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The current study aimed to measure perioperative changes in driving performance following arthroscopic shoulder surgery using a validated driving simulator.21 patients who underwent arthroscopic surgery for rotator cuff or labral pathology were tested on a driving simulator preoperatively, and 6 and 12 weeks postoperatively. An additional 21 subjects were tested to establish driving data in a control cohort. The number of collisions, centerline crossings, and off-road excursions were recorded for each trial. VAS and SPADI scores were obtained at each visit.The mean number of collisions in the study group significantly increased from 2.05 preoperatively to 3.75 at 6 weeks (p<0.001), and significantly decreased to 1.95 at 12 weeks (p<0.001). Centerline crossings and off-road excursions did not significantly change from preoperative through 12 weeks, although centerline crossings were statistically different from the controls at each time point (p<0.001). Surgery on the dominant driving arm resulted in greater collisions at 6 weeks than surgery on the non-dominant driving arm (p<0.001).Preliminary data shows that driving performance is impaired for at least 6 weeks postoperatively, with a return to normal driving by 12 weeks. Driving is more profoundly affected in conditions that require avoiding a collision and when the dominant driving arm is involved.
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Artroscopia , Condução de Veículo , Manguito Rotador/cirurgia , Articulação do Ombro/cirurgia , Acidentes de Trânsito , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Adulto JovemRESUMO
The purpose of the current study was to determine if the application of platelet-rich fibrin matrix could improve regeneration of the tendon-bone insertion site in a rat rotator cuff repair model. 25 Lewis syngeneic rats underwent bilateral tenotomy and repair of the supraspinatus tendon. 10 separate rats were used for PRFM harvest. All left (control) shoulders underwent transosseous rotator cuff repair, while all right (treatment) shoulders were repaired similarly with PRFM augmentation. 9 rats were sacrificed at 2-weeks and ten at 4-weeks for biomechanical testing. 3 separate rats were sacrificed at 2-weeks and 4-weeks each for histologic analysis of the insertion site. At 2 weeks, the experimental group repairs were significantly stronger in ultimate load to failure (P=0.01), stress (P=0.03), and stiffness (P=0.03). Differences in biomechanical testing were not found between the groups at 4 weeks. Histological analysis revealed less collagen organization and cartilage formation at the insertion site in the experimental group. Semiquantitative histologic analysis confirmed our qualitative assessment of the specimens. PRFM does not recapitulate the native enthesis, but rather induces an exuberant and disordered healing response that is characterized by fibrovascular scar tissue.
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Fibrina/farmacologia , Plasma Rico em Plaquetas , Lesões do Manguito Rotador , Cicatrização/efeitos dos fármacos , Animais , Fenômenos Biomecânicos , Colágeno/metabolismo , Masculino , Modelos Animais , Ratos Endogâmicos Lew , Manguito Rotador/patologia , Manguito Rotador/fisiologia , Manguito Rotador/cirurgia , Resistência à Tração , Cicatrização/fisiologiaRESUMO
We present a universal method to create a tunable, artificial vector gauge potential for neutral particles trapped in an optical lattice. The necessary Peierls phase of the hopping parameters between neighboring lattice sites is generated by applying a suitable periodic inertial force such that the method does not rely on any internal structure of the particles. We experimentally demonstrate the realization of such artificial potentials, which generate ground-state superfluids at arbitrary nonzero quasimomentum. We furthermore investigate possible implementations of this scheme to create tunable magnetic fluxes, going towards model systems for strong-field physics.
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OBJECTIVE: To evaluate efficacy and safety of clobazam, a 1,5-benzodiazepine, as adjunctive therapy for Lennox-Gastaut syndrome (LGS). METHODS: Patients aged 2-60 years were randomized to placebo or clobazam 0.25, 0.5, or 1.0 mg/kg/day. Study consisted of 4-week baseline, 3-week titration, and 12-week maintenance phases, followed by a 2- or 3-week taper or continuation in an open-label extension. Primary endpoint was percentage decrease in mean weekly drop seizure rates during maintenance vs baseline phases for modified intention-to-treat (mITT) population. Secondary outcomes included other seizure types, responder rates, and physicians' and caregivers' global assessments. RESULTS: A total of 305 patients were screened, 238 were randomized, and 217 composed the mITT population. Of patients enrolled after a protocol amendment, 125/157 (79.6%) completed. Average weekly drop seizure rates decreased 12.1% for placebo vs 41.2% (p = 0.0120), 49.4% (p = 0.0015), and 68.3% (p < 0.0001) for the clobazam 0.25-, 0.5-, and 1.0-mg/kg/day groups. Responder rates (≥50%) were 31.6% (placebo) vs 43.4% (p = 0.3383), 58.6% (p = 0.0159), and 77.6% (p < 0.0001) for clobazam 0.25-, 0.5-, and 1.0-mg/kg/day groups. Physicians' and caregivers' assessments indicated clobazam significantly improved symptoms. Somnolence, pyrexia, upper respiratory infections, and lethargy were the most frequent adverse events reported for clobazam. CONCLUSIONS: Clobazam significantly decreased weekly drop seizure rates in LGS. No new safety signals were identified. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that clobazam as adjunctive therapy is efficacious, in a dosage-dependent manner, in reducing mean weekly drop seizure rates of patients with LGS over 12 weeks.
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Anticonvulsivantes/uso terapêutico , Benzodiazepinas/uso terapêutico , Deficiência Intelectual/tratamento farmacológico , Espasmos Infantis/tratamento farmacológico , Adolescente , Adulto , Austrália , Criança , Pré-Escolar , Clobazam , Relação Dose-Resposta a Droga , Método Duplo-Cego , Europa (Continente) , Feminino , Seguimentos , Humanos , Cooperação Internacional , Síndrome de Lennox-Gastaut , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Adulto JovemRESUMO
Adeno-associated virus (AAV) provides a promising platform for clinical treatment of neurological disorders owing to its established efficacy and lack of apparent pathogenicity. To use viral vectors in treating neurological disease, however, transduction must occur under neuropathological conditions. Previous studies in rodents have shown that AAV5 more efficiently transduces cells in the hippocampus and piriform cortex than AAV2. Using the kainic acid (KA) model of temporal lobe epilepsy and AAV2 and 5 carrying a hybrid chicken ß-actin promoter driving green fluorescent protein (GFP), we found that limbic seizure activity caused substantial neuropathology and resulted in a significant reduction in subsequent AAV5 transduction. Nonetheless, this reduced transduction still was greater than AAV2 transduction in control rats. Although KA seizures compromise blood-brain barrier function, potentially increasing exposure of target tissue to circulating neutralizing antibodies, we observed no interaction between KA seizure-induced damage and immunization status on AAV transduction. Finally, while we confirmed the near total neuronal-specific transgene expression for both serotypes in control rats, AAV5-GFP expression was increasingly localized to astrocytes in seizure-damaged areas. Thus, the pathological milieu of the injured brain can reduce transduction efficacy and alter viral tropism- both relevant concerns when considering viral vector gene therapy for neurological disorders.
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Dependovirus , Epilepsia do Lobo Temporal/patologia , Epilepsia do Lobo Temporal/terapia , Terapia Genética/métodos , Vetores Genéticos/uso terapêutico , Transdução Genética/métodos , Actinas/genética , Análise de Variância , Animais , Anticorpos Neutralizantes/imunologia , Astrócitos/metabolismo , Epilepsia do Lobo Temporal/induzido quimicamente , Epilepsia do Lobo Temporal/imunologia , Proteínas de Fluorescência Verde/metabolismo , Imuno-Histoquímica , Ácido Caínico/toxicidade , Masculino , Regiões Promotoras Genéticas/genética , Ratos , Ratos Sprague-DawleyRESUMO
Control over an aversive experience can greatly impact the organism's response to subsequent stressors. We compared the effects of escapable (ES) and yoked inescapable (IS) electric tail shocks on the hypothalamic-pituitary-adrenal (HPA) axis hormonal (corticosterone and adrenocorticotropic hormone (ACTH)), neural (c-fos mRNA) and behavioral (struggling) response to subsequent restraint. We found that although the HPA axis response during restraint of both previously stressed groups were higher than stress-naïve rats and not different from each other, lack of control over the tailshock experience led to an increase in restraint-induced struggling behavior of the IS rats compared to both stress-naïve and ES rats. Additionally, c-fos expression in the basolateral amygdala was increased selectively in the IS group, and relative c-fos mRNA expression in the basolateral amygdala positively correlated with struggling behavior. Restraint-induced c-fos expression in the medial prefrontal cortex, a brain area critical for mediating some of the differential neurochemical and behavioral effects of ES and IS, was surprisingly similar in both ES and IS groups, lower than that of stress-naïve rats, and did not correlate with struggling behavior. Our findings indicate that basolateral amygdala activity may be connected with the differential effects of ES and IS on subsequent behavioral responses to restraint, without contributing to the concurrent HPA axis hormone response.
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Reação de Fuga/fisiologia , Regulação da Expressão Gênica , Imobilização/fisiologia , Proteínas Proto-Oncogênicas c-fos/biossíntese , Estresse Psicológico/metabolismo , Tonsila do Cerebelo , Animais , Estudos de Coortes , Estimulação Elétrica/métodos , Imobilização/métodos , Imobilização/psicologia , Masculino , Proteínas Proto-Oncogênicas c-fos/genética , Ratos , Ratos Sprague-Dawley , Restrição Física/métodos , Restrição Física/fisiologia , Restrição Física/psicologia , Estresse Psicológico/genética , Estresse Psicológico/psicologiaRESUMO
Recent findings suggest that the expression of hypothalamic-pituitary-adrenal (HPA) axis stress response adaptation in rats depends on top-down neural control. We therefore examined whether the medial prefrontal cortex (mPFC) modulates expression of stress response habituation. We transiently suppressed (muscimol microinfusion) or stimulated (picrotoxin microinfusion) mPFC neural activity in rats and studied the consequence on the first time response to psychological stress (restraint) or separately on the development and expression of habituation to repeated restraint. We monitored both the hormonal (corticosterone) and neural (forebrain c-fos mRNA) response to stress. Inactivation of the mPFC had no effect on the HPA-axis response to first time restraint, however increased mPFC activity attenuated stress-induced HPA-axis activity. In a three day repeated restraint stress regimen, inactivation of the mPFC on days 1 and 2, but not day 3, prevented the expression of HPA-axis hormone response habituation. In these same rats, the mPFC activity on day 3 interfered with the expression of c-fos mRNA habituation selectively within the mPFC, lateral septum and hypothalamic paraventricular nucleus. In contrast, inactivation of the mPFC only on day 3, or on all 3 days did not interfere with the expression of habituation. We conclude that the mPFC can permit or disrupt expression of HPA-axis stress response habituation, and this control depends on alteration of neural activity within select brain regions. A possible implication of these findings is that the dysregulation of PFC activity associated with depression and post-traumatic stress disorder may contribute to impaired expression of stress-response adaptation and consequently exacerbation of those disorders.
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Habituação Psicofisiológica , Córtex Pré-Frontal/fisiopatologia , Estresse Psicológico/psicologia , Adaptação Fisiológica , Animais , Corticosterona/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Masculino , Muscimol/farmacologia , Picrotoxina/farmacologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Proteínas Proto-Oncogênicas c-fos/biossíntese , Proteínas Proto-Oncogênicas c-fos/genética , RNA Mensageiro/biossíntese , Ratos , Ratos Sprague-Dawley , Restrição Física , Estresse Psicológico/fisiopatologiaRESUMO
To date, few studies have examined suicidality in women with postpartum depression. Reports of suicidal ideation in postpartum women have varied (Lindahl et al. Arch Womens Ment Health 8:77-87, 2005), and no known studies have examined the relationship between suicidality and mother-infant interactions. This study utilizes baseline data from a multi-method evaluation of a home-based psychotherapy for women with postpartum depression and their infants to examine the phenomenon of suicidality and its relationship to maternal mood, perceptions, and mother-infant interactions. Overall, women in this clinical sample (n = 32) had wide ranging levels of suicidal thinking. When divided into low and high groups, the mothers with high suicidality experienced greater mood disturbances, cognitive distortions, and severity of postpartum symptomotology. They also had lower maternal self-esteem, more negative perceptions of the mother-infant relationship, and greater parenting stress. During observer-rated mother-infant interactions, women with high suicidality were less sensitive and responsive to their infants' cues, and their infants demonstrated less positive affect and involvement with their mothers. Implications for clinical practice and future research directions are discussed.
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Depressão Pós-Parto/psicologia , Relações Mãe-Filho , Tentativa de Suicídio/psicologia , Adulto , Afeto , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/psicologia , Transtornos Cognitivos/terapia , Depressão Pós-Parto/diagnóstico , Depressão Pós-Parto/terapia , Feminino , Visita Domiciliar , Humanos , Lactente , Recém-Nascido , Comportamento Materno/psicologia , Apego ao Objeto , Poder Familiar/psicologia , Inventário de Personalidade , Gravidez , Psicologia da Criança , Psicoterapia , Autoimagem , Tentativa de Suicídio/prevenção & controleRESUMO
Several studies have shown that patients with anterior cruciate ligament (ACL) reconstruction have an improved proprioceptive function compared to subjects with ACL-deficient knees. The measurement of functional scores and proprioception potentially provides clinicians with more information on the status of the ACL-reconstructed knees. To evaluate proprioception in patients following ACL reconstruction with a bone-tendon-bone (BTB) graft, we used the angle reproduction in the sitting, lying and standing positions and the one-leg hop test. Forty-five patients between 19 and 52 years of age were investigated in a 36-month period after the operation. For functional performance measurement, the International Knee Documentation Committee (IKDC) score was used. Very good and good results were seen in 95% of cases. All patients returned to the same activity level as seen before ACL repair. There was a significant difference in the active angle reproduction test between the ACL-reconstructed knees and normal knees in the active sitting position. Tests with passive angle adjustment in the sitting, lying and active standing positions did not show any differences in proprioceptive skills. Good to very good results in the one-leg hop test we found in 95% of patients. After ACL reconstruction, deficiencies in the active angle reproduction test were very small but, nevertheless, were still observed. Overall, the functional and proprioceptive outcomes demonstrate results to recommend the procedure.
Assuntos
Lesões do Ligamento Cruzado Anterior , Enxerto Osso-Tendão Patelar-Osso , Traumatismos do Joelho/cirurgia , Articulação do Joelho/fisiopatologia , Propriocepção , Ligamento Cruzado Anterior/inervação , Ligamento Cruzado Anterior/cirurgia , Enxerto Osso-Tendão Patelar-Osso/fisiologia , Feminino , Humanos , Traumatismos do Joelho/fisiopatologia , Traumatismos do Joelho/reabilitação , Masculino , Mecanorreceptores/fisiologia , Pessoa de Meia-Idade , Período Pós-Operatório , Recuperação de Função Fisiológica , Adulto JovemRESUMO
The present study evaluated the interactive behavior of three groups of mothers and their 3-month-old infants in the Face-to-Face Still-Face paradigm. The mothers had either a clinical diagnosis of major depressive disorder (MDD, n = 33) with no comorbidity, a clinical diagnosis of panic disorder (PD, n = 13) with no comorbidity, or no clinical diagnosis (n = 48). The sample was selected to be at otherwise low social and medical risk, and all mothers with PD or MDD were in treatment. The findings indicated that (a) infants of mothers with PD or MDD displayed the traditional still-face and reunion effects described in previous research with nonclinical samples; (b) the 3-month-old infants in this study showed similar, but not identical, gender effects to those described for older infants; and (c) there were no patterns of maternal or infant interactive behavior that were unique to the PD, MDD, or control groups. These results are discussed in light of mothers' risk status, receipt of treatment, severity of illness, and comorbidity of PD and MDD.
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This study evaluated similarities and differences in 2½ year-old children's reactions to maternal unavailability during a brief still-face episode and subsequent resumption of social interaction during a reunion episode. Seventy mothers and children were videotaped in the Toddler Still-Face paradigm (T-SF), an age appropriate adaptation of the Face-to-Face Still-Face paradigm. Similar to their younger counterparts, 2½ year-olds displayed the traditional "still-face effect," including an increase in negative affect, gaze aversion, and a wide array of behaviors indicative of proximity seeking to the mother, solicitation of her attention, and avoidance and a "reunion effect," characterized by a carryover of negative affect and avoidance behavior (e.g., moving away from the mother) from the still-face episode to the reunion play episode. However, differences in toddlers' behaviors during the still-face and reunion episodes were also observed, which highlight age-related changes in the toddlers' ability to cope with the stress of maternal unavailability during the still-face during the third year of life. Contrary to reports for younger infants, few gender differences were found in toddlers' reactions to the still-face. The findings support the hypothesis that the toddlers are attempting to make meaning out of an unexpected and senseless event.
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The protein product of the fra-2 gene (Fra-2), a fos-family member, can compete with Fos protein for participation in activating protein-1 (AP-1) transcription factor complexes and each protein can contribute different transactivational consequences to an AP-1 complex. To date, there is limited characterization of fra-2 mRNA expression in the rat forebrain. We examined basal and restraint-induced mRNA expression (in situ hybridization) of fra-2 in the rat forebrain and compared its temporal-spatial pattern to c-fos. In contrast to the very low basal expression of c-fos, fra-2 basal expression was moderately high throughout cortex and some subcortical structures, including prominent basal expression in the hypothalamic paraventricular nucleus (PVN). Restraint-induced fra-2 expression was quantified in the prefrontal cortex (PFC), lateral septum (LS) and PVN. Maximal fra-2 gene induction in the PFC and LS was delayed (60 min) after restraint onset with respect to c-fos (15 min), whereas in the PVN, fra-2 mRNA increased within 15 min of restraint. Additionally we compared c-fos and fra-2 gene expression in rats given shorter or longer restraint durations, but equal total time from stress onset to sample collection, to determine the extent to which the kinetics of gene induction matched that of a hypothalamic-pituitary-adrenal axis hormone response. Rats given 45 min recovery after 15 min restraint showed less c-fos expression in the PVN, less fra-2 expression in the prelimbic and infralimbic PFC, and no difference in the LS compared with rats restrained for 60 min. Thus, the expression of both genes was sensitive to stressor duration, but this sensitivity varied with brain region. Differential basal and stress-induced expression patterns of the fra-2 and c-fos genes are likely to have important functional consequences for AP-1 transcription factor dependent regulation of neural plasticity.
Assuntos
Antígeno 2 Relacionado a Fos/genética , Regulação da Expressão Gênica/genética , Prosencéfalo/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , Estresse Psicológico/genética , Estresse Psicológico/metabolismo , Hormônio Adrenocorticotrópico/sangue , Hormônio Adrenocorticotrópico/metabolismo , Animais , Antígeno 2 Relacionado a Fos/metabolismo , Hidrocortisona/sangue , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Hibridização In Situ , Masculino , Plasticidade Neuronal/genética , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/fisiopatologia , Prosencéfalo/anatomia & histologia , Prosencéfalo/fisiopatologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Restrição Física , Estresse Psicológico/fisiopatologia , Fatores de Tempo , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo , Ativação TranscricionalRESUMO
The current treatment regimen for HIV-infected individuals combines two or more drugs targeting different viral proteins such as RT and gag. Resistance to conventional drugs can develop quickly, and typically persists. The prospect of longer, continuous antiretroviral therapy brings with it the need for new antiretroviral drugs and approaches. In this context, gene therapies have the potential to prolong life and quality of life as an additional therapeutic class and may serve as an adjuvant to traditional treatments. This review focuses on RNA-based hematopoietic cell gene therapy for treatment of HIV infection. Recent advances in our understanding of RNA interference (RNAi) make this an especially attractive candidate for anti-HIV gene therapy although ribozyme and RNA decoy/aptamer approaches can be combined with RNAi to make a combinatorial therapy akin to highly active anti-retroviral therapy.
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Infecções por HIV/terapia , HIV-1 , Interferência de RNA , RNA Interferente Pequeno/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Terapia Combinada , Genes Virais , Terapia Genética , Humanos , RNA Antissenso/administração & dosagemRESUMO
Activating the RNA interference (RNAi) pathway to achieve silencing of specific genes is one of the most exciting new developments of molecular biology. A particularly interesting use of this technology is inhibition of defined viral gene expression. In this review, we discuss the potential application of RNAi to treatment of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Globally, these hepatotropic viruses are the most important causes of cirrhosis and liver cancer. Available treatments have their limitations, which makes development of novel effective RNAi-based therapies for HBV and HCV especially significant. Several investigations carried out in vitro and in vivo are summarized, which demonstrate proof of principle that HBV and HCV can be inhibited by RNAi activators. Challenges facing further development of this technology to a stage of clinical application are discussed.
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Hepatite B Crônica/terapia , Hepatite C Crônica/terapia , Interferência de RNA , RNA Interferente Pequeno/uso terapêutico , Animais , Hepacivirus/genética , Hepacivirus/metabolismo , Vírus da Hepatite B/genética , Vírus da Hepatite B/metabolismo , Hepatite B Crônica/virologia , Hepatite C Crônica/virologia , Humanos , Camundongos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Viral/genética , RNA Viral/metabolismo , Proteínas Virais/genética , Proteínas Virais/metabolismoRESUMO
Inflammation has been implicated in all stages of cardiovascular disease. This has driven a very fruitful search for new biomarkers, which potentially can be used as tools in the diagnosis and prognosis of atherothrombotic disease. While these new markers might prove useful in predicting the onset of atherosclerosis in healthy individuals, the utility of biomarkers in risk assessment for events in those patients with established disease and/or those with acute coronary syndrome requires further work. Effective biomarkers must be standardized, logistically simple to analyze, and clinically useful. Understanding what impact sex, age, ethnicity, and comorbid conditions may have on biomarkers is also of importance. Unfortunately, many of the candidate markers have yet to satisfy these requirements.
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Aterosclerose/complicações , Aterosclerose/diagnóstico , Animais , Dor no Peito/diagnóstico , Marcadores Genéticos , Hemostáticos , Humanos , InflamaçãoRESUMO
BACKGROUND: The goal of this study was to evaluate the interactions of mothers with normative or high levels of depressive symptomatology on the Center for Epidemiologic Studies-Depression Scale (CES-D) and their 3-month-old infants. Although successful mutual regulation of affect is critical to children's socio-emotional development, little is known about the factors that influence dyadic processes such as synchrony, matching, mismatching, and bi-directionality during early infancy. Therefore, this study evaluated the effects of maternal depressive symptom status, infant gender, and interactional context on mother-infant affective expressiveness and the dyadic features of their interactions. METHODS: Participants were 133 mothers and their healthy full-term infants. Mothers were classified into three groups on the basis of their total score on the CES-D at 2 months of infant age: a high symptom group (CES-D score > or = 16), a mid symptom control group (CES-D score = 2-12), and a low symptom group (CES-D score = 0-1). Mothers and infants were then videotaped in the Face-to-Face Still-Face paradigm at 3 months of infant age. The mothers' and infants' affect during the interactions prior to (first play) and following the still-face (reunion play) were coded microanalytically using Izard's AFFEX system. RESULTS: Results indicated that male as compared to female infants were more vulnerable to high levels of maternal depressive symptoms and that high symptom mothers and their sons had more difficult interactions in the challenging reunion episode. CONCLUSIONS: The findings suggest that a cycle of mutual regulatory problems may become established between high symptom mothers and their sons, particularly in challenging social contexts. The long-term consequences of this early social interactive vulnerability in terms of later development need to be further investigated.
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Depressão/epidemiologia , Depressão/psicologia , Relações Mãe-Filho , Mães/psicologia , Mães/estatística & dados numéricos , Núcleo Familiar , Adulto , Afeto , Feminino , Seguimentos , Nível de Saúde , Humanos , Lactente , Comportamento do Lactente/psicologia , Masculino , Programas de Rastreamento/métodos , Índice de Gravidade de Doença , Inquéritos e Questionários , Gravação de VideoteipeRESUMO
Glioblastoma is the most malignant and prevalent brain tumor that still remains incurable. Recent studies reported anti-cancer effect of the broccoli-derived compound sulforaphane. We explored the mechanisms of sulforaphane-mediated apoptosis in human glioblastoma T98G and U87MG cells. Wright staining and ApopTag assay confirmed apoptosis in glioblastoma cells treated with sulforaphane. Increase in intracellular free Ca2+ was detected by fura-2 assay, suggesting activation of Ca2+-dependent pathways for apoptosis. Western blotting was used to detect changes in expression of Bax and Bcl-2 proteins resulting in increased Bax:Bcl-2 ratio that indicated a commitment of glioblastoma cells to apoptosis. Upregulation of calpain, a Ca2+-dependent cysteine protease, activated caspase-12 that in turn caused activation of caspase-9. With the increased Bax:Bcl-2 ratio, cytochrome c was released from mitochondria to cytosol for sequential activation of caspase-9 and caspase-3. Increased calpain and caspase-3 activities generated 145 kD spectrin breakdown product and 120 kD spectrin breakdown product, respectively. Activation of caspase-3 also cleaved the inhibitor-of-caspase-activated-DNase. Accumulation of apoptosis-inducing-factor in cytosol suggested caspase-independent pathway of apoptosis as well. Two of the inhibitor-of-apoptosis proteins were downregulated because of an increase in 'second mitochondrial activator of caspases/Direct inhibitor-of-apoptosis protein binding protein with low pI.' Decrease in nuclear factor kappa B and increase in inhibitor of nuclear factor kappa B alpha expression favored the process of apoptosis. Collectively, our results indicated activation of multiple molecular mechanisms for apoptosis in glioblastoma cells following treatment with sulforaphane.
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Anticarcinógenos/uso terapêutico , Apoptose/efeitos dos fármacos , Ganglioglioma/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Tiocianatos/uso terapêutico , Análise de Variância , Western Blotting/métodos , Cálcio/metabolismo , Caspases/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Fura-2 , Humanos , Marcação In Situ das Extremidades Cortadas/métodos , Isotiocianatos , Modelos Biológicos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais/fisiologia , Sulfóxidos , Proteína X Associada a bcl-2/metabolismoRESUMO
Prenatal cocaine and opiate exposure are thought to subtly compromise social and emotional development. The authors observed a large sample of 236 cocaine-exposed and 459 nonexposed infants (49 were opiate exposed and 646 nonexposed) with their mothers in the face-to-face still-face paradigm. Infant and maternal behaviors were microanalytically coded. No opiate-exposure effects were detected. However, mothers of cocaine-exposed infants showed more negative engagement than other mothers. The cocaine-exposed dyads also showed higher overall levels of mismatched engagement states than other dyads, including more negative engagement when the infants were in states of neutral engagement. Infants exposed to heavier levels of cocaine showed more passive-withdrawn negative engagement and engaged in more negative affective matching with their mothers than other infants. Although effect sizes were small, cocaine exposure, especially heavy cocaine exposure, was associated with subtly negative interchanges, which may have a cumulative impact on infants' later development and their relationships with their mothers.
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Afeto , Transtornos Relacionados ao Uso de Cocaína/epidemiologia , Comunicação , Face , Expressão Facial , Comportamento Materno/psicologia , Relações Mãe-Filho , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Comportamento Social , Adolescente , Adulto , Demografia , Feminino , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , GravidezRESUMO
Studies have demonstrated cytomegalovirus (CMV) DNA particles in restenotic lesions in atherosclerotic coronary arteries. We have shown that high (>1:800) anti-CMV IgG antibody titers in the serum are associated with active coronary disease and with post coronary angioplasty restenosis. In this study we assessed the anti-CMV antibody titer in patients with risk factors for atherosclerosis (but without documented clinical manifestations). One hundred and eighly-seven patients (men and women aged 40-80 years) that were admitted to the Department of Internal Medicine were recruited to this prospective study. All had at least one risk factor for atherosclerosis, and none had documented coronary artery disease. Fasting blood samples were drawn on admission. Risk factors included hypertension, diabetes mellitus, active smoking, hyperlipidemia, and a positive family history. Ninety-three age- and sex-matched individuals without atherosclerosis risk factors served as the control group. One Hundred and twentysix patients had high anti-CMV antibody titers (>/=1:800) compared with none in the control group. Although 80 patients (90%) in the control group were seropositive, none had anti-CMV IgG antibody titers higher than 1:400. The statistical difference between the patients and the control group was highly significant ( p<0.0001). An immunological response against CMV (expressed as an anti-CMV IgG antibody titer) could be a marker of a long-standing immunological reaction causing an inflammatory response that eventually would cause advanced clinical atherosclerosis. We suggest that anti-CMV antibody titer should be used as an early predictor of atherosclerosis. Our findings support the infectious theory and an association between CMV infection and atherosclerosis at an early stage, maybe even years before clinical events occur.
Assuntos
Anticorpos Antivirais/sangue , Arteriosclerose/imunologia , Arteriosclerose/virologia , Citomegalovirus/imunologia , Imunoglobulina G/sangue , Adulto , Idoso , Arteriosclerose/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Fatores de RiscoRESUMO
OBJECTIVES: The goals of this longitudinal study were to evaluate 1) the prevalence and stability of high depressive symptom levels during the first 18 months postpartum in a sample of otherwise healthy Black mothers varying in socio-economic status and 2) the relation of sociodemographic variables and level of socio-demographic risk to maternal depressive symptom levels during this time period. METHODS: Participants were 163 Black adult mothers of healthy, full-term infants. The level of mothers' depressive symptomatology was assessed at 2, 3, 6, 12, and 18 months postpartum using the Center for Epidemiological Studies-Depression Scale (CES-D). Mothers provided socio-demographic information at each assessment. Univariate and bivariate analyses were used to analyze the data. RESULTS: The percentage of mothers with an elevated CES-D score (16 or higher) at single visits ranged from 13.5 to 14.7%, and 35.0% had at least one elevated CES-D score by 18 months postpartum. CES-D total scores were significantly correlated across each pair of visits (mean r = 0.57, all p's < 0.0001), and average CES-D scores did not change significantly over time. Single marital status, low-income status, and more negative maternal perceptions of the adequacy of income for meeting familial needs were significantly related to higher maternal CES-D scores at each assessment (all p's < 0.05). Level of socio-demographic risk, as assessed with a composite risk score derived from these variables, was significantly related to higher average CES-D scores (averaged across visits) (p < 0.0001) and to a greater frequency of elevated CES-D scores (16 or higher) during the first 18 months postpartum (p = 0.0002). CONCLUSIONS: The prevalence and stability of high levels of maternal depressive symptomatology during the first 18 months postpartum in this sample of Black women are consistent with those reported in prior studies of community samples of mothers unselected for race. Mothers with higher socio-demographic risk profiles had higher levels of maternal depressive symptoms at each assessment point.