Advances and challenges in therapeutic monoclonal antibodies drug development

The use of serum containing polyclonal antibodies from animals immunized with toxins marked the beginning of the application of antibody-based therapy in late nineteenth century. Advances in basic research led to the development of the hybridoma technology in 1975. Eleven years later, the first therapeutic monoclonal antibody (mAb) was approved, and since then, driven by technological advances, the development of mAbs has played a prominent role in the pharmaceutical industry. In this review, we present the developments to circumvent problems of safety and efficacy arising from the murine origin of the first mAbs and generate structures more similar to human antibodies. As of October 2017, there are 61 mAbs and 11 Fc-fusion proteins in clinical use. An overview of all mAbs currently approved is provided, showing the development of sophisticated mAbs formats that were engineered based on the challenges posed by therapeutic indications, including antibody-drug conjugates (ADC) and glycoengineered mAbs. In the field of immunotherapy, the use of immunomodulators, bispecific mAbs and CAR-T cells are highlighted. As an example of promising therapy to treat infectious diseases, we discuss the generation of neutralizing monoclonal-oligoclonal antibodies obtained from human B cells. Scientific and technological advances represent mAbs successful translation to the clinic

Aspectos socioeconômicos e tecnológicos da atividade leiteira na microrregião de Erechim, RS / Socioeconomic and technologycal aspects of dairy activity in the micro-region of Erechim, RS / Aspectos socioeconómicos y tecnológicos de la producción lechera en la microrregión de Erechim, RS

Objetivou-se com o trabalho caracterizar as propriedades leiteiras na microrregião de Erechim, RS, quanto às condições socioeconômicas, produtivas e de mecanização para a obtenção e armazenamento do leite. Foram realizadas visitas em 229 propriedades leiteiras nos municípios de Erechim, Aratiba e Severiano de Almeida. Questionário contendo perguntas acerca da área da propriedade, da área destinada à produção leiteira, do número de vacas em lactação, da produção diária de leite, da mecanização empregada no processo de obtenção e armazenamento do leite e da higiene dos tetos dos animais antes e após a ordenha foi aplicado aos produtores. O tamanho médio das propriedades rurais foi de 25,4 ha, com área destinada ao leite de 8,0 ha, média de 12,8 vacas em lactação por propriedade e 159,8 litros de leite por dia. O número de investimentos na atividade leiteira pode ser considerado elevado, visto que 40,2% dos produtores de leite realizavam algum tipo de financiamento. A ordenhadeira tipo balde ao pé foi o equipamento mais empregado para a obtenção do leite. A região destaca-se por apresentar propriedades de pequeno porte e produção leiteira e evidente envelhecimento dos agricultores produtores de leite.(AU)

The present research aimed to characterize dairy farms in the Erechim area regarding the socioeconomic, production, mechanization and hygiene conditions for obtaining and storing milk. Visits were carried out on 229 dairy farms in the cities of Erechim, Aratiba and Severiano de Almeida. A questionnaire containing questions about the farm area, the area used for dairy production, the number of dairy cows, daily milk production, mechanization employed in the process of obtaining and storing milk and the process of sanitation of the animal tits before and after milking was applied to the producers. The average size of the farms is 25.4 ha, with area destined for milk of 8.0 ha, with an average of 12.8 lactating cows per farm and 159.8 liters of milk per day. The number of investments in dairy farms can be considered high, since 40.2% of the dairy farmers had some type of financing.(AU)

Se ha buscado con ese estudio caracterizar las granjas lecheras en la microrregión de Erechim, RS, cuanto a las condiciones socioeconómicas, productivas y de mecanización para la extracción y almacenamiento de la leche. Las visitas se llevaron a cabo en 229 granjas lecheras en las ciudades de Erechim, Aratiba y Severiano de Almeida. Cuestionario conteniendo preguntas sobre la cantidad de tierras de la propiedad, la cantidad de tierras dedicada a la producción de leche, el número de vacas lecheras en la granja, área destinada a la producción de leche, número de vacas en lactación, producción diaria de leche, mecanización empleada en el proceso de obtención y almacenamiento de la leche y de la higiene de los locales de los animales, antes y después de la ordeña, se aplicó a los productores. El tamaño promedio de las granjas fue de 25,4 hectáreas, con áreas destinadas a la leche de 8,0 ha, promedio de 12,8 vacas lecheras lactantes por granja y 159,8 litros de leche por día. El número de inversiones en la actividad lechera se puede considerar alto, ya que el 40,2% de los productores de leche realizaban algún tipo de financiación. La ordeñadera tipo balde al pie fue el equipo más utilizado para la obtención de leche. La región se destaca por presentar propiedades de pequeño porte y producción lechera y evidente envejecimiento de los agricultores productores de leche.(AU)

Ecografía en técnicas de Reproducción Asistida / Ultrasound in Assisted Reproductive techniques

La presente revisión de las aplicaciones de la ecografía en las técnicas de reproducción asistida tiene como misión una puesta al día de los últimos datos acerca de su utilidad en el diagnóstico de patologías previas a la realización de la técnica (endometriosis, pólipos endometriales, malformaciones uterinas, miomas, adenomiosis, síndrome de Asherman, ovarios poliquísticos, , hidrosálpinx, etc), la valoración de la reserva ovárica y receptividad endometrial, la diferenciación entre formaciones funcionales que frecuentemente encontramos durante los tratamientos y el uso como guía tanto para controlar el desarrollo multifolicular como la punción ovárica y la transferencia embrionaria. Por último se trata la ayuda que presta la ecografía en el diagnóstico y tratamiento del síndrome de hiperestimulación ovárica y durante el diagnóstico precoz de la gestación normal y patológica, así como su papel en la reducción embrionaria y terminación selectiva de la gestación (AU)

The aim of this review is to present the latest data about the applications of ultrasound in assisted reproductive techniques (ARTs) and their relevance in the diagnosis of pathologies related with infertility (endometriosis, endometrial polyps, uterine malformations, myomas, adenomyosis, Asherman syndrome, polycystic ovaries, hydrosalpinx, etc.). The usefulness of this technique to assess ovarian reserve, to recognize functional ovarian cysts frequently found during treatments, its use as guide for multiple follicular development and its potential to evaluate endometrial receptivity is also updated. Besides, the role of ultrasound during the realization of the oocyte pick up and embryo transfer is also evaluated. Finally, the relevance of ultrasound in other aspects related with reproduction as the diagnosis and treatment of ovarian hyperstimulation syndrome (OHS), the early diagnosis of normal and pathological pregnancy, as well as fetal reduction and selective termination of pregnancies is also covered (AU)