RESUMO
There is growing evidence supporting the role of inflammation in early brain injury and cerebral vasospasm following subarachnoid hemorrhage (SAH). Matrix metalloproteinases (MMPs) are released by inflammatory cells and can mediate early brain injury via disruption of the extracellular matrix and mediate vasospasm by cleaving endothelin-1 into vasoactive fragments. We hypothesize that inflammation marked by neutrophil elevation and MMP-9 release in human SAH is associated with vasospasm and with poor clinical outcome. We enrolled consecutive SAH subjects (N = 55), banked serial blood and cerebrospinal fluid (CSF) samples, and evaluated their 3-month modified Rankin scores (mRS). Vasospasm was defined as >50% vessel caliber reduction on angiography 6-8 days post-SAH. A poor outcome was defined as mRS > 2. We compared blood leukocyte and neutrophil counts during post-SAH days 0-14 with respect to vasospasm and 3-month outcome. In a subset of SAH subjects (N = 35), we compared blood and CSF MMP-9 by enzyme-linked immunosorbent assay (ELISA) on post-SAH days 0-1, 2-3, 4-5, 6-8, and 10-14 with respect to vasospasm and to 3-month outcome. Persistent elevation of blood leukocyte (p = 0.0003) and neutrophil (p = 0.0002) counts during post-SAH days 0-14 are independently associated with vasospasm after adjustment for major confounders. In the same time period, blood neutrophil count (post-SAH days 2-3, p = 0.018), blood MMP-9 (post-SAH days 4-5, p = 0.045), and CSF MMP-9 (post-SAH days 2-3, p = 0.05) are associated with poor 3-month SAH clinical outcome. Neutrophil count correlates with blood MMP-9 (post-SAH days 6-8, R = 0.39; p = 0.055; post-SAH days 10-14, R = 0.79; p < 0.0001), and blood MMP-9 correlates with CSF MMP-9 (post-SAH days 4-5, R = 0.72; p = 0.0002). Elevation of CSF MMP-9 during post-SAH days 0-14 is associated with poor 3-month outcome (p = 0.0078). Neither CSF nor blood MMP-9 correlates with vasospasm. Early rise in blood neutrophil count and blood and CSF MMP-9 are associated with poor 3-month SAH clinical outcome. In blood, neutrophil count correlates with MMP-9 levels, suggesting that neutrophils may be an important source of blood MMP-9 early in SAH. Similarly, CSF and blood MMP-9 correlate positively early in the course of SAH, suggesting that blood may be an important source of CSF MMP-9. Blood and CSF MMP-9 are associated with clinical outcome but not with vasospasm, suggesting that MMP-9 may mediate brain injury independent of vasospasm in SAH. Future in vitro studies are needed to investigate the role of MMP-9 in SAH-related brain injury. Larger clinical studies are needed to validate blood and CSF MMP-9 as potential biomarkers for SAH outcome.
RESUMO
Polychlorinated biphenyls are environmental contaminants known to affect neurobehavioral development in many laboratory studies using different animal models. Because of their bioaccumulation and long half-life they are a serious concern for our own species. The dioxin-like PCB congener 3,4,3',4'-tetrachlorobiphenyl (PCB 77) has estrogenic and anti-estrogenic properties, and has been shown to affect brain chemistry and behavior of developing rats when administered during gestation. Since many developmental outcomes in mammals depend upon the type of maternal care provided by the dams, we investigated the effects of two doses of PCB 77 (2 and 4 mg/kg administered during gestational days 6-18) on the maternal behavior of the treated dams. Both doses of PCB 77 reduced the amount of nursing time in which the dams displayed the high-crouch posture over postnatal days 1-6. In addition, the high dose increased the amount of maternal licking and grooming of the litters and the amount of time the dams spent on the nest. The high dose also increased pup mortality, and both doses reduced the weight gain of the litters during the first 6 days of life. These results document effects of PCB 77 on maternal behavior and serve to raise questions about the importance of maternal contributions to the developmental effects of this and similar contaminants.
Assuntos
Poluentes Ambientais/toxicidade , Comportamento Materno/efeitos dos fármacos , Bifenilos Policlorados/toxicidade , Prenhez/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Fatores Etários , Análise de Variância , Animais , Animais Recém-Nascidos , Comportamento Animal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Química Encefálica/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Asseio Animal/efeitos dos fármacos , Masculino , Comportamento de Nidação/efeitos dos fármacos , Gravidez , Ratos , Ratos Long-Evans , Comportamento de Sucção/efeitos dos fármacosRESUMO
The occurrence and distribution of magnetotactic bacteria (MB) were studied as a function of the physical and chemical conditions in meromictic Salt Pond, Falmouth, Mass., throughout summer 2002. Three dominant MB morphotypes were observed to occur within the chemocline. Small microaerophilic magnetite-producing cocci were present at the top of the chemocline, while a greigite-producing packet-forming bacterium occurred at the base of the chemocline. The distributions of these groups displayed sharp changes in abundance over small length scales within the water column as well as strong seasonal fluctuations in population abundance. We identified a novel, greigite-producing rod in the sulfidic hypolimnion that was present in relatively constant abundance over the course of the season. This rod is the first MB that appears to belong to the gamma-Proteobacteria, which may suggest an iron- rather than sulfur-based respiratory metabolism. Its distribution and phylogenetic identity suggest that an alternative model for the ecological and physiological role of magnetotaxis is needed for greigite-producing MB.
Assuntos
Água Doce/microbiologia , Bactérias Gram-Negativas/isolamento & purificação , Magnetismo , Água do Mar/microbiologia , DNA Bacteriano/genética , DNA Ribossômico/genética , Óxido Ferroso-Férrico , Bactérias Gram-Negativas/classificação , Bactérias Gram-Negativas/genética , Bactérias Gram-Negativas/fisiologia , Ferro , Biologia Marinha , Massachusetts , Dados de Sequência Molecular , Movimento , Óxidos , Filogenia , Estações do Ano , Cloreto de Sódio , SulfetosRESUMO
A statistical riverine litter propagation (RLP) model based on importance sampling Monte Carlo (ISMC) simulation was developed in order to predict the frequency distribution of certain litter types in river reaches. The model was preliminarily calibrated for plastic sheeting by a pilot study conducted on the River Taff, Wales (UK). Litter movement was predominantly controlled by reach characteristics, such as vegetation overhang and water-course obstructions. These affects were modeled in the simulations, by utilizing geometric distributions of river reaches in the time domain. The proposed model satisfactorily simulated the dosing experiments performed at the River Taff. It was concluded from the preliminary calibrations that, the RLP model can be efficiently utilized to portray litter propagation at any arbitrarily selected river site, provided that the stream flows and reach characteristics are calibrated by representative probability distributions of similar sections. Therefore, the RLP model can be considered as a new statistical technique that can predict litter propagation in river sections.