Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 235
Filtrar
1.
Integr Comp Biol ; 56(5): 1022-1031, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27471227

RESUMO

Studies of venom variability have advanced from describing the mechanisms of action and relative potency of medically important toxins to understanding the ecological and evolutionary causes of the variability itself. While most studies have focused on differences in venoms among taxa, populations, or age-classes, there may be intersexual effects as well. Striped bark scorpions (Centruroides vittatus) provide a good model for examining sex differences in venom composition and efficacy, as this species exhibits dramatic sexual dimorphism in both size and defensive behavior; when threatened by an enemy, larger, slower females stand and fight while smaller, fleeter males prefer to run. We here add evidence suggesting that male and female C. vittatus indeed have different defensive propensities; when threatened via an electrical stimulus, females were more likely to sting than were males. We reasoned that intersexual differences in defensive phenotypes would select for venoms with different functions in the two sexes; female venoms should be effective at predator deterrence, whereas male venoms, less utilized defensively, might be better suited to capturing prey or courting females. This rationale led to our predictions that females would inject more venom and/or possess more painful venom than males. We were wrong. While females do inject more venom than males in a defensive sting, females are also larger; when adjusted for body size, male and female C. vittatus commit equal masses of venom in a sting to a potential enemy. Additionally, house mice (Mus musculus) find an injection of male venom more irritating than an equal amount of female venom, likely because male venom contains more of the toxins that induce pain. Taken together, our results suggest that identifying the ultimate causes of venom variability will, as we move beyond adaptive storytelling, be hard-won.


Assuntos
Comportamento Animal/fisiologia , Escorpiões/fisiologia , Animais , Tamanho Corporal , Feminino , Masculino , Camundongos , Venenos de Escorpião/química , Escorpiões/química , Fatores Sexuais
2.
J Anim Sci ; 90(12): 4523-35, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22829616

RESUMO

Objective and issue-neutral qualitative assessments of livestock behavior could provide a powerful assessment of welfare, augmenting quantitative measures such as autonomic and endocrine changes, which are often difficult to assess under many commercial livestock conditions. We set out to validate the use of qualitative behavioral assessment (QBA) in sheep using controlled experimental conditions (transport as a challenge) and comparing assessments against physiological variables. The behavioral expression of 14 Merino wethers, which had never experienced land transport, were assessed during their first road event (naïve to transport), and then again on their seventh event, 8 d later (habituated to transport). Blood samples were collected immediately before loading and after unloading, and heart rate and core body temperature were measured continuously throughout each event. Continuous video footage recorded during each event was used to provide clips of individual animals that were shown to observers for QBA. There was significant consensus (P < 0.001) amongst 63 observers in terms of their assessment of the behavioral expression of the sheep. Transport-naïve sheep were assessed as being more 'alert', 'anxious', and 'aware', whereas transport-habituated sheep were more 'comfortable', 'tired', and 'confident' (P = 0.015). Heart rate and heart rate variability, core body temperature and a stress leukogram were greater (P < 0.05) in sheep during the first (naïve) event compared with the habituated event, and were significantly correlated with the QBA scores (P < 0.05). In conclusion, QBA is a valid, practical and informative measure of behavioral responses to transport.


Assuntos
Comportamento Animal , Ovinos/fisiologia , Estresse Fisiológico , Meios de Transporte , Animais , Biomarcadores/sangue , Temperatura Corporal , Feminino , Frequência Cardíaca , Humanos , Masculino , Variações Dependentes do Observador , Ovinos/sangue
3.
J Dairy Sci ; 95(4): 1971-82, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22459843

RESUMO

The effects of grain, fructose, and histidine on ruminal pH and fermentation products were studied in dairy cattle during an induced subacute acidosis protocol. Thirty Holstein heifers were randomly allocated to 5 treatment groups: (1) control (no grain); (2) grain [fed at a crushed triticale dry matter intake (DMI) of 1.2% of body weight (BW)]; (3) grain (0.8% of BW DMI)+fructose (0.4% of BW DMI); (4) grain (1.2% of BW DMI)+histidine (6 g/head); and (5) grain (0.8% of BW DMI)+fructose (0.4% of BW DMI)+histidine (6 g/head) in a partial factorial arrangement. Heifers were fed 1 kg of grain daily with ad libitum access to ryegrass silage and alfalfa hay for 10 d. Feed was withheld for 14 h before challenge day, on which heifers were fed 200 g of alfalfa hay and then the treatment diets immediately thereafter. Rumen samples were collected 5 min after diet ingestion, 60 min later, and at 3 subsequent 50-min intervals. Grain decreased ruminal pH and increased ammonia, total volatile fatty acid (VFA), acetate, butyrate, propionate, and valerate concentrations compared with controls. The addition of grain had no effect on ruminal D- and L-lactate concentrations. Fructose markedly decreased ruminal pH and markedly increased D- and L-lactate concentrations. Fructose increased total VFA and butyrate and decreased valerate concentrations. Although histidine did not have a marked effect on ruminal fermentation, increased concentrations of histamine were observed following feeding. This study demonstrates that the substitution of some grain for fructose can lower ruminal pH and increase VFA and lactate concentrations, warranting further investigation into the role of sugars on the risk of acidosis in dairy cattle.


Assuntos
Acidose/veterinária , Doenças dos Bovinos/etiologia , Grão Comestível , Frutose/administração & dosagem , Histidina/administração & dosagem , Rúmen/metabolismo , Acidose/etiologia , Acidose/metabolismo , Amônia/análise , Animais , Bovinos , Doenças dos Bovinos/metabolismo , Dieta/veterinária , Ácidos Graxos Voláteis/análise , Feminino , Fermentação/efeitos dos fármacos , Histamina/sangue , Concentração de Íons de Hidrogênio , Ácido Láctico/análise , Ácido Láctico/sangue , Rúmen/química , Gastropatias/etiologia , Gastropatias/veterinária
4.
Leukemia ; 25(10): 1570-7, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21647154

RESUMO

To investigate the frequency of isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) mutations in pediatric acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL), we sequenced these genes in diagnostic samples from 515 patients (227 AMLs and 288 ALLs). Somatic IDH1/IDH2 mutations were rare in ALL (N=1), but were more common in AML, occurring in 3.5% (IDH1 N=3 and IDH2 N=5), with the frequency higher in AMLs with a normal karyotype (9.8%). The identified IDH1 mutations occurred in codon 132 resulting in replacement of arginine with either cysteine (N=3) or histidine (N=1). By contrast, mutations in IDH2 did not affect the homologous residue but instead altered codon 140, resulting in replacement of arginine with either glutamine (N=4) or tryptophan (N=1). Structural modeling of IDH2 suggested that codon 140 mutations disrupt the enzyme's ability to bind its substrate isocitrate. Accordingly, recombinant IDH2 R140Q/W were unable to carry out the decarboxylation of isocitrate to α-ketoglutarate (α-KG), but instead gained the neomorphic activity to reduce α-KG to R(-)-2-hydroxyglutarete (2-HG). Analysis of primary leukemic blasts confirmed high levels of 2-HG in AMLs with IDH1/IDH2 mutations. Interestingly, 3/5 AMLs with IDH2 mutations had FLT3-activating mutations, raising the possibility that these mutations cooperate in leukemogenesis.


Assuntos
Isocitrato Desidrogenase/genética , Leucemia Mieloide Aguda/genética , Mutação , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Sequência de Bases , Criança , Cromatografia por Troca Iônica , Primers do DNA , Humanos , Hibridização in Situ Fluorescente , Leucemia Mieloide Aguda/enzimologia , Mutagênese Sítio-Dirigida , Reação em Cadeia da Polimerase , Leucemia-Linfoma Linfoblástico de Células Precursoras/enzimologia , Espectrometria de Massas em Tandem
5.
J Anim Sci ; 89(9): 2782-92, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21512121

RESUMO

The objective of this study was to evaluate whether altering the timing of the secondary anti-gonadotropin-releasing factor (GnRF) immunization closer to slaughter in male finishing pigs would reduce the increase in P2 fat depth (6.5 cm from the midline over the last rib), while still limiting the incidence of boar taint. Entire male pigs are immunized against GnRF to reduce the concentration of testicular steroids that in turn limits the incidence of boar taint. Additionally, testicle measurements and color measurements were taken to examine whether they could be used to differentiate nonimmunized entire males from immunized male pigs. A total of 175 Large White × Landrace entire male pigs aged 16 wk (59 kg of BW) were used in a completely randomized design with 5 treatment groups based on the time that pigs received the secondary immunization before slaughter. Pigs were housed in groups of 7 and randomly allocated to 1 of 5 treatments with 5 replicates per treatment. The treatment groups were as follows: no secondary immunization before slaughter, and the secondary immunization given at 2, 3, 4, or 6 wk before slaughter. The P2 fat depth levels were reduced (P = 0.054) with the secondary immunization closer to slaughter (11.7, 11.3, 12.8, 12.6, and 13.7 mm for no secondary immunization, secondary immunization at 2, 3, 4, and 6 wk before slaughter, respectively). Androstenone concentration did not exceed the generally accepted industry sensory threshold of 1.0 µg/g of fat, and both androstenone concentration in the adipose tissue and testosterone concentrations in the blood were suppressed (P < 0.001) in all immunized pigs regardless of timing of the secondary immunization compared with pigs that did not receive the secondary immunization. Skatole concentration of all pigs in the experiment did not exceed the generally accepted industry sensory threshold of 0.2 µg/g. Testes weight was reduced (P < 0.001) with increased time between slaughter and the secondary immunization. Immunized pigs, regardless of time before slaughter, had greater L* (lightness) and b* (yellowness) color of the testicle surface (P < 0.001 and P = 0.020, respectively), and less a* (redness) color compared with entire males (P < 0.001). The study provides further evidence of the efficacy of the anti-GnRF immunization and indicates that the secondary immunization can be moved closer to slaughter, while still limiting the incidence of boar taint. Testicle measurements and color measurements together could provide a method of discrimination between carcasses from immunized entire males clear of boar taint and tainted carcasses.


Assuntos
Hormônio Liberador de Gonadotropina/fisiologia , Carne/normas , Suínos/crescimento & desenvolvimento , Tecido Adiposo/química , Tecido Adiposo/imunologia , Tecido Adiposo/fisiologia , Androsterona/análise , Criação de Animais Domésticos/métodos , Animais , Hormônio Liberador de Gonadotropina/imunologia , Imunização/veterinária , Masculino , Escatol/análise , Suínos/imunologia , Testículo/anatomia & histologia , Testículo/química , Testículo/fisiologia , Fatores de Tempo
6.
Reprod Fertil Dev ; 23(2): 329-38, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21211466

RESUMO

Long-term nutritional background is thought to influence hypothalamic appetite and reproductive neuroendocrine responses to short-term nutritional feedback. In order to investigate this phenomenon, the effects of intracerebroventricular administration of insulin or neuropeptide-Y (NPY) on LH secretion and voluntary food intake (VFI) were examined in sheep that were initially thin and kept on an increasing nutritional plane (INP), or initially fat and kept on a decreasing nutritional plane (DNP), for 10 weeks. Intracerebroventricular insulin stimulated LH secretion and suppressed VFI in INP sheep when initially thin, but not when they became fat, and had no effect on LH in DNP sheep when initially fat, and stimulated LH secretion when they became thin. Intracerebroventricular NPY had no effect on LH or VFI in INP sheep when initially thin, decreased LH secretion and increased VFI when they became fat, and decreased LH secretion in DNP sheep when initially fat but had no effect when they became thin. Therefore, sensitivity to insulin increases with low or decreasing nutritional status and decreases with high or increasing nutritional status, whereas sensitivity to NPY increases with high or increasing nutritional status and decreases with low or decreasing nutritional status. In conclusion, reproductive neuroendocrine and appetite responses to acute changes in nutritional feedback signals depend on the individual's longer-term nutritional background.


Assuntos
Apetite/efeitos dos fármacos , Insulina/administração & dosagem , Neuropeptídeo Y/administração & dosagem , Estado Nutricional/fisiologia , Reprodução/efeitos dos fármacos , Ovinos/fisiologia , Adiposidade/fisiologia , Animais , Ingestão de Alimentos/efeitos dos fármacos , Infusões Intraventriculares , Insulina/sangue , Leptina/sangue , Hormônio Luteinizante/metabolismo , Masculino
7.
Bull Exp Biol Med ; 150(6): 679-81, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22235415

RESUMO

Measurement of α-synuclein level in the peripheral blood was proposed as a diagnostic test for Parkinson's disease. However, the results of these studies remain contradictory, probably because the examined samples included patients with different etiology of Parkinson's disease. To verify this assumption we studied the levels of α-synuclein in peripheral blood leukocytes of patients with Parkinson's disease associated with mutations in the gene of leucine-rich kinase 2 (LRRK2). The mean α-synuclein level was significantly lower in patients with LRRK2-associated Parkinson's disease (N=8) than in patients with sporadic form of the disease (N=33; p<0.02) and in controls (N=18; p<0.05). On the other hand, we found no differences in the level of α-synuclein level between patients with sporadic form of the disease and controls. We hypothesize that the level of α-synuclein in the peripheral blood largely depends on the etiology of the disease and cannot be used as a universal diagnostic test for Parkinson's disease.


Assuntos
Doença de Parkinson/genética , Proteínas Serina-Treonina Quinases/genética , alfa-Sinucleína/metabolismo , Idoso , Feminino , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Leucócitos/citologia , Masculino , Pessoa de Meia-Idade , Mutação , Doença de Parkinson/sangue
8.
Pharmazie ; 65(11): 835-9, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21155391

RESUMO

Concurrent application of insect repellent picaridin or DEET with sunscreens has become prevalent due to concerns on West Nile virus and skin cancer. The objectives of this study were to characterize the percutaneous permeation of picaridin and sunscreen oxybenzone from commercially available preparations and to compare the differences in permeability between picaridin and DEET in association with oxybenzone. In vitro diffusion studies were carried out to measure transdermal permeation of picaridin and oxybenzone from four different products, using various application concentrations and sequences. Results were then compared to those of repellent DEET and sunscreen oxybenzone under identical conditions. Transdermal permeation of picaridin across human epidermis was significantly lower than that of DEET, both alone and in combination with oxybenzone. Concurrent use resulted in either no changes or suppression of transdermal permeation of picaridin and oxybenzone. This finding was different from concurrent use of DEET and oxybenzone in which a synergistic permeation enhancement was observed. In addition, permeation of picaridin, DEET and oxybenzone across human epidermis was dependent on application concentration, use sequence, and preparation type. It was concluded from this comparative study that picaridin would be a better candidate for concurrent use with sunscreen preparations in terms of minimizing percutaneous permeation of the chemicals.


Assuntos
Benzofenonas/farmacocinética , DEET/farmacocinética , Repelentes de Insetos/farmacocinética , Piperidinas/farmacocinética , Protetores Solares/farmacocinética , Benzofenonas/administração & dosagem , Cromatografia Líquida de Alta Pressão , DEET/administração & dosagem , Difusão , Cultura em Câmaras de Difusão , Combinação de Medicamentos , Sinergismo Farmacológico , Humanos , Técnicas In Vitro , Repelentes de Insetos/administração & dosagem , Piperidinas/administração & dosagem , Absorção Cutânea , Protetores Solares/administração & dosagem
9.
Phys Med Biol ; 55(23): 7081-96, 2010 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-21076200

RESUMO

All particle beam scanning systems are subject to dose delivery errors due to errors in position, energy and intensity of the delivered beam. In addition, finite scan speeds, beam spill non-uniformities, and delays in detector, detector electronics and magnet responses will all contribute errors in delivery. In this paper, we present dose errors for an 8 × 10 × 8 cm(3) target of uniform water equivalent density with 8 cm spread out Bragg peak and a prescribed dose of 2 Gy. Lower doses are also analyzed and presented later in the paper. Beam energy errors and errors due to limitations of scanning system hardware have been included in the analysis. By using Gaussian shaped pencil beams derived from measurements in the research room of the James M Slater Proton Treatment and Research Center at Loma Linda, CA and executing treatment simulations multiple times, statistical dose errors have been calculated in each 2.5 mm cubic voxel in the target. These errors were calculated by delivering multiple treatments to the same volume and calculating the rms variation in delivered dose at each voxel in the target. The variations in dose were the result of random beam delivery errors such as proton energy, spot position and intensity fluctuations. The results show that with reasonable assumptions of random beam delivery errors, the spot scanning technique yielded an rms dose error in each voxel less than 2% or 3% of the 2 Gy prescribed dose. These calculated errors are within acceptable clinical limits for radiation therapy.


Assuntos
Terapia com Prótons , Doses de Radiação , Radioterapia/métodos , Humanos , Movimento , Imagens de Fantasmas , Dosagem Radioterapêutica , Espalhamento de Radiação , Água
10.
Animal ; 4(7): 1214-26, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22444618

RESUMO

In mature male sheep and goats, changes in feed intake seem to have little effect on gonadal endocrine function but induce profound changes on sperm production. These outcomes are due to changes in size of the seminiferous tubules and in spermatogenic efficiency. Except with severe underfeeding, there are only minor changes in the endocrine function of the testis (testosterone production) unless season-long treatments are imposed. For cattle, nutrition clearly affects testicular development and the production of spermatozoa in young bulls, as it does in other species but, after the period of rapid growth has ended, there appears to be little or no response to nutrition. We are developing a clear picture of the metabolic signals, neuroendocrine processes and hormonal control systems that are involved, particularly for the mature male sheep. The energetic components of the diet, rather than protein, seem to be responsible, so we have envisaged a model of the relationship between energy balance and reproduction that has 4 'dimensions': genotype, structure (organs), communication (chemical and neural signals, nutrient sensing) and time (dynamics, metabolic memory, programming). We have linked these perspectives to 'resource allocation theory' and incorporated them into strategies for 'clean, green and ethical animal production'. In contrast to the clear outcomes with respect to spermatogenesis, the effects of nutrition on sexual behaviour are more difficult to define, perhaps because the behaviour is affected by a complex mix of physiological factors and because of flawed methods for quantifying male behaviour. For example, sexual behaviour is compromised by severe feed restriction, but male sexual behaviour requires intensive motor activity so a decline in libido could be caused by general weakness rather than specific nutritional limitations. The interaction between sexual activity and feeding behaviour also complicates the issue under field conditions. At the other end of the scale, overweight males can show reduced sexual success because they have difficulty courting and mounting. For this reason, exercise can enhance the fertilising capacity of rams. This will be important in extensive mating systems where males need to assemble and guard a harem and then mate many times for several weeks. For artificial insemination centres, there seems to be very few data on the nutritional management of males, but problems with overfed animals appear to be a risk. Future research should concentrate on the intra-testicular systems mediating the effects of nutrition on the production of spermatozoa.

11.
Reproduction ; 131(1): 113-24, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16388015

RESUMO

This study aimed to determine whether reduced fetal ovary folliculogenesis in ewes undernourished during early/midpregnancy is associated with altered ovarian cell proliferation and/or the expression of apoptosis-regulating genes. Groups of ewes (n = 11-19) were fed either 100% (high; H) or 50% (low; L) of metabolisable energy requirements for live-weight maintenance during selected windows of gestation. All animals were killed at days 50, 65 or 110 of gestation. Between mating and slaughter, control animals were fed the H ration, while animals of other subgroups were fed the L ration from (a) mating to slaughter at 50, 65 or 110 days; (b) 0 to 30 days; (c) 31 to 50 or 65 days; or (d), in the day 110 slaughter group only, from 66 to 110 days. Bouin's-fixed fetal ovaries were examined for (a) Ki67 immunoexpression (proliferation) and (b) Bax and Mcl-1 (apoptosis-regulating genes) expression by in situ hybridisation (day 110) and immunohistochemistry (days 50, 65 and 110). At day 50, maternal nutrition had no effect on Ki67, predominant in germ cells, or Bax and Mcl-1, predominant in the oocytes. Restricted maternal food intake from 0 to 30 days significantly reduced staining for Ki67 in germ cells at day 65 (P < 0.05) but increased staining in granulosa cells at day 110 (P < 0.05). In animals fed the L ration for 110 days, primordial follicle Bax and Mcl-1 were significantly increased (Bax: P < 0.01; Mcl-1: P < 0.05). Granulosa cell Bax was also increased (P < 0.05). When the L ration was fed from 66 to 110 days, granulosa cell Bax (P < 0.05) and primordial follicle Mcl-1 (P < 0.01) were also significantly increased. In the fetal ovarian vasculature, animals underfed for 0-110 days had significantly elevated perivascular Mcl-1 (P < 0.001) and endothelial Bax expression (P < 0.05). Moreover, at day 110, endothelial Mcl-1 was increased by underfeeding from 0 to 30 days (P < 0.05). These data indicate that maternal undernutrition alters proliferation and the expression of apoptosis-regulating genes in the developing fetal ovary. The precise mechanism depends on the window of maternal food restriction.


Assuntos
Regulação da Expressão Gênica , Fenômenos Fisiológicos da Nutrição Materna/fisiologia , Ovário/embriologia , Ovário/metabolismo , Ovinos/metabolismo , Fenômenos Fisiológicos da Nutrição Animal , Animais , Apoptose/genética , Endotélio Vascular/química , Feminino , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica/métodos , Hibridização In Situ/métodos , Antígeno Ki-67/análise , Desnutrição , Proteína de Sequência 1 de Leucemia de Células Mieloides , Proteínas de Neoplasias/genética , Ovário/irrigação sanguínea , Gravidez , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Mensageiro/análise , Proteína X Associada a bcl-2/genética
12.
Inflamm Res ; 54(9): 375-9, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16273336

RESUMO

BACKGROUND: Formulations of amphotericin include a deoxycholate suspension (d-Amph), an amphotericin-B lipid complex (Ablc), and a liposomal product (L-Amph). Fever is most frequent with d-Amph, intermediate with Ablc, and lowest with L-Amph. OBJECTIVE: To determine if the release of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1) from brain endothelium corresponds to the incidence of amphotericin fever. RESULTS: Release of TNF-alpha and IL-1beta after L-Amph treatment was similar to negative controls while after d-Amph treatment release was similar to lipopolysaccharide. Ablc treatment produced intermediate pyrogen release.NF-kappaB expression, a transcriptional regulator for TNF-alpha and IL-1beta genes, corresponded to this secretion pattern. TNF-alpha release was elevated 2 hours (p = 0.0021) after treatment while significant elevations in IL-1beta required 6 hours (p = 0.0009). CONCLUSION: Results from this in vitro study suggest that amphotericin fever may be directly mediated by brain endothelium. These experiments also suggest that amphotericin fever is initially mediated by TNF-alpha.


Assuntos
Anfotericina B/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Febre/induzido quimicamente , Interleucina-1/metabolismo , Pirogênios/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Anfotericina B/administração & dosagem , Anfotericina B/química , Animais , Química Farmacêutica , Ácido Desoxicólico , Endotélio/efeitos dos fármacos , Endotélio/metabolismo , Lipídeos , Lipossomos , NF-kappa B/metabolismo , Pirogênios/química , Estereoisomerismo , Suspensões , Suínos , Fatores de Tempo
13.
J Neural Transm (Vienna) ; 112(12): 1613-24, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16284907

RESUMO

alpha-Synuclein is a major constituent of glial cytoplasmic inclusions (GCIs), which are pathognomic for multiple system atrophy (MSA). We have previously demonstrated that in normal human brain, alpha-synuclein mRNA has a restricted pattern of neuronal expression and no apparent glial expression. The current study used double-label in situ hybridization to determine if alpha-synuclein mRNA is expressed by oligodendroglia of MSA cases. Analysis of MSA brain tissue revealed depletion of regional signal for this transcript in many brain areas due to extensive neurodegeneration. Cellular analysis of oligodendroglia in crus cerebri, a GCI-rich region ventral to substantia nigra, revealed an absence of alpha-synuclein mRNA signal in control and MSA cases. However, an abundance of this transcript was detected in melanin-containing neurons of substantia nigra. Therefore, oligodendroglia do not express alpha-synuclein mRNA in control and MSA cases suggesting that involvement of alpha-synuclein in GCI pathology of MSA is due to its ectopic presence in oligodendroglia.


Assuntos
Encéfalo/metabolismo , Regulação da Expressão Gênica/fisiologia , Atrofia de Múltiplos Sistemas/metabolismo , RNA Mensageiro/biossíntese , alfa-Sinucleína/biossíntese , Idoso , Idoso de 80 Anos ou mais , Encéfalo/patologia , Humanos , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/genética , Atrofia de Múltiplos Sistemas/patologia , Oligodendroglia/metabolismo , RNA Mensageiro/genética , alfa-Sinucleína/genética
14.
Phys Rev Lett ; 94(12): 121301, 2005 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-15903903

RESUMO

Hypothetical axionlike particles with a two-photon interaction would be produced in the sun by the Primakoff process. In a laboratory magnetic field ("axion helioscope"), they would be transformed into x-rays with energies of a few keV. Using a decommissioned Large Hadron Collider test magnet, the CERN Axion Solar Telescope ran for about 6 months during 2003. The first results from the analysis of these data are presented here. No signal above background was observed, implying an upper limit to the axion-photon coupling g(agamma)<1.16x10(-10) GeV-1 at 95% C.L. for m(a) less, similar 0.02 eV. This limit, assumption-free, is comparable to the limit from stellar energy-loss arguments and considerably more restrictive than any previous experiment over a broad range of axion masses.

15.
Brain Res ; 1048(1-2): 24-31, 2005 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-15916752

RESUMO

The involvement of nuclear factor kappa B (NF-kappaB) in TNF-induced increases in cerebral microvascular permeability was evaluated both in vitro, using primary cultured bovine brain microvessel endothelial cells (BBMEC), and in vivo, using the rat cranial window model. In primary cultured BBMEC, TNF exposure resulted in an increased appearance of the Rel A subunit of NF-kappaB in immunoblots of cell lysates. Increases in the Rel A subunit of NF-kappaB were observed as early as 30-min after administration of TNF. The increased permeability and the secretion of prostaglandin E2 in response to TNF exposure in BBMEC monolayers were significantly reduced by several different NF-kappaB inhibitors, including PDTC, CAPE, BAY 11-7085, and lactacystin. Similar results were also obtained in the rat cranial window model where treatment with the COX-2 inhibitor, NS-398 (0.1 microM), or the NF-kappaB inhibitor, PDTC (10 microM), significantly reduced the permeability increases produced by TNF. These studies suggest that the increases in BBB permeability following TNF exposure are attributable to activation of an NF-kappaB-mediated signaling pathway in the cerebral microvasculature.


Assuntos
Encéfalo/citologia , Células Endoteliais/efeitos dos fármacos , NF-kappa B/metabolismo , Transdução de Sinais/fisiologia , Fator de Necrose Tumoral alfa/farmacologia , Animais , Western Blotting/métodos , Ácidos Cafeicos/farmacologia , Permeabilidade Capilar/efeitos dos fármacos , Bovinos , Células Cultivadas , Dextranos/farmacocinética , Dinoprostona/metabolismo , Relação Dose-Resposta a Droga , Interações Medicamentosas , Inibidores Enzimáticos/farmacologia , Ensaio de Imunoadsorção Enzimática/métodos , Nitrilas/farmacologia , Proteínas Oncogênicas v-rel/metabolismo , Álcool Feniletílico/análogos & derivados , Prolina/análogos & derivados , Prolina/farmacologia , Sulfonas/farmacologia , Tiocarbamatos/farmacologia , Fatores de Tempo
16.
Technol Cancer Res Treat ; 4(3): 275-81, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15896083

RESUMO

Replacement of current CT-based, three-dimensional (3D) treatment planning systems by newer versions capable of automated multi-modality image registration may be economically prohibitive for most radiation oncology clinics. We present a low-cost technique for MR-CT image registration on a "first generation" CT-based, 3D treatment planning system for intracranial tumors. The technique begins with fabrication of a standard treatment mask. A second truncated mask, the "minimask," is then made, using the standard mask as a mold. Two orthogonal leveling vials glued onto the minimask detect angular deviations in pitch and roll. Preservation of yaw is verified by referencing a line marked according to the CT laser on the craniocaudal axis. The treatment mask immobilizes the patient's head for CT. The minimask reproduces this CT-based angular treatment position, which is then maintained by taping the appropriately positioned head to the MR head coil for MR scanning. All CT and MR images, in DICOM 3.0 format, are entered into the treatment planning system via a computer network. Interactive registration of MR to CT images is controlled by real-time visual feedback on the computer monitor. Translational misalignments at the target are eliminated or minimized by iterative use of qualitative visual inspection. In this study, rotational errors were measured in a retrospective series of 20 consecutive patients who had undergone CT-MR image registration using this technique. Anatomic structures defined the three CT orthogonal axes from which angular errors on MR image were measured. Translational errors at the target isocenter were within pixel size, as judged by visual inspection. Clinical setup using the minimask resulted in overall average angular deviation of 3 degrees +/-2 degrees (mean +/- SD) and translational deviation within the edges of the target volume of typically less than 2 mm. The accuracy of this registration technique for target delineation of intracranial tumors is compatible with practice guidelines. This method, then, provides a cost-effective means to register MR and CT images for target delineation of intracranial tumors.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Neoplasias Encefálicas/radioterapia , Humanos , Imageamento Tridimensional , Estudos Retrospectivos , Sensibilidade e Especificidade
17.
Neurology ; 62(10): 1835-8, 2004 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-15159488

RESUMO

The authors recently demonstrated that genetic triplication of the SNCA locus causes Parkinson disease. Here it is shown that SNCA triplication results in a doubling in the amount of alpha-synuclein protein in blood. Examination of brain tissue showed a doubling in the level of SNCA message. However, at the protein level in brain, there was a greater effect on deposition of aggregated forms into insoluble fractions than on net expression of soluble alpha-synuclein.


Assuntos
Química Encefálica , Amplificação de Genes , Dosagem de Genes , Mutação , Proteínas do Tecido Nervoso/análise , Doença de Parkinson/genética , RNA Mensageiro/biossíntese , Humanos , Peso Molecular , Proteínas do Tecido Nervoso/sangue , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/genética , Doença de Parkinson/sangue , Doença de Parkinson/metabolismo , Solubilidade , Sinucleínas , alfa-Sinucleína
18.
Reprod Suppl ; 61: 283-97, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14635942

RESUMO

There is a growing literature on the role of leptin in appetite and neuroendocrine regulation in domestic ruminants. Circulating leptin concentration is higher in fat than in thin sheep, is reduced by chronic underfeeding and is higher in sheep subjected to long-day rather than short-day photoperiods. Leptin is reduced acutely by fasting and increases after meals so that there are long- and short-term components to the systemic leptin signal. Nutritional stimulation of reproductive neuroendocrine output is associated with increased circulating concentrations of leptin; peripheral leptin administration restores LH secretion in fasted sheep, and leptin is permissive (although not a trigger) for puberty. Intracerebroventricular (i.c.v.) pharmacological leptin infusion stimulates LH in underfed but not in well-fed sheep, and reduces food intake in well-fed sheep. A single i.c.v. pharmacological injection or physiological infusion of leptin stimulates LH in well-fed sheep, with or without a concomitant decrease in appetite. Furthermore, these appetite and LH responses are differentially affected by photoperiod, indicating that different neuronal pathways may mediate the two responses. Hypothalamic leptin receptors co-localize with orexigenic and anorexigenic neurones, some of which contact GnRH cells, but the confluence of leptin signalling with photoperiod (melatonin) signalling remains unresolved. Photoperiod-entrained sheep provide potential models of altered central leptin sensitivity, in which downstream mechanisms regulating appetite and GnRH may be dissociated.


Assuntos
Leptina/metabolismo , Sistemas Neurossecretores/fisiologia , Reprodução/fisiologia , Estações do Ano , Ovinos/fisiologia , Transdução de Sinais/fisiologia , Animais , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Hormônio Liberador de Gonadotropina/metabolismo , Hipotálamo/metabolismo , Leptina/farmacologia , Hormônio Luteinizante/metabolismo
19.
Technol Cancer Res Treat ; 2(5): 445-7, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14529309

RESUMO

The Loma Linda University Proton Treatment Facility has treated over 5,000 patients for prostate cancer. Other institutions may find information regarding field size and range requirements for this population of patients useful for designing new proton beamlines. The maximum range, range modulation, and maximum field radius for 240 fields of prostate patients undergoing treatment were sampled and analyzed. Most fields required a range less than 290 mm of water, a modulation width less than or equal to 120 mm, and a radius less than 75 mm.


Assuntos
Neoplasias da Próstata/radioterapia , Terapia com Prótons , Radioterapia (Especialidade)/métodos , Humanos , Masculino , Neoplasias da Próstata/patologia , Água
20.
Ophthalmologe ; 100(9): 702-7, 2003 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-14504894

RESUMO

PURPOSE: In the majority of patients with full-thickness macular hole, closure can be achieved with vitreoretinal surgery techniques. However, postoperative function is variable and the prognostic determinants for visual acuity are incompletely understood. We evaluated the incidence and extent of macular edema after macular foramen surgery with and without combined cataract-surgery. METHODS: Between October 1997 and March 2001 macular foramen surgery was performed in 125 eyes from 116 patients. Fluorescein angiograms with sufficient quality were obtained from 59 eyes using a confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph, HRA, Heidelberg Engineering, Heidelberg) and were evaluated by two independent observers. RESULTS: Angiographic macular edema was noted on average 4.2 months after the operation in 47 out of 59 (79.7%) eyes. The incidence of macular edema was 87% in eyes after a combined cataract operation compared to 66.7 % in eyes with no simultaneous operation ( p=0.735). Mean postoperative visual acuity was 0.4 (min 0.1-max 1.2) with no significant difference between eyes with (4.1 lines) and without macular edema (3.5 lines) with regard to visual improvement from baseline. CONCLUSIONS: The results indicate a high incidence of macular edema in eyes after macular hole surgery with subsequent anatomical success. Apparently, the presence of macular edema is not associated with short term visual impairment. Furthermore it seems that a combined cataract operation compared to a consecutive procedure is not associated with disadvantages regarding the functional outcome.


Assuntos
Extração de Catarata/efeitos adversos , Angiofluoresceinografia/métodos , Edema Macular/diagnóstico , Edema Macular/etiologia , Retina/cirurgia , Perfurações Retinianas/cirurgia , Vitrectomia/efeitos adversos , Idoso , Feminino , Seguimentos , Humanos , Incidência , Masculino , Procedimentos Cirúrgicos Oftalmológicos/efeitos adversos , Recuperação de Função Fisiológica , Resultado do Tratamento , Acuidade Visual
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...