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1.
Sensors (Basel) ; 24(3)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38339682

RESUMO

Black carbon (BC) or soot contains ultrafine combustion particles that are associated with a wide range of health impacts, leading to respiratory and cardiovascular diseases. Both long-term and short-term health impacts of BC have been documented, with even low-level exposures to BC resulting in negative health outcomes for vulnerable groups. Two aethalometers-AethLabs MA350 and Aerosol Magee Scientific AE33-were co-located at a Utah Division of Air Quality site in Bountiful, Utah for just under a year. The aethalometer comparison showed a close relationship between instruments for IR BC, Blue BC, and fossil fuel source-specific BC estimates. The biomass source-specific BC estimates were markedly different between instruments at the minute and hour scale but became more similar and perhaps less-affected by high-leverage outliers at the daily time scale. The greater inter-device difference for biomass BC may have been confounded by very low biomass-specific BC concentrations during the study period. These findings at a mountainous, high-elevation, Greater Salt Lake City Area site support previous study results and broaden the body of evidence validating the performance of the MA350.


Assuntos
Poluentes Atmosféricos , Poluentes Atmosféricos/análise , Fuligem/análise , Carbono/análise , Monitoramento Ambiental/métodos , Material Particulado/análise , Aerossóis
2.
Cureus ; 13(12): e20634, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35103199

RESUMO

Each year there are an estimated 1.7 million adults in the United States that develop sepsis and nearly 16% of these adult patients die because of this disease process. Sepsis, however, can impact patients of all ages. Neonatal sepsis is currently one of the leading causes of morbidity and mortality among neonates. There are many complications of neonatal sepsis including meningitis, seizures, and hypoxic ischemic encephalopathy (HIE). HIE is estimated to impact one to five in 1000 live births worldwide, primarily impacting neonates. It is more commonly seen in premature infants and infants with low birth weights due to immature organ systems and a lack of adequate auto-regulatory mechanisms that would otherwise manage brain perfusion. In premature neonates, the most commonly recognized pathological pattern found on MRI is focal non-cystic white matter injury. HIE can also impact term infants as well. In these neonates, there exist two common MRI patterns that include either basal ganglia-thalamus ischemia, most often involving deep gray nuclei and perirolandic cortex, or watershed predominant ischemic changes that involve cortical gray matter.  We report a 38-week-old male neonate born at gestation diagnosed with HIE secondary to neonatal sepsis with an MRI finding of isolated insular cortex hypersensitivity on fluid-attenuated inversion recovery (FLAIR) and T1-weighted imaging. Isolated insular cortex hypersensitivity can be seen in non-lacunar ischemic middle cerebral artery (MCA) territory strokes but it is not common for it to present as a sole finding. In our case, these findings persisted for several weeks without evidence of any common patterns of hypoxia-induced cerebrovascular insult on MRI imaging.

3.
Neurobiol Aging ; 78: 111-120, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30925299

RESUMO

Ovariectomy (OVX), a menopause model, leads to cognition and neuronal plasticity deficits that are rescued by estrogen administration or downregulation of pituitary luteinizing hormone (LH). LH is present in the brain. However, whether LH levels differ across brain regions, change across reproductive stages, or whether brain-specific LHR signaling play a role in OVX-related cognitive and neuroplasticity losses is completely unknown. To address this, we measured brain LH in cycling and OVX C57Bl/6 across brain regions and determined whether OVX-related functional and plasticity deficits could be rescued by intracerebroventricular administration of the LHR agonist (hCG). Here, we show that while pituitary LH is increased in OVX, brain LH is decreased, primarily in spatial memory and navigation areas. Furthermore, intracerebroventricular hCG delivery after OVX rescued dendritic spine density and spatial memory. In vitro, we show that hCG increased neurite outgrowth in primary hippocampal neurons in a receptor-specific manner. Taken together, our data suggest that loss of brain LH signaling is involved in cognitive and plasticity losses associated with OVX and loss of ovarian hormones.


Assuntos
Gonadotropina Coriônica/administração & dosagem , Gonadotropina Coriônica/farmacologia , Hormônio Luteinizante/metabolismo , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/etiologia , Menopausa/fisiologia , Plasticidade Neuronal/fisiologia , Ovariectomia/efeitos adversos , Receptores do LH/metabolismo , Receptores do LH/fisiologia , Animais , Encéfalo/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Feminino , Hipocampo/fisiologia , Transtornos da Memória/prevenção & controle , Camundongos Endogâmicos C57BL , Crescimento Neuronal/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Hipófise/metabolismo , Receptores do LH/agonistas , Transdução de Sinais/fisiologia
4.
PLoS One ; 13(12): e0207200, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30521538

RESUMO

This study aimed to characterize bone cancer pain (quantitative sensory testing (QST), stance asymmetry index, actimetry, scores of pain and quality of life (QoL)) in dogs with appendicular osteosarcoma (OSA), and to evaluate a stepwise palliative analgesic treatment. The pain profile of thirteen client-owned dogs with OSA was compared with seven healthy dogs. Dogs with OSA were then enrolled in a prospective, open-label, clinical trial. Outcome measures included: primary and secondary mechanical thresholds (MT), conditioned pain modulation (CPM), stance asymmetry index, actimetry (most and least active periods), visual analog scales and QoL. After baseline assessments, stepwise treatment comprised orally administered cimicoxib (2 mg/kg q 24h), amitriptyline (1-1.5 mg/kg q 24h) and gabapentin (10 mg/kg q 8h); re-evaluations were performed after 14 (D14), 21 (D21) and 28 (D28) days, respectively. Statistics used mixed linear models (α = 5%; one-sided). Centralized nociceptive sensitivity (primary and secondary MT, and dynamic allodynia) was recorded in OSA dogs. Healthy dogs had responsive CPM, but CPM was deficient in OSA dogs. Construct validity was observed for the QST protocol. Asymmetry index was significantly present in OSA dogs. The CPM improved significantly at D14. When compared with baseline (log mean ± SD: 4.1 ± 0.04), most active actimetry significantly improved at D14 (4.3 ± 0.04), D21 and D28 (4.2 ± 0.04 for both). When compared with baseline, least active actimetry significantly decreased after treatment at all time-points indicating improvement in night-time restlessness. No other significant treatment effect was observed. Except for tactile threshold and actimetry, all outcomes worsened when gabapentin was added to cimicoxib-amitriptyline. Dogs with bone cancer are affected by widespread somatosensory sensitivity characterized by peripheral and central sensitization and have a deficient inhibitory system. This severe pain is mostly refractory to palliative analgesic treatment, and the latter was only detected by specific and sensitive outcomes.


Assuntos
Osteossarcoma/terapia , Manejo da Dor/métodos , Dor/prevenção & controle , Amitriptilina/uso terapêutico , Analgésicos/uso terapêutico , Animais , Neoplasias Ósseas , Sensibilização do Sistema Nervoso Central/efeitos dos fármacos , Doenças do Cão , Cães , Feminino , Gabapentina/uso terapêutico , Imidazóis/uso terapêutico , Masculino , Osteossarcoma/veterinária , Dor/veterinária , Medição da Dor , Limiar da Dor , Cuidados Paliativos/métodos , Estudos Prospectivos , Qualidade de Vida , Limiar Sensorial , Sulfonamidas/uso terapêutico
5.
Artigo em Inglês | MEDLINE | ID: mdl-30319538

RESUMO

Pervasive age-related dysfunction in hypothalamic-pituitary-gonadal (HPG) axis is associated with cognitive impairments in aging as well as pathogenesis of age-related neurodegenerative diseases such as the Alzheimer's disease (AD). As a major regulator of the HPG axis, the steroid hormone estrogen has been widely studied for its role in regulation of memory. Although estrogen modulates both cognition as well as cognition associated morphological components in a healthy state, the benefits of estrogen replacement therapy on cognition and disease seem to diminish with advancing age. Emerging data suggests an important role for luteinizing hormone (LH) in CNS function, which is another component of the HPG axis that becomes dysregulated during aging, particularly in menopause. The goal of this review is to highlight the current existing literature on LH and provide new insights on possible mechanisms of its action.

6.
Horm Behav ; 78: 60-6, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26497249

RESUMO

Age-related changes in reproductive hormone levels are a well-known risk factor for the development of cognitive dysfunction and dementia in women. We and others have shown an important contribution of gonadotropins in this process. Lowering serum gonadotropin levels is able to rescue cognitive function in Alzheimer's disease and menopause models, but whether this is time-dependent and the exact mechanism through which gonadotropins regulate cognitive function is unknown. We show that pharmacologically lowering serum levels of luteinizing hormone lead to cognitive improvement immediately after ovariectomy and with a 4month interval after ovariectomy, when the benefits of 17ß-estradiol are known to disappear in rodents. Importantly, we show that these improvements are associated with spine density changes at both time points. These findings suggest a role of luteinizing hormone in learning and memory and neuroplasticity processes as well as provide an alternative therapeutic strategy of menopause associated cognitive loss.


Assuntos
Densidade Óssea/efeitos dos fármacos , Cognição/efeitos dos fármacos , Estrogênios/farmacologia , Hormônio Luteinizante/sangue , Ovariectomia/efeitos adversos , Animais , Cognição/fisiologia , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/prevenção & controle , Regulação para Baixo/efeitos dos fármacos , Estradiol/sangue , Estradiol/farmacologia , Terapia de Reposição de Estrogênios , Feminino , Camundongos Endogâmicos C57BL , Osteoporose/etiologia , Osteoporose/prevenção & controle , Ovariectomia/psicologia , Reprodução/efeitos dos fármacos , Coluna Vertebral/efeitos dos fármacos , Fatores de Tempo
7.
Horm Behav ; 76: 57-62, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26172857

RESUMO

This article is part of a Special Issue "SBN 2014". Hormonal dysfunction due to aging, especially during menopause, plays a substantial role in cognitive decline as well as the progression and development of neurodegenerative diseases. The hypothalamic-pituitary-gonadal (HPG) axis has long been implicated in changes in behavior and neuronal morphology. Most notably, estrogens have proven beneficial in the healthy brain through a host of different mechanisms. Recently, luteinizing hormone (LH) has emerged as a candidate for further investigation for its role in the CNS. The basis of this is that both LH and the LH receptor are expressed in the brain, and serum levels of LH correlate with cognitive deficits and Alzheimer's disease (AD) incidence. The study of LH in cognition and AD primarily focuses on evaluating the effects of downregulation of this peptide. This literature has shown that decreasing peripheral LH, through a variety of pharmacological interventions, reduces cognitive deficits in ovariectomy and AD models. However, few studies have researched the direct actions of LH on neurons and glial cells. Here we summarize the role of luteinizing hormone in modulating cognition, and we propose a mechanism that underlies a role for brain LH in this process.


Assuntos
Envelhecimento/metabolismo , Sistema Nervoso Central/metabolismo , Transtornos Cognitivos/metabolismo , Hormônio Luteinizante/metabolismo , Neurônios/metabolismo , Receptores do LH/metabolismo , Humanos
8.
J Neurochem ; 130(1): 115-25, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24601954

RESUMO

Development of Alzheimer's disease (AD) has been linked to the de-regulation of estrogen and gonadotropins such as luteinizing hormone (LH). In this study, we found increases in AD pathology in the hippocampi of aged female 3xTg AD mice after ovariectomy that were unable to be reduced by estrogen therapy or down-regulation of serum LH levels. Despite the lack of effect of these treatments on AD pathology, down-regulation of serum LH but not estrogen improved factors associated with neuronal plasticity such as spatial memory, inhibition of glycogen synthase kinase-3 beta, expression of beta-catenin, and brain-derived neurotrophic factor transcription. Contrasting previous studies in younger mice, estrogen replacement was not able to rescue behavioral deficits, reduced glycogen synthase kinase-3 beta inhibition and increased hippocampal phosphorylation of tau. Of critical importance, serum LH was negatively correlated with brain LH in regions associated with spatial memory, and increases in brain LH correlated with cognitive improvement. This paralleled changes in human female AD brains which showed a significant reduction in brain LH mRNA compared to healthy age- and PMI-matched controls. Taken together, these findings should promote further research into the LH-dependent mechanisms associated with AD cognitive deficits as well as the effects of estrogen within the aged brain. In the aged triple transgenic Alzheimer's disease (AD) mouse model (3xAD-Tg), estrogen replacement after ovariectomy does not improve cognitive function, increases phosphorylated Tau levels and decreases inhibition of GSK3 beta. Luprolide acetate rescues ovariectomy-dependent cognitive function, increases signaling events associated with synaptic plasticity including GSK3 beta inhibition, but does not alter AD pathology. In the human AD female brain, luteinizing hormone (LH) mRNA levels are reduced. In the 3XAD-tg model, brain LH protein levels are reduced by ovariectomy and normalized by leuprolide acetate treatment. These treatment-dependent normalization of LH positively correlates with markers of neuroplasticity and cognitive improvement.


Assuntos
Envelhecimento/sangue , Cognição/fisiologia , Regulação para Baixo/fisiologia , Terapia de Reposição de Estrogênios/métodos , Estrogênios/administração & dosagem , Hormônio Luteinizante/sangue , Ovariectomia , Animais , Biomarcadores/sangue , Células Cultivadas , Feminino , Gonadotropinas/sangue , Hipocampo/metabolismo , Camundongos , Camundongos Transgênicos , Ratos , Ratos Sprague-Dawley
9.
Neurobiol Aging ; 35(4): 793-801, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24239383

RESUMO

Amylin is a metabolic peptide hormone that is co-secreted with insulin from beta cells in the pancreas and activates many of the downstream targets of insulin. To investigate the relationship between this hormone and Alzheimer's disease (AD), we measured plasma human amylin levels in 206 subjects with AD, 64 subjects with mild cognitive impairment, and 111 subjects with no cognitive impairment and found significantly lower amylin levels among subjects with AD and mild cognitive impairment compared with the cognitively intact subjects. To investigate mechanisms underlying amylin's effects in the brain, we administered chronic infusions of the amylin analog pramlintide in the senescence-accelerated prone mouse, a mouse model of sporadic AD. Pramlintide administration improved performance in the novel object recognition task, a validated test of memory and cognition. The pramlintide-treated mice had increased expression of the synaptic marker synapsin I and the kinase cyclin-dependent kinase-5 in the hippocampus, as well as decreased oxidative stress and inflammatory markers in the hippocampus. A dose-dependent increase in cyclin-dependent kinase-5 and activation of extracellular-signal-regulated-kinases 1/2 by pramlintide treatment in vitro was also present indicating functionality of the amylin receptor in neurons. Together these results suggest that amylin analogs have neuroprotective properties and might be of therapeutic benefit in AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/psicologia , Cognição/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Polipeptídeo Amiloide das Ilhotas Pancreáticas/farmacologia , Polipeptídeo Amiloide das Ilhotas Pancreáticas/uso terapêutico , Fármacos Neuroprotetores , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/metabolismo , Animais , Células Cultivadas , Quinase 5 Dependente de Ciclina/metabolismo , Modelos Animais de Doenças , Feminino , Hipocampo/metabolismo , Humanos , Polipeptídeo Amiloide das Ilhotas Pancreáticas/metabolismo , Masculino , Memória/efeitos dos fármacos , Camundongos , Pessoa de Meia-Idade , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Neurônios/metabolismo , Estresse Oxidativo , Receptores de Polipeptídeo Amiloide de Ilhotas Pancreáticas/metabolismo , Sinapsinas/metabolismo
10.
Antimicrob Agents Chemother ; 55(8): 3752-7, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21628541

RESUMO

Yersinia pestis initiates infection as a facultative intracellular parasite in host macrophages; however, little is known about the efficacy of antibiotics commonly used to treat human plague against intracellular Y. pestis. Intracellular minimal bactericidal concentrations (MBCs) were determined using a high-throughput broth microdilution assay in which human THP-1 macrophage-like cells were infected with Y. pestis strain KIM6-2053.1+ and exposed to 2-fold serial dilutions of antibiotics for 24 h in 96-well plates. The numbers of CFU, upon which minimal bactericidal concentrations were based, were determined by counting "microcolonies" in wells of 96-well plates following lysis of tissue culture cells to release surviving Y. pestis, replica dilution, and plating in soft tryptic soy broth agar. For THP-1 cells, streptomycin and ciprofloxacin had comparable efficacies for intra- and extracellular Y. pestis, but the MBCs for chloramphenicol, gentamicin, doxycycline, and amoxicillin were two-, three-, four-, and five 2-fold serial dilutions greater, respectively, for intracellular than for extracellular Y. pestis. During the initial stage of plague, intracellular Y. pestis may be less susceptible to antibiotic killing by particular antibiotics recommended for treatment of plague, such as gentamicin or doxycycline, whereas others, such as streptomycin and ciprofloxacin, may have similar efficacies against extracellular or intracellular Y. pestis. This may be of particular importance in the selection of antibiotics for prophylactic treatment in the case of a bioterrorism event.


Assuntos
Antibacterianos/farmacologia , Ensaios de Triagem em Larga Escala/métodos , Peste/tratamento farmacológico , Yersinia pestis/efeitos dos fármacos , Yersinia pestis/patogenicidade , Amoxicilina/farmacologia , Animais , Linhagem Celular , Cloranfenicol/farmacologia , Ciprofloxacina/farmacologia , Doxiciclina/farmacologia , Gentamicinas/farmacologia , Humanos , Macrófagos/microbiologia , Camundongos , Testes de Sensibilidade Microbiana , Peste/prevenção & controle , Estreptomicina/farmacologia
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