RESUMO
Periodontal disease is the most common osteolytic disease in humans and is significantly increased by diabetes mellitus. We tested the hypothesis that bacterial infection induces bone loss in diabetic animals through a mechanism that involves enhanced apoptosis. Type II diabetic rats were inoculated with Aggregatibacter actinomycetemcomitans and treated with a caspase-3 inhibitor, ZDEVD-FMK, or vehicle alone. Apoptotic cells were measured with TUNEL; osteoblasts and bone area were measured in H&E sections. New bone formation was assessed by labeling with fluorescent dyes and by osteocalcin mRNA levels. Osteoclast number, eroded bone surface, and new bone formation were measured by tartrate-resistant acid phosphatase staining. Immunohistochemistry was performed with an antibody against tumor necrosis factor-α. Bacterial infection doubled the number of tumor necrosis factor-α-expressing cells and increased apoptotic cells adjacent to bone 10-fold (P < 0.05). Treatment with caspase inhibitor blocked apoptosis, increased the number of osteoclasts, and eroded bone surface (P < 0.05); yet, inhibition of apoptosis resulted in significantly greater net bone area because of an increase in new bone formation, osteoblast numbers, and an increase in bone coupling. Thus, bacterial infection in diabetic rats stimulates periodontitis, in part through enhanced apoptosis of osteoblastic cells that reduces osseous coupling through a caspase-3-dependent mechanism.
Assuntos
Aggregatibacter actinomycetemcomitans , Perda do Osso Alveolar , Complicações do Diabetes , Diabetes Mellitus Experimental , Infecções por Pasteurellaceae , Periodontite , Perda do Osso Alveolar/metabolismo , Perda do Osso Alveolar/microbiologia , Perda do Osso Alveolar/patologia , Animais , Apoptose , Complicações do Diabetes/metabolismo , Complicações do Diabetes/microbiologia , Complicações do Diabetes/patologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/microbiologia , Diabetes Mellitus Experimental/patologia , Feminino , Humanos , Masculino , Osteoclastos/metabolismo , Osteoclastos/patologia , Infecções por Pasteurellaceae/metabolismo , Infecções por Pasteurellaceae/microbiologia , Infecções por Pasteurellaceae/patologia , Periodontite/metabolismo , Periodontite/microbiologia , Periodontite/patologia , Ratos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Patient and regimen persistence in HIV-infected drug users are largely unknown. We evaluated patterns of medication non-persistence among HIV-infected drug users enrolled in a prospective, 6-month randomized controlled trial of directly administered antiretroviral therapy (DAART). Medication-taking behavior was assessed via direct observation and MEMS data. Of 74 participants who initiated DAART, 59 (80%) subjects were non-persistent with medication for 3 or more consecutive days. Thirty-one participants (42%) had 2 or more episodes of non-persistence. Higher depressive symptoms were strongly associated with non-persistence episodes of ≥ 3 days (AOR: 17.4, P = 0.02) and ≥ 7 days AOR: 5.4, P = 0.04). High addiction severity (AOR 3.2, P = 0.03) was correlated with non-persistence ≥ 7 days, and injection drug use (AOR: 15.2, P = 0.02) with recurrence of non-persistence ≥ 3 days. Time to regimen change was shorter for NNRTI-based regimens compared to PI-based ones (HR: 3.0, P = 0.03). There was no significant association between patterns of patient non-persistence and virological outcomes.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Diretamente Observada , Usuários de Drogas/psicologia , Infecções por HIV/tratamento farmacológico , Adesão à Medicação , Abuso de Substâncias por Via Intravenosa/complicações , Adulto , Fármacos Anti-HIV/administração & dosagem , Terapia Antirretroviral de Alta Atividade , Comportamento Aditivo , Contagem de Linfócito CD4 , Connecticut , Usuários de Drogas/estatística & dados numéricos , Feminino , Infecções por HIV/complicações , Infecções por HIV/virologia , Humanos , Entrevistas como Assunto , Estimativa de Kaplan-Meier , Masculino , Modelos de Riscos Proporcionais , RNA Viral/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Abuso de Substâncias por Via Intravenosa/tratamento farmacológico , Resultado do Tratamento , Carga ViralRESUMO
There is evidence for enlargement of association cortex in humans compared to other primate species. Expansion of temporal association cortex appears to have displaced extrastriate cortex posteriorly and inferiorly in humans compared to macaques. However, the details of the organization of these recently expanded areas are still being uncovered. Here, we used diffusion tractography to examine the organization of extrastriate and temporal association cortex in chimpanzees, humans, and macaques. Our goal was to characterize the organization of visual and auditory association areas with respect to their corresponding primary areas (primary visual cortex and auditory core) in humans and chimpanzees. We report three results: (1) Humans, chimpanzees, and macaques show expected retinotopic organization of primary visual cortex (V1) connectivity to V2 and to areas immediately anterior to V2; (2) In contrast to macaques, chimpanzee and human V1 shows apparent connectivity with lateral, inferior, and anterior temporal regions, beyond the retinotopically organized extrastriate areas; (3) Also in contrast to macaques, chimpanzee and human auditory core shows apparent connectivity with temporal association areas, with some important differences between humans and chimpanzees. Diffusion tractography reconstructs diffusion patterns that reflect white matter organization, but does not definitively represent direct anatomical connectivity. Therefore, it is important to recognize that our findings are suggestive of species differences in long-distance white matter organization rather than demonstrations of direct connections. Our data support the conclusion that expansion of temporal association cortex, and the resulting posterior displacement of extrastriate cortex, occurred in the human lineage after its separation from the chimpanzee lineage. It is possible, however, that some expansion of the temporal lobe occurred prior to the separation of humans and chimpanzees, reflected in the reorganization of long white matter tracts in the temporal lobe that connect occipital areas to the fusiform gyrus, middle temporal gyrus, and anterior temporal lobe.
Assuntos
Mapeamento Encefálico , Lobo Temporal/anatomia & histologia , Campos Visuais/fisiologia , Vias Visuais/anatomia & histologia , Animais , Mapeamento Encefálico/métodos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Macaca mulatta , Pan troglodytes/anatomia & histologia , Córtex VisualRESUMO
We present a patient originally treated with definitive chemoradiation therapy for small cell lung cancer (SCLC) of the right lower lobe. At 8 years post-therapy tumor recurred at the site of the original lesion without evidence of distant disease and was treated with lobectomy. Pathology demonstrated the tumor was a basaloid carcinoma (BC) rather than SCLC. She is alive and well at 2 years following her resection and 10 years following her definitive chemoradiation therapy.
RESUMO
Persistence, continuous treatment with a prescribed medication or intervention, is an important, but underrecognized aspect of medication treatment, especially for HIV. In contrast to adherence, which measures the percentage of patient behavior to a prescribed therapy, persistence measures the duration during which a patient remains on a prescribed therapy. Decreased persistence for HIV treatment, or shorter duration on therapy, is associated with increased rates of virological failure, development of antiretroviral resistance, and increased morbidity and mortality. Additionally, frequency and duration of nonpersistent episodes rather than adherence may be a better predictor of clinical outcomes in HIV-infected patients on certain regimens. In this review, we codify the constructs of persistence and adherence, and further define persistence as either patient or regimen persistence. Furthermore, current literature on the clinical consequences of and factors associated with suboptimal persistence is summarized. Finally, methods to measure persistence as well as interventions that may improve persistence and clinical outcomes are suggested.