RESUMO
Current understanding of blood oxygenation level dependent (BOLD) fMRI physiology predicts a close relationship between BOLD signal and blood hematocrit level. However, neither this relationship nor its effect on BOLD percent activation (BPA) has been empirically examined in man. To that end, BPA in primary visual cortex in response to photic stimulation was determined in a group of 24 normal subjects. A positive linear relationship between BPA and hematocrit was seen, particularly in men. To evaluate the effect of change in hematocrit on BPA, 9 men were studied before and following isotonic saline hemodilution, resulting in an average 6% reduction in hematocrit and an 8-31% reduction in BPA. No significant change in the number of activated pixels was seen. A model of predicted BPA as a function of hematocrit and vessel size was developed, and results from this model closely mirrored the empiric data. These results suggest that hematocrit significantly influences the magnitude of BPA and that such baseline factors should be accounted for when comparing BOLD data across groups of subjects, particularly in the many instances in which hematocrit may vary systematically. Such instances include several disease states as well as studies involving sex differences, drug administration, stress and other factors. Finally, the robust agreement between predicted and empiric data serves to validate a semiquantitative approach to the analysis of BOLD fMRI data.
Assuntos
Encéfalo/fisiologia , Hematócrito , Hemodiluição , Imageamento por Ressonância Magnética/métodos , Oxigênio/sangue , Encéfalo/irrigação sanguínea , Feminino , Humanos , Masculino , Modelos Biológicos , Estimulação Luminosa , Análise de RegressãoRESUMO
BACKGROUND: Chronic cocaine abusing women experience fewer cerebral perfusion defects and less neuronal injury than men with comparable drug use histories. This study assessed whether a basis for this discrepancy is a sex difference in cocaine's acute cerebrovascular effects. METHODS: The subjects in this study were 13 healthy and neurologically normal women, reporting occasional cocaine (mean 13, range 1-40 lifetime cocaine exposures). All subjects were administered cocaine (0.4 mg/kg) intravenously, during both the follicular (days 3-8) and luteal (days 18-24) menstrual cycle phases. Dynamic susceptibility contrast magnetic resonance imaging assessments of relative global cerebral blood volume (CBV) changes were conducted on both study days, 10 min after cocaine administration. RESULTS: Cocaine did not alter CBV in follicular phase women, but reduced luteal phase CBV by 10%, indicative of vasoconstriction (analysis of variance [ANOVA], F = 5.1, p <.05). Postcocaine CBV was lower in men administered the drug via an identical protocol relative to follicular phase women (ANOVA, F = 5.4, p <.04). Postcocaine CBV was also lower in the male referent group relative to luteal phase women, but this difference did not achieve statistical significance. No measurable sex or menstrual cycle phase differences in cocaine's cardiovascular effects were noted. CONCLUSIONS: These findings suggest both menstrual cycle phase and sex differences in cocaine's acute cerebrovascular effects, which may contribute to sex differences in the severity of brain dysfunction found in chronic cocaine abusers. These findings imply that gonadal steroids or the factors they modulate merit study as possible therapeutic agents for reducing cocaine-induced cerebrovascular disorders.
Assuntos
Encéfalo/irrigação sanguínea , Cocaína/farmacologia , Ciclo Menstrual/fisiologia , Vasoconstrição/efeitos dos fármacos , Adulto , Volume Sanguíneo/fisiologia , Encéfalo/anatomia & histologia , Cocaína/sangue , Meios de Contraste , Eletrocardiografia , Feminino , Gadolínio , Compostos Heterocíclicos , Humanos , Imageamento por Ressonância Magnética , Compostos Organometálicos , Fatores Sexuais , Método Simples-Cego , Fatores de TempoRESUMO
RATIONALE AND OBJECTIVES: The safety and diagnostic efficacy of MultiHance (gadobenate dimeglumine) in the central nervous system (CNS) were evaluated in a double-blind, multicenter, phase III clinical trial. METHODS: Two hundred five patients highly suspected of having a CNS lesion (by previous imaging exam) were enrolled at 16 sites in the United States. Patients were randomized to one of three incremental dosing regimens. Magnetic resonance imaging with Omniscan (gadodiamide) at doses of 0.1 and 0.3 mmol/kg was compared with MultiHance (gadobenate dimeglumine) at doses of 0.05 and 0.15 mmol/kg and at 0.1 and 0.2 mmol/kg. RESULTS: Compared with predose images alone, efficacy was demonstrated in each of the gadobenate dimeglumine and gadodiamide groups (single and cumulative doses) as indicated by the level of diagnostic information, number of lesions detected, and contrast-to-noise ratio measurements. The level of diagnostic information from gadobenate dimeglumine at 0.1 mmol/kg was equivalent to that with gadodiamide at the same dose. One of the two blinded reviewers found equivalence between the gadobenate dimeglumine 0.05 mmol/kg dose and gadodiamide at 0.1 mmol/kg. Both reviewers found the level of diagnostic information to be equivalent after the second dose of contrast for all three dosing regimens. The cumulative doses of gadobenate dimeglumine were well tolerated and as safe as gadodiamide. CONCLUSIONS: Gadobenate dimeglumine is comparable to gadodiamide in terms of safety and efficacy for imaging of CNS lesions, with a possible advantage in imaging applications owing to enhanced T1 relaxivity.
Assuntos
Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/secundário , Meios de Contraste/administração & dosagem , Gadolínio DTPA , Imageamento por Ressonância Magnética , Meglumina , Compostos Organometálicos , Meios de Contraste/efeitos adversos , Método Duplo-Cego , Feminino , Gadolínio/administração & dosagem , Gadolínio/efeitos adversos , Gadolínio DTPA/administração & dosagem , Gadolínio DTPA/efeitos adversos , Humanos , Masculino , Meglumina/administração & dosagem , Meglumina/efeitos adversos , Meglumina/análogos & derivados , Pessoa de Meia-Idade , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/efeitos adversosRESUMO
Satellite cells derived from fast- and slow-twitch muscles have different properties in culture. We have used the differential display technique to retrieve genes differentially expressed in fast- and slow-twitch muscle satellite cell cultures. Amongst these genes we have identified, cloned, sequenced and studied the expression in muscle of rabbit secreted frizzled related protein 2 (SFRP2) mRNA, whose importance in cell fate determination has been well documented. It has been shown that SFRP2 is widely expressed in the developing embryo but its expression in the adult is much more restricted. We show that primary cultures of satellite cells from adult rabbit fast- and slow-twitch muscles strongly and differentially express SFRP2 mRNA. Embryonic rabbit muscle cell primary cultures also strongly express SFRP2 mRNA whereas the myoblast C2.7 cell line shows little expression. We also studied SFRP2 mRNA expression in growing, regenerating and denervated muscles. Embryonic rabbit muscles express SFRP2 mRNA but this rapidly falls off after birth. In adult rabbit muscles SFRP2 mRNA is detected within 1 day of either muscle damage or denervation. Thereafter the SFRP2 mRNA expression profiles are different for fast- and slow-twitch muscle. The function of SFRP2 in muscle is unknown but its putative activity as a Wnt antagonist and its precocious expression after muscle damage suggest a role in satellite cell activation.
Assuntos
Músculo Esquelético/metabolismo , Biossíntese de Proteínas , Células-Tronco/metabolismo , Envelhecimento/genética , Envelhecimento/metabolismo , Sequência de Aminoácidos , Animais , Células Cultivadas , Embrião de Mamíferos , Perfilação da Expressão Gênica/métodos , Perfilação da Expressão Gênica/estatística & dados numéricos , Dados de Sequência Molecular , Denervação Muscular , Fibras Musculares de Contração Rápida/metabolismo , Fibras Musculares de Contração Lenta/metabolismo , Músculo Esquelético/embriologia , Músculo Esquelético/crescimento & desenvolvimento , RNA Mensageiro/biossíntese , CoelhosRESUMO
Studies using a variety of investigative methods, including functional brain imaging and electroencephalography (EEG), have suggested that changes in central nervous system (CNS) dopamine function result in altered visual system processing. The discovery of abnormal retinal blue cone, but not red cone, electroretinogram in association with cocaine withdrawal and Parkinson's disease suggests that visual system response to blue light might be a marker for CNS dopamine tone. As there are numerous sex-related differences in central nervous system dopamine function, we predicted that blue and red light stimulation would produce sex-specific patterns of response in primary visual cortex when studied using the blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) technique. We analyzed the BOLD response to red and blue light in male and female human volunteers (N=20). Red and blue light responses in primary visual cortex (V1) to stepped intensities of red and blue light were compared by sex for threshold to detectable BOLD signal increase and for stimulus intensity vs. BOLD signal response. Near threshold, males and females showed similar BOLD signal change to red light, but males showed a threefold greater increase (0.52%) to blue light stimulation when compared to females (0.14%). Log-linear regression modeling revealed that the slope coefficients for the red light stimulus intensity vs. signal change curve were not significantly different for males and females (z=0.995, P=0.320), whereas the slope coefficients for the blue light stimulus intensity vs. signal change curve were significantly larger in males (z=2.251, P=0.024). These findings support a sex and color-dependent differential pattern of primary visual cortical response to photic stimulation and suggest a method for assessing the influence of specific dopamine agonist/antagonist medications on visual function.
Assuntos
Percepção de Cores/fisiologia , Imageamento por Ressonância Magnética , Córtex Visual/fisiologia , Adulto , Mapeamento Encefálico , Dopamina/fisiologia , Estrogênios/fisiologia , Feminino , Humanos , Aumento da Imagem , Masculino , Oxigênio/sangue , Estimulação Luminosa , Limiar Sensorial/fisiologia , Fatores SexuaisRESUMO
OBJECTIVE: The purpose of this study was to evaluate the ossification state of the meniscus in the guinea-pig stifle joint using micro-computerized tomography. DESIGN: Hind limbs from six (N=12) and 24 (N=11) month-old male Hartley guinea-pigs were removed and the joints were imaged using high resolution micro-computerized tomography. The ossified volume of the medial and lateral menisci from both groups of animals was quantified. RESULTS: Ossification of both the medial and lateral menisci of the both the 6- and 24-month-old animals was observed. In both age groups, the ossified region of the medial meniscus was significantly larger than the lateral meniscus. In addition, there is a significant increase in ossified volume of the medial meniscus between 6 and 24 months of age. CONCLUSIONS: There is a significant amount of ossification of the menisci in the male Hartley guinea-pig, with the medial compartment showing more bone than the lateral. In addition, as the animals age, there is an increase in ossification within the medial compartment. Bone remodeling and cartilage degeneration is evident in the medial compartment within these animals as they age. It is possible that the increased ossification of the medial meniscus could alter the joint biomechanics and, in part, stimulate this medial compartment joint destruction.
Assuntos
Doenças das Cartilagens/complicações , Meniscos Tibiais , Ossificação Heterotópica/complicações , Osteoartrite/etiologia , Envelhecimento/patologia , Animais , Doenças das Cartilagens/diagnóstico por imagem , Doenças das Cartilagens/patologia , Cobaias , Membro Posterior , Masculino , Meniscos Tibiais/diagnóstico por imagem , Ossificação Heterotópica/diagnóstico por imagem , Ossificação Heterotópica/patologia , Tomografia Computadorizada por Raios XRESUMO
This study evaluated whether cocaine use patterns changed following investigational intravenous cocaine administration to intravenous-naive cocaine users. Subjects were respondents to a follow-up survey who had participated in one to three intravenous double-blind cocaine (0.2 or 0.4 mg/kg) administration studies. The group included healthy men (n = 17) and women (n = 8) with histories of occasional cocaine use (lifetime self-reported use of 12+/-12 (mean +/- S.D.) exposures, primarily via nasal insufflation) who were recontacted an average of 39 weeks (range 7-107 weeks) after study participation. The recontacted group constituted 45% of the total eligible sample of 55 subjects. Baseline demographics for the recontacted and non-recontacted (n = 30) samples were similar, suggesting that the recontacted sample was representative of the group as a whole. Investigational cocaine exposure did not induce adverse health events in any subject. Self-reported cocaine use estimates obtained at follow-up were compared to baseline estimates obtained with identical questionnaires and were highly concordant (Spearman rank correlation p = 0.52 and 0.78, respectively; P < 0.02 and < 0.0002, respectively). This suggests that participants provided stable and reliable reports of cocaine use. No subject reported either illicit intravenous cocaine use or altered frequency of illicit cocaine use by the customary route after investigational intravenous cocaine exposure. These data suggest that illicit cocaine use frequencies and routes of administration are not altered following investigational intravenous cocaine administration to healthy, occasional cocaine users.
Assuntos
Transtornos Relacionados ao Uso de Cocaína , Cocaína/administração & dosagem , Adulto , Análise de Variância , Encéfalo/metabolismo , Cocaína/metabolismo , Feminino , Seguimentos , Humanos , Injeções Intravenosas , Imageamento por Ressonância Magnética , Masculino , Distribuição de Poisson , Projetos de Pesquisa , AutoadministraçãoRESUMO
Preclinical and clinical studies suggest that females may be less vulnerable to cocaine's toxic effects than males. The pharmacokinetics of intravenous cocaine (0.2 and 0.4 mg/kg) were measured in 12 men and 22 women with a history of cocaine abuse, matched with respect to age and body mass index (BMI). Women were studied during the follicular and the luteal phases of the menstrual cycle. There were no differences between men and women in pharmacokinetic measures [peak plasma cocaine levels (Cmax), elimination half-life (T 1/2 min), area under the curve (AUC)] or cardiovascular or subjective effects "high" measures. Heart rate increases were cocaine dose-related (p < .01-.02) and also did not differ between men and women. Cocaine's pharmacokinetic and pharmacodynamic effects were similar in men and women, and in women during the follicular and mid-luteal phases of the menstrual cycle.
Assuntos
Cocaína/farmacocinética , Fase Folicular/fisiologia , Fase Luteal/fisiologia , Adulto , Pressão Sanguínea/efeitos dos fármacos , Índice de Massa Corporal , Cocaína/administração & dosagem , Cocaína/sangue , Transtornos Relacionados ao Uso de Cocaína/reabilitação , Estradiol/sangue , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Injeções Intravenosas , Masculino , Progesterona/sangue , Valores de Referência , Análise de Regressão , Caracteres SexuaisRESUMO
The physiology of alcohol's effects on brain function is poorly understood. Emission tomographic imaging has revealed both acute and chronic alterations in resting cerebral hemodynamics and metabolism following alcohol ingestion. However, cerebral functional integrity under these conditions has received less attention. Functional magnetic resonance imaging (fMRI) offers a non-invasive method for assessing brain functional activation. In order to assess its utility for studying the effect of alcohol on brain function, we performed fMRI with photic stimulation before and after administration of either 0.7 mg/kg alcohol (N = 12) or placebo (N = 5), resulting in peak breath alcohol levels averaging 0.069 g/dl. We found that the amplitude of visual cortical activation in response to photic stimulation was significantly reduced by approximately 33% following alcohol administration (4.0 +/- 1.7% vs. 2.7 +/- 1.3%, P = 0.02), but not following placebo (4.2 +/- 1.5% vs. 4.1 +/- 1.4%, P = 0.7). The results also suggest that the baseline right hemispheric predominance of activation in response to photic stimulation may be reduced following alcohol, suggesting a greater effect on the right hemisphere, consistent with previous studies and alcohol's known effects on visuospatial processing. In addition, through the course of each activation session, there was a progressive reduction in response following alcohol. These data demonstrate that the cerebral effects of alcohol intoxication can be studied with fMRI, and that the effects on brain function of even moderate alcohol intoxication may be widespread, may be lateralized, and may include the visual system.
Assuntos
Encéfalo/efeitos dos fármacos , Etanol/farmacologia , Estimulação Luminosa , Adulto , Encéfalo/fisiologia , Feminino , Lateralidade Funcional/fisiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Oxigênio/sangueRESUMO
Cocaine has substantial effects on cerebral hemodynamics which may partly underlie both its euphorigenic and toxic effects. Dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) was used to determine whether a dose-effect relationship could be detected between cocaine administration and cerebral blood volume reduction in human brain. Twenty-three healthy and neurologically normal adult males with a history of recreational cocaine use (3-40 lifetime exposures) participated. Subjects underwent DSC-MRI measurements of relative cerebral blood volume (rCBV) at baseline and 10 min after i.v. double-blind placebo or cocaine (0.2 or 0.4 mg/kg) administration. Placebo administration resulted in superimposable rCBV curves with post-placebo CBV averaging 104+/-4% (mean+/-SE) of baseline, indicating no CBV change. Both cocaine doses induced CBV decreases which were statistically equivalent and post-cocaine CBV averaged 77+/-4% of baseline (P < 0.002), when measured 10 min following drug administration. These data suggest that DSC-MRI can detect cocaine-induced CBV reductions indicative of vasoconstriction, and that it may be useful for evaluating treatments designed to reduce the cerebrovascular effects of cocaine.
Assuntos
Volume Sanguíneo , Encéfalo/efeitos dos fármacos , Circulação Cerebrovascular/efeitos dos fármacos , Cocaína/farmacologia , Entorpecentes/farmacologia , Adulto , Afeto/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Encéfalo/fisiopatologia , Cocaína/sangue , Frequência Cardíaca/efeitos dos fármacos , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Entorpecentes/sangue , Fatores de Tempo , VasoconstriçãoRESUMO
Residual effects of an initial bolus of gadolinium contrast agent have been previously demonstrated in sequential dynamic susceptibility contrast MR experiments. While these residual effects quickly reach a saturation steady state, their etiology is uncertain, and they can lead to spurious estimates of hemodynamic parameters in activation experiments. The possible influence of T1 effects is now investigated with experiments in which T1 weighting is varied as well as with serial regional T1 measurements. Little evidence for significant residual T1 effects is found, suggesting instead that susceptibility effects underlie these observations. An initial saturation dose of contrast agent minimizes this effect.
Assuntos
Encéfalo/irrigação sanguínea , Imageamento por Ressonância Magnética , Adulto , Velocidade do Fluxo Sanguíneo/fisiologia , Circulação Cerebrovascular/fisiologia , Meios de Contraste/administração & dosagem , Gadolínio , Compostos Heterocíclicos/administração & dosagem , Humanos , Injeções Intravenosas , Masculino , Compostos Organometálicos/administração & dosagemRESUMO
The purpose of this study was to determine the covariance between plasma cocaine and ACTH pharmacokinetics. Twelve healthy male occasional cocaine users participated in a double blind study. Intravenous cocaine (0.2 mg/kg) or placebo was infused over 1 min, and samples for cocaine, ACTH and cortisol analysis were collected at 2, 4, 8, 12, 16, 20, 30, 40, 60, 80, 120, 180, and 240 min. Peak cocaine plasma levels averaged 101.2 +/- 14.6 ng/mL. ACTH increases were significantly correlated (P < 0.0001) with increases in plasma cocaine levels (r = 0.67; r2 = 0.44). Pharmacokinetic analysis showed that the t(max) (observed time to maximum concentration) values for cocaine (6.0 +/- 1.4 min) and ACTH (7.3 +/- 1.2 min) were almost identical. The area under the curve was calculated using the trapezoidal rule. The area under the curve for plasma cocaine was 6463 +/- 1070 ng/min x mL, and the area under the curve for ACTH was 1873 +/- 188 pmol/min x L. The mean half-life for plasma cocaine was 46.7 +/- 4.0 min, and that for ACTH was 35.8 +/- 5.1 min. Cardiovascular and subjective effect measures were correlated with concurrent increases in plasma cocaine and ACTH levels.
Assuntos
Hormônio Adrenocorticotrópico/sangue , Cocaína/sangue , Adulto , Cocaína/farmacologia , Método Duplo-Cego , Frequência Cardíaca/efeitos dos fármacos , Humanos , Injeções Intravenosas , MasculinoRESUMO
OBJECTIVE: The authors evaluated the effect of sex on data derived from activation studies using blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (MRI). METHOD: Gradient echo-echo planar imaging was used to measure BOLD signal response in the primary visual cortex in response to binocular photic stimulation in 16 healthy, young subjects (eight women and eight men). RESULTS: BOLD signal response was 38% lower in women than in men, and much of the difference was lateralized to the right hemisphere. CONCLUSIONS: Lower BOLD signal response in women may reflect a sex difference in the brain's response to a primary visual stimulation or in the physiology underlying BOLD functional MRI signal changes.
Assuntos
Imageamento por Ressonância Magnética/estatística & dados numéricos , Córtex Visual/fisiologia , Percepção Visual/fisiologia , Adulto , Feminino , Humanos , Masculino , Oxigênio/sangue , Estimulação Luminosa , Fatores SexuaisRESUMO
CONTEXT: Clinical observations and case reports suggest that there are important cerebrovascular complications of cocaine use, but no studies have documented a direct link. OBJECTIVE: To determine whether low-dose cocaine administration induces cerebral vasoconstriction in healthy cocaine users. DESIGN: Randomized controlled trial. SUBJECTS: Twenty-four healthy and neurologically normal men (mean age, 29 years) reporting median cocaine use of 8 lifetime exposures (range, 3 to >40). INTERVENTION: Double-blind intravenous administration of cocaine (0.4 or 0.2 mg/kg) or placebo, with cerebral magnetic resonance angiography performed at baseline and 20 minutes following infusion. MAIN OUTCOME MEASURE: Cocaine-induced angiographic change indicative of vasoconstriction, as independently and concordantly rated by 2 reviewers blind to treatment condition. RESULTS: Cocaine-induced cerebral vasoconstriction in a dose-related fashion (P=.03), with angiograms indicative of vasoconstriction found in 5 of 8 and 3 of 9 subjects receiving 0.4- and 0.2-mg/kg cocaine, respectively, compared with 1 of 7 subjects administered placebo. Outcome stratification by frequency of self-reported lifetime cocaine use (3-10 times, 11-40 times, or >40 times) revealed a statistically stronger dose-related effect (P<.001), suggesting that greater lifetime cocaine use was associated with a greater likelihood of vasoconstriction. CONCLUSIONS: Cocaine administration induced dose-related cerebral vasoconstriction on magnetic resonance angiograms. These changes occurred at low cocaine doses and in the absence of other risk factors, including polydrug abuse, hypertension, or cerebrovascular disease. Outcome stratification by prior cocaine use statistically strengthened the relationship between cocaine administration and vasoconstriction, suggesting that cocaine may have a cumulative residual effect in promoting cerebrovascular dysfunction.
Assuntos
Circulação Cerebrovascular/efeitos dos fármacos , Transtornos Cerebrovasculares/induzido quimicamente , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Cocaína/farmacologia , Vasoconstrição/efeitos dos fármacos , Adulto , Análise de Variância , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Angiografia Cerebral , Transtornos Cerebrovasculares/diagnóstico , Cocaína/administração & dosagem , Transtornos Relacionados ao Uso de Cocaína/diagnóstico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Humanos , Injeções Intravenosas , Angiografia por Ressonância Magnética , MasculinoRESUMO
There is a tremendous unmet therapeutic need for the treatment of osteoporosis and osteoarthritis. The ovariectomized rat and the guinea pig are widely used animal models for the evaluation of new therapeutics for osteoporosis and osteoarthritis, respectively. We have utilized X-ray micro-CT techniques to quantitatively evaluate the differences in trabecular bone in the rat proximal tibia following ovariectomy and treatment with estrogen (17-B-estradiol). Results demonstrate a loss of trabecular bone and architecture following ovariectomy (p < 0.001), and a marked inhibition of trabecular bone loss in the estrogen treated group (p < 0.001). A similar change in architecture can be visualized in images obtained by high resolution MR microscopy. In addition, a good correlation was observed between the values of trabecular bone fraction (BV/TV) in the rat tibiae as obtained from 3-dimensional micro-CT data and 2-dimensional static histomorphometry (r = 0.89, 0.73, 0.79 for sham, OVX, and treated groups, respectively). Micro-CT images were also obtained from a set of lumbar vertebrae from sham operated and ovariectomized rats. Significant bone loss can be measured as early as 8 weeks following ovariectomy (p < 0.005). Micro-CT and MR images were also obtained to study age related changes in the stifle joint of the guinea pig. Significant boney changes can be seen in the tibia and femur from the animals at various ages. Changes in cartilage and joint space can also be visualized in the images. The utility of micro-CT imaging in evaluating the mouse skeletal system is illustrated by obtaining morphological and architectural details from high resolution images of the mouse hind limb and proximal tibia, respectively. The results demonstrate the advantages that multi-dimensional imaging techniques can offer in evaluating bone and joint related changes in animal models of osteoporosis and osteoarthritis.
Assuntos
Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Osteoartrite/patologia , Osteoporose/patologia , Tomografia Computadorizada por Raios X/métodos , Animais , Artrografia/métodos , Modelos Animais de Doenças , Terapia de Reposição de Estrogênios , Cobaias , Membro Posterior/diagnóstico por imagem , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Osteoporose/terapia , Ratos , Ratos Sprague-Dawley , Coluna Vertebral/diagnóstico por imagem , Tíbia/diagnóstico por imagemRESUMO
This paper presents a simple and robust secondary structure prediction scheme (SIMPA96) based on an updated version of the nearest neighbour method. Using a larger database of known structures, the Blosum 62 substitution matrix and a regularization algorithm, the three state prediction accuracy is increased by 4.7 percentage points to 67.7% for a single sequence and up to 72.8% when using multiple alignments. The increase in prediction accuracy with respect to the previous version can be almost entirely ascribed to the sevenfold increase in the size of the database. A more detailed analysis of the results shows that badly predicted regions of a protein sequence are randomly distributed throughout the database and that the goal of perfect secondary structure predictions by methods which use only local sequence information is illusory.
Assuntos
Estrutura Secundária de Proteína , Algoritmos , Bases de Dados Factuais , Estudos de Avaliação como Assunto , Engenharia de Proteínas , Alinhamento de SequênciaRESUMO
Many functional imaging studies have demonstrated age-related alterations in cerebral blood flow during the resting state. However, few studies have addressed possible differences in functional response to cerebral activation. We assessed the response of visual cortex to photic stimulation in 9 normal elderly subjects and 17 normal younger subjects with blood oxygenation level dependent functional magnetic resonance imaging. We found that the amplitude of response in elderly subjects was significantly decreased compared to younger subjects (2.5 +/- 1.0% versus 4.0 +/- 1.6%, p = 0.01), suggesting a reduction in functional activation or an age-related alteration in the coupling of blood oxygenation to focal activation.
Assuntos
Envelhecimento/fisiologia , Encéfalo/fisiologia , Circulação Cerebrovascular , Imageamento por Ressonância Magnética , Oxigênio/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/sangue , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Estimulação LuminosaRESUMO
Dynamic susceptibility contrast magnetic resonance imaging (DSC MRI) provides a noninvasive means to create high resolution maps of the regional distribution of cerebral blood volume (CBV). Most DSC MRI studies conducted to date have focused on the evaluation of patients with cerebral neoplasms, ischemia or infarction, and epilepsy. However, preliminary work suggests that DSC MRI may also provide clinically important information for the evaluation of patients with neuropsychiatric disorders, especially dementia and schizophrenia. Additionally, with appropriate modification, DSC MRI may be used to reliably evaluate the effects of pharmacological challenges on cerebral hemodynamics. As pharmacotherapy is an important component in the treatment of a range of psychiatric disorders, the dynamic assessment of changes in cerebral perfusion associated with drug administration may ultimately lead to the development of "brain function tests" for a wide range of disorders.
Assuntos
Meios de Contraste , Aumento da Imagem , Imageamento por Ressonância Magnética , Neuropsicologia/métodos , Encéfalo/irrigação sanguínea , Encefalopatias/diagnóstico , Encefalopatias/fisiopatologia , Hemodinâmica , Humanos , Aumento da Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/estatística & dados numéricosRESUMO
Functional neuroimaging has assumed an important role in the cognitive and clinical neurosciences. Recently, substantial progress has been made toward developing functional magnetic resonance imaging techniques for the examination of cerebral hemodynamic changes that accompany brain function and toward earlier and better diagnosis of brain disease. Dynamic susceptibility contrast (DSC) MRI offers unique information about cerebral hemodynamics both at rest and in response to brain activation. We review the clinical applications of DSC MRI and present our experience with this modality in the evaluation of patients with neuropsychiatric disorders. Our experience suggests that DSC MRI may afford new insights into the diagnosis and treatment of cognitive disorders.