Influence of ß2-adrenergic selective agonist formoterol on the motor unit of a mouse model of a congenital myasthenic syndrome with complete VAChT deletion.

Congenital Myasthenic Syndromes (CMS) are a set of genetic diseases that affect the neuromuscular transmission causing muscular weakness. The standard pharmacological treatment aims at ameliorating the myasthenic symptom by acetylcholinesterase inhibitors. Most patients respond well in the short and medium term, however, over time the beneficial effects rapidly fade, and the efficacy of the treatment diminishes. Increasing evidence shows that ß2-adrenergic agonists can be a suitable choice for the treatment of neuromuscular disorders, including CMS, as they promote beneficial effects in the neuromuscular system. The exact mechanism on which they rely is not completely understood, although patients and animal models respond well to the treatment, especially over extended periods. Here, we report the use of the long-lasting specific ß2-adrenergic agonist formoterol in a myasthenic mouse model (mnVAChT-KD), featuring deletion of VAChT (Vesicular Acetylcholine Transporter) specifically in the α-motoneurons. Our findings demonstrate that formoterol treatment (300 µg/kg/day; sc) for 30 days increased the neuromuscular junction area, induced skeletal muscle hypertrophy and altered fibre type composition in myasthenic mice. Interestingly, ß2-adrenergic agonists have shown efficacy even in the absence of ACh (acetylcholine). Our data provide important evidence supporting the potential of ß2-adrenergic agonists in treating neuromuscular disorders of pre-synaptic origin and characterized by disruptions in nerve-muscle communication, through a direct and beneficial action within the motor unit.

Luxación intrusiva en dentición primaria: reporte de caso / Luxação intrusiva na dentição decídua: relato de caso clínico / Intrusive luxation in primary dentition: clinical report

La luxación intrusiva es el tipo más común de lesión traumática en la dentición primaria, caracterizada por el desplazamiento del diente hacia el interior del alvéolo. Requieren minucioso examen clínico, buena radiografía y seguimiento del caso, siendo el prognóstico desfavorable, principalmente por la probabilidad de daño al germen del diente permanente. Este trabajo tiene como objetivo reportar un caso clínico de luxación intrusiva en dentición primaria, desde el diagnóstico hasta el seguimiento. Se trata de un paciente masculino, de 3 años, que acudió a la Emergencia de la Clínica de Especialidades Infantiles ­ Universidad Estatal de Londrina (UEL) por traumatismo dentoalveolar en la región antero-superior ocurrido hace tres días. En el examen físico, se observó que el diente 61 presentaba intrusión de grado II con un tercio de la corona visible y el diente 62 intrusión de grado I, con más de un tercio de la corona visible. Radiográficamente se observa inclinación vestibular, sin fractura de la placa ósea, por lo que se optó por un tratamiento conservador, a la espera de la reerupción espontánea de los dientes afectados. Se informó a los padres sobre posibles consecuencias de este tipo de traumatismo y la necesidad de consultas de seguimiento clínico y radiológico. Después de ocho meses de seguimiento, los dientes erupcionaron satisfactoriamente. Es de suma importancia establecer un protocolo de observación y control del diente en el cual se ha identificado el trauma, observando signos y síntomas de los tejidos involucrados en el trauma para reducir secuelas en ambas denticiones

A luxação intrusiva é o tipo de lesão traumática mais frequente na dentição decídua, caracterizada pelo deslocamento do dente para o alvéolo. As intrusões requerem exame físico minucioso, radiografias de valor diagnóstico e acompanhamento do caso, pois o prognóstico é desfavorável, principalmente pela probabilidade de danos ao germe dentário permanente. Este trabalho tem como objetivo relatar um caso clínico de luxação intrusiva na dentição decídua, desde o diagnóstico até o acompanhamento. Trata-se de paciente do sexo masculino, 3 anos de idade, atendido no Pronto Socorro do Ambulatório de Especialidades Infantis da Universidade Estadual de Londrina (UEL) devido a trauma dento-alveolar em região ântero-superior ocorrido há três dias. Ao exame físico intraoral, observou-se que o dente 61 apresentava intrusão grau II (um terço da coroa visível) e o dente 62 apresentava intrusão grau I, com mais de um terço da coroa visível. Radiograficamente foi observada inclinação vestibular, sem fratura da tábua óssea. Assim, optou-se pelo tratamento conservador, aguardando a reerupção espontânea dos dentes envolvidos. Além disso, os pais foram informados sobre as possíveis consequências deste tipo de trauma e a necessidade de consultas de proservação clínica e radiográfica. Após oito meses de acompanhamento, os dentes erupcionaram satisfatoriamente. É de extrema importância estabelecer um protocolo de observação e controle do dente traumatizado, observando sinais e sintomas dos tecidos envolvidos no trauma para reduzir sequelas em ambas as dentições.

Intrusive dislocation is the most frequent type of traumatic injury in the primary dentition, characterized by displacement of the tooth into the alveolus. Intrusions require a thorough physical examination, radiographs of diagnostic value, and follow-up of the case, since the prognosis is unfavorable, mainly due to the probability of damage to the permanent tooth germ. This work aims to report a clinical case of intrusive dislocation in the primary dentition, from diagnosis to follow-up. This is a male patient, 3 years old, who attended in the Emergency of the Children's Specialty Clinic ­ State University of Londrina (UEL) due to dento-alveolar trauma in the antero-superior region that occurred three days ago. On clinical examination, tooth 61 had grade II intrusion (one-third of the crown visible), and tooth 62 with grade I intrusion, with more than one-third of the crown visible. Radiographically, a buccal inclination was observed, with no fracture of the bone plate. Thus, we opted for conservative treatment, waiting for the spontaneous re-eruption of the teeth involved. Furthermore, parents were informed about the possible consequences of this type of trauma and the need for clinical and radiographic follow-up consultations. After eight months of follow-up, the teeth erupted satisfactorily. It is extremely important to establish a protocol for observation and control of the traumatized tooth, observing signs and symptoms of the tissues involved in the trauma to reduce sequelae in both dentitions

A suitable model to investigate acute neurological consequences of coronavirus infection.

OBJECTIVE AND DESIGN: The present study aimed to investigate the neurochemical and behavioral effects of the acute consequences after coronavirus infection through a murine model. MATERIAL: Wild-type C57BL/6 mice were infected intranasally (i.n) with the murine coronavirus 3 (MHV-3). METHODS: Mice underwent behavioral tests. Euthanasia was performed on the fifth day after infection (5 dpi), and the brain tissue was subjected to plaque assays for viral titration, ELISA, histopathological, immunohistochemical and synaptosome analysis. RESULTS: Increased viral titers and mild histological changes, including signs of neuronal degeneration, were observed in the cerebral cortex of infected mice. Importantly, MHV-3 infection induced an increase in cortical levels of glutamate and calcium, which is indicative of excitotoxicity, as well as increased levels of pro-inflammatory cytokines (IL-6, IFN-γ) and reduced levels of neuroprotective mediators (BDNF and CX3CL1) in the mice brain. Finally, behavioral analysis showed impaired motor, anhedonia-like and anxiety-like behaviors in animals infected with MHV-3. CONCLUSIONS: In conclusion, the data presented emulate many aspects of the acute neurological outcomes seen in patients with COVID-19. Therefore, this model may provide a preclinical platform to study acute neurological sequelae induced by coronavirus infection and test possible therapies.

Neuromuscular defects after infection with a beta coronavirus in mice.

COVID-19 affects primarily the lung. However, several other systemic alterations, including muscle weakness, fatigue and myalgia have been reported and may contribute to the disease outcome. We hypothesize that changes in the neuromuscular system may contribute to the latter symptoms observed in COVID-19 patients. Here, we showed that C57BL/6J mice inoculated intranasally with the murine betacoronavirus hepatitis coronavirus 3 (MHV-3), a model for studying COVID-19 in BSL-2 conditions that emulates severe COVID-19, developed robust motor alterations in muscle strength and locomotor activity. The latter changes were accompanied by degeneration and loss of motoneurons that were associated with the presence of virus-like particles inside the motoneuron. At the neuromuscular junction level, there were signs of atrophy and fragmentation in synaptic elements of MHV-3-infected mice. Furthermore, there was muscle atrophy and fiber type switch with alteration in myokines levels in muscles of MHV-3-infected mice. Collectively, our results show that acute infection with a betacoronavirus leads to robust motor impairment accompanied by neuromuscular system alteration.

Retrospective analysis of surgical and oncological results of laparoscopic surgeries performed by residents of coloproctology.

INTRODUCTION: with the improvement and wide acceptance of laparoscopy in colorectal operations, there was a need for specific training of surgeons in training. There are few studies evaluating the postoperative results of laparoscopic colectomies performed by resident physicians and their impact on patient safety. PURPOSE: to analyze the surgical and oncological results of laparoscopic colectomies performed by coloproctology residents and compare them with data in the literature. METHODS: this is a retrospective analysis of patients undergoing laparoscopic colorectal surgery performed by resident physicians at the Hospital das Clínicas de Ribeirão Preto, between 2014 and 2018. The clinical characteristics of the patients were studied, as well as the main surgical and oncological aspects in a period of one year. RESULTS: we analyzed 191 operations, whose main surgical indication was adenocarcinoma, most of them stage III. The mean duration of surgeries was 210±58 minutes. There was a need for a stoma in 21.5% of the patients, mainly loop colostomy. The conversion rate was 23%, with 79.5% due to technical difficulties, and the main predictors of conversion were obesity and intraoperative accidents. The median length of stay was 6 days. Preoperative anemia was associated with a higher rate of complications (11.5%) and reoperations (12%). Surgical resection margins were compromised in 8.6% of cases. The one-year recurrence rate was 3.2% and the mortality rate was 6.3%. CONCLUSIONS: videolaparoscopic colorectal surgery performed by residents showed efficacy and safety similar to data found in the literature.

Retrospective analysis of surgical and oncological results of laparoscopic surgeries performed by residents of coloproctology / Análise retrospectiva dos resultados cirúrgicos e oncológicos em cirurgias videolaparoscópicas realizadas por residentes de coloproctologia

ABSTRACT Introduction: with the improvement and wide acceptance of laparoscopy in colorectal operations, there was a need for specific training of surgeons in training. There are few studies evaluating the postoperative results of laparoscopic colectomies performed by resident physicians and their impact on patient safety. Purpose: to analyze the surgical and oncological results of laparoscopic colectomies performed by coloproctology residents and compare them with data in the literature. Methods: this is a retrospective analysis of patients undergoing laparoscopic colorectal surgery performed by resident physicians at the Hospital das Clínicas de Ribeirão Preto, between 2014 and 2018. The clinical characteristics of the patients were studied, as well as the main surgical and oncological aspects in a period of one year. Results: we analyzed 191 operations, whose main surgical indication was adenocarcinoma, most of them stage III. The mean duration of surgeries was 210±58 minutes. There was a need for a stoma in 21.5% of the patients, mainly loop colostomy. The conversion rate was 23%, with 79.5% due to technical difficulties, and the main predictors of conversion were obesity and intraoperative accidents. The median length of stay was 6 days. Preoperative anemia was associated with a higher rate of complications (11.5%) and reoperations (12%). Surgical resection margins were compromised in 8.6% of cases. The one-year recurrence rate was 3.2% and the mortality rate was 6.3%. Conclusions: videolaparoscopic colorectal surgery performed by residents showed efficacy and safety similar to data found in the literature.

RESUMO Introdução: com o aperfeiçoamento e a ampla aceitação da laparoscopia nas operações colorretais, houve necessidade de treinamento específico dos cirurgiões em formação. Existem poucos estudos avaliando os resultados pós operatórios das colectomias videolaparoscópicas realizadas por médicos residentes e seu impacto na segurança do paciente. Objetivo: analisar os resultados cirúrgicos e oncológicos das colectomias videolaparoscópicas realizadas por residentes de coloproctologia e comparar com dados da literatura. Métodos: trata-se de uma análise retrospectiva de pacientes submetidos a cirurgias colorretais laparoscópicas, realizadas por médicos residentes do Hospital das Clínicas de Ribeirão Preto, entre 2014 e 2018. Foram estudadas as características clínicas dos pacientes bem como os principais aspectos cirúrgicos e oncológicos em um período de um ano. Resultados: analisou-se 191 operações, cuja principal indicação cirúrgica foi adenocarcinoma, a maioria estadio III. A duração média das cirurgias foi 210±58 minutos. Houve necessidade de estoma em 21,5% dos pacientes, principalmente colostomia em alça. A taxa de conversão foi 23%, sendo 79,5% por dificuldades técnicas, e os principais fatores preditores de conversão foram obesidade e acidentes intra-operatórios. A mediana do tempo de internação foi 6 dias. Anemia pré operatória associou-se a uma maior taxa de complicações (11,5%) e reoperações (12%). Houve comprometimento das margens de ressecção cirúrgica em 8,6% dos casos. A taxa de recidiva em um ano foi de 3,2%, e a taxa de mortalidade, 6,3%. Conclusões: a cirurgia colorretal videolaparoscópica realizada por residentes apresentou eficácia e segurança semelhante aos dados encontrados na literatura.

Effects of Curcuma longa on the intestinal health of chicks infected with Salmonella Typhimurium

This study was conducted to evaluate the effects of Curcuma longa on the growth performance, intestinal integrity, and antimicrobial activity of chicks colonized by Salmonella Typhimurium. The study included 672 one-day-old male chicks of the CobbTM lineage, which were divided into eight treatment groups with 14 birds per group and six repetitions, for a total of 48 experimental units per treatment. A randomized 4×2 factorial design scheme (C. longa levels × inoculation by Salmonella Typhimurium) was used. Chicks were orally inoculated with 1.2×104 cfu/mL of Salmonella Typhimurium in 0.5 mL of 0.85% buffered saline solution. Curcuma was added to the feed of chicks at 0, 1, 2, and 3% for 35 days. Data were analyzed by analysis of variance and Tukey's test. Optimal feed conversion was observed in chicks given feed supplemented with 1% C. longa, regardless of infection, and 1% C. longa prevented intestinal colonization by Salmonella Typhimurium. Supplementation and bacterial infection influenced the histomorphometry and pH of the intestine. Bacterial infection reduced the intestinal pH, whereas C. longa supplementation increased the pH, but only in infected chicks. Thus, supplementation with 1% C. longa favors feed conversion, inhibits intestinal colonization by Salmonella Typhimurium, and does not alter intestinal integrity. In contrast, supplementation with 3% Curcuma longa decreases feed intake, affecting the performance of 35-day-old chicks.(AU)

Atividade antimicrobiana in vitro das folhas de araçá (Psidium cattleianum Sabine) contra micro-organismos da mucosa oral / In vitro antimicrobial activity of leaves of araçá (Psidium cattleianum Sabine) against oral micro-organisms

Introdução: A espécie Psidium cattleianum Sabine tem despertado o interesse dos pesquisadores por apresentar, além de atividade cicatrizante, analgésica e antioxidante, propriedades antimicrobianas frente a micro-organismos da mucosa oral que podem atuar como agentes cariogênicos. Objetivo: Foi avaliada, neste trabalho, a atividade antimicrobiana de extratos bruto e fracionados das folhas do araçá, além do seu perfil cromatográfico. Material e método: Para avaliação da atividade antimicrobiana, foi utilizada a técnica de microdiluição, para determinação da Concentração Inibitória Mínima (CIM), e repique do inóculo em Ágar Muller Hinton (Himedia), para averiguação da Concentração Bactericida Mínima (CBM). O extrato foi testado nas concentrações entre 10 e 500 µg/mL. O perfil cromatográfico foi realizado pelo método de Cromatografia Líquida de Alta Eficiência (CLAE). Resultado: Os resultados obtidos foram submetidos a uma análise descritiva e foi possível observar a atividade inibitória dos extratos do P. cattleianum contra S. mutans e S. oralis. Conclusão: A atividade antimicrobiana dos extratos de P. cattleianum contra micro-organismos orais justifica maiores estudos para a utilização medicinal dessa espécie, como, por exemplo, sua utilização em enxaguantes bucais.

Introduction: The specie Psidium cattleianum Sabine has aroused the interest of researchers to exhibit, healing activity, analgesic, antioxidant, antimicrobial properties against the micro-organisms of the oral mucosa that can act as cariogenic agents. Objective: It was analyzed in this study the antimicrobial activity of crude extracts and fractions and chromatographic profile of araçá. Material and method: For antimicrobial activity, we used the technique of on broth microdilution for determining the Minimum Inhibitory Concentration (MIC) and replating of inoculum in Muller Hinton (Himedia) agar for finding the Minimum Bactericidal Concentration (MBC). The extract was tested at concentrations between 10 and 500 µg/mL. The chromatographic profile was performed by the method of High Performance Liquid Chromatography. Result: The results were submitted to a descriptive analysis was possible to observe the inhibitory activity of the extracts of P. cattleianum against S. oralis and S. mutans. Conclusion: The antimicrobial activity of P. cattleianum extracts against oral microorganisms justifies the use of this species as a medicinal plant.

In vivo analgesic activity, toxicity and phytochemical screening of the hydroalcoholic extract from the leaves of Psidium cattleianum Sabine.

ETHNOPHARMACOLOGICAL RELEVANCE: Psidium cattleianum Sabine is extensively used in Brazilian traditional medicine to treat several diseases including painful disorders. Aim of the study to investigate the toxicity and the possible analgesic activities of the hydroalcoholic extract from the leaves of Psidium cattleianum Sabine (ELPCS), to support its use in folk medicine. To screen the major phytochemical constituents of this extract and evaluate their antioxidant activity. MATERIALS AND METHODS: ELPCS was assessed for its antioxidant activity using the DPPH model. Its analgesic activity was examined using mouse models of acetic acid-induced writhing and hot plate paw licking models. The major phytochemical constituents of the extract were screened; their toxicity on LLC-MK2 mammalian cells was evaluated. RESULTS: ELPCS exhibited significant peripheral analgesic activity at doses of 60, 80, 100, 200 and 400mg/kg in mice, but it did not display central analgesic activity and not was toxic to LLC-MK2 cell (LD50>400 µg/mL). The extract exhibited free radical scavenging activity as evidenced by IC50 values (15.9 µg/mL) obtained by the DPPH method. Phytochemical screening detected flavonoids, saponins, cardiac glycosides, anthraquinones, and tannins. CONCLUSIONS: The results of the experimental studies proved the analgesic activity of ELPCS and supported the traditional use of this plant.