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Background: Radiation proctitis affects 1-20% of cancer patients undergoing radiation exposure due to pelvic malignancies, including prostate, gynecological and rectum cancers. The patients manifest rectal discomfort, pain, discharge, and bleeding. Notably, the efficacy of prophylactic measures remains controversial due to the lack of adequate animal models that mimic this condition. Objective: The present study then aimed to develop a murine model of high-dose-rate (HDR) brachytherapy-induced proctitis. Material/Methods: C57BL/6 male mice were subjected to HDR (radiation source: iridium-192 [Ir-192]) through a cylindrical propylene tube inserted 2 cm far from the anal verge into the rectum. The animals received radiation doses once a day for three consecutive days (fractions of 9.5 Grays [Gy]), 3.0 mm far from the applicator surface. The sham group received only the applicator with no radiation source. The survival rate was recorded, and a colonoscopy was performed to confirm the tissue lesion development. Following euthanasia, samples of the rectum were collected for histopathology, cytokines dosage (IL-6 and KC), and immunohistochemical analysis (TNF-α and COX-2). Results: HDR significantly reduced animals' survival ten days post first radiation exposure (14% survival vs. 100% in the non-irradiated group). Day seven was then used for further investigation. Mice exposed to radiation presented with rectum injury confirmed by colonoscopy and histopathology (P < 0.05 vs. the control group). The tissue damage was accompanied by an inflammatory response, marked by increased KC and IL-6 tissue levels, and immunostaining for TNF-α and COX-2 (P < 0.05 vs. control group). Conclusions: We established a novel animal model of actinic proctitis induced by HDR brachytherapy, marked by inflammatory damage and low animal mortality.
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BACKGROUND: Retrospectively to evaluate the influence of radiochemotherapy (RCT) in the treatment of surgically and non-surgically treated Oral Squamous Cell Carcinoma (OSCC). MATERIAL AND METHODS: We analysed 934 patients treated in Hospital Haroldo Juaçaba (2000-2014; 15 years of study) by extraction of data type of cancer, localization of tumour, sex, age, race, education level, risk factors (smoking and alcohol use), year of diagnosis, TNM stage, therapeutic approach, health system used (public or private) and overall survival (OS). Surgically and non-surgically treated OSCC were compared by chi-square and Fisher's exact tests, and their prognostic factors were analysed by log-rank Mantel-Cox plus Cox regression tests (SPSS 20.0, p<0.05). RESULTS: Non-surgically treated OSCC patients had a lower OS than surgically treated OSCC patients (p<0.001), but an increase in OS was shown in both groups. Although the 2010-2014 period (p=0.003), education level (p=0.032), tongue/mouth floor/palate localization (p=0.023) and TNM stage (p<0.05) were important in non-surgically treated OSCC OS, the major prognostic factors were node metastasis (p=0.003) and non-use of RCT (p=0.039) (multivariate analysis). In surgically treated OSCC patients, higher OS was shown in the 2010-2014 period (p<0.001), females (p=0.012), non-drinkers (p=0.011), non-smokers (p=0.009) and those with lower TNM stage (p<0.05), but the major prognostic factor was the 2010-2014 period (p=0.004) (multivariate analysis), which was directly associated with an increase in RCT indication (p<0.001). CONCLUSIONS: The increase in RCT improved the OS in this large cohort of surgically and non-surgically treated OSCC patients. Key words:Mouth neoplasms, neck, radiotherapy, drug therapy, combination.
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A pandemia revolucionou a assistência médica global de uma maneira sem precedentes e com repercussões inimagináveis. A prática diária ortopédica foi significativamente afetada. O trauma e a ortopedia estão na linha de frente do coronavírus, uma vez que as operações ortopédicas de emergência ainda estão entre os procedimentos cirúrgicos de emergência mais comuns. No entanto, as indicações cirúrgicas foram reformuladas, com casos eletivos sendo adiados. De acordo com as diretrizes propostas pela Academia Americana de Cirurgiões Ortopédicos (AAOS) e Colégio Americano de Cirurgiões (ACS) as cirurgias eletivas devem ser criteriosamente adiadas, dependendo do local, prevalência de COVID-19 e disponibilidade de recursos. Estudos demonstraram que a chance do paciente que será operado ser portador assintomático do SARS-Cov-2 é de 0,07%, cerca de 1 em 1.400. A partir dessa informação, calcula-se que a chance de um paciente assintomático evoluir a óbito devido a COVID-19 após cirurgia ortopédica é de 1 em 7.000 casos. O risco de morte em cirurgia eletiva em um contexto de pandemia por COVID-19 serão cumulativos; no entanto, o risco do COVID-19 será menor do que o risco de morte por todas as causas em um determinado ano.
The COVID-19 pandemic has revolutionized global health care in an unprecedented way and with unimaginable repercussions. Daily orthopedic practice was significantly affected. Trauma and orthopedics surgeries are at the forefront of coronavirus, since emergency orthopedic operations are still among the most common emergency surgical procedures. However, surgical indications have been reformulated, with elective cases being postponed. According to the guidelines proposed by the American Academy of Orthopedic Surgeons (AAOS) and American College of Surgeons (ACS), elective surgeries should be carefully postponed, depending on the location, prevalence of COVID-19 and availability of resources. Studies have shown that the chance that the patient to be operated on will be asymptomatic with SARS-Cov-2 is 0.07%, about 1 in 1,400. From this information, it is estimated that the chance of an asymptomatic patient evolving to death due to COVID-19 after orthopedic surgery is 1 in 7,000 cases. The risk of death from elective surgery in a context of a COVID-19 pandemic will be cumulative; however, the risk of COVID-19 will be less than the risk of death from all causes in a given year.
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Humanos , Masculino , Feminino , Procedimentos Ortopédicos , COVID-19 , Ortopedia , Medidas de Segurança , Procedimentos Cirúrgicos Operatórios , Coronavirus , Assistência Perioperatória , SARS-CoV-2RESUMO
Canine otitis externa is a disease that affects the external acoustic meatus of about 20% of dogs at some point in life, without predilection for race, age, or sex. It is a multifactorial disease whose etiology involves several microorganisms, detaching Staphylococcus aureus. Antimicrobials are the basis for treating this illness; however, due to the increase in antimicrobial resistance, conventional drugs have become ineffective, requiring the search for alternative therapies. In this context, essential oils (EOs) have great therapeutic potential due to their broad antimicrobial action. This study aimed to evaluate the minimum inhibitory concentration (MIC) in order to measure the MIC50 and MIC90 of gentamicin and EOs of Eugenia caryophyllata, Thymus vulgaris, Cymbopogon winterianus, Cymbopogon citratus, and Cinnamomum cassia against 62 Staphylococcus aureus strains isolated from the external acoustic meatus of dogs. All EOs showed antibacterial action against the studied microorganisms, and their MIC50 and MIC90 were as follows: Eugenia caryophyllata, 2.42 mg mL-1 and 7.25 mg mL-1; Thymus vulgaris, 9.51 mg mL-1 and 22.94 mg mL-1; Cymbopogon winterianus, 26.78 mg mL-1 and 157.79 mg mL-1; Cinnamomum cassia and Cymbopogon citratus, lower than 16.48 and 27.81 mg mL-1, with the same MIC for all isolates. The MIC50 and MIC90 found for gentamicin were 1µg mL-1 and 8 µg mL-1. The MIC range found to antibiotic in this assay was 0.5 µg mL-1 to 128 µg mL-1, and the isolates were classified as susceptible [48 strains (77.41%) - MIC range of 0.5-4.0 µg mL-1], intermediate [eight strains (12.90%) - (MIC = 8.0 µg mL-1], or resistant [six strains (9.68%) - MIC ≥ 16 µg mL-1]. The results, according to the in vitro assays, showed that resistance to gentamicin, one of the antimicrobials most commonly used to treat canine otitis, is present in the Staphylococcus aureus population evaluated. Additionally, the tested EOs have great potential for therapeutic use, however future studies should be carried out to evaluate their in vivo efficacy.(AU)
A otite canina externa é uma doença que afeta o meato acústico externo de até 20% dos cães em algum período de suas vidas, sem predileção por raça, idade ou sexo. Trata-se de uma doença multifatorial que tem Staphylococcus aureus como um dos principais agentes etiológicos. Antimicrobianos constituem a base para o tratamento desta enfermidade, entretanto, devido ao incremento da resistência antimicrobiana, os fármacos convencionais tem se tornado pouco eficazes, o que requer a busca por terapias alternativas. Neste contexto, os óleos essenciais (OE) apresentam grande potencial terapêutico devido a sua ampla ação antimicrobiana. Este trabalho visou detectar a concentração inibitória mínima (CIM), a partir da qual foram obtidos os índices de MIC50 e MIC90 para a gentamicina e para os OE de Eugenia caryophyllata, Thymus vulgaris, Cymbopogon winterianus, Cymbopogon citratus e Cinnamomum cassia contra 62 Staphylococcus aureus isolados do meato acústico externo de cães otopatas. Todos os OE mostraram ação antibacteriana contra os microrganismos estudados e foram detectadas as seguintes CIM50 e CIM90: Eugenia caryophyllata, 2,42 mg mL-1 e 7,45 mg mL-1; Thymus vulgaris, 9,51 mg mL-1 e 22,94 mg mL-1; Cymbopogon winterianus, 26,78 mg mL-1 e 157,79 mg mL-1; Cinnamomum cassia e Cymbopogon citratus com CIM menores que 16,48 e 27,81 mg mL-1, respectivamente já que estes apresentaram CIM única para todos os isolados testados. Para a gentamicina, foram obtidas CIM50 e CIM90 1µg mL-1 e 8 µg/m, respectivamente. Ademais, a faixa de CIM encontrada para o antibiótico variou de 0,5 a 128 µg mL-1, e os isolados foram classificados em susceptíveis [48 isolados (77,41%) - CIM na faixa de 0,5-4 µg mL-1], intermediários [8 isolados (12,90%) - (CIM = 8µg mL-1] e resistentes [6 isolados (9,68%) - CIM ≥16]. Os resultados encontrados mostraram que os micro-organismos testados tem potencial para desenvolver resistência antimicrobiana a terapêutica tradicional e que os OE, de acordo com os resultados in vitro, apresentam potencial de uso terapêutico, entretanto futuros estudos devem ser realizados para avaliar a eficácia dos OE in vivo.(AU)
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Animais , Cães , Otite Externa , Staphylococcus aureus , Óleos Voláteis , Testes de Sensibilidade Microbiana , Cymbopogon , Antibacterianos , Técnicas In VitroRESUMO
PURPOSE: Penile cancer is highly prevalent in low- and middle-income countries, with significant morbidity and mortality rates. The first Brazilian consensus provides support to improve penile cancer patients' outcomes, based on expert's opinion and evidence from medical literature. METHODS: Fifty-one Brazilian experts (clinical oncologists, radiation oncologists, urologists, and pathologists) assembled and voted 104 multiple-choice questions, confronted the results with the literature, and ranked the levels of evidence. RESULTS: Healthcare professionals need to deliver more effective communication about the risk factors for penile cancer. Staging and follow-up of patients include physical examination, computed tomography, and magnetic resonance imaging. Close monitoring is crucial, because most recurrences occur in the first 2-5 years. Lymph-node involvement is the most important predictive factor for survival, and management depends on the location (inguinal or pelvic) and the number of lymph nodes involved. Conservative treatment may be helpful in selected patients without compromising oncological outcomes; however, surgery yields the lowest rate of local recurrence. CONCLUSION: This consensus provides an essential decision-making orientation regarding this challenging disease.
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Países em Desenvolvimento , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Penianas/epidemiologia , Brasil/epidemiologia , Humanos , Linfonodos/patologia , Metástase Linfática , Masculino , Recidiva Local de Neoplasia/economia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Neoplasias Penianas/economia , Neoplasias Penianas/patologia , Neoplasias Penianas/terapia , Fatores de RiscoRESUMO
Resumen Introducción: El dengue se encuentra en 128 países a nivel mundial, produciendo 390 millones de infecciones cada año, solo 96 millones se manifiestan clínicamente. En el Paraguay, la primera epidemia se registró en el período 1988-1989 con la circulación de DEN-1. En el año 2018, se ha registrado 3.414 casos confirmados en todo el país, en Itapúa se registraron 684 probables y167 confirmados. Objetivo: Describir la situación epidemiológica del Dengue en Encarnación 2018. Materiales y Métodos: Estudio observacional de diseño retrospectivo en el cual se revisaron fichas epidemiológicas del 2018, se incluyeron solo aquellas notificaciones de pacientes provenientes de la ciudad de Encarnación. Este estudio contó con la aprobación del Comité de Ética de la Universidad Autónoma. Resultados: En el 2018 se registraron en Encarnación 1418 notificaciones de los cuales 8% fueron confirmados, y 48% sospechosos, el 33 % correspondieron a la zona rural y el 67 % a la zona urbana. Discusión: Al observar las cifras de casos confirmados para Dengue se tienen valores inferiores al 10%, sin embargo, el 2018 se caracterizó por tener una epidemia a nivel regional, así como también nacional, por lo tanto, resulta clave el análisis en el contexto epidemiológico. Conclusión: El reporte de casos confirmados revela un bajo porcentaje de la enfermedad, en contraposición al alto valor en número de casos sospechosos, por lo tanto, allí radica la importancia de la epidemiología pues en caso de no ser confirmada por métodos laboratoriales podrá ser igualmente tratada a tal manera de evitar posibles complicaciones.
Abstract Introduction : Dengue is found in 128 countries worldwide, producing 390 million infections every year, only 96 million manifests clinically. In Paraguay, the first epidemic was recorded in the period 1988-1989 with the circulation of DEN-1. In 2018, 3,414 confirmed cases were registered throughout the country, in Itapúa 167 confirmed and 684 probable were registered. Objective: Describe the epidemiological situation of Dengue in Encarnacion 2018 Materials and Methods : An observational retrospective study in which epidemiological records of 2018 were reviewed, only those notifications of patients from the city of Encarnacion were included. This study was approved by the Ethics Committee of the Autonomous University. Results: In 2018, 1418 notifications were registered in Encarnacion, 8% of which were confirmed, and 48% suspected, 33% corresponded to the rural area and 67% to the urban area, 39% corresponded to the San Pedro neighborhood, 25% the downtown area, 19% San Isidro and 18% San Roque Gonzales. The age range with the highest number of cases was 20 to 39 years, 34% corresponded to the male sex and 39% to the female sex. Conclusion: The report of confirmed cases reveals a low percentage of the disease, as opposed to the high value in the number of suspected cases, therefore, therein lies the importance of epidemiology because if it is not confirmed by laboratory methods it can also be treated Such a way to avoid possible deaths
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The pathophysiology of bipolar disorder remains incompletely elucidated. The purinergic receptor, P2X7 (P2X7R), plays a central role in neuroinflammation, the establishment, and maintenance of microglial activation and neuronal damage/death, all characteristics of bipolar disorder pathology. The present study aims to explore the participation of the P2X7R in a preclinical pharmacological model of mania. We analyzed the modulatory effects of the P2X7R antagonist, brilliant blue, on behavior, monoamines, gene expression, serum purine levels, and cell typing in a pharmacological model of mania induced by D-amphetamine (AMPH) in mice. Our results corroborate an association between the P2X7 receptor and the preclinical animal model of mania, as demonstrated by the decreased responsiveness to AMPH in animals with pharmacologically blocked P2X7R. This study further suggests a possible dopaminergic mechanism for the action of P2X7 receptor antagonism. Additionally, we observed increased peripheral levels of adenosine, a neuroprotective molecule, and increased central expression of Entpd3 and Entpd1 leading to the hydrolysis of ATP, a danger signal, possibly as an attempt to compensate for the damage induced by AMPH. Lastly, P2X7R antagonism in the AMPH model was found to potentially modulate astrogliosis. Our results support the hypothesis that P2X7R plays a vital role in the pathophysiology of mania, possibly by modulating the dopaminergic pathway and astrogliosis, as reflected in the behavioral changes observed. Taken together, this study suggests that a purinergic system imbalance is associated with the AMPH-induced preclinical animal model of mania. P2X7R may represent a promising molecular therapeutic target for bipolar disorder.
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Transtorno Bipolar/fisiopatologia , Hipocampo/efeitos dos fármacos , Antagonistas do Receptor Purinérgico P2X/farmacologia , Receptores Purinérgicos P2X7/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Animais , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/metabolismo , Morte Celular/efeitos dos fármacos , Modelos Animais de Doenças , Gliose/tratamento farmacológico , Hipocampo/metabolismo , Hipocampo/patologia , Masculino , Camundongos Endogâmicos C57BL , Receptores Purinérgicos P2X7/metabolismoRESUMO
Introduction: The main barrier to the management of breast cancer cases in Brazil is mainly due to the long periods of time between the diagnosis of the patient and the beginning of treatment. Objective: To improve access to information, treatment and screening of cancer cases through the training of primary health care professionals. Methods: Two "booklets" containing information on breast cancer were created: one for the Community Health Agents (CHAs) and the other for the Primary Health Care Nurses and Doctors (PHCND). Two theoretical and practical training modules were also created: one for the CHAs and another for the PHCNDs. The theoretical module consisted of lectures about breast cancer, and in the practical module, doctors and nurses were inserted in the mastology outpatient service of the Alcides Carneiro Hospital. Results: Clinical procedures in 2016 (before training) and 2017 (after training) showed a 31% increase in mastologist consultations, 41% in the number of patients undergoing surgeries and 42% in breast surgeries. From 2016 to 2017 there was a 16.5% reduction in the incidence of breast cancer and the number of deaths remained stable. Conclusions: Primary health care training increased and qualified the early detection of breast cancer in the city of Petrópolis-RJ, optimized the population's access to the specialized service and improved the quality of life of women with breast cancer. Prmary health care training was effective, low cost and could be replicated in other Brazilian municipalities.
Introdução: A principal barreira na condução do câncer mama no Brasil ocorre principalmente por conta do elevado tempo entre o diagnóstico e o tratamento efetivo da paciente. Objetivo: Melhorar o acesso à informação, ao tratamento e ao rastreamento dos casos de câncer por meio da capacitação dos profissionais da atenção básica. Métodos: Duas cartilhas contendo informações sobre o câncer de mama foram elaboradas: uma para os agentes comunitários de saúde (ACS) e a outra para enfermeiros e médicos da atenção básica (EMAB). Dois módulos de treinamentos teóricos e práticos também foram criados: um para os ACS e outro para EMAB. O módulo teórico consistiu de palestras sobre câncer de mama, e no módulo prático, médicos e enfermeiros foram inseridos nos ambulatórios de mastologia do Hospital Alcides Carneiro. Resultados: Os procedimentos clínicos em 2017 (após as capacitações) mostraram um aumento de 31% nas consultas com um mastologista, 41% no número de pacientes operados e 42% nas cirurgias de mamas, em comparação com 2016 (antes das capacitações). De 2016 para 2017 houve uma redução de 16,5% dos casos de câncer de mama e o número de óbitos ficou estável. Conclusões: A capacitação da atenção básica ampliou e qualificou a detecção precoce do câncer de mama no município de Petrópolis, Rio de Janeiro, agilizou o acesso da população ao serviço especializado e melhorou a qualidade de vida da mulher com câncer de mama. A capacitação na atenção básica foi efetiva, de baixo custo e poderá ser replicada em outros municípios brasileiros.
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OBJECTIVE: Nystatin and chlorhexidine are extensively used in oral medicine; however, there is some controversy about the possibility of these drugs showing antagonism. To clarify this issue, this study investigated the efficacy and stability of nystatin and chlorhexidine in combination. DESIGN: An in vitro study was conducted to analyze the effect of nystatin and chlorhexidine combined on Candida albicans ATCC 18804, using the drugs mixed as a single formulation and as independent formulations used sequentially with different time intervals between them. The minimum inhibitory concentration (MIC) and effects on C. albicans suspensions and biofilms were evaluated. Also, the stability of nystatin and chlorhexidine in a mixture was tested by high performance liquid chromatography (HPLC). RESULTS: When nystatin and chlorhexidine were mixed in a single formulation, there was no significant difference in MIC compared to that of the drugs used alone (as the only treatment). However, when these drugs were used as independent formulations, sequentially with time intervals in between, their MICs were higher than the respective MIC of the drug used alone, except for the MIC of chlorhexidine with a 10-min interval. Nystatin/chlorhexidine combinations showed lower activity against C. albicans biofilms, except for that with a 30-min interval. The drugs when combined showed high percentages of degradation at all the times evaluated. CONCLUSIONS: The combination of nystatin and chlorhexidine seems to interfere with the efficacy of the drugs and to increase their rate of degradation.
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Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Clorexidina/farmacologia , Nistatina/farmacologia , Antifúngicos/química , Biofilmes/crescimento & desenvolvimento , Candida albicans/crescimento & desenvolvimento , Clorexidina/administração & dosagem , Clorexidina/análogos & derivados , Clorexidina/química , Combinação de Medicamentos , Estabilidade de Medicamentos , Sinergismo Farmacológico , Testes de Sensibilidade Microbiana , Nistatina/administração & dosagem , Nistatina/química , Medicina Bucal , SuspensõesRESUMO
Background Breast cancer is highly prevalent among women worldwide. It is classified into three main subtypes: estrogen receptor positive (ER+), human epidermal growth factor receptor 2 positive (HER2+), and triple negative breast cancer (TNBC). This study has evaluated the effects of aspirin and metformin, isolated or in a combination, in breast cancer cells of the different subtypes. Methods The breast cancer cell lines MCF-7, MDA-MB-231, and SK-BR-3 were treated with aspirin and/or metformin (0.01 mM - 10 mM); functional in vitro assays were performed. The interactions with the estrogen receptors (ER) were evaluated in silico. Results Metformin (2.5, 5 and 10 mM) altered the morphology and reduced the viability and migration of the ER+ cell line MCF-7, whereas aspirin triggered this effect only at 10 mM. A synergistic effect for the combination of metformin and aspirin (2.5, 5 or 10 mM each) was observed in the TNBC cell subtype MDA-MB-231, according to the evaluation of its viability and colony formation. Partial inhibitory effects were observed for either of the drugs in the HER2+ cell subtype SK-BR-3. The effects of metformin and aspirin partly relied on cyclooxygenase-2 (COX-2) upregulation, without the production of lipoxins. In silico, metformin and aspirin bound to the ERα receptor with the same energy. Conclusion We have provided novel evidence on the mechanisms of action of aspirin and metformin in breast cancer cells, showing favorable outcomes for these drugs in the ER+ and TNBC subtypes.
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Antineoplásicos/farmacologia , Aspirina/farmacologia , Neoplasias da Mama/tratamento farmacológico , Metformina/farmacologia , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Receptores de Estrogênio/metabolismoRESUMO
Nickel is a heavy metal that, at high concentrations, leads to environmental contamination and causes health problems. We evaluated the effects of NiCl2 exposure on cognition and behavior in larval and adult zebrafish. Larval and adult zebrafish were exposed to NiCl2 concentrations (0.025, 2.0, 5.0, and 15.0mg/L) or water (control) in two treatment regimens: acute and subchronic. Larvae were exposed to NiCl2 for 2h (acute treatment: 5-day-old larvae treated for 2h, tested after treatment) or 11days (subchronic treatment: 11-day-old larvae treated since fertilization, tested at 5, 8 and 11days post-fertilization, dpf). Adults were exposed for 12h (acute treatment) or 96h (subchronic treatment) and were tested after the treatment period. In both regimens, exposed zebrafish showed concentration-dependent increases in body nickel levels compared with controls. For larvae, delayed hatching, decreased heart rate and morphological alterations were observed in subchronically treated zebrafish. Larvae from subchronic treatment tested at 5dpf decrease distance and mean speed at a low concentration (0.025mg/L) and increased at higher concentrations (5.0 and 15.0mg/L). Subchronic treated larvae decrease locomotion at 15.0mg/L at 8 and 11dpf, whereas decreased escape responses to an aversive stimulus was observed at 2.0, 5.0 and 15.0mg/L in all developmental stages. For adults, the exploratory behavior test showed that subchronic nickel exposure induced anxiogenic-like behavior and decrease aggression, whereas impaired memory was observed in both treatments. These results indicate that exposure to nickel in early life stages of zebrafish leads to morphological alterations, avoidance response impairment and locomotor deficits whereas acute and subchronic exposure in adults resulst in anxiogenic effects, impaired memory and decreased aggressive behavior. These effects may be associated to neurotoxic actions of nickel and suggest this metal may influence animals' physiology in doses that do not necessarily impact their survival.
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Comportamento Animal/efeitos dos fármacos , Larva/efeitos dos fármacos , Locomoção , Níquel/toxicidade , Peixe-Zebra , Animais , Frequência Cardíaca , Testes de ToxicidadeRESUMO
ATP and adenosine, the main signaling molecules of purinergic system, are involved in toxicological effects induced by metals. The manganese (Mn) exposure induces several cellular changes, which could interfere with signaling pathways, such as the purinergic system. In this study, we evaluated the effects of exposure to manganese(II) chloride (MnCl2) during 96 h on nucleoside triphosphate diphosphohydrolase (NTPDase), ecto-5'-nucleotidase, and adenosine deaminase (ADA) activities, followed by analyzing the gene expression patterns of NTPDases (entpd1, entpd2a.1, entpd2a.2, entpd2-like, entpd3) and ADA (ADA 1 , ADA 2.1 , ADA 2.2 , ADAasi, ADAL) families in zebrafish brain. In addition, the brain metabolism of nucleotides and nucleosides was evaluated after MnCl2 exposure. The results showed that MnCl2 exposure during 96 h inhibited the NTPDase (1.0 and 1.5 mM) and ecto-ADA (0.5, 1.0, and 1.5 mM) activities, further decreasing ADA2.1 expression at all MnCl2 concentrations analyzed. Purine metabolism was also altered by the action of MnCl2. An increased amount of ADP appeared at all MnCl2 concentrations analyzed; however, AMP and adenosine levels are decreased at the concentrations of 1.0 and 1.5 mM MnCl2, whereas decreased inosine (INO) levels were observed at all concentrations tested. The findings of this study demonstrated that MnCl2 may inhibit NTPDase and ecto-ADA activities, consequently modulating nucleotide and nucleoside levels, which may contribute for the toxicological effects induced by this metal.
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Envelhecimento/metabolismo , Encéfalo/metabolismo , Cloretos/farmacologia , Compostos de Manganês/farmacologia , Nucleosídeos/metabolismo , Nucleotídeos/metabolismo , Peixe-Zebra/metabolismo , Adenosina Desaminase/metabolismo , Animais , Antígenos CD , Apirase , Feminino , MasculinoRESUMO
Haemostasis is a physiological process that prevents excessive blood loss. In laboratory, the prothrombin time (PT) and the activated partial thromboplastin time (aPTT) are used to examine clotting systems. However, the influence of sex on PT and aPTT values is unknown. The present work aimed to determine the values for PT and aPTT in adult sheep and to evaluate their dependence on the sex of the animal. Blood samples were collected from 40 adults (1-6 years old) of mixed breed sheep (20 males and 20 females) via jugular venepuncture conducted using vacuum tubes containing 3.8% sodium citrate as an anticoagulant. PT and aPTT were determined by visual detection of clot formation. The mean PT and aPTT values for all sheep were 7.71 ± 0.87 s and 35.7 ± 3.57 s, respectively. The aPTT values showed a significant difference (P = 0.0013) between male and female samples, while the difference in PT values was not significant (P = 0.0565). Thus, the animal sex influences the function of the plasma blood-clotting system in sheep. In contrast with table 1 data, in particular, aPTT values are significantly higher in female sheep than in males.
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Tempo de Tromboplastina Parcial , Tempo de Protrombina , Ovinos/sangue , Animais , Feminino , Masculino , Caracteres SexuaisRESUMO
This study investigated the effects of caffeine in the behavioral and inflammatory alterations caused by copper in zebrafish larvae, attempting to correlate these changes with the modulation of adenosine receptors. To perform a survival curve, 7dpf larvae were exposed to 10µM CuSO4, combined to different concentrations of caffeine (100µM, 500µM and 1mM) for up to 24h. The treatment with copper showed lower survival rates only when combined with 500µM and 1mM of caffeine. We selected 4 and 24h as treatment time-points. The behavior evaluation was done by analyzing the traveled distance, the number of entries in the center, and the length of permanence in the center and the periphery of the well. The exposure to 10µM CuSO4 plus 500µM caffeine at 4 and 24h changed the behavioral parameters. To study the inflammatory effects of caffeine, we assessed the PGE2 levels by using UHPLC-MS/MS, and TNF, COX-2, IL-6 and IL-10 gene expression by RT-qPCR. The expression of adenosine receptors was also evaluated with RT-qPCR. When combined to copper, caffeine altered inflammatory markers depending on the time of exposure. Adenosine receptors expression was significantly increased, especially after 4h exposure to copper and caffeine together or separately. Our results demonstrated that caffeine enhances the inflammation induced by copper by decreasing animal survival, altering inflammatory markers and promoting behavioral changes in zebrafish larvae. We also conclude that alterations in adenosine receptors are related to those effects.
Assuntos
Cafeína/efeitos adversos , Cobre/toxicidade , Larva/efeitos dos fármacos , Antagonistas de Receptores Purinérgicos P1/efeitos adversos , Receptores Purinérgicos P1/metabolismo , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/fisiologia , Animais , Comportamento Animal/efeitos dos fármacos , Biomarcadores/metabolismo , Cafeína/agonistas , Cafeína/antagonistas & inibidores , Cobre/agonistas , Cobre/química , Sulfato de Cobre/administração & dosagem , Dinoprostona/agonistas , Dinoprostona/antagonistas & inibidores , Dinoprostona/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Mediadores da Inflamação/agonistas , Mediadores da Inflamação/metabolismo , Larva/crescimento & desenvolvimento , Larva/imunologia , Larva/metabolismo , Concentração Osmolar , Agonistas do Receptor Purinérgico P1/química , Agonistas do Receptor Purinérgico P1/toxicidade , Antagonistas de Receptores Purinérgicos P1/química , Receptores Purinérgicos P1/química , Receptores Purinérgicos P1/genética , Análise de Sobrevida , Poluentes Químicos da Água/agonistas , Poluentes Químicos da Água/antagonistas & inibidores , Peixe-Zebra/crescimento & desenvolvimento , Peixe-Zebra/imunologia , Proteínas de Peixe-Zebra/agonistas , Proteínas de Peixe-Zebra/antagonistas & inibidores , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismoRESUMO
Manganese (Mn) is an essential metal for organisms, but high levels can cause serious neurological damage. The aim of this study was to evaluate the effects of MnCl2 exposure on cognition and exploratory behavior in adult and larval zebrafish and correlate these findings with brain accumulation of Mn, overall brain tyrosine hydroxylase (TH) levels, dopamine (DA) levels, 3,4-dihydroxyphenylacetic acid (DOPAC) levels and cell death markers in the nervous system. Adults exposed to MnCl2 for 4days (0.5, 1.0 and 1.5mM) and larvae exposed for 5days (0.1, 0.25 and 0.5mM) displayed decreased exploratory behaviors, such as distance traveled and absolute body turn angle, in addition to reduced movement time and an increased number of immobile episodes in larvae. Adults exposed to MnCl2 for 4days showed impaired aversive long-term memory in the inhibitory avoidance task. The overall brain TH levels were elevated in adults and larvae evaluated at 5 and 7 days post-fertilization (dpf). Interestingly, the protein level of this enzyme was decreased in larval animals at 10dpf. Furthermore, DOPAC levels were increased in adult animals exposed to MnCl2. Protein analysis showed increased apoptotic markers in both the larvae and adult nervous system. The results demonstrated that prolonged exposure to MnCl2 leads to locomotor deficits that may be associated with damage caused by this metal in the CNS, particularly in the dopaminergic system.
Assuntos
Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Cloretos/toxicidade , Memória/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/fisiologia , Animais , Biomarcadores/metabolismo , Encéfalo/metabolismo , Morte Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Larva/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Masculino , Compostos de Manganês , Atividade Motora/efeitos dos fármacos , Testes de ToxicidadeRESUMO
Autism is a neurodevelopmental disorder characterized by symptoms related to stereotyped movements, deficits in social interaction, impaired communication, anxiety, hyperactivity, and the presence of restricted interests. Evidence indicates an important role of extracellular ATP and adenosine as signaling molecules in autism. ATP hydrolysis by ectonucleotidases is an important source of adenosine, and adenosine deaminase (ADA) contributes to the control of the nucleoside concentrations. Considering zebrafish is an animal model that may contribute towards to understanding the mechanisms that underlie social behavior, we investigated the purinergic signaling in a model of embryological exposure to valproic acid (VPA) that induces social interaction deficit in adult zebrafish. We demonstrated embryological exposure to VPA did not change ATP and ADP hydrolysis in zebrafish at 120 dpf, and the cytosolic (soluble) ADA activity was not altered. However, we observed an increase of AMP hydrolysis (12.5 %) whereas the ecto-ADA activity was decreased (19.2 %) in adult zebrafish submitted to embryological exposure to VPA. Quantitative reverse transcription PCR (RT-PCR) analysis showed changes on ntpd8, ADA 2.1, and A2a1 mRNA transcript levels. Brain ATP metabolism showed a rapid catabolism of ATP and ADP, whereas the extracellular metabolism of AMP and adenosine (ADO) occurred slowly. We demonstrated that embryological exposure to VPA altered biochemical and molecular parameters related to purinergic system in adult zebrafish. These findings indicate that the enzyme activities involved in the control of ATP and adenosine levels may be involved in the pathophysiological mechanisms of diseases related to the impairment of social interaction, such as autism.
Assuntos
Envelhecimento/metabolismo , Embrião não Mamífero/metabolismo , Espaço Extracelular/metabolismo , Nucleotídeos/metabolismo , Ácido Valproico/farmacologia , Peixe-Zebra/embriologia , Peixe-Zebra/metabolismo , 5'-Nucleotidase/genética , 5'-Nucleotidase/metabolismo , Adenosina Desaminase/genética , Adenosina Desaminase/metabolismo , Animais , Encéfalo/enzimologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Hidrólise , Solubilidade , Peixe-Zebra/genéticaRESUMO
This study evaluated the effects of inclusion of Yucca schidigera extract (YSE) in two diets with different levels of crude protein (CP) for dogs on facal odour, nutrient digestibility, ammonia concentration in feces and hematological and serum biochemical profiles. Twenty adults Beagles were used, distributed in a randomized block design in a 2 × 4 factorial design (two diets, 25% and 34% CP, and four YSE levels: 0, 250, 500 and 750 mg/kg) with five replicates, obtained during two experimental periods. The fecal odour reduced (P < 0.05) when 500 mg/kg of YSE was used in diets with higher CP. The inclusion of YSE reduced (P < 0.05) fecal ammonia, and the inclusion of 250 and 500 mg/kg YSE reduced intestinal gas. The inclusion of 750 mg/kg YSE increased the mean corpuscular hemoglobin (MCH), alanine aminotransferase (ALT) activity and tended to increase the serum cholesterol concentration, regardless of the protein level of the diets. There was no effect on the digestibility of nutrients, fecal consistency, nitrogen balance and thickness of the intestinal wall. The inclusion of 500 mg/kg YSE is effective in reducing fecal odour in dogs receiving diets with 34% of CP. Regardless of the protein content, YSE reduces fecal ammonia, but may cause adverse effects if included at higher doses.
Assuntos
Dieta/veterinária , Proteínas Alimentares/administração & dosagem , Cães/sangue , Cães/metabolismo , Fezes/química , Odorantes/análise , Extratos Vegetais/farmacologia , Yucca/química , Alanina Transaminase/metabolismo , Amônia/análise , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição Animal/fisiologia , Animais , Colesterol/sangue , Digestão/efeitos dos fármacos , Hemoglobinas/metabolismo , Nitrogênio/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/efeitos adversos , Extratos Vegetais/isolamento & purificação , SaponinasRESUMO
Changes in social behavior are associated with brain disorders, including mood disorders, stress, schizophrenia, Alzheimer's disease, and autism spectrum disorders (ASD). Autism is a complex neurodevelopmental disorder characterized by deficits in social interaction, impaired communication, anxiety, hyperactivity, and the presence of restricted interests. Zebrafish is one of the most social vertebrates used as a model in biomedical research, contributing to an understanding of the mechanisms that underlie social behavior. Valproic acid (VPA) is used as an anti-epileptic drug and mood stabilizer; however, prenatal VPA exposure in humans has been associated with an increased incidence of autism and it can also affect fetal brain development. Therefore, we conducted a behavioral screening at different periods of zebrafish development at 6, 30, 70, and 120dpf (days postfertilization) after VPA exposure in the early development stage to investigate social behavior, locomotion, aggression, and anxiety. VPA (48µM) exposure during the first 48hpf (hours postfertilization) did not promote changes on survival, morphology, and hatching rate at 24hpf, 48hpf, and 72hpf. The behavioral patterns suggest that VPA exposure induces changes in locomotor activity and anxiety at different developmental periods in zebrafish. Furthermore, a social interaction deficit is present at 70dpf and 120dpf. VPA exposure did not affect aggression in the adult stage at 70dpf and 120dpf. This is the first study that demonstrated zebrafish exposed to VPA during the first 48h of development exhibit deficits in social interaction, anxiety, and hyperactivity at different developmental periods.
Assuntos
Comportamento Animal/efeitos dos fármacos , Embrião não Mamífero/efeitos dos fármacos , Relações Interpessoais , Ácido Valproico/toxicidade , Agressão/efeitos dos fármacos , Animais , Ansiedade/induzido quimicamente , Desenvolvimento Embrionário/efeitos dos fármacos , Feminino , Masculino , Atividade Motora/efeitos dos fármacos , Gravidez , Ácido Valproico/análise , Peixe-ZebraRESUMO
Mephedrone and methedrone are cathinone-related compounds, which act as non-selective substrates for monoamine transporters, facilitating a neurotransmitter release. We compared the acute pharmacological effects of mephedrone and methedrone, attempting to further evaluate the action mechanisms of methedrone by responsibly and ethically using mice under approved procedures. The effects of both compounds were examined from 10 to 60 min, in a series of behavioral paradigms, namely open-field, plus-maze, hot-plate and tail suspension tests, whereas neurotransmitter brain tissue levels were determined ex vivo by HPLC. Separate groups were pre-treated with the dopamine (DA) antagonist haloperidol, or the serotonin (5-HT) synthesis inhibitor ρCPA, to further assess the mechanisms underlying methedrone effects. The compounds caused marked hyperlocomotion, displaying dissimilar stereotyped behavior, in an open-field arena. Mephedrone caused anxiolytic-like effects, while methedrone induced anxiogenic-like actions in the elevated plus-maze. Both compounds displayed thermal antinociception, with a reduced immobility time in the tail suspension model. Mephedrone triggered a 2- and 3-fold increment of dopamine and serotonin tissue levels, respectively, in the nucleus accumbens, with a 1.5-fold elevation of tissue dopamine in the frontal cortex. Methedrone caused a 2-fold increment of tissue dopamine in the nucleus accumbens and in the striatum, and a 1.5-fold increment of serotonin tissue levels in the hippocampus and striatum. In vivo methedrone effects were partially inhibited by a pre-treatment with haloperidol or ρCPA. Despite similar actions on locomotion, analgesia, and depression-like behavior, the acute administration of mephedrone and methedrone elicited divergent effects on anxiety-like behavior and stereotyped movements in mice, which might be related to the distinct modulation of brain tissue neurotransmitter levels.
Assuntos
Ansiolíticos/farmacologia , Encéfalo/efeitos dos fármacos , Metanfetamina/análogos & derivados , Propiofenonas/farmacologia , Animais , Temperatura Corporal/efeitos dos fármacos , Encéfalo/metabolismo , Relação Dose-Resposta a Droga , Comportamento Exploratório/efeitos dos fármacos , Feminino , Alucinógenos/farmacologia , Haloperidol/farmacologia , Elevação dos Membros Posteriores , Locomoção/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Metanfetamina/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Neurotransmissores/metabolismo , Medição da Dor/efeitos dos fármacos , Fenciclidina/farmacologia , Comportamento Estereotipado/efeitos dos fármacosRESUMO
An x-ray microtomography station implemented at the X-ray Applied Crystallography Laboratory of the State University of Campinas is described. The station is based on a propagation based phase contrast imaging setup with a microfocus source and digital x-ray area detectors. Due to its simplicity, this setup is ideal for fast, high resolution imaging and microtomography of small biological specimens and materials research samples. It can also be coupled to gratings to use and develop new techniques as the harmonic spatial coherent imaging, which allow scattering contrast imaging. Details of the experimental setup, equipment, and software integration are described. Test microtomography for setup commissioning and characterization is shown. We conclude that phase contrast enhanced x-ray imaging and microtomography with resolution below 5 µm voxel size are possible and data sets as wide as 2000 × 2000 × 2000 voxels are obtained with this instrumentation.