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Indoor air quality was characterized in 10 recently built energy-efficient French schools during two periods of 4.5 days. Carbon dioxide time-resolved measurements during occupancy clearly highlight the key role of the ventilation rate (scheduled or occupancy indexed), especially in this type of building, which was tightly sealed and equipped with a dual-flow ventilation system to provide air refreshment. Volatile organic compounds (VOCs) and inorganic gases (ozone and NO2 ) were measured indoors and outdoors by passive techniques during the occupied and the unoccupied periods. Over 150 VOC species were identified. Among them, 27 species were selected for quantification, based on their occurrence. High concentrations were found for acetone, 2-butanone, formaldehyde, toluene, and hexaldehyde. However, these concentrations are lower than those previously observed in conventional school buildings. The indoor/outdoor and unoccupied/occupied ratios are informative regarding emission sources. Except for benzene, ozone, and NO2 , all the pollutants in these buildings have an indoor source. Occupancy is associated with increased levels of acetone, 2-butanone, pentanal, butyl acetate, and alkanes.
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Poluição do Ar/análise , Dióxido de Nitrogênio/análise , Ozônio/análise , Instituições Acadêmicas , Compostos Orgânicos Voláteis/análise , Conservação de Recursos Energéticos/métodos , Monitoramento Ambiental/métodos , França , Humanos , Ventilação/métodosRESUMO
Regeneration of orofacial tissues is hampered by the lack of adequate vascular supply. Implantation of in vitro engineered, prevascularized constructs has emerged as a strategy to allow the rapid vascularization of the entire graft. Given the angiogenic properties of dental pulp stem cells, we hereby established a preclinical model of prevascularized constructs loaded with stem cells from human exfoliating deciduous teeth (SHED) in a 3-dimensional-printed material and provided a functional analysis of their in vivo angiogenesis, vascular perfusion, and permeability. Three different cell-loaded collagen hydrogels (SHED-human umbilical vein endothelial cell [HUVEC], HUVEC with SHED-conditioned medium, and SHED alone) were cast in polylactic acid (PLA) grids and ectopically implanted in athymic mice. At day 10, in vivo positron emission tomography (PETscan) revealed a significantly increased uptake of radiotracer targeting activated endothelial cells in the SHED-HUVEC group compared to the other groups. At day 30, ex vivo micro-computed tomography imaging confirmed that SHED-HUVEC constructs had a significantly increased vascular volume compared to the other ones. Injection of species-specific lectins analyzed by 2-photon microscopy demonstrated blood perfusion of the engineered human vessels in both prevascularized groups. However, in vivo quantification showed increased vessel density in the SHED-HUVEC group. In addition, coinjection of fluorescent lectin and dextran revealed that prevascularization with SHED prevented vascular leakage, demonstrating the active role of SHED in the maturation of human-engineered microvascular networks. This preclinical study introduces a novel PLA prevascularized and implantable construct, along with an array of imaging techniques, to validate the ability of SHED to promote functional human-engineered vessels, further highlighting the interest of SHED for orofacial tissue engineering. Furthermore, this study validates the use of PETscan for the early detection of in vivo angiogenesis, which may be applied in the clinic to monitor the performance of prevascularized grafts.
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BACKGROUND: Infant mortality rates (IMR) remain high in many sub-Saharan African countries, especially in rural settings where access to health services may be limited. Studies in such communities can provide relevant data on the burden of and risk factors for infant death. We measured IMR and explored risk factors for infant death in a cohort of children born in Banfora Health District, a rural area in South-West Burkina Faso. METHODS: A prospective community-based cohort study was nested within the PROMISE-EBF trial (NCT00397150) in 24 villages of the study area. Maternal and infant baseline characteristics were collected at recruitment and after birth, respectively. Home visits were conducted at weeks 3, 6, 12, 24 and 52 after birth. Descriptive statistics were calculated using robust standard errors to account for cluster sampling. Cox multivariable regression was used to investigate potential risk factors for infant death. RESULTS: Among the 866 live born children included in the study there were 98 infant deaths, yielding an IMR of 113 per 1000 live births (95% CI: 89-143). Over 75% of infant deaths had occurred by 6 months of age and the post neonatal infant mortality rate was 67 per 1000 live births (95% CI: 51-88). Infections (35%) and preterm births complications (23%) were the most common probable causes of death by 6 months. Multivariable analyses identified maternal history of child death, polygyny, twin births and poor anthropometric z-scores at week-3 as factors associated with increased risk of infant death. CONCLUSIONS: We observed a very high IMR in a rural area of Burkina Faso, a country where 75% of the population lives in rural settings. Community-based health interventions targeting mothers and children at high risk are urgently needed to reduce the high burden of infant deaths in these areas.
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Mortalidade Infantil , Adulto , Fatores Etários , Burkina Faso/epidemiologia , Causas de Morte , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Estimativa de Kaplan-Meier , Masculino , Paridade , Gravidez , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , População Rural/estatística & dados numéricos , Fatores Socioeconômicos , Adulto JovemRESUMO
Women with antiphospholipid syndrome (APS) may have diverse pregnancy outcomes. The objective of this study was to evaluate pregnancy outcome in women with APS according to their clinical phenotype, i.e. thrombotic and obstetric APS. Eighty-three pregnancies in 67 women with APS were included in the study, including 21 with recurrent miscarriage (Group 1), 21 with late fetal loss or early delivery due to placental dysfunction (Group 2) and 41 with thrombotic APS (Group 3). Group 3 had higher rates of preterm delivery (26.8% versus 4.7%, p = 0.05) than Group 1 and more small for gestational age (SGA) babies than Group 2 (39.5% versus 4.8%, p = 0.003). Group 2 had significantly longer gestations compared with their pretreatment pregnancies (38.4 [28.4-41.4] versus 24.0 [18-35] weeks, p < 0.0001) and 100% live birth rate after treatment with aspirin and low-molecular-weight heparin (LMWH). In conclusion, women with thrombotic APS (Group 3) have higher rates of pregnancy complications than those with obstetric APS (Groups 1 and 2). Treatment with aspirin and LMWH is associated with improved outcomes for women with previous late fetal loss or early delivery due to placental dysfunction (Group 2).
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Síndrome Antifosfolipídica/complicações , Complicações na Gravidez , Adulto , Síndrome Antifosfolipídica/tratamento farmacológico , Aspirina/uso terapêutico , Feminino , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Trabalho de Parto Prematuro/epidemiologia , Fenótipo , Pré-Eclâmpsia/epidemiologia , Gravidez , Estudos RetrospectivosRESUMO
Few empirical data address naturalistic outcomes of residential eating disorder (ED) treatment. Study aims were to evaluate course, effectiveness, and predictors of outcome in a residential treatment program. We evaluated 80 consecutively admitted female adolescents with the SCID-IV. Primary outcomes were treatment completion, subsequent readmission, clinical global impressions, and changes in body weight. Mean length of stay was 51 days, and 80% of patients were discharged according to treatment plans. Mean expected body weight (EBW) for AN patients increased from 80% to 91%. Patients reported significant improvements in ED symptoms, depression, and quality of life. Low admission %EBW and previous psychiatric hospitalizations were associated with premature termination. Overall, findings support that residential treatment is largely acceptable to patients, and that residential care may provide an opportunity for substantive therapeutic gains.
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Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Adolescente , Arteterapia , Peso Corporal , Terapia Cognitivo-Comportamental , Depressão/terapia , Transtornos da Alimentação e da Ingestão de Alimentos/fisiopatologia , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Feminino , Humanos , Tempo de Internação , Prognóstico , Tratamento Domiciliar , Problemas Sociais , Resultado do Tratamento , Adulto JovemRESUMO
Cissus quadrangularis (C. quadrangularis) is a plant of the Vitaceae family known for its anticonvulsant effects in traditional medicine. The objective of this study was to elucidate the anxiolytic and antiepileptic effects of aqueous extract of C. quadrangularis. The mice were divided into different groups and treated for seven consecutive days as follows: a negative control group that received distilled water, po, four test groups that received four doses of the plant (37.22, 93.05, 186.11, and 372.21 mg/kg, po), and a positive control group that received sodium valproate (300 mg/kg, ip). One hour after the first treatment (first day), epilepsy was induced by intraperitoneal administration of a single dose of pilocarpine (360 mg/kg). On the seventh day, the anxiolytic effects of the extract were evaluated in the epileptic mice using the elevated plus maze (EPM) and open field (OP) paradigms. Antioxidant activities and the involvement of gabaergic neurotransmission were determined by measuring the levels of malondialdehyde, reduced glutathione (GSH), GABA, and GABA-transaminase (GABA-T) in the hippocampus of sacrificed epileptic mice. The results show that the extract of C. quadrangularis significantly and dose-dependently increased the latency to clonic and generalized tonic-clonic seizures and decreased the number and duration of seizures. In the EPM, the extract of C. quadrangularis significantly increased the number of entries and the time spent into the open arms and reduced the number of entries and the time spent into the closed arms as well as the number of rearing. The extract of C. quadrangularis also increased the number of crossing, and the time spent in the center of the OP. The level of MDA and the activity of GABA-T were significantly decreased by the extract of C. quadrangularis while reduced GSH and GABA levels were increased. The results suggest that the anticonvulsant activities of C. quadrangularis are accompanied by its anxiolytics effects. These effects may be supported by its antioxidant properties and mediated at least in part by the GABA neurotransmission.
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INTRODUCTION: Infra-popliteal angioplasty continues to be widely performed with minimal evidence to guide practice. Endovascular device selection is contentious and there is even uncertainty over which artery to treat for optimum reperfusion. Direct reperfusion (DR) targets the artery supplying the ischaemic tissue. Indirect reperfusion (IR) targets an artery supplying collaterals to the ischaemic area. Our unit practice for the last eight years has been to attempt to open all tibial arteries at the time of angioplasty. When successful, this results in both direct and indirect; or combined reperfusion (CR). The aim was to review the outcomes of CR and compare them with DR or IR alone. METHODS: An eight year retrospective review from a single unit of all infra-popliteal angioplasties was undertaken. Wound healing, limb salvage, amputation-free and overall survival data as well as re-intervention rates were captured for all patients. Subgroup analysis for diabetics was undertaken. Kaplan Meier curves are presented for survival outcomes. All odds and hazard ratios (HR) and p values were corrected for bias from confounders using multivariate analysis. RESULTS: 250 procedures were performed: 22 (9%) were CR; 115 (46%) DR and 113 (45%) IR. Amputation-free survival (HR 0.504, p = 0.039) and re-intervention and amputation-free survival (HR 0.414, p = 0.005) were significantly improved in patients undergoing CR compared to IR. Wound healing was similarly affected by reperfusion strategy (OR = 0.35, p = 0.047). Effects of CR over IR were similar when only diabetic patients were considered. CONCLUSIONS: Combined revascularisation can only be achieved in approximately 10% of patients. However, when successful, it results in significant improvements in wound healing and amputation-free survival over simple indirect reperfusion techniques.
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Angioplastia , Isquemia/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Complicações do Diabetes/complicações , Complicações do Diabetes/patologia , Intervalo Livre de Doença , Feminino , Humanos , Isquemia/mortalidade , Estimativa de Kaplan-Meier , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Artéria Poplítea/diagnóstico por imagem , Artéria Poplítea/cirurgia , Modelos de Riscos Proporcionais , Reperfusão , Estudos Retrospectivos , CicatrizaçãoRESUMO
In this study, we investigated antiepileptogenic and neuroprotective effects of the aqueous extract of Pergularia daemia roots (PDR) using in vivo and in vitro experimental models. In in vivo studies, status epilepticus caused by pilocarpine injection triggers epileptogenesis which evolves during about 1-2 weeks. After 2 h of status epilepticus, mice were treated during the epileptogenesis period for 7 days with sodium valproate and vitamin C (standards which demonstrated to alter epileptogenesis), or Pergularia daemia. The animals were then, 1 week after status epilepticus, challenged with acute pentylenetetrazole (PTZ) administration to test behaviorally the susceptibility to a convulsant agent of animals treated or not with the plan extract. Memory was assessed after PTZ administration in the elevated plus maze and T-maze paradigms at 24 and 48 h. Antioxidant and acetylcholinesterase activities were determined in the hippocampus after sacrifice, in vitro studies were conducted using embryonic rat primary cortical cultures exposed to L-glutamate. Cell survival rate was measured and apoptotic and necrotic cell death determined. The results showed that chronic oral administration of PDR significantly and dose-dependently increased the latency to myoclonic jerks, clonic seizures and generalized tonic-clonic seizures, and the seizure score. In addition, PDR at all doses (from 4.9 to 49 mg/kg) significantly decreased the initial and retention transfer latencies in the elevated plus maze. Interestingly PDR at the same doses significantly increased the time spent and the number of entries in T-maze novel arm. PDR significantly increased the activities of acetylcholinesterase and antioxidant enzymes superoxide dismutase, catalase, and total glutathione and proteins, and decreased malondialdehyde level. Furthermore, PDR increased viability rate of primary cortical neurons after L-glutamate-induced excitotoxicity, in a dose dependent manner. Altogether these results suggest that PDR has antiepileptogenic and neuroprotective effects, which could be mediated by antioxidant and antiapoptotic activities.
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Alzheimer's disease the most common form of dementia in the elderly is a neurodegenerative disease that affects 44 millions of people worldwide. The first treatments against Alzheimer's disease are acetylcholinesterase inhibitors; however, these medications are associated with many side effects. Dichrocephala integrifolia is a traditional herb widely used by indigenous population of Cameroon to treat and prevent Alzheimer's disease and for memory improvement. In this study, we evaluated the effect of the decoction prepared from leaves of D. integrifolia, on scopolamine-induced memory impairment in mice. Seven groups of six animals were used. The first two groups received distilled water for the distilled water and scopolamine groups. The four test groups received one of the four doses of the decoction of the plant (35, 87.5, 175 or 350 mg/kg p.o.) and the positive control group received tacrine (10 mg/kg), a cholinesterase inhibitor used in the treatment of Alzheimer's disease, during 10 consecutive days. Scopolamine (1 mg/kg), a cholinergic receptor blocker, administered 30 min after treatments, was used to induce memory impairment to all groups except the distilled water group on day 10 of drug treatment. The behavioral paradigms used to evaluate the effects of the treatment were the elevated plus maze for learning and memory, Y maze for spatial short-term memory, the novel object recognition for recognition memory and Morris water maze for the evaluation of spatial long-term memory. After behavioral tests, animals were sacrificed and brains of a subset were used for the assessment of some biomarkers of oxidative stress (malondialdehyde and reduced glutathione levels) and for the evaluation of the acetylcholinesterase activity. From the remaining subset brains, histopathological analysis was performed. The results of this study showed that, D. integrifolia at the doses of 87.5 and 350 mg/kg significantly (p < 0.01) improved spatial short-term and long-term memory, by increasing the percentage of spontaneous alternation in the Y maze and reducing the escape latency in the Morris water maze. Furthermore, the results of histopathological evaluation showed that D. integrifolia attenuated the neuronal death in the hippocampus induced by scopolamine. The main finding of this work is that D. integrifolia improves learning capacities and counteracts the memory impairment induced by scopolamine. Thus, D. integrifolia can be a promising plant resource for the management of Alzheimer's disease and memory loss.
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To assess the feasibility of using the renin promoter for expressing Cre recombinase in juxtaglomerular (JG) cells only, we generated five independent transgenic mouse lines (designated hRen-Cre) expressing Cre recombinase under control of a 12.2-kb human renin promoter. In the kidneys of adult mice Cre mRNA (RT-PCR) was found in the renal cortex, with Cre protein (immunohistochemistry) being localized in afferent arterioles and to a lower degree in interlobular arteries. Cre mRNA levels were regulated in a renin-typical fashion by changes in oral salt intake, water restriction, or isoproterenol infusion, indicating the presence of key regulatory elements within 12.2 kb of the 5'-flanking region of the human renin gene. hRen-Cre mice were interbred with both the ROSA26-EGFP and ROSA26-lacZ reporter strains to assess renin promoter activity from Cre-mediated excision of a floxed stop cassette and subsequent enhanced green fluorescent protein (EGFP) and beta-galactosidase (beta-gal) detection. In adult mice, beta-gal staining and EGFP were observed in afferent arterioles and interlobular arteries, overlapping with Cre protein expression. In addition, intense beta-gal staining was found in cortical and medullary collecting ducts where Cre expression was minimal. In embryonic kidneys, beta-gal staining was detected in the developing collecting duct system beginning at embryonic day 12, showing substantial activity of the human renin promoter in the branching ureteric bud. Our data indicate that besides its well-known activity in JG cells and renal vessels the human renin promoter is transiently active in the collecting duct system during kidney development, complicating the use of this approach for JG cell-specific excision of floxed targets.
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Genes Reporter , Integrases/genética , Sistema Justaglomerular/metabolismo , Túbulos Renais Coletores/metabolismo , Regiões Promotoras Genéticas/genética , Recombinação Genética , Renina/genética , Animais , Humanos , Imuno-Histoquímica , Integrases/metabolismo , Medula Renal/embriologia , Medula Renal/metabolismo , Túbulos Renais Coletores/embriologia , Óperon Lac , Camundongos , Camundongos Transgênicos , RNA Mensageiro/metabolismo , Renina/metabolismo , Fatores de Tempo , Transgenes , beta-GalactosidaseRESUMO
Neural crest cells (NCCs) are a population of multipotent cells that migrate extensively during vertebrate development. Alterations to neural crest ontogenesis cause several diseases, including cancers and congenital defects, such as Hirschprung disease, which results from incomplete colonization of the colon by enteric NCCs (ENCCs). We investigated the influence of the stiffness and structure of the environment on ENCC migration in vitro and during colonization of the gastrointestinal tract in chicken and mouse embryos. We showed using tensile stretching and atomic force microscopy (AFM) that the mesenchyme of the gut was initially soft but gradually stiffened during the period of ENCC colonization. Second-harmonic generation (SHG) microscopy revealed that this stiffening was associated with a gradual organization and enrichment of collagen fibers in the developing gut. Ex-vivo 2D cell migration assays showed that ENCCs migrated on substrates with very low levels of stiffness. In 3D collagen gels, the speed of the ENCC migratory front decreased with increasing gel stiffness, whereas no correlation was found between porosity and ENCC migration behavior. Metalloprotease inhibition experiments showed that ENCCs actively degraded collagen in order to progress. These results shed light on the role of the mechanical properties of tissues in ENCC migration during development.
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Movimento Celular/fisiologia , Embrião de Mamíferos/embriologia , Embrião de Mamíferos/ultraestrutura , Trato Gastrointestinal/embriologia , Trato Gastrointestinal/ultraestrutura , Crista Neural/embriologia , Crista Neural/ultraestrutura , Animais , Embrião de Galinha , Colagenases/metabolismo , Matriz Extracelular/metabolismo , Matriz Extracelular/ultraestrutura , Camundongos , Microscopia de Força AtômicaRESUMO
Calu-6 cells were characterized for studying the transcriptional regulation of the human renin gene. Analysis of cis-acting elements of the renin promoter showed the highest activity within the first 582 bp in serum-free conditions and of the 892 bp in the presence of serum. cAMP activates renin mRNA synthesis parallel to renin production (20-fold increase) as well renin promoter activity (2-fold). cAMP response element and the (-77 to -67) element are both necessary for activation of the renin promoter but do not act independently. Functional analysis of Intron A revealed the presence of a silencer specific to renin-producing cells.
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Regulação Enzimológica da Expressão Gênica , Regiões Promotoras Genéticas , Renina/genética , Renina/metabolismo , Transcrição Gênica , Animais , Células CHO , Colforsina/farmacologia , Cricetinae , AMP Cíclico/farmacologia , Imunofluorescência , Genes Reporter , Células HeLa , Humanos , Íntrons , Luciferases/biossíntese , Luciferases/genética , Neoplasias Pulmonares , Deleção de Sequência , Transfecção , Células Tumorais CultivadasRESUMO
The purpose of the present study was to investigate the effect of a concentrated preparation (EPA 30) containing eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3) on the limiting desaturation steps of the polyunsaturated fatty acid biosynthesis in spontaneously hypertensive rats (SHR). Adult SHR were divided into two groups: one group received a standard diet, and the experimental group the standard diet including 0.8% of EPA30 for 9 weeks. Blood pressure was measured at the end of the diets. The desaturase activities and fatty acid composition were determined in isolated hepatocytes. The blood pressure did not decrease in the experimental group. The desaturated products of the n-6 family (gamma-linolenic acid, 18:3 n-6 and arachidonic acid, 20:4 n-6) were lowered in the EPA30 group, when their respective substrates (18:2 n-6 and 20:3 n-6) were increased. EPA and DHA were higher in the experimental group delta 6 n-3, delta 6 n-6 and delta 5 n-6 desaturase activities were depressed approximately 20% in the EPA30 group. EPA30 being an active nutrient on the EFAs cascade, increasing the level of PG3 precursors and decreasing the level of PG2 precursors, favourable conditions have been established to reduce hypertension. The underlying mechanism related to the regulation of desaturase activities by these fatty nutrients remains to be elucidated.
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Ácidos Graxos Dessaturases/metabolismo , Ácidos Graxos/metabolismo , Hipertensão/fisiopatologia , Ratos Endogâmicos SHR/metabolismo , Animais , Ingestão de Energia , Ácidos Graxos Insaturados/metabolismo , Fígado/metabolismo , RatosRESUMO
OBJECTIVE: A silencer within the renin first intron (intron A) was identified using Calu-6 cells, a pulmonary carcinoma cell line which produced renin. In the present study, a dissection of the first intron was performed to determine precisely the cis-regulatory elements involved in the silencer transcriptional effects. MATERIALS AND METHODS: Intron A was completely sequenced to characterize potential binding sites for known transcription factors. Partial portions of intron A were subcloned upstream the 892 bp of the renin promoter and transfected in different models of renin-producing cells: primary culture of human chorionic cells, human Calu-6 cells and mouse As4.1 cells. RESULTS: There is significant DNA homology (67%) between the 3' and 5' ends of the human and rat renin first intron. Several transcription factor binding sites identified in human first intron, but not in rat intron, do not contribute to the reported silencer activity. Transfections of renin/ luciferase constructs containing partial portions of first intron inserted upstream of the 892 bp in both renin-producing cells do not allow the precise characterization of cis-elements involved in the silencer effect. CONCLUSIONS: The silencer located renin intron A is cell specific. The integrity of the human first intron seems necessary for its repressor activity on renin proximal promoter in renin-producing cells.
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Íntrons/genética , Renina/genética , Animais , Sequência de Bases , Clonagem Molecular , Humanos , Camundongos , Dados de Sequência Molecular , Ratos , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência do Ácido Nucleico , TransfecçãoRESUMO
Acyl-CoA:cholesterol acyltransferase (ACAT) is the primary enzyme involved in intracellular cholesterol esterification. Arterial wall infiltration by macrophages and subsequent uncontrolled esterification of cholesterol leading to foam cell formation is believed to be an important process which leads to the development of fatty streaks. Inhibitors of the ACAT enzyme may retard this atherogenic process. We have recently discovered a series of imidazoles which are potent in vitro ACAT inhibitors in the J774 macrophage cell culture assay. This paper will describe the design, synthesis, and structure--activity relationship for this very potent series of compounds.
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Macrófagos/enzimologia , Esterol O-Aciltransferase/antagonistas & inibidores , Animais , Linhagem Celular , Desenho de Fármacos , Imidazóis/síntese química , Imidazóis/farmacologia , Isoenzimas/antagonistas & inibidores , Camundongos , Microssomos Hepáticos/enzimologia , Ratos , Relação Estrutura-AtividadeRESUMO
We have proposed that the maternal syndrome of pre-eclampsia is caused by a systemic inflammatory response involving both leucocytes and endothelium. This inflammatory response is present also in normal pregnancy, but in a milder form. The inflammatory stimulus is most likely to come from the placenta. Syncytiotrophoblast apoptotic debris, which is shed into the maternal circulation in normal pregnancy and in increased amounts in pre-eclampsia, may be the stimulus for this response. It may also contribute to the suppression of Th1 responses seen in pregnancy.
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Inflamação/imunologia , Placenta/imunologia , Pré-Eclâmpsia/imunologia , Trofoblastos/fisiologia , Endotélio Vascular/fisiologia , Feminino , Humanos , Inflamação/etiologia , Troca Materno-Fetal , Placenta/irrigação sanguínea , Placenta/fisiologia , Pré-Eclâmpsia/etiologia , Pré-Eclâmpsia/fisiopatologia , GravidezRESUMO
Non-insulin-dependent, or type II, diabetes mellitus is characterized by a progressive impairment of glucose-induced insulin secretion by pancreatic beta cells and by a relative decreased sensitivity of target tissues to the action of this hormone. About one third of type II diabetic patients are treated with oral hypoglycemic agents to stimulate insulin secretion. These drugs however risk inducing hypoglycemia and, over time, lose their efficacy. An alternative treatment is the use of glucagon-like peptide-1 (GLP-1), a gut peptidic hormone with a strong insulinotropic activity. Its activity depends of the presence of normal blood glucose concentrations and therefore does not risk inducing hypoglycemia. GLP-1 can correct hyperglycemia in diabetic patients, even in those no longer responding to hypoglycemic agents. Because it is a peptide, GLP-1 must be administered by injection; this may prevent its wide therapeutic use. Here we propose to use cell lines genetically engineered to secrete a mutant form of GLP-1 which has a longer half-life in vivo but which is as potent as the wild-type peptide. The genetically engineered cells are then encapsulated in semi-permeable hollow fibers for implantation in diabetic hosts for constant, long-term, in situ delivery of the peptide. This approach may be a novel therapy for type II diabetes.
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Diabetes Mellitus Tipo 2/terapia , Glucagon/metabolismo , Membranas Artificiais , Fragmentos de Peptídeos/metabolismo , Precursores de Proteínas/metabolismo , Animais , Engenharia Genética , Glucagon/genética , Glucagon/uso terapêutico , Peptídeo 1 Semelhante ao Glucagon , Humanos , Camundongos , Mutação , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/uso terapêutico , Precursores de Proteínas/genética , Precursores de Proteínas/uso terapêuticoRESUMO
The aim of the present study was to investigate whether a mixture of dietary n-6 and n-3 PUFA could lower blood pressure in spontaneously hypertensive rats (SHR) of different ages. In addition, we studied how such a treatment could normalize the FA composition of plasma TAG and cholesterol esters (CE), and of red blood cell (RBC) total lipids. SHR (ages 4, 19, and 50 wk) were fed a normal diet (control groups) or a semisynthetic diet containing a mixture of gamma-linolenic acid (GLA), EPA, and DHA (experimental groups). Systolic blood pressure was measured at regular intervals. After 11 wk of consuming this diet, plasma TAG and CE were separated by TLC and analyzed for their FA composition. Total FA composition of RBC was also determined. The degree to which blood pressure was elevated was reduced in SHR after 11 wk of diet. The largest decrease was obtained with the oldest animals. In RBC, EPA and DHA contents increased. In plasma TAG and CE, EPA, DHA, and GLA increased whereas arachidonic acid decreased. The n-6 and n-3 unsaturated FA mix slowed the development of hypertension in young SHR and decreased blood pressure in adult and aged SHR. In addition, the present treatment altered the n-3 and n-6 PUFA content of SHR lipids to that seen in normotensive rats.
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Anti-Hipertensivos/farmacologia , Ácidos Graxos Insaturados/farmacologia , Animais , Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea , Peso Corporal , Membrana Eritrocítica/metabolismo , Ácidos Graxos/sangue , Ácidos Graxos Insaturados/administração & dosagem , Comportamento Alimentar , Ratos , Ratos Endogâmicos SHRRESUMO
Docosahexaenoic acid (DHA, 22:6n-3) is an n-3 polyunsaturated fatty acid which attenuates the development of hypertension in spontaneously hypertensive rats (SHR). The effects of DHA on delta-9-desaturase activity in hepatic microsomes and fatty acid composition were examined in young SHR. Two groups of SHR were fed either a DHA-enriched diet or a control diet for 6 wk. Desaturase activity and fatty acid composition were determined in hepatic microsomes following the dietary treatments. Delta-9-desaturase activity was decreased by 53% in DHA-fed SHR and was accompanied by an increase in 16:0 and a reduction in 16:1n-7 content in hepatic microsomes. The DHA diet also increased the levels of eicosapentaenoic acid (20:5n-3) and DHA. The n-6 fatty acid content was also affected in DHA-fed SHR as reflected by a decrease in gamma-linolenic acid (18:3n-6), arachidonic acid (20:4n-6), adrenic acid (22:4n-6), and docosapentaenoic acid (22:5n-6). A higher proportion of dihomo-gamma-linolenic acid (20:3n-6) and a lower proportion of 20:4n-6 is indicative of impaired delta-5-desaturase activity. The alterations in fatty acid composition and metabolism may contribute to the antihypertensive effect of DHA previously reported.