RESUMO
Opioid use disorder is marked by a progressive change in the motivation to administer the drug even in the presence of negative consequences. After long periods of abstinence, the urge to return to taking the drug intensifies over time, known as incubation of craving. Conditioned responses to drug-related stimuli, can acquire motivational properties and exert control over motivated behaviors leading to relapse. Although, preclinical data suggest that the behavioral expression of opioid use is similar between male and female rodents, we do not have conclusive results on sex differences on craving and relapse across abstinence periods. Here, we investigated the effects of abstinence from oxycodone self-administration on neurotransmission in the paraventricular thalamus (PVT) to nucleus accumbens shell (NAcSh) pathway in male and female rats. Using optogenetics and ex vivo electrophysiology, we assessed synaptic strength and glutamate release probability in this pathway, as well as NAcSh medium spiny neurons (MSN) intrinsic excitability, in slices from rats which were subjected to either 1 (acute) or 14 (prolonged) days of forced abstinence after self-administration. Our results revealed no sex differences in oxycodone self-administration or somatic withdrawal symptoms following acute abstinence. However, we found a sex-specific enhancement in cue-induced relapse after prolonged, but not acute, abstinence from oxycodone self-administration, with females exhibiting higher relapse rates. Notably, prolonged abstinence led to similar increases in synaptic strength at PVT-NAcSh inputs compared to saline controls in both sexes, which was not observed after acute abstinence. Thus, prolonged abstinence results in a time-dependent increase in PVT-NAcSh synaptic strength and sex-specific effects on cue-induced relapse rates. These findings suggest that prolonged abstinence leads to significant synaptic changes, contributing to heightened relapse vulnerability, highlighting the need for targeted therapeutic strategies in opioid use disorder.
RESUMO
Epidemiological data suggest that body mass index and obesity are strong risk factors for depression and anxiety. However, it is difficult to separate cause from effect, as predisposition to obesity may enhance susceptibility to anxiety, or vice versa. Here, we examined the effect of diet and obesity on anxiety-like behaviors in male and female selectively bred obesity-prone and obesity-resistant rats, and outbred Sprague-Dawley rats. We found that when obesity-prone and obesity-resistant rats do not differ in weight or fat mass, measures of anxiety-like behavior in the elevated plus maze and open field are similar between the two groups. However, once weight and fat mass diverge, group differences emerge, with greater anxiety in obesity-prone relative to obesity-resistant rats. This same pattern was observed for males and females. Interestingly, even when obesity-resistant rats were "forced" to gain fat mass comparable to obesity-prone rats (via prolonged access to 60% high-fat diet), anxiety-like behaviors did not differ from lean chow fed controls. In addition, a positive correlation between anxiety-like behaviors and adiposity were observed in male but not in female obesity-prone rats. Finally, diet-induced weight gain in and of itself was not sufficient to increase measures of anxiety in outbred male rats. Together, these data suggest that interactions between susceptibility to obesity and physiological alterations accompanying weight gain may contribute to the development of enhanced anxiety.
Assuntos
Ansiedade/fisiopatologia , Predisposição Genética para Doença/genética , Obesidade/complicações , Obesidade/genética , Caracteres Sexuais , Aumento de Peso , Animais , Dieta Hiperlipídica/efeitos adversos , Comportamento Exploratório/fisiologia , Feminino , Locomoção/fisiologia , Masculino , Aprendizagem em Labirinto/fisiologia , Obesidade/induzido quimicamente , Ratos , Ratos Sprague-Dawley , Estatísticas não ParamétricasRESUMO
BACKGROUND: Work-related diseases contribute immensely to the global burden of diseases. Better understanding of attitudes of health care workers towards occupational safety and health (OSH) is important for planning. OBJECTIVE: To assess the attitude of medical students towards OSH around the globe. METHODS: A questionnaire assessing the attitude towards OSH was administered to medical and paramedical students of 21 Medical Universities across the globe. In the current study 1895 students, aged 18-36 years, from 17 countries were included. After having performed a principal components analysis, the associations of interest between the identified components and other socio demographic characteristics were assessed by multivariate linear regression. RESULTS: Principal component analysis revealed 3 components. Students from lower and lower-middle-income countries had a more positive attitude towards OSH, but the importance of OSH was still rated higher by students from upper-income countries. Although students from Asian and African continents showed high interest for OSH, European and South-Central American students comparatively rated importance of OSH to be higher. Paramedical students had more positive attitude towards OSH than medical students. CONCLUSION: The attitude of students from lower-income and lower-middle-income towards importance of OSH is negative. This attitude could be changed by recommending modifications to OSH courses that reflect the importance of OSH. Since paramedical students showed more interest in OSH than medical students, modifications in existing health care system with major role of paramedics in OSH service delivery is recommended.
Assuntos
Atitude do Pessoal de Saúde , Renda , Saúde Ocupacional , Estudantes de Medicina , Adolescente , Adulto , Países Desenvolvidos , Países em Desenvolvimento , Feminino , Humanos , Masculino , Análise de Componente Principal , Faculdades de Medicina , Inquéritos e Questionários , Universidades , Adulto JovemRESUMO
Objetivos. A propósito de un caso de glucagonoma, describir las principales características clínico-patológicas. Métodos. Se resume la historia clínica de una paciente a quien se le diagnóstico por inmunohistoquímica glucagonoma. Se revisa la literatura. Resultados. Paciente femenina de 54 años de edad, quien consulta por presentar dolor abdominal de moderada intensidad, mal definido, localizado a nivel de epigástrico con irradiación a mesogastrio; concomitantemente presenta pérdida de peso, poliuria, nicturia, estreñimiento severo y cifras de glucemias elevadas. Antecedentes de colecistectomía por litiasis biliar hace 3 años. En el examen físico refirió dolor a la palpación profunda a nivel de epigastrio y mesogastrio, resto del examen físico dentro de la normalidad. El estudio de laboratorio reveló una glucemia en ayunas de 325 mg/dL y postprandial de 531 mg/dL. Se inició tratamiento con insulina sin mejoría del control metabólico, por lo cual se aumento la dosis de insulina asociándola con un sensibilizador de la misma. Se realizó tomografía axial computarizada del abdomen observándose una tumoración ecomixta, bien delimitada, de 55.3 x 54.8 x 51.7 mm, localizada en el abdomen posterior, sin compromiso de la cabeza del páncreas. Debido al mal control metabólico y ante la sospecha de tumor funcionante del páncreas, se planteó la utilización de análogos de somatostatina, sin que pudiera ser utilizado por el costo del medicamento. La paciente fue llevada a quirófano realizándose recesión total de la tumoración. El control metabólico mejoró posterior a la cirugía. Los hallazgos histológicos fueron compatibles con células insulares pancreáticas con inmunohistoquímica positiva para glucagon. Conclusiones. El Glucagonoma es una entidad clínico-patológica poco frecuente pudiéndose presentar como una diabetes. La dificultad para un buen control metabólico de la diabetes y la pérdida incontrolada de peso pueden ser la clave para el diagnóstico.
Objectives. Based on a patient with a glucagonome, the clinical and histopathological characteristics of this tumor are described. Methods. A brief clinical history of a patient who was diagnosed to have a glucagonome, based on immunohistochemical analyses, is presented. Medical literature is reviewed about this entity. Results. A 54 years-old female patient, was admitted because of moderate, abdominal poorly localized pain, at the epigastric level, and referred to the mesogastric area. Concomitantly body-weight loss, polyuria, severe constipation, and hyperglycemia, were present. Cholecistectomy was performed because of cholelithiasis three years prior to admission. On physical examination, she presented pain with deep palpatory maneuvers at the epigastric and mesogastric areas. Without other particular findings. She presented fasting-blood glucose of 325 mg/dL, and 531 mg/dL in postprandial conditions. Insulin treatment was started, without improvement of the metabolic alteration. Consequently, insulin was administered associated with a sensitized, improving the glycemic control. An abdominal TAC was performed, revealing a mixed tumor, located in the posterior abdomen, well delimited, and measuring 55.3 x 54.8 x 51.7 mm. The head of the pancreas was not compromised. Due to difficulties in the control of the metabolic alterations, and under the suspicion of a pancreas functional tumor, it was considered the use of a somatostin analogous, which was never applied because of its high cost. Laparotomy was performed, and a total tumor resection was accomplished. The metabolic conditions improved after surgery. The histopathological findings were compatible with pancreatic insular cells, and immunohistochemically positive for glucagon. Conclusions. The glucagonome is rare clinical and pathological entity. It could be expressed as a diabetes. The difficulties to achieve a good metabolic control of the diabetes, and the continued weight loss, could be the clue for the diagnosis.
RESUMO
Conocer las principales características clínico-patológicas del glucagonoma, mediante la realización de un estudio descriptivo. Se revisaron artículos publicados en la literatura internacional referente a la patología, que abarcaron un período de 25 años (1979 2004), de los cuales se seleccionaron 135 casos, a estos se les sumó un caso examinado por el grupo de investigadores. La edad promedio del estudio general fue de 53.08 años; donde 58.82 por ciento de los pacientes eran hombres y 41.18 por ciento mujeres. El grupo etario predominante fue el de 50 a 59 años que representó 29.41 por ciento de la población total en estudio. Entre las principales características clínicas tenemos que 64.71 por ciento de los pacientes presentaron eritema migratorio necrolítico, 48.53 por ciento pérdida de peso y 43.38 por ciento diabetes mellitus, 6.62 por ciento de los casos fue asintomático. La ubicación más frecuente fue a nivel de la cola del páncreas con 41.91 por ciento. El 9.56 por ciento se encontró asociado a neoplasia endocrina múltiple tipo I (MEN I). El Glucagonoma es una entidad clínico-patológica inusual, asociada a tumor de las células alfa 2 de los islotes pancreático que secreta excesiva cantidad de glucagón. Está caracterizado por: eritema migratorio necrolítico, diabetes mellitus, pérdida de peso, anemia normocítica y normocrómica, hipoaminoacidemia, trombosis venosa, entre otros. Localizado más frecuentemente en la cola del páncreas. Se presenta típicamente en la quinta década de vida; aunque estudios previos reportaron ser más frecuente en el sexo femenino, en nuestro estudio no se observó esta tendencia