Histological and immunohistochemical findings of the action of botulinum toxin in salivary gland: systematic review / Achados histológicos e imunohistoquímicos da ação da toxina botulínica em glândula salivar: revisão sistemática

Abstract The treatment of sialorrhea is necessary for the constant risks posed by hypersalivation. A new therapeutic option comes up with the application of botulinum toxin in salivary glands. However, little is known about its mechanism of action in glandular tissue. Based on the above, this work had the objective to systematically review the literature about the action of botulinum toxin on submandibular and parotid salivary glands tissues. Electronic search was performed in databases of great relevance for this study (PubMed, SciELO, HighWire, Crossref, Scopus, Science Direct, MEDLINE, OLDMEDLINE, Serials Database, NLM Catalog, LILACS and IBECS). Inclusion and exclusion criteria for articles were established, and a total number of 14 articles were selected and used. There are few publications that clarify how the salivary gland acini behave with application of botulinum toxin. Although, the immunohistochemical findings were consistent among authors, showing weak immunoreactivity in glands treated with botulinum toxin. Histometric data are divergent, requiring more detailed studies to answer the questions about the efficacy and safety of botulinum toxin in salivary glands.

Resumo O tratamento da sialorreia se faz necessário pelos constantes riscos trazidos por este estado de hipersalivação. Uma nova opção terapêutica surge com a aplicação da toxina botulínica em glândulas salivares. Entretanto, pouco se sabe sobre o seu mecanismo de ação no tecido glandular. Com base no exposto, este trabalho teve o objetivo de revisar sistematicamente na literatura a ação da toxina botulínica sobre o tecido das glândulas salivares submandibular e parótida. Foi realizada uma busca eletrônica em bases de dados de grande relevância para este estudo (PubMed, SciELO, HighWire, Crossref, Scopus, Science Direct, MEDLINE, OLDMEDLINE, Serials Database, NLM Catalog, LILACS e IBECS). Foram estabelecidos critérios de inclusão e exclusão para os artigos, e um "n" de 14 trabalhos foram selecionados e utilizados. São poucas as publicações que esclarecem como os ácinos das glândulas salivares se comportam mediante aplicação da toxina botulínica. Apesar de os achados imunohistoquímicos entre os autores serem concordantes, com imunorreatividade mais fracas nas glândulas tratadas com a toxina botulínica, os dados histométricos são divergentes e há questionamentos metodológicos, necessitando de mais estudos pormenorizados para responder as questões sobre a eficácia e segurança da toxina botulínica nas glândulas salivares.

Fatores associados aos óbitos entre homens envenenados por carbamato ("chumbinho") / Factores de muertes de hombres envenenados por carbamato ("chumbinho") / Factors associated with the deaths of men poisoned by carbamato ("chumbinho")

RESUMO Objetivo Determinar os fatores associados aos óbitos em vítimas de envenenamento por carbamato (“chumbinho”). Método Estudo retrospectivo, epidemiológico tipo caso-controle, baseado nas fichas de notificação de intoxicação do centro de controle de intoxicações localizado na região metropolitana do Rio de Janeiro. Foram utilizadas 24 fichas de notificação de intoxicações de homens dos 20 aos 59 anos com história de envenenamento por carbamato entre 2005 e 2009. As fichas foram sorteadas aleatoriamente, respeitando-se a razão de 1:3 (um caso para três controles). A faixa etária variou de 23 a 58 anos; a média 43,83 anos. Resultados Os sintomas mais recorrentes foram: miose (OR = 1.0; IC 95%: 0,27 – 3,69. p= 1.0), sialorreia (OR = 0,83; IC 95%: 0,22 – 3,12. p= 0,78), dispneia (OR = 0,66; IC 95%: 0.14 – 3,03. p= 0,59). Conclusão Os óbitos apresentaram associação com sialorreia, miose e dispneia e uma forte associação com estertores pulmonares, broncoespasmos e os roncos pulmonares.

RESUMEN Objetivo Determinar los factores asociados a la muerte en las víctimas de envenenamiento por carbamato (“Chumbinho”). Método Estudio retrospectivo, epidemiológico de caso y control sobre el envenenamiento en los formularios de notificación un centro de control de envenenamiento localizado en la región metropolitana de Río de Janeiro. Utilizamos 24 formularios de notificación de envenenamiento en hombres de 20 a 59 años con intoxicación por el carbamato de 2005 a 2009. Los registros fueron seleccionados al azar, respetando la proporción de 1:3 (un caso y tres controles). El rango de edad fue de 23 a 58 años, promedio de 43,83 años. Resultados Los síntomas más frecuentes fueron miosis (OR = 1,0; IC del 95%: 0,27 a 3,69 p = 1.0.), Babeo (OR = 0,83, IC 95% 0,22-3,12 p. = 0,78), disnea (OR = 0,66; IC del 95%: 0:14 - 3.03 p = 0.59). Conclusión Las muertes se asociaron con babeo, miosis y disnea, y una fuerte asociación con estertores pulmonares, broncoespasmo y el ronquido pulmonar.

ABSTRACT Objective To determine the factors associated with death in poisoning victims by carbamate (“Chumbinho”). Method Retrospective study, epidemiological case-control based on poisoning reporting forms, a poison control center located in the metropolitan region of Rio de Janeiro. We used 24 notification forms of poisoning in men aged 20 to 59 years with poisoning by carbamate history from 2005 to 2009. The records were randomly selected, respecting the ratio 1:3 (a case to three controls). The age range was 23-58 years, average 43.83 years. Results The most frequent symptoms were myosis (OR=1.0; 95% CI: 0.27 to 3.69 p=1.0.), drooling (OR=0.83; 95% CI. 0.22 to 3.12 p=0.78), and dyspnea (OR=0.66; 95% CI: 0:14-3.03 p=0.59). Conclusion The deaths were associated with drooling, miosis and dyspnea and a strong association with pulmonary rales, bronchospasm and pulmonary snoring.

Experiencia clínica con el antipsicótico clozapina en niños y adolescentes menores de 18 años en Chile / Clinical experience in Chile with clozapine in child and adolescents under 18 years

Objective: Increase in severe psychopathology in adolescents who are resistant to common treatment creates a need to search new alternatives in pharmacological treatment. Background: To describe a sample 47 child and adolescent patients treated with clozapine between 1985 and 2010, indicating: age, gender, diagnoses, hospitalization, electroconvulsive therapy, dosing, adverse effects specially hematological ones. Methods: 47patients between the ages of 10 and 18 were treated with clozapine. Review of clinical charts, protocol investigation and Excel statistic analysis. Results: The sample consisted in: male: 40 percent, female: 60 percent, the youngest was 10 and the oldest 17years and 11 months old; the most frequent age was 15 years. The mean number of hospitalization was 1.5. Diagnosis Axis I,DSM IV: Affective disorders 64 percent, Schizophreniform disorder 23 percent. Electroconvulsive Therapy: 57 percent. Treatment indications: irreducible psychosis 23 percent, suicidability: 33 percent. Average dosing 200 mg. Adverse effects: sedation: 76 percent, hypersalivation: 68 percent, increase in weight: 66 percent. Neutropenia: not severe (more than 2000/ mm³): 17 percent; severe 1:15 percent, severe II: 2 percent, severe III: 2 percent. Conclusions: Clozapine appears as an effective drug, with moderate but frequent adverse effects. Hematologic adverse effects where transient; only one in 47 patients presented a severe neutropenia and require cancellation of treatment, which was reinstalled after three month without mayor side effects. There is a need for control studies with larger population and a longer period of time.

Introducción: El aumento de psicopatología severa en la clínica infanto-juvenil y la resistencia a los tratamientos habituales, lleva a los clínicos buscar nuevas alternativas farmacológicas. Surge entonces la clozapina como una alternativa útil, avalada por la literatura para tratamiento de estas patologías. Objetivos: Describir una muestra de 47 pacientes niños y adolescentes entre 10 y 18 años tratados con clozapina entre los años 1985 y 2010. Se indican: variables demográficas, diagnósticos, hospitalizaciones, dosis y efectos adversos, especialmente los hematológicos. Material y Método: Estudio descriptivo, retrospectivo consistente en revisión de fichas clínicas, protocolo de investigación y análisis estadístico con plantilla Excel. Resultados: Muestra de 47 pacientes; 40 por ciento hombres, 60 por ciento mujeres, el menor de 10 años y el mayor de 17 años y 11 meses; la edad más frecuente fue de 15 años. El 80 por ciento presentó al menos una hospitalización. Diagnósticos agrupados: Trastornos a predominio afectivo el 64 por ciento, Trastornos esquizomorfo el 23 por ciento y Trastornos a predominio del descontrol de los impulsos y agresión 9 por ciento. Un 57 por ciento recibió TEC. Causa de indicación: psicosis irreductible 36 por ciento, suicidalidad alta 33 por ciento, conducta heteroagrsiva 25 por ciento, efectos laterales con otros fármacos 23 por ciento. La dosis promedio de mantención fue de 200 mg. Los efectos adversos más frecuentes fueron: sedación 76 por ciento, salivación 68 por ciento, alza peso 66 por ciento. Baja inespecífica de neutrófilos: 17 por ciento, alarma 1:15 por ciento, alarma II: 2 por ciento, alarma III: 2 por ciento. Discusión: Clozapina aparece como fármaco útil, con efectos adversos frecuentes, pero en nuestra muestra fueron graves no y transitorios. Hubo un caso con alarma III que requirió de suspensión, pero se reinstaló 3 meses después; sin reincidir, ni presentar otros efectos adversos de gravedad...

Novel insertion mutation of ABCB1 gene in an ivermectin-sensitive Border Collie

P-glycoprotein (P-gp) is encoded by the ABCB1 gene and acts as an efflux pump for xenobiotics. In the Border Collie, a nonsense mutation caused by a 4-base pair deletion in the ABCB1 gene is associated with a premature stop to P-gp synthesis. In this study, we examined the full-length coding sequence of the ABCB1 gene in an ivermectin-sensitive Border Collie that lacked the aforementioned deletion mutation. The sequence was compared to the corresponding sequences of a wild-type Beagle and seven ivermectin-tolerant family members of the Border Collie. When compared to the wild-type Beagle sequence, that of the ivermectin-sensitive Border Collie was found to have one insertion mutation and eight single nucleotide polymorphisms (SNPs) in the coding sequence of the ABCB1 gene. While the eight SNPs were also found in the family members' sequences, the insertion mutation was found only in the ivermectin-sensitive dog. These results suggest the possibility that the SNPs are species-specific features of the ABCB1 gene in Border Collies, and that the insertion mutation may be related to ivermectin intolerance.