Carl Djerassi: “In memoriam”. Pionero de la creación del “anticonceptivo oral” y hombre polifacético

ResumenCarl Djerassi nació en Viena en 1923 y emigró a New York en 1939 donde escribió una carta a Eleanor Roosevelt solicitando un apoyo para continuar sus estudios, graduándose en química en 1942 y obteniendo su doctorado en química en la Universidad de Wisconsin en 1945. Sintetizó el esteroide básico del “anticonceptivo oral”, genéricamente conocido como noretisterona. Desde el siglo pasado se sabía que la administración parenteral de estrógenos y progesterona inhibía la ovulación, pero resultaba de un costo muy elevado. Jorge Rosenkranz invitó a Djerassi a incorporarse a Syntex para buscar la síntesis de progesterona, quienes junto con Luis E. Miramontes emplearon el esteroide esencial obtenido del barbasco descubierto por Rusell E. Marker. De esta manera se consiguió industrializar el anticonceptivo hormonal oral conocido trivialmente como la “píldora”.Djerassi se podría considerar como un conspicuo químico, biólogo y sociólogo; incursionó en la literatura, fue coleccionista de arte y benefactor de artistas. Fue presidente de Syntex en México y en Palo Alto. Falleció el 30 de enero de 2015 a la edad de 91 años en San Francisco California.AbstractCarl Djerassi (Vienna, 1923) immigrated to New York in 1939, where he wrote to Eleanor Roosevelt requesting funding to continue his studies, graduating in chemistry in 1942, and acquiring a doctorate in chemistry at the University of Wisconsin in 1945. He synthesised the basic “oral contraceptive” steroid, known generically as norethisterone. Since the preceding century parenteral estrogens and progesterone had been known to inhibit ovulation, but producing them was very expensive. Jorge Rosenkranz invited Djerassi to join Syntex to work on progesterone synthesis; together with Luis E. Miramontes, the researchers used the essential steroid from barbasco [a Mexican yam] discovered by Russell E. Marker to make it possible to industrialise the oral hormonal contraceptive commonly known as “the pill”.Djerassi could be considered as a distinguished chemist, biologist and sociologist, who also pursued literature and was an art collector and artists’ benefactor. Past president of Syntex in Mexico and in Palo Alto, he died on 30 January 2015 at the age of 91 in San Francisco, California

Cambios diarios en la composición y abundancia de copépodos planctónicos al sur de Bahía de La Paz (Octubre 2002)

The goal of this work to analyze the changes in the copepods community, and its relationships with the sea temperature, chl-a concentration and tidal level south of Bahía de La Paz during October 2002. The statistical analysis split the study period with different communities. During the first phase, the oceanic and neritic-oceanic species were dominant (e.g. Labidocera acutifrons, L. acuta, L. diandra, and L. trispinosa), whereas during the second period an increase of the abundance and species richness of coastal and estuarine species was measured (e.g. Acartia lilljeborgii, A. clausi, Nannocalanus minor, and Canthocalanus pauper). These changes were mainly associated with changes in the tide level with respect to de mean sea level as well as with the chlorophyll-a concentration.El objetivo de este trabajo fue analizar los cambios de la comunidad de copépodos y su relación con la temperatura del mar, concentración de Cl a y la altura de la marea al sur de Bahía de La Paz durante octubre del 2002. El análisis estadístico dividió el periodo de estudio en dos etapas con distintas comunidades. En la primera etapa dominaron especies oceánicas y neríticooceánicas (Ej. Labidocera acutifrons, L. acuta, L. diandra, L. trispinosa), y en la segunda se incrementó la abundancia y número de especies costeras y lagunares (Ej. Acartia lilljeborgii, A. clausi, Nannocalanus minor y Canthocalanus pauper). Estos cambios, se asociaron principalmente a cambios en la altura de la marea con respecto al nivel medio del mar y a incrementos en la concentración de Cl a

Enantiopure 4‐oxazolin‐2‐ones and 4‐methylene‐2‐oxazolidinones as chiral building blocks in a divergent asymmetric synthesis of heterocycles

En este trabajo se describe la reactividad de las oxazolidin-2-onas en un ambiente quiral obteniéndose resultados novedosos, los cuales se describen extensamente.Enantiopure 3‐((R)‐ and 3‐((S)‐1‐phenylethyl)‐4‐oxazoline‐2‐ones were evaluated as chiral building blocks for the divergent construction of heterocycles with stereogenic quaternary centers. The N‐(R)‐ or N‐(S)‐1‐phenylethyl group of these compounds proved to be an efficient chiral auxiliary for the asymmetric induction of the 4‐ and 5‐positions of the 4‐oxazolin‐2‐one ring through thermal and MW‐promoted nucleophilic conjugated addition to Michael acceptors and alkyl halides. The resulting adducts were transformed via a cascade process into fused six‐membered carbo‐ and heterocycles. The structure of the reaction products depended on the electrophiles and reaction conditions used. Alternative isomeric 4‐methylene‐2‐oxazolidinones served as chiral precursors for a versatile and divergent approach to highly substituted cyclic carbamates. DFT quantum calculations showed that the formation of bicyclic pyranyl compounds was generated by a diastereoselective concerted hetero‐Diels‐Alder cycloaddition.Instituto Politécnico Nacional, Secretaria de Investigación y Estudios Avanzados de la Universidad Autónoma del Estado de México, Universidad de Guanajuato y CONACYT

Antitumor efficacy of silver nanoparticles reduced with β-D-glucose as neoadjuvant therapy to prevent tumor relapse in a mouse model of breast cancer

Introduction: Neoadjuvant therapy constitutes a valuable modality for diminishing tumor volume prior to surgical resection. Nonetheless, its application encounters limitations in the context of recurrent tumors, which manifest resistance to conventional treatments. Silver nanoparticles (AgNPs) have emerged as a promising alternative for cancer treatment owing to their cytotoxic effects.Methods: Cellular viability was assessed by Alamar blue assay in 4T1 breast cancer cell line. Silver biodistribution was detected by an inductively coupled plasma optical emission spectrometer in an in vivo mice model. For neoadjuvant evaluation, mice were randomized and treated intratumoral with AgNPs-G or intraperitoneally with doxorubicin (DOX) as a control. Recurrence was determined after 170 days by counting lung metastatic nodules (dyed with Bouin solution) with histological confirmation by H&E. Masson’s stain, Ki67 immunohistochemistry, and a TUNEL assay were performed in lungs from treated mice.Results: AgNPs-G reduced 4T1 cell viability and in an ex vivo assay the AgNPs-G decreased the tumor cell viability. After intravenous administration of AgNPs-G were detected in different organs. After intratumor administration, AgNPs-G are retained. The AgNPs-G treatment significantly reduced tumor volume before its surgical resection. AgNPs-G reduced the development of lung metastatic nodules and the expression of Ki67. TUNEL assay indicated that AgNPs-G didn’t induce apoptosis.Conclusions: We concluded that intratumor administration of AgNPs-G reduced tumor volume before surgical resection, alongside a reduction in lung metastatic nodules, and Ki67 expression. These findings provide valuable insights into the AgNPs-G potential for intratumor and neoadjuvant cancer therapies. However, further research is needed to explore their full potential and optimize their use in clinical settings

Valoración funcional tras tratamiento neurointensivo pediátrico. Nueva escala de estado funcional (FSS)

Introducción: La salud funcional, parámetro adecuado de morbilidad, debería constituir un estándar pronóstico de las unidades de cuidados intensivos pediátricos (UCIP), siendo fundamental el desarrollo de escalas para su valoración. Las categorías de estado global y cerebral pediátrico (CEGP-CECP) se han empleado clásicamente en estudios pediátricos; el desarrollo de la nueva Escala de estado funcional (FSS) busca mejorar la objetividad. El objetivo del trabajo es comprobar si la escala FSS es un instrumento válido frente a la clásica CEGP-CECP, y si, incluso, posee mejores cualidades evaluadoras de la funcionalidad neurológica. Pacientes y método: Estudio retrospectivo descriptivo de los 266 niños con enfermedad neurológica ingresados en la UCIP durante 3 años (2012-2014). Se valora su salud funcional al alta y tras un año del ingreso en UCIP, según las categorías CEGP-CECP y la nueva FSS, comparando ambas escalas mediante análisis de correlación (Rho de Spearman). Resultados: La comparación de varianzas de FSSglobal en cada intervalo de CEGP muestra buena correlación para todas las comparaciones (p < 0, 001), excepto en la categoría «5 = coma-vegetativo». La dispersión de FSSglobal aumenta a medida que lo hace la categoría CEGP. La correlación es similar en la versión neurológica de ambas escalas. Discusión: La nueva escala FSS parece ser un método útil para evaluar salud funcional en nuestro medio, tras su comparación con las clásicas categorías CEGP-CECP. La dispersión de los valores de la escala FSS indica falta de precisión del sistema CEGP-CECP, comparado con la nueva escala FSS, más desglosada y objetiva

Guía Mexicana de Práctica Clínica de Inmunoterapia 2011

Existen varias guías internacionales para la práctica clínica de in- munoterapia, que aplican solo parcialmente en México. La primera guía mexicana de inmunoterapia data de 1998

COVID-19 outbreaks in a transmission control scenario: challenges posed by social and leisure activities, and for workers in vulnerable conditions, Spain, early summer 2020

Severe acute respiratory syndrome coronavirus 2 community-wide transmission declined in Spain by early May 2020, being replaced by outbreaks and sporadic cases. From mid-June to 2 August, excluding single household outbreaks, 673 outbreaks were notified nationally, 551 active (>6,200 cases) at the time. More than half of these outbreaks and cases coincided with: (i) social (family/friends’ gatherings or leisure venues) and (ii) occupational (mainly involving workers in vulnerable conditions) settings. Control measures were accordingly applied

Differing patterns of selection and geospatial genetic diversity within two leading Plasmodium vivax candidate vaccine antigens

Although Plasmodium vivax is a leading cause of malaria around the world, only a handful of vivax antigens are being studied for vaccine development. Here, we investigated genetic signatures of selection and geospatial genetic diversity of two leading vivax vaccine antigens--Plasmodium vivax merozoite surface protein 1 (pvmsp-1) and Plasmodium vivax circumsporozoite protein (pvcsp). Using scalable next-generation sequencing, we deep-sequenced amplicons of the 42 kDa region of pvmsp-1 (n = 44) and the complete gene of pvcsp (n = 47) from Cambodian isolates. These sequences were then compared with global parasite populations obtained from GenBank. Using a combination of statistical and phylogenetic methods to assess for selection and population structure, we found strong evidence of balancing selection in the 42 kDa region of pvmsp-1, which varied significantly over the length of the gene, consistent with immune-mediated selection. In pvcsp, the highly variable central repeat region also showed patterns consistent with immune selection, which were lacking outside the repeat. The patterns of selection seen in both genes differed from their P. falciparum orthologs. In addition, we found that, similar to merozoite antigens from P. falciparum malaria, genetic diversity of pvmsp-1 sequences showed no geographic clustering, while the non-merozoite antigen, pvcsp, showed strong geographic clustering. These findings suggest that while immune selection may act on both vivax vaccine candidate antigens, the geographic distribution of genetic variability differs greatly between these two genes. The selective forces driving this diversification could lead to antigen escape and vaccine failure. Better understanding the geographic distribution of genetic variability in vaccine candidate antigens will be key to designing and implementing efficacious vaccines

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio