Considerations on genetic engineering: regarding the birth of twins subjected to gene edition.

In this essay, the bioethical implications of the recent genetic manipulation in human embryos with CRISPR-Cas9 to eliminate the CCR5 gene and the birth of a pair of discordant twin girls are analyzed. The experiment was disseminated via social media. The main bioethical flaws identified include the justification of the model, the informed consent process and the lack of disclosure of evident conflicts of interest. The consequences of the experiment on the life of the twins that were born were not properly evaluated, such as the impact on their autonomy, the alleged benefits to be received and the future risks of harm during their lifetime. Having manipulated the germ cell line, the effects on their future offspring were not considered. This type of actions negatively affects the way society conceives science. Genetic engineering should be reserved to the basic experimental context or as clinical research for the correction of known serious diseases of genetic origin under strict regulatory and bioethical supervision and using a gradualist approach in accordance with the advances of gene editing techniques.

En este ensayo se analizan las implicaciones bioéticas de la reciente manipulación genética en embriones humanos con CRISPR-Cas9 para eliminar el gen CCR5 y el nacimiento de dos gemelas discordantes. El experimento se divulgó en medios sociales. Los principales problemas bioéticos identificados son la justificación del modelo, el proceso de consentimiento informado y la falta de declaración de evidentes conflictos de interés. No se evaluaron apropiadamente las consecuencias del experimento sobre la vida de las gemelas nacidas como la afectación a su autonomía, los supuestos beneficios por recibir y los riesgos futuros de daño durante su vida. Habiendo manipulado la línea celular germinal, no se consideraron los efectos sobre su descendencia futura. Este tipo de acciones tiene un impacto negativo en la forma como la sociedad concibe la ciencia. La ingeniería genética debe reservarse al contexto experimental básico o bien como investigación cínica para la corrección de enfermedades conocidas graves de origen genético, bajo estricta supervisión regulatoria y bioética y de manera gradualista de acuerdo con el progreso de las técnicas de edición genética.

Reflexiones sobre la ingeniería genética: a propósito del nacimiento de gemelas sometidas a edición génica / Considerations on genetic engineering: regarding the birth of twins subjected to gene edition

Resumen En este ensayo se analizan las implicaciones bioéticas de la reciente manipulación genética en embriones humanos con CRISPR-Cas9 para eliminar el gen CCR5 y el nacimiento de dos gemelas discordantes. El experimento se divulgó en medios sociales. Los principales problemas bioéticos identificados son la justificación del modelo, el proceso de consentimiento informado y la falta de declaración de evidentes conflictos de interés. No se evaluaron apropiadamente las consecuencias del experimento sobre la vida de las gemelas nacidas como la afectación a su autonomía, los supuestos beneficios por recibir y los riesgos futuros de daño durante su vida. Habiendo manipulado la línea celular germinal, no se consideraron los efectos sobre su descendencia futura. Este tipo de acciones tiene un impacto negativo en la forma como la sociedad concibe la ciencia. La ingeniería genética debe reservarse al contexto experimental básico o bien como investigación cínica para la corrección de enfermedades conocidas graves de origen genético, bajo estricta supervisión regulatoria y bioética y de manera gradualista de acuerdo con el progreso de las técnicas de edición genética.

Abstract In this essay, the bioethical implications of the recent genetic manipulation in human embryos with CRISPR-Cas9 to eliminate the CCR5 gene and the birth of a pair of discordant twin girls are analyzed. The experiment was disseminated via social media. The main bioethical flaws identified include the justification of the model, the informed consent process and the lack of disclosure of evident conflicts of interest. The consequences of the experiment on the life of the twins that were born were not properly evaluated, such as the impact on their autonomy, the alleged benefits to be received and the future risks of harm during their lifetime. Having manipulated the germ cell line, the effects on their future offspring were not considered. This type of actions negatively affects the way society conceives science. Genetic engineering should be reserved to the basic experimental context or as clinical research for the correction of known serious diseases of genetic origin under strict regulatory and bioethical supervision and using a gradualist approach in accordance with the advances of gene editing techniques.

Doxazosin Treatment Attenuates Carbon Tetrachloride-Induced Liver Fibrosis in Hamsters through a Decrease in Transforming Growth Factor ß Secretion.

BACKGROUND/AIMS: The development of therapeutic strategies for the treatment of cirrhosis has become an important focus for basic and clinical researchers. Adrenergic receptor antagonists have been evaluated as antifibrotic drugs in rodent models of carbon tetrachloride (CCl4)-induced cirrhosis. The aim of the present study was to evaluate the effects of carvedilol and doxazosin on fibrosis/cirrhosis in a hamster animal model. METHODS: Cirrhotic-induced hamsters were treated by daily administration of carvedilol and doxazosin for 6 weeks. Hepatic function and histological evaluation were conducted by measuring biochemical markers, including total bilirubin, aspartate aminotransferase, alanine aminotransferase and albumin, and liver tissue slices. Additionally, transforming growth factor ß (TGF-ß) immunohistochemistry was analyzed. RESULTS: Biochemical markers revealed that hepatic function was restored after treatment with doxazosin and carvedilol. Histological evaluation showed a decrease in collagen type I deposits and TGF-ß-secreting cells. CONCLUSIONS: Taken together, these results suggest that the decrease in collagen type I following treatment with doxazosin or carvedilol is achieved by decreasing the profibrotic activities of TGF-ß via the blockage of α1- and ß-adrenergic receptor. Consequently, a diminution of fibrotic tissue in the CCl4-induced model of cirrhosis is achieved.

Clinical case of cerebral amebiasis caused by E. histolytica.

Although amebic brain abscess is a rare form of invasive amebiasis, when present, it is frequently lethal. This disorder always begins with the infection of the colon by Entamoeba histolytica trophozoites, which then travel to extra-intestinal tissues through the bloodstream. Amebic brain abscesses are produced when trophozoites invade the central nervous system. Computerized axial tomography scans can be used to diagnose the presence or absence of a brain abscess with a certainty of 100%. However, this diagnostic tool does not reveal the etiological agent of disease. By analyzing the clinical case of a patient that died due to untimely treatment of this malady, the present study aims to identify a diagnostic tool that can give a precise determination of the etiological agent and therefore permit adequate and opportune treatment. Currently, diagnosis of amebic brain abscess is often done by identification of the ameba in a biopsy or autopsy. By immunohistochemistry and immunofluorescence with specific antibodies, we identified the existence of E. histolytica, which presents proteins similar to Naegleria fowleri in its membrane.

Osteomielitis de rótula y artritis séptica de rodilla por Pseudomonas aeruginosa / Pseudomonas aeruginosa-associated osteomyelitis of the patella and septic arthritis of the knee

Introducción. La osteomielitis de rótula es una infección poco frecuente que afecta principalmente a los niños. En la mayoría de los casos la causa es Staphylococcus aureus. El diagnóstico se sospecha si hay dolor e hinchazón perirrotuliano, celulitis, bursitis prerrotuliana (séptica o no), o artritis séptica que no responde al tratamiento estándar. Caso clínico. Paciente diabético tipo 1 de 14 años de edad con dolor e inflamación de la rodilla izquierda por una herida superficial con un objeto metálico punzante sin respuesta a antibióticos orales y antiinflamatorios. Se confirmó infección de articulación y de rótula por gammagrafía y ultrasonido músculo-esquelético, así como por estudio histológico del tejido sinovial obtenido por cirugía. El cultivo reveló Pseudomonas aeruginosa. El tratamiento con ceftazidima seguido de ciprofloxacina fue efectivo con resolución del proceso infeccioso. Conclusión. Se requiere de un alto nivel de sospecha y de un abordaje exhaustivo para el diagnóstico de osteomielitis de rótula, asociado o no a artritis séptica.

Introduction. Osteomyelitis of the patella is an infrequent infection that predominantly affects children. The most frequent microorganism is Staphylococcus aureus. Diagnosis should be considered in patients with pain and swelling around the patella, cellulitis, prepatellar bursitis (septic or not), and in patients with septic arthritis with no response to the standard treatment. Case report. We report the case of a 14-year-old male patient with type 1 diabetes mellitus with pain and swelling of the left knee after being injured with a sharp metallic object. No response was obtained with oral antibiotics and anti-inflammatory drugs. Surgery, gammagraphy, and musculoskeletal ultrasound, together with the histology, confirmed septic arthritis of the knee and osteomyelitis of the patella due to Pseudomonas aeruginosa. Treatment with ceftazidime and subsequent ciprofloxacin resulted in total remission of symptoms. Conclusion. A high level of suspicion and an exhaustive approach are required for definitive diagnosis of osteomyelitis of the patella, associated or not with septic arthritis.

Adenomatoid Tumor of the Right Adrenal Gland in a Patient with AIDS.

An autopsy case with an incidentally discovered adenomatoid tumor (AT) arising in the right adrenal gland of a 34-yr-old man with AIDS is presented. The immediate cause of death was disseminated coccidioidomycosis. The affected right adrenal gland was partially substituted by a firm 3.O cm nodule enclosed by cortical adrenal tissue. Histologically, the tumor had the typical appearance of those adenomatoid neoplasms described in the genital tract. The mesothelial origin of the neoplasm was confirmed by immunopositive cells for low weight cytokeratin and vimentin. Uncommon neoplasms in the adrenal glands of AIDS patients include leiomyosarcomas, leiomyomas, and malignant nerve sheath tumors. This report may represent the first case of an adrenal gland AT in a patient with AIDS, and probably the third well-documented histologically and immunohistochemically adrenal gland AT.

Concordancia diagnóstica clínico-patológica en 429 autopsias del Instituto Nacional de la Nutrición Salvador Zubirán / Diagnostic concordance in 429 autopsies in the Instituto Nacional de la Nutricion Salvador Zubiran

Se revisaron los expedientes clínicos y los protocolos de las autopsias realizadas en el Departamento de Patología del Instituto Nacional de la Nutrición Salvador Zubirán, de 1984 a 1988, con el objeto de establecer el grado de concordancia entre los diagnósticos clínicos y de autopsia. El total de casos analizados fue de 429. A partir de 1985, se observó un descenso progresivo en el porcentaje de autopsias, de 34.65 por ciento que se efctuaron ese año a 21.16 por ciento en 1988, con un promedio de 27.31 por ciento en el lapso estudiado. En 229 casos (53.8 por ciento) hubo 353 hallazgos de relevancia clínica, de los cuales 86 fueron en la enfermedad principal y 267 en la causa de muerte. Hubo 171 sobrediagnósticos con implicaciones terapéuticas, 38 en la enfermedad principal y 133 en la causa de muerte. El mayor número de discordancias ocurrieron en las enfermedades infecciosas, seguidas por las gastroenterológicas y respiratorias y el menor número en enfermedades endócrinas y reumatológicas. El tiempo de hospitalización no influyó en el grado de concordancia. Se hace un breve análisis de las probables causas del descenso en el número de autopsias y se concluye que, a pesar de los notables avances tecnológicos con que contamos y del apoyo de especialistas de alto nivel, el porcentaje de discordancia diagnóstica clinico-patológica sigue siendo alto y justifica por ese sólo hecho que se continúen realizando autopsias