Tratamento integrado para correção do sorriso gengival: relato de caso / Integrated treatment for correction of gingival smile: case report

O sorriso gengival possui inúmeras causas, podendo acontecer por motivos esqueléticos, musculares ou por alteração no desenvolvimento dos tecidos de suporte. No entanto, na atualidade, a estética vermelha e a branca têm se apresentado completamente passíveis de transformações e com uma gama de procedimentos cirúrgicos ou não cirúrgicos para sanar as queixas dos pacientes. O objetivo geral deste trabalho é mostrar o poder que a odontologia tem frente às questões estéticas, como, por exemplo, a vergonha de sorrir por não se sentir confortável com os dentes curtos e com uma grande faixa de gengiva sendo exposta. O método utilizado foi um relato de caso. Que descreve todos os passos clínicos do tratamento de um paciente de 40 anos, que estava insatisfeita com o seu sorriso por apresentar erupção passiva alterada juntamente com hiperatividade do lábio superior. O plano de tratamento escolhido foi de realizar a cirurgia de aumento de coroa clínica estético, seguido de clareamento dentário e posteriormente um reposicionamento labial, com ajuda da toxina botulínica. Finalizando, para ajudar na cicatrização, o uso de laserterapia. O resultado de todo o processo cirúrgico envolvido neste trabalho, é satisfação do paciente, materializando o sonho deste, devolvendo segurança e espontaneidade ao sorrir. Pôde-se observar que através da combinação de técnicas cirúrgicas periodontais para tratar o sorriso gengival, obtém-se êxito tanto no sentido científico quanto no biológico, alcançando um sorriso esteticamente mais atrativo(AU)

Gummy smile has numerous causes, which can occur for skeletal or muscular reasons or due to changes in the development of supporting tissues. However, nowadays, the red and white aesthetics have been completely capable of transformation and with a range of surgical or non-surgical procedures to resolve patients' complaints. The general objective of this work is to show the power that dentistry has in the face of aesthetic issues, such as, for example, the shame of smiling due to not feeling comfortable with short teeth and a large strip of gum being exposed. The method used was a case report. Which describes all the clinical steps of the treatment of a 40-year-old patient, who was dissatisfied with her smile due to an altered passive eruption together with hyperactivity of the upper lip. The chosen treatment plan was to perform aesthetic clinical crown augmentation surgery, followed by tooth whitening and later lip repositioning, with the help of botulinum toxin. Finally, to help with healing, the use of laser therapy. The result of the entire surgical process involved in this work is patient satisfaction, materializing the patient's dream, restoring security and spontaneity when smiling. It was observed that through the combination of periodontal surgical techniques to treat gummy smile, success is achieved both in the scientific and biological sense, achieving a more aesthetically attractive smile(AU)

Preparation of rabbit polyclonal antibody and development and identification of quantitative ELISA detection method for pertussis toxin / 中国生物制品学杂志

@#Objective To prepare rabbit polyclonal antibodies against pertussis toxin(PT) and develop a double antibody sandwich ELISA for quantitative determination of PT antigen,identify and apply the method.Methods The rabbit polyclonal antibody against PT was prepared by immunizing Chinchilla rabbit with PT using traditional method.The reaction conditions of ELISA system were optimized,the double antibody sandwich ELISA method for quantitative determi-nation of PT was developed,and the specificity,linearity,accuracy,precision and sensitivity were verified.The developed method was used to detect PT antigen content in fimbriae proteins(FIM) stock solution of samples during detoxification and other purification process of pertussis antigen.Results The working condition of double antibody sandwich ELISA for detection of PT antigen content was the coating concentration of PT rabbit polyclonal antibody of 1 μg/mL,and the enzyme-labeled antibody dilution of 1:8 000.This detection system showed specific reaction with PT purified protein,but had no cross reaction with filamentous hemagglutinin,diphtheria toxoid and tetanus toxoid;the linear detection range of the developed double antibody sandwich ELISA was within 25—400 ng/mL;the recovery rates of PT at high,moderate and low concentrations were 103.27%,91.48% and 103.52%,respectively;both the intra-and inter-coefficients of variation(CVs)were less than 10%;the sensitivity of the method was 20.719 ng/mL,and the detection limit was 41.438 ng/mL.Thirty-five batches of samples were detected under five different detoxification process conditions and at different sampling time points,and the changes of antigen content were all consistent with the trend of detoxification reaction.Conclusion The PT rabbit polyclonal antibody was successfully prepared,and a double antibody sandwich ELISA with high precision and accuracy was developed for the quantitative determination of PT antigen content,which can be used for the antigen content detection of chemically detoxified samples in the production process of component DPT vaccines

Pathogenesis and Traditional Chinese Medicine Prevention and Treatment Strategy of Refractory Angina Based on Theory of Stasis and Toxin / 中国实验方剂学杂志

Refractory angina is characterized by recurrent and persistent angina with a duration of not less than three months， which is related to reversible ischemia and hypoxia caused by coronary stenosis and obstruction. It mainly involves obstructive coronary artery disease and non-obstructive coronary artery disease with coronary artery spasm and coronary microvascular dysfunction. “Stasis and toxin” play an important role in the pathogenesis of cardiovascular diseases. The pathogenesis of stasis and toxin is stubborn filthy turbidity featured by slow accumulation and sudden onset，and rapid changes，which coincides with the characteristics of refractory angina which is complex and changeable，prolonged and difficult to cure. The pathogenesis of refractory angina involves a combination of underlying deficiency and excessive manifestation， with "stasis and toxin" playing a crucial role as an important pathological factor in the whole process of refractory angina. Traditional Chinese medicine （TCM） employs a holistic approach known as "activating blood circulation and removing toxins"， which is supplemented by various methods to tonify Qi and warm Yang， nourish the kidneys and invigorate the spleen， clear heat and transform phlegm. This approach applies anti-inflammatory measures， regulates lipid metabolism， inhibits oxidative stress and thrombus formation， protects endothelial function in blood vessels， as well as establishes collateral circulation for the prevention and treatment of refractory angina. Therefore，based on the theory of "stasis and toxin"，combined with TCM theory and modern medical research，this paper discusses the pathogenesis of refractory angina and the prevention and treatment strategy of TCM，and elucidates the reasons for the difficulty in curing refractory angina and the relationship between refractory angina and common angina pectoris，coronary microvascular dysfunction，coronary artery spasm and obstructive coronary artery disease，hoping to provide certain theoretical basis and clinical ideas for the prevention and treatment of refractory angina with TCM.

Comprehensive Clinical Evaluation of Yiqing Capsules in Treating Heat-toxin Syndrome / 中国实验方剂学杂志

ObjectiveTo systematically review the studies about Yiqing Capsules in the treatment of pharyngitis， tonsillitis， gingivitis， and oral ulcers with heat-toxin syndrome and clarify the advantages and therapeutic characteristics of Yiqing capsules， thus providing reference for the decision-making by relevant departments and clues for the clinical and basic research. MethodThe multi-criteria decision analysis （MCDA） model and CSC v2.0 were employed to comprehensively evaluate Yiqing capsules from multiple aspects. ResultThe serious adverse reactions in the spontaneous reporting system （SRS） monitoring data of Yiqing capsules included pruritus， rash， an ddiarrhea， all of which were relieved or cured， without aggravation or interhospital transfer for treatment. Literature data showed that the main clinical adverse reactions were abdominal pain， diarrhea， etc. Both acute toxicity and long-term toxicity tests showed good safety， and thus the safety of Yiqing capsules was rated as grade B. The results of Meta-analysis showed that Yiqing capsules used alone or in combination with other medicines outperformed Niuhuang Jiedu capsules or Western medicine in the treatment of pharyngitis， tonsillitis， gingivitis， and oral ulcers with heat toxin in terms of symptom alleviation， disappearance rate of main symptoms， and recurrence rate of aphtha. Pharmacological and pharmacodynamic studies showed that Yiqing capsules had antimicrobial， antiviral， and anti-inflammatory effects， with the effectiveness rated as grade B. The decision tree model was adopted to analyze the incremental cost-effectiveness ratio. With the threshold of 1 fold per capita GDP and the disappearing rate of pain in gingivitis as the indicator， Yiqing capsules had an economic advantage in the treatment of gingivitis due to heat-toxin compared with Niuhuang Jiedu capsules， and the incremental cost-effectiveness ratio was 0.39 yuan/%， which indicated acceptable cost， with the economy rated as grade B. Yiqing capsules can not only clear heat from Qi aspect but also purge blood fire， serving as the representative prescription of clearing and purging for heat-toxin syndrome. Considering the industrial service system and enterprise innovation， the comprehensive innovation of Yiqing capsules was rated as grade B. Generally， this product does not require personalized treatment plans and features convenient supply， storage， transportation， policy publicity， drug information standards， and easy operation for medical care and patients. The Chinese patent medicine information was complete and in line with national standards， and thus the suitability of Yiqing capsules was rated as grade A. With a low price and good availability and affordability， the accessibility of Yiqing capsules was rated as grade A. The Yiqing capsules prescription， Sanhuang Xiexin decoction， originated from ancient medical books， with rich real-world studies， and thus the traditional Chinese medicine characteristics of Yiqing capsules was rated as grade C. ConclusionThe clinical value of Yiqing capsules was rated as grade B from the "6+1" dimensions， suggesting that it could be conditionally converted into the relevant policy results of basic clinical drug management according to the procedure.

Development and Verification of a Traditional Chinese Medicine Diagnostic Scale for Type 2 Diabetes Mellitus with Turbid-Toxin Accumulation Syndrome / 中医杂志

To develop a traditional Chinese medicine （TCM） diagnostic scale for type 2 diabetes mellitus with turbid-toxin accumulation syndrome and to validate the performance of the scale. A candidate pool was established through literature review and expert consultation， and a clinical case information collection form was developed accordingly. Patients with type 2 diabetes mellitus admitted to the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from July 2021 to January 2022 were investigated， and 312 valid clinical case information collection forms were obtained， which were randomly divided into 235 cases in the study group and 77 cases in the validation group. Four statistical methods， namely， differentiation analysis， Cronbach's coefficient， correlation coefficient， and stepwise regression， were used to screen out the candidate items， and Logistic regression analysis and factor analysis were used to assign weights to the items， and the final diagnostic model was determined by the receiver operating characteristic （ROC） curve， and the diagnostic thresholds were calculated for the Yoden index. The final TCM diagnostic scale for type 2 diabetes mellitus was composed of 8 items： turbid dirt coating （with a weight value of 23， the same below）， sticky stools （16）， fullness in the epigastrium and abdomen （12）， dark complexion （12）， irritability （11）， brown spots on the skin （11）， heaviness of head （10）， and chest stuffiness （5）， and the degree score was 0， 0.5， 1.0， and 1.5 points corresponding to no， mild， moderate and severe symptoms， respectively. The total score was the sum of the degree score multiplied by the weighted value of each item， and when the total score reached 33 points， it is diagnosed as the turbid-toxin accumulation syndrome. The established scale was tested and evaluated in the study group and the validation group， and the results showed that the sensitivity of the study group and the validation group was 89.38% and 89.47%， with the specificity of 95.90% and 89.74%， the Yoden index of 0.85 and 0.79， the positive predictive value of 95.28% and 89.47%， the negative predictive value of 90.70% and 89.74%， the diagnostic advantage ratios of 198.18 and 72.67， and the Kappa values of 0.86 and 0.79， which indicated that the TCM diagnostic scale for turbid-toxin accumulation syndrome of type 2 diabetes mellitus showed good diagnostic ability.

The state of the art in therapeutic administration of botulinum toxin in children with cerebral palsy: an integrative review / O estado da arte em aplicação terapêutica de toxina botulínica em crianças com paralisia cerebral: uma revisão integrativa

ABSTRACT Objective: To describe the current state of the art in the therapeutic administration of botulinum toxin with indications, efficacy, and safety profile for children and adolescents with cerebral palsy. Data source: An integrative review was conducted. The MEDLINE/PubMed database was searched twice within the last decade using distinct terms, and only studies written in the English language were included. The study population was limited to those aged 0-18 years. Articles that were duplicates or lacked sufficient methodology information were excluded. Data synthesis: We found 256 articles, of which 105 were included. Among the included studies, most were conducted in developed countries. Botulinum toxin demonstrated good safety and efficacy in reducing spasticity, particularly when administered by a multidisciplinary rehabilitation team. It is primarily utilized to improve gait and upper limb function, facilitate hygiene care, reduce pain, prevent musculoskeletal deformities, and even decrease sialorrhea in patients without a functional prognosis for walking. Conclusions: The administration of botulinum toxin is safe and efficacious, especially when combined with a multi-professional rehabilitation team approach, which increases the probability of functional improvement. It can also be beneficial for patients with significant functional impairments to help with daily care tasks, such as hygiene, dressing, and reducing sialorrhea. Pediatricians must be familiar with this treatment and its indications to attend to and refer patients promptly when necessary, and to exploit their neuroplasticity. Further research on this topic is required in developing countries.

RESUMO Objetivo: Descrever o estado da arte em aplicação terapêutica de toxina botulínica com indicações, eficácia e perfil de segurança em crianças e adolescentes com paralisia cerebral. Fontes de dados: Realizada revisão integrativa através de busca na base de dados MEDLINE/PubMed em dois momentos nos últimos 10 anos, e termos distintos, em inglês, numa população entre 0 e 18 anos de idade. Excluiu-se artigos duplicados ou com informações insuficientes de metodologia. Síntese dos dados: 256 artigos foram encontrados e 105 foram incluídos, sendo a maior parte realizados em países desenvolvidos. A toxina botulínica mostrou boa segurança e efetividade na redução da espasticidade, especialmente administrada por uma equipe de reabilitação multiprofissional, usada principalmente para: melhora da marcha e da função dos membros superiores, facilitação dos cuidados de higiene, analgesia e prevenção de deformidades musculoesqueléticas, além de redução da sialorreia, inclusive em pacientes sem prognóstico funcional de marcha. Conclusões: A aplicação de toxina botulínica foi efetiva e segura, principalmente quando atrelada a uma abordagem por equipe de reabilitação multiprofissional, o que aumenta as chances de melhora funcional. Mostrou-se benéfica também para pacientes com grandes comprometimentos funcionais para facilitar os seus cuidados diários em relação à higiene, colocar e tirar roupas e redução da sialorreia. O pediatra deve estar familiarizado com esse tratamento e suas indicações para atender e direcionar pacientes o mais breve possível quando indicado e aproveitar o máximo de neuroplasticidade. Há necessidade de investimentos em mais pesquisas sobre este tema em países em desenvolvimento.

Botulinum toxin A for the treatment of strabismus in children with neurological impairment / Toxına botulínica tipo A para o tratamento de estrabısmo em crianças neurologicamente comprometidas

ABSTRACT Purposes: To assess the efficacy of botulinum toxin A injection in the treatment of strabismus in patients with neurological impairment and evaluate the factors associated with treatment success. Methods: The study included 50 patients with strabismus and neurological impairment. In all children, botulinum toxin injection was performed into the appropriate extraocular muscle. The relationship between demographic features, clinical characteristics, and treatment success were analyzed. Results: In the study group, 34 patients had esotropia, and 16 patients had exotropia. As neurological problems, 36 patients had cerebral palsy, and 14 had hydrocephalus. The average follow-up period was 15.3 ± 7.3 months. The mean number of injections was 1.4 ± 0.6. The mean angle of deviation was 42.5 ± 13.2 PD before the treatment, which decreased to 12.8 ± 11.9 PD after the treatment. Successful motor alignment (orthotropia within 10 PD) was achieved in 60% of the patients. Binary logistic regression analysis revealed that esotropic misalignment and shorter duration of strabismus was significantly associated with treatment success in the study group. Patients with esotropia and lower angles of misalignment were more likely to be treated with a single injection. Conclusion: The use of botulinum toxin A for the treatment of strabismus in children with neurological impairment is a good alternative to conventional surgical therapy with a lower risk of overcorrection. The treatment outcome is better in esodeviations and shorter duration of strabismus, implying an advantage of early treatment.

RESUMO Objetivos: Avaliar a eficácia do uso de toxina bo-tulínica tipo A no tratamento do estrabismo em pacientes com comprometimento neurológico e avaliar os fatores associados ao sucesso do tratamento. Métodos: Cinquenta pacientes com estrabismo e comprometimento neurológico foram incluídos no estudo. Em todas as crianças, a toxina botulínica tipo A foi injetada no músculo extraocular apropriado. A relação entre características demográficas, características clínicas e o sucesso do tratamento foram analisadas. Resultados: No grupo de estudo, 34 pacientes tiveram esotropia e 16 pacientes tiveram exotropia, sendo trinta e seis pacientes com paralisia cerebral e 14 pacientes com hidrocefalia. O tempo médio de acompanhamento foi de 15,3 ± 7,3 meses. O número médio de aplicações foi de 1,4 ± 0,6. O ângulo de desvio médio foi de 42,5 ± 13,2 DP antes do tratamento e diminuiu para 12,8 ± 11,9 DP após o tratamento. Alinhamento motor bem sucedido (ortotropia dentro de 10 DP) foi alcançado em 60% dos pacientes. A análise de regressão logística binária revelou que o desalinhamento esotrópico e uma menor duração do estrabismo foram significativamente associados ao sucesso do tratamento no grupo de estudo. Pacientes esotrópicos com ângulos de desalinhamento menores são mais propensos a serem tratados com uma única aplicação. Conclusão: O uso da toxina botulínica tipo A para o tratamento de estrabismo em crianças com comprometimento neurológico é uma boa alternativa para a terapia cirúrgica convencional com menor risco de hipercorreção. O resultado do tratamento é melhor em exodesvios e em pacientes com estrabismo de menor duração, implicando em vantagem para o tratamento precoce.

Comparison on Rat Models of Acute Cerebral Infarction Due to Stasis Combined with Toxin Complicated with Cerebral-cardiac Syndrome / 中国实验方剂学杂志

ObjectiveTo observe and compare the electrocardiogram index， myocardial morphology， and connexin 43 （Cx43） expression of two rat models of acute cerebral infarction （ACI） due to stasis combined with toxin complicated with cerebral-cardiac syndrome （CCS）， and to provide experimental evidence for the research on the occurrence mechanism of cardiac diseases induced by ACI and the clinical diagnosis and treatment of CCS. MethodSixty SPF-grade male SD rats were randomized into six groups （n=10）： normal ， syndrome of stasis combined with toxin induced by carrageenin combined with dry yeast （CA/Y）， multi-infarct induced by micro-embolism （ME）， middle cerebral artery occlusion （MCAO）， CA/Y+ME， and CA/Y+MCAO groups. The model of syndrome of stasis combined with toxin was established by intraperitoneal injection with carrageenan （CA） at 10 mg·kg-1 on the first day and subcutaneous injection with dry yeast （Y） suspension （2 mg·kg-1） on the second day of modeling. Twenty-four hours after the modeling of ACI， the electrocardiograms （ECGs） of rats in each group were collected and the number/percentage （%） of abnormal ECG was calculated. The infarct area of the brain was evaluated by 2，3，5-triphenyltetrazolium chloride （TTC） staining， and myocardial injury was assessed by hematoxylin-eosin （HE） staining. Immumohistochemical staining and Western blot were employed to determine the expression of Cx43 in the myocardium. ResultA certain number of rats in each model group presented abnormal ECG. Compared with the normal group and CA/Y group， CA/Y+MCAO group had the highest rate of abnormal ECG （P<0.01）. Compared with the normal， CA/Y， ME， and CA/Y+ME groups， the CA/Y+ME and CA/Y+MCAO groups showed decreased amplitudes of P-wave and T-wave， shortened P-R interval， and extended Q-T interval， which were particularly obvious in the CA/Y+MCAO group （P<0.05， P<0.01） and in accordance with the cerebral infarction area and pathological changes. The expression of Cx43 was up-regulated in both CA/Y+ME and CA/Y+MCAO groups， especially in the CA/Y+MCAO group （P<0.01）. ConclusionThe two rat models of ACI due to stasis combined with toxin complicated with CCS can be used to study the mechanism of heart diseases caused by cerebrovascular diseases and the therapeutic effects of Chinese medicines with the functions of resolving stasis and detoxifying. Moreover， the CA/Y+MCAO method has higher abnormal electrocardiogram rate， severer myocardial pathological injury， and higher expression of Cx43 protein. The models can be chosen according to specific experimental purpose.

First report of the prevalence of Shiga toxinproducing Escherichia coli in ground beef in Quindío, Colombia

Introduction. Shiga toxin-producing Escherichia coli (STEC) is a foodborne pathogen associated with clinical cases of diarrhea in humans. Its main virulence factors are the Shiga toxins (Stx1 and Stx2). Cattle are the main reservoir of STEC, and many outbreaks in humans have been related to the consumption of undercooked ground beef contaminated with this pathogen. Objective. To determine the prevalence of STEC in ground beef commercialized in all the butcher shops of a township in the department of Quindío and to characterize the virulence genes of the strains found. Materials and methods. Thirty ground beef samples were taken in three different times; stx genes and other STEC virulence factors (eae, ehxA, saa) were detected by multiplex PCR. Results. The overall prevalence of STEC was 33.33 % (10/30 positive samples). We isolated eight non-O157 (LEE-negative) strains with four different genetic profiles: stx 2 / stx 2-ehxA-saa / stx 1-stx 2-ehxA-saa / stx 1-saa. Conclusion. This is the first report on the prevalence of STEC in ground beef in a township in the department of Quindío.

Introducción. Escherichia coli productora de toxina Shiga (STEC) es un agente patógeno de origen alimentario asociado a casos clínicos de diarrea en humanos; sus principales factores de virulencia son las toxinas Shiga (Stx1 y Stx2). El principal reservorio de STEC es el ganado bovino y muchos brotes en humanos se han relacionado con el consumo de carne mal cocida contaminada con este agente patógeno. Objetivo. El objetivo de este trabajo fue determinar la prevalencia de STEC en carne molida comercializada en todas las carnicerías de un municipio del departamento del Quindío y caracterizar los genes de virulencia de las cepas encontradas. Materiales y métodos. Se tomaron 30 muestras de carne molida en tres momentos diferentes; se detectaron los genes stx y otros factores de virulencia de STEC (eae, ehxA, saa) mediante PCR Multiplex. Resultados. Los resultados mostraron una prevalencia global de STEC del 33,33 % (10/30 muestras positivas). En total se aislaron ocho cepas STEC no-O157 (LEE-negativas) con cuatro perfiles genéticos diferentes: stx 2 / stx 2-ehxA-saa / stx 1-stx 2-ehxA-saa / stx 1-saa. Conclusión. Este es el primer reporte que muestra la prevalencia de STEC en carne molida en un municipio del departamento del Quindío.

Cirugía de desfuncionalización de glándulas salivales mayores en sialorrea masiva / Major salivary gland defunctionalization surgery in massive sialorrhea

Introducción: La sialorrea es la pérdida involuntaria de saliva de la boca, ya sea debido a la producción excesiva de saliva o disminución de la frecuencia de deglución. Se habla de sialorrea patológica cuando persiste más allá de los 4 años de edad. Además de las implicaciones sociales, cambios de ropa frecuentes, puede provocar neumonías por aspiración y deshidratación. El manejo de la sialorrea requiere una evaluación completa con un enfoque de equipo multidisciplinario para el tratamiento, que incluye terapias no farmacológicas, farmacológicas y quirúrgicas. Objetivo: Presentar resultados quirúrgicos y farmacológicos en el tratamiento de sialorrea masiva. Material y Método: Se realizó revisión de historias clínicas de 7 pacientes portadores de sialorrea masiva. Todos los pacientes incluidos fueron refractarios a tratamiento médico. El diagnóstico fue obtenido por un equipo multidisciplinario. Se les realizó desfuncionalización quirúrgica y farmacológica de glándulas salivales. Se les aplicó Escala de Severidad (DSS) y escala de frecuencia (DFS), previo a cirugía y posterior a procedimiento hasta el año. Resultados: Mejoría clínica subjetiva posterior a desfuncionalización quirúrgica con disminución de DSS y DFS. Disminución promedio de baberos a 10/día. Conclusión: Los resultados obtenidos son buenos, si se consideran las escalas DSS, DFS y el número de baberos al día, que son mediciones tanto subjetivas y objetivas respectivamente.

Introduction: Massive Sialorrhea is the involuntary loss of saliva from the mouth, either due to excessive saliva production or decreased swallowing frequency. We speak of pathological sialorrhea when it persists beyond 4 years old. In addition to the social implications and frequent clothing changes. It can cause aspiration pneumonia and dehydration. Treatment for sialorrhea requires a comprehensive evaluation with a multidisciplinary team approach. Including non-pharmacological, pharmacological, and surgical therapies. Aim: Presentation of the results of surgical defunctionalization of the salivary glands plus injection of Botulinum Toxin in the treatment of massive sialorrhea. Material and Method: A review of the clinical records of 7 patients with massive sialorrhea was carried out. All included patients were refractory to medical treatment. The diagnosis was obtained by a multidisciplinary team. Surgical and pharmacological dysfunctionalization of salivary glands was performed. Severity Scale (DSS) and Frequency Scale (DFS) were applied before surgery and after the procedure up to a year. Results: Subjective clinical improvement after surgical defunctionalization with decreased SHD and DFS. Average decrease in bibs to 10/day. Conclusion: The evaluated strategy presented similar benefits with respect to the literature. The SHD and DFS scales and the number of bibs per day are both subjective and objective measurements, respectively, and allow the clinical improvement and quality of life of patients undergoing surgery to be evaluated individually.

Manejo exitoso de síndrome de vejiga hiperactiva refractaria con toxina botulínica A / Successful management of refractory overactive bladder syndrome with botulinum toxin A

Introducción: El síndrome de vejiga hiperactiva (VHA) afecta hasta al 43% de las mujeres. La terapia escalonada incluye cambios de hábitos, fármacos y neuromodulación. Hasta el 40% de las pacientes llegan a requerir terapia avanzada alternativa, como toxina botulínica (TB). Objetivo: Reportar los resultados del tratamiento con toxina botulínica en mujeres con VHA refractaria a tratamiento de primera y segunda línea, en un hospital público en Chile. Método: Estudio de cohorte retrospectivo desde una base de datos recolectada prospectivamente del Hospital Sótero del Río entre 2018 y 2022. Se incluyeron 33 pacientes con tratamiento farmacológico y neuromodulación previa, con una edad promedio de 57 años, sometidas a inyección cistoscópica de TB a detrusor, analizando datos demográficos, antecedentes y complicaciones. Se realizó seguimiento con frecuencia miccional, paños/día, escala de gravedad de Sandvik (ISI) y encuesta Patient Global Impression Improvement (PGI-I). Resultados: Los datos comparativos pre/post TB, respectivamente, fueron: frecuencia miccional diurna 11/6 y nocturna 5/1; paños/día 5/3; ISI 8/3. Veinte de 33 mujeres refirieron estar excelente o mucho mejor (PGI-I). Conclusiones: Es posible realizar manejo con TB en mujeres con VHA refractaria a primera y segunda línea, con buenos resultados e impacto significativo en la calidad de vida.

Introduction: Overactive bladder syndrome (OABS) affects up to 43% of women. Staggered therapy includes habit changes, drugs, and peripheral neuromodulation. Up to 40% of patients may require advanced alternative therapy such as botulinum toxin A (BT). Objective: To report the results of treatment with TB in women with OABS refractory to first- and second-line treatment in a public hospital in Chile. Method: Retrospective cohort study from prospectively collected database from Hospital Sótero del Río between 2018 and 2022. Thirty-three patients with previous pharmacological treatment and neuromodulation were included, with an average age of 57 years, undergoing cystoscopic injection of TB to detrusor. Demographic data, history, and complications were analyzed. Follow-up was performed with voiding frequency, cloths/day, Sandvik Severity Scale (ISI) and Patient Global Impression Improvement (PGI-I) survey. Results: Comparative data pre/post TB, respectively showed: daytime voiding frequency 11/6 and nighttime 5/1; cloths/day 5/3; ISI 8/3. 20 of 33 women reported being excellent or much better (PGI-I). Conclusions: TB management in women with OABS refractory to first- and second-line treatment has good results and significant impact on quality of life.

Cierre dinámico y toxina botulínica: una alternativa novedosa para el cierre definitivo del abdomen abierto y contenido / Dynamic closure system and botulinum toxin: a novel alternative for definitive closure of open abdomen

RESUMEN Se presenta el caso de un paciente masculino de 54 años que, cursando internación por neumonía- COVID-19, intercurrió con shock séptico por diverticulitis aguda Hinchey IV, por lo que se realizó cirugía de Hartmann. Evolucionó con isquemia colónica, se realizó colectomía total y abdomen abierto y contenido (AAyC). El manejo del AAyC se realizó con sistema de vacío (VAC) durante 7 semanas, resultando un AAyC tipo IIIa (Björck) con un gap de 16 cm. Se decidió iniciar, una vez dadas las condiciones clínicas del paciente, el cierre dinámico (CD) con tracción fascial con malla de polipropileno asociado a inyección de toxina botulínica (TB). Esta estrategia permitió el cierre fascial primario (CFP) de la pared abdominal en la quinta semana de comenzado el tratamiento, evitando de esta manera la morbilidad de un cierre por segunda intención.

ABSTRACT We report the case of a 54-year-old male patient hospitalized for COVID-19 pneumonia who developed septic shock due to acute Hinchey IV diverticulitis and required Hartmann's surgery. The patient evolved with colonic ischemia and underwent total colectomy and open abdomen (OA) with temporary abdominal closure (TAC) that was managed with a vacuum-assisted wound closure (VAWC) system for 7 weeks, resulting in a Björck grade 3A OA with a 16-cm gap. As he had a favorable clinic course, dynamic closure with mesh-mediated fascial traction was decided, associated with botulinum toxin (BT) injection. This strategy allowed primary fascial closure (PFC) of the abdominal wall 5 weeks after treatment was initiated, thus avoiding the complications of healing by secondary intention.

Evaluation of toxin-antitoxin genes, antibiotic resistance, and virulence genes in Pseudomonas aeruginosa isolates

SUMMARY OBJECTIVE: Toxin-antitoxin genes RelBE and HigBA are known to be involved in the formation of biofilm, which is an important virulence factor for Pseudomonas aeruginosa. The purpose of this study was to determine the presence of toxin-antitoxin genes and exoenzyme S and exotoxin A virulence genes in P. aeruginosa isolates and whether there is a relationship between toxin-antitoxin genes and virulence genes as well as antibiotic resistance. METHODS: Identification of the isolates and antibiotic susceptibilities was determined by a VITEK 2 (bioMérieux, France) automated system. The presence of toxin-antitoxin genes, virulence genes, and transcription levels were detected by real-time polymerase chain reaction. RESULTS: RelBE and HigBA genes were detected in 94.3% (82/87) of P. aeruginosa isolates, and exoenzyme S and exotoxin A genes were detected in all of the isolates (n=87). All of the isolates that harbor the toxin-antitoxin and virulence genes were transcribed. There was a significant increase in the RelBE gene transcription level in imipenem- and meropenem-sensitive isolates and in the HigBA gene transcription level in amikacin-sensitive isolates (p<0.05). There was a significant correlation between RelBE and exoenzyme S (p=0.001). CONCLUSION: The findings suggest that antibiotic resistance may be linked to toxin-antitoxin genes. Furthermore, the relationship between RelBE and exoenzyme S indicates that toxin-antitoxin genes in P. aeruginosa isolates are not only related to antibiotic resistance but also play an influential role in bacterial virulence. Larger collections of comprehensive studies on this subject are required. These studies should contribute significantly to the solution of the antibiotic resistance problem.

Pulmonary involvement from animal toxins: the cellular mechanisms

Abstract Venomous animals and their venom have always been of human interest because, despite species differences, coevolution has made them capable of targeting key physiological components of our bodies. Respiratory failure from lung injury is one of the serious consequences of envenomation, and the underlying mechanisms are rarely discussed. This review aims to demonstrate how toxins affect the pulmonary system through various biological pathways. Herein, we propose the common underlying cellular mechanisms of toxin-induced lung injury: interference with normal cell function and integrity, disruption of normal vascular function, and provocation of excessive inflammation. Viperid snakebites are the leading cause of envenomation-induced lung injury, followed by other terrestrial venomous animals such as scorpions, spiders, and centipedes. Marine species, particularly jellyfish, can also inflict such injury. Common pulmonary manifestations include pulmonary edema, pulmonary hemorrhage, and exudative infiltration. Severe envenomation can result in acute respiratory distress syndrome. Pulmonary involvement suggests severe envenomation, thus recognizing these mechanisms and manifestations can aid physicians in providing appropriate treatment.

HipBST Toxin-antitoxin System of Prokaryotes / 中国生物化学与分子生物学报

Toxin-antitoxin system (TA) is a genetic element widely found in chromosomes and plasmids of bacteria, archaea and prophages. TA usually consists a toxin that inhibits the growth of bacteria and an antitoxin that neutralizes its toxicity. Since the discovery of the first CcdB / CcdA TA in the 1980s, TA has been proved to exist in almost all sequenced microorganisms and plays an important role in maintaining plasmid stability, anti-phage and promoting biofilm formation. At present, TA is divided into type I-VIII, among which type IITA is the most widely studied. HipBA is a type II TA. The toxin HipA in Escherichia coli HipBA is a serine / threonine kinase, which inhibits protein translation by phosphorylating bacterial Glutamyl tRNA synthetase (GltX), and its toxicity can be specifically neutralized by HipB. Recently, it has been found that Escherichia coli HipA homologous proteins exist widely in microorganisms, and they form a potential novel TA with genes of the same promoter, in which HipBST has been confirmed by experiments. The toxin HipT and the antitoxin HipS in this TA are similar to the C-terminal and N-terminal of E. coli HipA respectively, and the neutralization mechanism and the substrate of the toxin are different from that of E. coli toxin HipA. This study summarizes the recent discovery of special TA, especially the neutralization mechanism of HipBST which widely exists in prokaryotes.

A non-toxic recombinant protein rSUMO-CPBm4 as a potential vaccine candidate against Clostridium perfringens type C beta enterotoxemia

@#Beta toxin (CPB) is a lethal toxin and plays a key role in enterotoxemia of ruminants caused by Clostridium perfringens type C strain. The existing vaccines based on crude CPB need time-consuming detoxification and difficult quality control steps. In this study, we synthesized the rCPBm4 of C. perfringens type C strain and small ubiquitin-like modifier (SUMO)-tag CPBm4 (rSUMO-CPBm4) by introducing four amino acid substitutions: R212E, Y266A, L268G, and W275A. Compared with rCPBm4, rSUMO-CPBm4 was expressed with higher solubility in Escherichia coli BL21 (DE3). Neither rCPBm4 nor rSUMO-CPBm4 was lethal to mice. Although rCPBm4 and rSUMO-CPBm4 were reactogenic with polyclonal antibodies against crude CPB, rabbits vaccinated with rSUMO-CPBm4 developed significant levels of toxin-neutralizing antibody (TNA) titers that conferred protection against crude toxin challenge. These data suggest that genetically detoxified rSUMO-CPBm4 is a promising subunit vaccine candidate for C. perfringens type C beta enterotoxemia.

Rac1 promotes the formation of heterotypic cell-in-cell structure / 生物工程学报

Heterotypic cell-in-cell structures (heCICs) are closely related to tumor development and progression, and have become a new frontier in life science research. Ras-related C3 botulinum toxin substrate 1 (Rac1) belongs to the classic Rho GTPase, which plays a key role in regulating the cytoskeleton and cell movement. To investigate the role and mechanism of Rac1 in the formation of heCICs, tumor cells and immune killer cells were labeled with cell-tracker, respectively, to establish the heCICs model. Upon treatment with the Rac1 inhibitor NSC23766, the formation of heCICs between tumor and immune cells was significantly reduced. The plasmid pQCXIP-Rac1-EGFP constructed by gene cloning was packaged into pseudoviruses that subsequently infect tumor cells to make cell lines stably expressing Rac1. As a result, the formation of heCICs was significantly increased upon Rac1 overexpression. These results demonstrated a promotive role of Rac1 in heCICs formation, which may facilitate treating cell-in-cell related diseases, such as tumors, by targeting Rac1.

Academician TONG Xiaolin's Understanding and Experience in Treating Severe Cases of COVID-19 / 中医杂志

This article highlighted the invaluable expertise of Academician TONG Xiaolin in managing severe cases of COVID-19， thereby providing ideas for the treatment of severe and critically ill patients with SARS-CoV-2 infection by integrating traditional Chinese and western medicine. It is believed that COVID-19 belongs to the “cold dampness epidemic” in traditional Chinese medicine， which is caused by pathogenic qi of cold and dampness. The course of the disease can be divided into four stages： constraint， block， collapse， and deficiency， and the severe cases are mainly in the block and collapse stages. The pathogenesis at the block stage is described as epidemic toxins blocking the lung， which should be treated by diffusing the lung and unblocking the bowels， resolving phlegm and unblocking collaterals. The primary formula used is Zilong Xuanbai Chengqi Decoction （子龙宣白承气汤） with modifications based on individual condition. The pathogenesis at the collapse stage is described as internal block and external collapse， which should be treated by restoring yang to save from collapse， boosting qi to relieve collapse， diffusing the lung and unblocking the bowels， resolving phlegm and unblocking collaterals， usually with the formula Poge Zilong Xuanbai Chengqi Decoction （破格子龙宣白承气汤） with modifications.

Towards better antivenoms: navigating the road to new types of snakebite envenoming therapies

Abstract Snakebite envenoming is a significant global health challenge, and for over a century, traditional plasma-derived antivenoms from hyperimmunized animals have been the primary treatment against this infliction. However, these antivenoms have several inherent limitations, including the risk of causing adverse reactions when administered to patients, batch-to-batch variation, and high production costs. To address these issues and improve treatment outcomes, the development of new types of antivenoms is crucial. During this development, key aspects such as improved clinical efficacy, enhanced safety profiles, and greater affordability should be in focus. To achieve these goals, modern biotechnological methods can be applied to the discovery and development of therapeutic agents that can neutralize medically important toxins from multiple snake species. This review highlights some of these agents, including monoclonal antibodies, nanobodies, and selected small molecules, that can achieve broad toxin neutralization, have favorable safety profiles, and can be produced on a large scale with standardized manufacturing processes. Considering the inherent strengths and limitations related to the pharmacokinetics of these different agents, a combination of them might be beneficial in the development of new types of antivenom products with improved therapeutic properties. While the implementation of new therapies requires time, it is foreseeable that the application of biotechnological advancements represents a promising trajectory toward the development of improved therapies for snakebite envenoming. As research and development continue to advance, these new products could emerge as the mainstay treatment in the future.