RESUMO
Gonadotropin releasing hormone (GnRH) synthesis and secretion regulates seasonal fertility. In the brain, the distribution of GnRH-positive neurons is diffuse, hindering efforts to monitor variations in its cellular and tissue levels. Here, we aim at assessing GnRH immunoreactivity in nuclei responsible for seasonal fertility regulation (SFR) within the posterior, anterior, and preoptic areas of the basal hypothalamus during estrous in ewes. We detected reaction products in the ventromedial basal hypothalamus in neurons, nerve fibers, non-neuronal immunoreactive bodies, and diffuse interstitial areas. Immunoreactivity correlated with the distribution of the main SFR nuclei in the arcuate, retrochiasmatic, periventricular, medial preoptic, supraoptic, and preoptic areas. By independent component analysis density segmentation and by interferential contrast, we identified GnRH non-neuronal positive bodies as microglial cells encapsulated within a dense halo of reaction products. These GnRH-positive microglial cells were distributed in patches and rows throughout the basal ventromedial hypothalamus, suggesting their role in paracrine or juxtacrine signaling. Moreover, as shown by ionized calcium-binding adaptor molecule 1 (IBA1) immunocytochemistry, the distribution of GnRH reaction products overlapped with the microglial dense reactive zones. Therefore, our findings support the assertion that a combined densitometric analysis of GnRH and IBA1 immunocytochemistry enables activity mapping for monitoring seasonal changes following experimental interventions.
Assuntos
Hormônio Liberador de Gonadotropina , Imuno-Histoquímica , Animais , Hormônio Liberador de Gonadotropina/metabolismo , Feminino , Ovinos/fisiologia , Estações do Ano , Proteínas de Ligação ao Cálcio/metabolismo , Hipotálamo/metabolismoRESUMO
Presbycusis or age-related hearing loss (ARHL) is one of the most prevalent chronic health problems facing aging populations. Along the auditory pathway, the stations involved in transmission and processing, function as a system of interconnected feedback loops. Regulating hierarchically auditory processing, auditory cortex (AC) neuromodulation can, accordingly, activate both peripheral and central plasticity after hearing loss. However, previous ARHL-prevention interventions have mainly focused on preserving the structural and functional integrity of the inner ear, overlooking the central auditory system. In this study, using an animal model of spontaneous ARHL, we aim at assessing the effects of multisession epidural direct current stimulation of the AC through stereotaxic implantation of a 1-mm silver ball anode in Wistar rats. Consisting of 7 sessions (0.1 mA/10 min), on alternate days, in awake animals, our stimulation protocol was applied at the onset of hearing loss (threshold shift detection at 16 months). Click- and pure-tone auditory brainstem responses (ABRs) were analyzed in two animal groups, namely electrically stimulated (ES) and non-stimulated (NES) sham controls, comparing recordings at 18 months of age. At 18 months, NES animals showed significantly increased threshold shifts, decreased wave amplitudes, and increased wave latencies after click and tonal ABRs, reflecting a significant, spontaneous ARHL evolution. Conversely, in ES animals, no significant differences were detected in any of these parameters when comparing 16 and 18 months ABRs, indicating a delay in ARHL progression. Electrode placement in the auditory cortex was accurate, and the stimulation did not cause significant damage, as shown by the limited presence of superficial reactive microglial cells after IBA1 immunostaining. In conclusion, multisession DC stimulation of the AC has a protective effect on auditory function, delaying the progression of presbycusis.
Assuntos
Córtex Auditivo , Presbiacusia , Ratos , Animais , Presbiacusia/prevenção & controle , Ratos Wistar , Envelhecimento/fisiologia , Audição , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Limiar Auditivo/fisiologiaRESUMO
Reward prediction error, the difference between the expected and obtained reward, is known to act as a reinforcement learning neural signal. In the current study, we propose a model fitting approach that combines behavioral and neural data to fit computational models of reinforcement learning. Briefly, we penalized subject-specific fitted parameters that moved away too far from the group median, except when that deviation led to an improvement in the model's fit to neural responses. By means of a probabilistic monetary learning task and fMRI, we compared our approach with standard model fitting methods. Q-learning outperformed actor-critic at both behavioral and neural level, although the inclusion of neuroimaging data into model fitting improved the fit of actor-critic models. We observed both action-value and state-value prediction error signals in the striatum, while standard model fitting approaches failed to capture state-value signals. Finally, left ventral striatum correlated with reward prediction error while right ventral striatum with fictive prediction error, suggesting a functional hemispheric asymmetry regarding prediction-error driven learning.
Assuntos
Recompensa , Estriado Ventral , Aprendizagem , Imageamento por Ressonância Magnética , Reforço Psicológico , Estriado Ventral/diagnóstico por imagemRESUMO
Visual cortex (VC) over-activation analysed by evoked responses has been demonstrated in congenital deafness and after long-term acquired hearing loss in humans. However, permanent hearing deprivation has not yet been explored in animal models. Thus, the present study aimed to examine functional and molecular changes underlying the visual and auditory cross-modal reaction. For such purpose, we analysed cortical visual evoked potentials (VEPs) and the gene expression (RT-qPCR) of a set of markers for neuronal activation (c-Fos) and activity-dependent homeostatic compensation (Arc/Arg3.1). To determine the state of excitation and inhibition, we performed RT-qPCR and quantitative immunocytochemistry for excitatory (receptor subunits GluA2/3) and inhibitory (GABAA-α1, GABAB-R2, GAD65/67 and parvalbumin-PV) markers. VC over-activation was demonstrated by a significant increase in VEPs wave N1 and by up-regulation of the activity-dependent early genes c-Fos and Arc/Arg3.1 (thus confirming, by RT-qPCR, our previously published immunocytochemical results). GluA2 gene and protein expression were significantly increased in the auditory cortex (AC), particularly in layers 2/3 pyramidal neurons, but inhibitory markers (GAD65/67 and PV-GABA interneurons) were also significantly upregulated in the AC, indicating a concurrent increase in inhibition. Therefore, after permanent hearing loss in the rat, the VC is not only over-activated but also potentially balanced by homeostatic regulation, while excitatory and inhibitory markers remain imbalanced in the AC, most likely resulting from changes in horizontal intermodal regulation.
Assuntos
Córtex Auditivo/fisiologia , Percepção Auditiva/fisiologia , Surdez/fisiopatologia , Neurônios/fisiologia , Privação Sensorial/fisiologia , Córtex Visual/fisiologia , Percepção Visual/fisiologia , Animais , Córtex Auditivo/metabolismo , Potenciais Evocados Auditivos do Tronco Encefálico , Potenciais Evocados Visuais , Expressão Gênica , Glutamato Descarboxilase/metabolismo , Parvalbuminas/metabolismo , Ratos Wistar , Receptores de AMPA/metabolismo , Córtex Visual/metabolismoRESUMO
OBJECTIVE: To improve the accuracy of the Acute Physiology and Chronic Health Evaluation (APACHE) II model for predicting hospital mortality in critically ill cancer patients. MATERIALS AND METHODS: This was a prospective cohort study of 522 patients admitted to ICU with a solid tumor. We developed the "APACHE II score for critically ill patients with a solid tumor" (APACHE IICCP score), in which typical variables of critically ill cancer patients were added to general APACHE II score. Calibration and discrimination were evaluated by Hosmer-Lemeshow test (H-L) and area under receiver operating characteristic curve (AROC), respectively. The improvement in predicting hospital mortality with the new model was assessed using a reclassification analysis by integrated discrimination improvement (IDI), net reclassification improvement (NRI; cut-off point of 20% in risk of death) and quantitative NRI (qNRI). RESULTS: The hospital mortality rate was 13%. Discrimination was superior for APACHE IICCP score (AROC=0.91 [95% CI 0.87-0.94; P<.0001]) compared to general APACHE II score (AROC=0.62 [95% CI 0.54-0.70; P=.002]). Calibration was better using APACHE IICCP score (H-L; P=.267 vs. P=.001). In reclassification analysis, an improved mortality prediction was observed with APACHE IICCP score (IDI=0.2994 [P<.0001]; total qNRI=134.3% [95% CI 108.8-159.8%; P<.0001]; total NRI=41.5% [95% CI 23.7-59.3%; P<.0001]). CONCLUSIONS: The performance of APACHE IICCP score was superior to that observed for general APACHE II score in predicting mortality in critically ill patients with a solid tumor. Other studies validating this new predictive model are required.
Assuntos
APACHE , Mortalidade Hospitalar , Neoplasias/classificação , Neoplasias/mortalidade , Idoso , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos ProspectivosRESUMO
Cross-modal reorganization in the auditory and visual cortices has been reported after hearing and visual deficits mostly during the developmental period, possibly underlying sensory compensation mechanisms. However, there are very few data on the existence or nature and timeline of such reorganization events during sensory deficits in adulthood. In this study, we assessed long-term changes in activity-dependent immediate early genes c-Fos and Arc/Arg3.1 in auditory and neighboring visual cortical areas after bilateral deafness in young adult rats. Specifically, we analyzed qualitatively and quantitatively c-Fos and Arc/Arg3.1 immunoreactivity at 15 and 90 days after cochlea removal. We report extensive, global loss of c-Fos and Arc/Arg3.1 immunoreactive neurons in the auditory cortex 15 days after permanent auditory deprivation in adult rats, which is partly reversed 90 days after deafness. Simultaneously, the number and labeling intensity of c-Fos- and Arc/Arg3.1-immunoreactive neurons progressively increase in neighboring visual cortical areas from 2 weeks after deafness and these changes stabilize three months after inducing the cochlear lesion. These findings support plastic, compensatory, long-term changes in activity in the auditory and visual cortices after auditory deprivation in the adult rats. Further studies may clarify whether those changes result in perceptual potentiation of visual drives on auditory regions of the adult cortex.
Assuntos
Córtex Auditivo/metabolismo , Proteínas do Citoesqueleto/metabolismo , Regulação da Expressão Gênica/fisiologia , Perda Auditiva/patologia , Proteínas do Tecido Nervoso/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Córtex Visual/metabolismo , Animais , Vias Auditivas/metabolismo , Cóclea/lesões , Cóclea/metabolismo , Cóclea/patologia , Modelos Animais de Doenças , Potenciais Evocados Auditivos , Perda Auditiva/metabolismo , Masculino , Ratos , Ratos Wistar , Gânglio Espiral da Cóclea/patologiaRESUMO
BACKGROUND: Use of breast magnetic resonance imaging (MRI) to detect breast cancer has generated significant debate. We analyze the role of breast MRI in the detection of additional disease and the need to perform additional biopsies in early breast carcinoma patients. In addition, we correlate the detection of new foci with tumor pathological features. METHODS: Early breast carcinoma patients that had undergone an MRI as well as a mammography as diagnostic procedures were included in the study. The following pathologic features were studied: carcinoma type, histological grade, estrogen receptors (ER), progesterone receptors (PR), HER2 and Ki67. Univariate analysis was conducted to ascertain significant correlation among detection of new foci and each of the tumor pathological features. RESULTS: Data from 98 patients have been analyzed: median age 49 years (range 35-79); carcinoma type: (a) infiltrative ductal carcinoma (n = 73, 74 %), (b) infiltrative lobular cancer (n = 12, 12 %), (c) ductal carcinoma in situ (n = 6, 6 %); amplified HER2 (n = 18, 18 %); grade III (n = 33, 33 %); Ki67 ≥ 25 % (n = 33, 33.67 %); positive ER and PR (n = 79, 80 %); triple negative tumors (n = 8, 8 %). MRI detected additional disease in 38 cases (39.58 %), and 20 led to an additional biopsy (20.4 %). Thirty-eight patients (39 %) underwent mastectomy. We found a statistically significant correlation between new foci in MRI and high Ki67 ≥ 25 % (p < 0.005). No other statistically significant correlation was established. CONCLUSION: MRI detected additional disease in 39 % cases, requiring an additional biopsy 20 %. Tumors with high proliferative index were significantly correlated with the detection of new foci in MRI.
Assuntos
Neoplasias da Mama/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Intraductal não Infiltrante/diagnóstico , Carcinoma Lobular/diagnóstico , Imageamento por Ressonância Magnética , Adulto , Idoso , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Carcinoma Intraductal não Infiltrante/metabolismo , Carcinoma Lobular/metabolismo , Detecção Precoce de Câncer , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
The breakthrough performance of stacks of dye-cellulosic fabric in affinity chromatography of lysozyme was investigated in batch and flow experiments. Breakthrough curves were significantly affected by flow rate and were not dependent on the feed solution concentration. System dispersion curves could not explain the flow-rate dependence. Breakthrough curves were analyzed by coupling the kinetic model for pore mass transfer as the only controlling resistance and a system dispersion model. From the analysis, pore film mass transfer resistance was found to be the leading rate-limiting factor when the residence time in the column is greater than 5 min. The model was used to predict the operating and design parameters needed to obtain sharp breakthrough curves. Selectivity studies using lysozyme and bovine serum albumin mixtures showed a high system selectivity for lysozyme.
RESUMO
Draw-fill culture was evaluated as a method for xylanase production by Cellulomonas flavigena on sugar cane bagasse. Specific xylanase activity and volumetric xylanase activities were measured by harvesting 50%, 55%, 60% and 70% of fermented broth at the end of each subculture. Maximum specific (64 IU mg(-1) protein) and volumetric (166 IU ml(-1)) xylanase activities were obtained by harvesting 50-55% of broth. Values were 3.4 and 3.8 times greater than those obtained in batch cultures carried out under the same conditions. Enzyme productivity of 4.2 IU ml(-1) h(-1) was significantly greater than that obtained in continuous cultures (2.4 IU ml(-1) h(-1)) (P<0.05).
Assuntos
Actinomycetales/enzimologia , Biotecnologia/métodos , Fermentação , Xilosidases/biossíntese , Actinomycetales/genética , Actinomycetales/crescimento & desenvolvimento , Biomassa , Biotecnologia/instrumentação , Celulose , Microbiologia Industrial , Especificidade por Substrato , Xilano Endo-1,3-beta-XilosidaseRESUMO
This manuscript evaluates the phytotoxicity and biotransformation of n-hexadecane as well as peroxidase activity and cytochrome P450 concentration in microsomes for cell suspension cultures of Cinchona robusta and Dioscorea composita. Phytotoxicity was evaluated based on viability and growth. Cell cultures were exposed to a 2 and 4% (v/v) dose of n-hexadecane. The biotransformation of n-hexadecane was determined based on labeled recovery in polar, nonpolar, and cell residue fractions after cell culture extraction during exponential cell growth phase and stationary phase. Differences were observed in accumulation of label during cell growth phase and stationary phase for the cells of the two plants. Differences also were observed between phases for label in polar and nonpolar fractions. Thin-layer chromatography determined labeled intermediates and some were identified. The activity of peroxidase and concentration of cytochrome P450 was lower in C. robusta than in controls and greater in D. composita than in controls. In vitro biotransformation was not successful.
Assuntos
Alcanos/metabolismo , Cinchona/fisiologia , Dioscorea/fisiologia , Poluentes Químicos da Água/metabolismo , Alcanos/toxicidade , Biotransformação , Técnicas de Cultura de Células , Cromatografia em Camada Fina , Cinchona/crescimento & desenvolvimento , Sistema Enzimático do Citocromo P-450/metabolismo , Dioscorea/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Microssomos , Peroxidase/metabolismo , Poluentes Químicos da Água/toxicidadeRESUMO
The aim of this study was to examine potential factors that modify blood cholesterol among children in countries in which dietary and lifestyle habits are becoming westernized. Population data on serum total and lipoprotein cholesterol, anthropometric indexes, and dietary intake were reviewed and compared for children aged 1-18 y from Japan, Spain, and the United States. The data show that total serum cholesterol in Japanese and Spanish children recently exceeded the 75th percentile for US children, primarily reflecting LDL cholesterol, although both LDL and HDL cholesterol contributed. Adiposity indexes do not explain the trends observed. Total and saturated fat intakes increased substantially in both Japan and Spain but in Japan are still lower than intakes in the United States. The Hegsted equation was used to relate differences in serum cholesterol to dietary fat intake. Changes in total serum cholesterol followed established dietary correlations among children in Spain, but not in Japan. Serum cholesterol in Japanese children was predicted to be 0.20-0.32 mmol/L lower than in US children; actual concentrations were considerably higher. These results suggest that a rapid westernization of children's blood cholesterol concentrations has occurred in Japan and Spain. Changes in fat intake predict changes in blood cholesterol in Spain, but not in Japan. Differences in genetic response to diet in certain populations, such as the Japanese, may explain higher blood cholesterol concentrations with lower fat intakes compared with the United States.
Assuntos
Fenômenos Fisiológicos da Nutrição Infantil , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dieta/tendências , Gorduras na Dieta/administração & dosagem , Adolescente , Povo Asiático/genética , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Japão , Estilo de Vida , Masculino , Espanha , Estados Unidos , População Branca/genéticaRESUMO
The priorities for the prevention of cardiovascular diseases should be focused on patients with established disease and high risk subjects, with individual global risk always being taken into account. The current evidence on the influence of the main risk factors are unanimous (dyslipemia, tobacco, hypertension and diabetes mellitus), being somewhat less so in cases of sedentarism, obesity and the metabolic syndrome. The evidence concerning other risk factors still remains controversial. Guidelines for the control of the different risk factors should be based on the evidence derived from both epidemiological or clinical trials. The recommendations published by several scientific societies should also be followed. There are, at present, important evidence on the efficacy of smoking cessation, the treatment of arterial hypertension and particularly on the successful control of lipid levels with lipid-lowering drugs, especially with statins. There is also evidence on the need for rigorous control of diabetic patients not only in relation to the glucose levels but also to dyslipemia. The most efficient measures for a reduction in morbidity and mortality are cessation of smoking, appropriate hypertensive therapy, a comprehensive program of cardiac rehabilitation and overall the successful control of lipid levels with statins.
Assuntos
Reabilitação Cardíaca , Doenças Cardiovasculares/prevenção & controle , Humanos , Fatores de Risco , Abandono do Hábito de Fumar , EspanhaRESUMO
BACKGROUND: Febrile nonhemolytic transfusion reactions (FNHTRs) to platelet transfusions have been linked to the presence of cytokines in supernatant plasma. Cytokine concentration is directly related to WBC content and storage time. This study evaluated the effect of limiting the storage time of random-donor platelet concentrates on the FNHTR rate. STUDY DESIGN AND METHODS: FNHTR rates were calculated retrospectively for single-donor apheresis platelet (SDP) and pooled random-donor platelet (PP) transfusions given during three consecutive 5-month study periods (November 1995 to February 1997) to patients on a single hematology/oncology/bone marrow transplant unit. Transfusion practice policies were: Baseline Period, SDPs preferred; Study Period A, PPs preferred; and Study Period B, < or =3-day-old PPs preferred. FNHTR rates were calculated from physicians' interpretations of reported reactions and the total number of SDP and PP transfusions in each period. SDPs were collected on two cell separators. All platelet components were filtered at issue in the laboratory by WBC-reduction filters. RESULTS: FNHTR rates for PP transfusions were: baseline, 11.1 percent (3/27); Study Period A, 4.6 percent (22/481); and Study Period B, 1.1 percent (3/282). The rates for SDP transfusions were 0. 15 percent (1/650), 0.75 percent (2/267), and 0.36 percent (1/273), respectively. The FNHTR rate for < or =3-day-old PPs was significantly less than the rate for older PPs (p = 0.0086 for Study Period A vs. Study Period B), and was not significantly different than that for SDPs (p = 0.33 for PPs vs. SDPs in Study Period B). CONCLUSION: Limiting transfusion of PPs to those stored =3 days is an effective strategy in reducing the rate of FNHTR and results in an FNHTR rate comparable to that seen with SDPs.
Assuntos
Plaquetas , Preservação de Sangue , Febre/etiologia , Hemólise/fisiologia , Reação Transfusional , Plaquetas/química , Citocinas/fisiologia , Humanos , Fatores de TempoRESUMO
OBJECTIVE: Transcranial Doppler is a technique which is being used ever more frequently in the study of intracranial arteries and is very useful in the study of cerebrovascular disease. The typical values of a healthy population in our country are unknown. The aim of this study was determine mean velocity and pulsatility index reference values in a healthy population. PATIENTS AND METHOD: Transcranial Doppler basal examination was carried out on 118 healthy volunteers without prior haematological or cerebrovascular conditions. Those found to have extracranial arterial stenoses were excluded as were those in whom bilateral temporal bone hyperostosis did not permit insonation in either middle cerebral arteries. The nine intracranial arteries were sounded systematically at fixed depths. The mean and standard deviations of each variable were calculated for side, age group and sex. RESULTS: 49% were males and average age was of 56 years (range, 21-87 years). A sufficient signal to determine the parameters of the study was obtained in 89% of middle cerebral arteries. Statistically significant differences in mean velocity and pulsatility index were found between age groups and sexes. CONCLUSIONS: Sex and age must be taken into account in establishing typical patterns in transcranial Doppler examination. Our results enable parameters of typical values to be established for the adult population in Spain.
Assuntos
Transtornos Cerebrovasculares/diagnóstico por imagem , Ultrassonografia Doppler Transcraniana , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Avaliação como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Estudos Retrospectivos , Espanha , Ultrassonografia Doppler Transcraniana/métodos , Ultrassonografia Doppler Transcraniana/estatística & dados numéricosRESUMO
BACKGROUND: Single-donor platelets (SDPs) are frequently preferred over pooled random-donor platelets (RDPs) to reduce donor exposures and the risk for virus transmission or HLA alloimmunization. Transfusion-associated virus-transmission risks have significantly decreased, which suggests that white cell reduction by filtration eliminates any difference in the risk of alloimmunization in transfused leukemic patients. Health care reform pressures of make it appropriate to examine the cost-effectiveness of SDPs versus RDPs in reducing donor exposures. STUDY DESIGN AND METHODS: A decision analysis model was developed and sensitivity analyses were used to assess the incremental cost (dollars/quality-adjusted life-year) associated with the use of SDPs versus RDPs for adult patients undergoing hematopoietic progenitor cell transplantation or primary coronary artery bypass grafting (CABG). RESULTS: Among transplant patients, the incremental cost of choosing SDPs as opposed to RDPs ranged from $168,700 to $519,822 per quality-adjusted life-year. For patients undergoing primary CABG, the incremental cost was $192,415 (females) and $216,280 (males). Variations in the cost differential between SDPs and RDPs, the number of random-donor platelets in the RDP, and the risk of bacterial sepsis markedly influenced cost-effectiveness. The model was minimally affected by variations in the risks of transmission of HIV and hepatitis B and C, and human T-lymphotropic viruses. CONCLUSION: In comparison with other accepted medical interventions, the use of SDPs as opposed to RDPs may not be a cost-effective method of reducing donor exposures in the adult patient populations studied. SDPs were more cost-effective in patients undergoing primary CABG than in leukemia patients undergoing hematopoietic progenitor cell transplantation. Regardless of diagnosis, decreasing the acquisition cost differential would have the greatest impact on improving the cost-effectiveness of SDPs, as opposed to RDPs, to decrease donor exposures.
Assuntos
Doadores de Sangue , Transfusão de Plaquetas/economia , Transfusão de Plaquetas/métodos , Adulto , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/transmissão , Doadores de Sangue/provisão & distribuição , Ponte de Artéria Coronária , Análise Custo-Benefício , Infecções por HIV/transmissão , Transplante de Células-Tronco Hematopoéticas , Hepatite C/transmissão , Humanos , Qualidade de Vida , Medição de Risco , Reação Transfusional , Viroses/epidemiologia , Viroses/mortalidade , Viroses/transmissãoRESUMO
Plasma lipid composition, platelet aggregation, cholesterol (Ch)/glycoprotein IIb-IIIa (GP) and phospholipid (Ph)/GP molar ratios, fatty acid composition and structural order (1, 6-diphenyl-1, 3, 5-hexatriene (DPH) fluorescence anisotropy at 35 degrees C (r(DPH,35)) of human platelet plasma membranes (HPPM) were measured in four DPH,35 groups of hyperlipidemic patients (II: plasma Ch < 250 mg/dl and TG (triglycerides) <220 mg/dl, n = 21; III: Ch > 250 mg/dl and TG < 220 mg/dl, n = 23; IV: Ch < 250 mg/dl and TG > 220 mg/dl, n = 18; and V: Ch > 250 mg/dl and TG > 220 mg/dl, n = 12) and compared with those of the control group (I). Our results were: (i) in groups III, IV and V the HPPM (Ch + Ph)/GP molar ratio increased 7.0+/-7.7% (mean SD); (ii) the Ph/GP molar ratio increased significantly in groups III, IV and V, but most in IV and V, while the Ch/GP molar ratio increased only in groups III and V; (iii) the mean relative increase of Ch with respect to Ph in the HPPM of groups III, IV and V was 140% 21% and 54%, respectively; (iv) the Ch/GP molar ratio was correlated with LDL-Ch (0.41+/-0.16, P < 0.002, n = 55, for all the subjects and 0.60+/-0.11, P < 2.10(-4), n = 33, for subjects with TG < 220 mg/dl), however, it was totally uncorrelated with HDL-Ch; (v) the HPPM Ch/Ph molar ratio was positively correlated with plasma Ch (r = 0.51+/-0.08, P < 1.10(-6), n = 83) and with (LDL + HDL) Ch (r = 0.64+/-0.07, P < 1.10(-6), n = 73), the former correlation increased significantly ( r = 0.67+/-0.07, P < 1.10(-6), n = 53) when done only for subjects with TG < 220 mg/dl; (vi) the Ch/Ph molar ratio was only increased in group III (0.70+/-0.03, P < 3.10(-5), n = 23) and decreased in group IV (0.62+/-0.02, P < 0.001, n = 18); (vii) the fatty acid/GP molar ratio was significantly increased in groups IV and V, however, a significant absolute and relative increase of C16:0 and C18:1 was observed only in severe hypertriglyceridemia (> 500 mg/dl), together with a relative decrease of C18:0 and C20:4 ( n - 6); (viii) the HPPM structural order, as probed by r(DPH,35), was negatively correlated with DPH,35 plasma TG (r =- 0.61+/-0.10, P < 4.10(-5), n = 39), the Ph/GP molar ratio (r =-0.58+/-0.10, P < 2.10(-4), n = 39) and the the (C18:1 + C18:2))/GP molar ratio (r =- 0.80+/-0.05, P < 1.10(-6), n = 39), however, it was independent of plasma and HPPM Ch; (ix) the higher HPPM Ch/Ph molar ratio in group III was associated (r = 0.58+/-0.12, P < 0.005, n = 22) with a moderately higher platelet reactivity to collagen. We conclude that Ch and Ph were distinctly incorporated to HPPM in the different groups of hyperlipidemia and, therefore, that the absolute increase of Ch and Ph was more informative to understand the structural and functional modifications of the HPPM in hyperlipidemias, than the Ch/Ph molar ratio. On the other hand, the r was sensitive to the DPH,35 increase in the content of HPPM Ph and C18:1 + C18:2 and it was insensitive to the increase in the Ch content.
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Spontaneous dissection of the vertebral artery (VA) is an infrequent cause of vertebral-basilar ischaemia in children and young adults, being responsible for 4% of cases of ischaemic infarct in this age group. The distinction between spontaneous dissection and traumatic dissection helps to clarify its vascular tendency, not brought on by laceration of the vessel wall secondary to traumatism. It appears clinically with neck pain and/or headache, followed by a clinical picture of ischaemia in the vertebral-basilar area. Diagnosis is based on clinical suspicion and identification of the angiographic signs of dissection prognosis is favourable with good recuperation in 88% of cases and low recurrence risk. We present a series of seven patients with ischaemic stroke of the brainstem brought about by spontaneous VA dissection. We studied the patients using computerized tomography (CT) scan, magnetic resonance (MR) and brain angiography. The group comprised six men and one woman aged from 9 to 44 years. In one case localization was intracranial, in five there was earlier arterial pathology (hypoplasia or dysplasia) and in the remaining case dissection was bilateral. After a long-term follow-up of between one and seven years, not one of our patients showed any recurrence of ischaemic signs. We would suggest that spontaneous VA dissection should be considered in differential diagnosis in clinical pictures of vertebral-basilar ischaemia in children and young adults since most probably its frequency is greater than that currently supposed. The discussed data would support underlying arterial pathology as a tendency factor.
Assuntos
Dissecção Aórtica/fisiopatologia , Isquemia Encefálica/fisiopatologia , Artéria Vertebral/fisiopatologia , Adulto , Dissecção Aórtica/complicações , Dissecção Aórtica/diagnóstico , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/etiologia , Angiografia Cerebral , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Inibidores da Agregação Plaquetária/uso terapêutico , Tomografia Computadorizada por Raios XRESUMO
The development and expansion of the CTS in Pittsburgh shows the feasibility of this transfusion medicine delivery system. Few of the changes driven by health care reform both improve patient care and reduce costs. When properly implemented, a CTS achieves these objectives, benefits the community as a whole, and enhances the role of transfusion medicine specialists and the blood center in the region.