT308. CONCLUSION: Our results suggest that DIM influences the insulin transduction pathway by exerting an antiinflammatory effect. The potential therapeutic benefits of DIM in the treatment of glucose metabolic disorders deserve further studies.


Assuntos
Adipócitos/efeitos dos fármacos , Anti-Inflamatórios não Esteroides/farmacologia , Indóis/farmacologia , Proteínas Substratos do Receptor de Insulina/metabolismo , Macrófagos/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células 3T3-L1 , Adipócitos/metabolismo , Animais , Anti-Inflamatórios não Esteroides/química , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Técnicas de Cocultura , Relação Dose-Resposta a Droga , Indóis/química , Proteínas Substratos do Receptor de Insulina/genética , Macrófagos/metabolismo , Camundongos , Estrutura Molecular , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/genética , Células RAW 264.7 , Relação Estrutura-Atividade
17.
Brain Struct Funct ; 220(5): 2721-38, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24972960

RESUMO

Although type 1 cannabinoid receptors (CB1Rs) are expressed abundantly throughout the brain, the presence of type 2 cannabinoid receptors (CB2Rs) in neurons is still somewhat controversial. Taking advantage of newly designed CB1R and CB2R mRNA riboprobes, we demonstrate by PCR and in situ hybridization that transcripts for both cannabinoid receptors are present within labeled pallidothalamic-projecting neurons of control and MPTP-treated macaques, whereas the expression is markedly reduced in dyskinetic animals. Moreover, an in situ proximity ligation assay was used to qualitatively assess the presence of CB1Rs and CB2Rs, as well as CB1R-CB2R heteromers within basal ganglia output neurons in all animal groups (control, parkinsonian and dyskinetic macaques). A marked reduction in the number of CB1Rs, CB2Rs and CB1R-CB2R heteromers was found in dyskinetic animals, mimicking the observed reduction in CB1R and CB2R mRNA expression levels. The fact that chronic levodopa treatment disrupted CB1R-CB2R heteromeric complexes should be taken into consideration when designing new drugs acting on cannabinoid receptor heteromers.


Assuntos
Gânglios da Base/metabolismo , Neurônios/metabolismo , Transtornos Parkinsonianos , Receptor CB1 de Canabinoide/metabolismo , Receptor CB2 de Canabinoide/metabolismo , Animais , Canabinoides/metabolismo , Levodopa/metabolismo , Macaca , Masculino
18.
J Nephrol ; 15(2): 136-43, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12018629

RESUMO

BACKGROUND: Low albumin and high C-reactive protein (CRP) are significant predictors of mortality in hemodialysis (HD) patients. Although, classically, hypoalbuminemia has been attributed to malnutrition, inflammation can also predict the serum albumin concentration in dialysis patients. OBJECTIVE: To establish the influence of nutritional status and inflammation on mortality in HD patients. METHODS: A cross-sectional study was conducted in 64 patients (35 males; 9 diabetics; mean age 64 +/- 12 years), who had been on HD for 64 +/- 58 months. Nutritional status was assessed from estimated protein caloric intake, dietary recall, anthropometric and biochemical parameters, and serum levels of insulin-like growth factor-1 (IGF-1). CRP was used as a marker of inflammation. Comorbidity was measured using a modified M. Charlson index. The dialysis doses (Kt/V) and protein catabolic rate (PCR) were measured and standardized for actual and ideal body weight. The incidence and causes of death were recorded during the two-year follow-up. RESULTS: During the follow-up period, 18 patients died and 11 were withdrawn from the study after receiving a renal transplant. In multivariante analysis (Cox proportional hazards model), total comorbidity and the levels of CRP and hematocrit (increased) and IGF-1 (decreased) were independent predictors of mortality. CONCLUSIONS: Inflammation, as measured by CRP, and malnutrition, as measured by IGF-1 levels, are associated with mid-term mortality in HD patients. High hematocrit was an independent risk factor for mortality. Comorbidity, measured by disease and the degree of functional impairment, was a good predictor of mortality.


Assuntos
Proteína C-Reativa/análise , Inflamação/etiologia , Falência Renal Crônica/mortalidade , Distúrbios Nutricionais/etiologia , Diálise Renal/efeitos adversos , Albumina Sérica/análise , Idoso , Feminino , Hematócrito , Humanos , Inflamação/sangue , Fator de Crescimento Insulin-Like I/análise , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Distúrbios Nutricionais/sangue , Estado Nutricional , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco
19.
Brain Struct Funct ; 217(2): 613-66, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22179107

RESUMO

A stereotaxic brain atlas of the basal ganglia and thalamus of Macaca fascicularis presented here is designed with a surgical perspective. In this regard, all coordinates have been referenced to a line linking the anterior and posterior commissures (ac-pc line) and considering the center of the ac at the midline as the origin of the bicommissural space. The atlas comprises of 43 different plates (19 coronal levels, 10 sagittal levels and 14 horizontal levels). In addition to 'classical' cyto- and chemoarchitectural techniques such as the Nissl method and the acetylcholinesterase stain, several immunohistochemical stains have been performed in adjacent sections, including the detection of tyrosine hydroxylase, enkephalin, neurofilaments, parvalbumin and calbindin. In comparison to other existing stereotaxic atlases for M. fasicularis, this atlas has two main advantages: firstly, brain cartography is based on a wide variety of cyto- and chemoarchitectural stains carried out on adjacent sections, therefore enabling accurate segmentation. Secondly and most importantly, sagittal and horizontal planes are included. Sagittal planes are very useful for calculating oblique trajectories, whereas, clinical researchers engaged in neuroimaging studies will be more familiar with horizontal sections, as they use horizontal (also called "axial") brain images in their daily routine of their clinical practices.


Assuntos
Gânglios da Base/anatomia & histologia , Macaca fascicularis/anatomia & histologia , Técnicas Estereotáxicas , Tálamo/anatomia & histologia , Animais , Gânglios da Base/metabolismo , Mapeamento Encefálico/métodos , Calbindinas , Encefalinas/metabolismo , Macaca fascicularis/metabolismo , Masculino , Parvalbuminas/metabolismo , Proteína G de Ligação ao Cálcio S100/metabolismo , Tálamo/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo
20.
Rev. cuba. cir ; 40(2): 112-118, abr.-jun. 2001.
Artigo em Espanhol | LILACS, CUMED | ID: lil-628177

RESUMO

Se realizó un estudio no observacional, de tipo ensayo clínico terapéutico, comparativo, prospectivo y aleatorizado a 60 pacientes a quienes se les realizó cirugía torácica electiva, con el objetivo de evaluar la eficacia del ácido épsilon aminocaproico (AEAC) en cuanto a la disminución del sangramiento posoperatorio y las transfusiones homólogas en este período, así como describir sus posibles reacciones indeseables. Se encontró que la cantidad de sangre colectada en el posoperatorio fue significativamente menor en el grupo tratado con AEAC que en el control tanto a las 6 como a las 24 horas de finalizada la intervención. Las unidades de glóbulos transfundidas en el transoperatorio fueron semejantes en los 2 grupos, pero la cantidad de glóbulos administrados en el posoperatorio resultó significativamente menor en el grupo estudio, al igual que la proporción de pacientes que necesitó transfusión homóloga en este grupo. No se hallaron diferencias entre ambos grupos en cuanto a las reacciones indeseables(AU)


A randomized, prospective and comparative clinicotherapeutic trial was conducted as part of a non-observational study that included 60 patients who underwent elective thoracic surgery in order to evaluate the effectiveness of epsilon aminocaproic acid (EACA) in connection with the decrease of postoperative bleeding and homologous transfusions in this period, as well as to describe its potential undesirable reactions. It was found that the quantity of blood collected in the postoperaive period was much lower in the group treated with EACA than in the control group, both at 6.00 and at 24.00 hrs postintervention. The units of red blood cells transfunded in the transoperative period were similar in both groups, but the quantity of red blood cells administered in the postoperative was significantly lower in the study group, as well as the proportion of patients requiring homologous transfusions in this group. There were no differences between both groups as for undesirable reactions(AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Cirurgia Torácica/métodos , Transfusão de Sangue/métodos , Ácido Aminocaproico/uso terapêutico , Antifibrinolíticos/uso terapêutico , Estudos Prospectivos , Estudos Observacionais como Assunto
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