Linfoma anaplásico de células grandes asociado a implante mamario. Reporte de un caso y revisión de la literatura. / Breast Implant Associated-Anaplastic Large Cell Lymphoma (BIA-ALCL) - Argentinian case

El linfoma anaplásico de células grandes asociado a implantes mamarios LACG-AI o BIA-ALCL, abreviatura en inglés de "Breast Implant Associated-Anaplastic Large Cell Lymphoma", es una nueva entidad reconocida por la OMS desde el 2016, de rara incidencia y que aún plantea muchos interrogantes. Desde su primera mención en 1997 (J. Keech - B. Creech) su incidencia ha ido en aumento. En julio de 2020, 953 casos en el mundo según el Registro de la Sociedad Americana de Cirujanos Plásticos (PROFILE), y las publicaciones se multiplican exponensialmente año a año demostrando el interés que suscita. Se ha descripto una fuerte asociación con las superficies texturizadas de los implantes mamarios y con el tipo de material (mayor textura "grado 4" y cubierta de poliuretano mayor riesgo) llegando a describirse tasas tan altas omo 1/2830 en Australia/Nueva Zelanda. Su presentación clínica en casi el 75% es bajo la forma de un seroma tardío y el tiempo de exposición promedio ronda entre los 7 a 11 años. El diagnóstico histo-patológico integra el examen morfológico con la caracterización molecular, visualizándose grandes célular anaplásicas CD30 (+), ALK (-). El tratamiento quirúrgico, capsulectomía bilateral en estadios tempranos es el gold standard. Su pronóstico es excelente con exérsis completas. Objetivo: actualizar la información sobre esta novel enfermedad y comentar un caso propio que presenta todas las características descriptas en la literatura, siendo el 14° registrado en Argentina

The anaplastic large cell lymphoma associated with breast implants, LACCG-AI o BIA-ALCL abbreviation in English, is an entity recognized by the WHO since 2016 of rare incidence and that still raises many questions. Since its firts mention in 1997 (J. Keech - B. Creech) its incidence has been increasing, In july 2020, 953 cases in the world according to the Registry of the America Society of Plastic Surgeons (PROFILE), and the publications multiply exponentially year after year, demonstrating the interest it arouses, A strong association has been described with the textured surfaces of breast implants and with the type of material (greater texture "grade 4" and higher risk polyurethane cover), reaching rates as high as 1/2830 in Australia / New Zealand. Its clinical presentation in almost 75% is in the form of a late seroma and the average exposure time is between 7 to 11 years. The pathological anatomical diagnosis integrates the morphological examination with the molecular characterization, visualizing large anaplastic CD30 (+), ALK (-) cells. Surgical treatment, bilateral capsulectomy in early stages, is the gold standard. Her prognosis is excellent with complete exeresis. Objetive: to update the information on this novel disease and comment on an own case that presents all the characteristics described in the literature, the 14th being registered in Argentina

Fluoro artemisinins: difluoromethylene ketones.

The reactions of the ring-contracted aldehydes, derived from anhydrodihydroartemisinin, with gem-difluoroenoxysilanes in the presence of BF(3).Et(2)O afforded the corresponding difluoromethylene ketol adducts in good yields. Similar Lewis acid catalyzed reactions of dihydroartemisinin acetate with the difluoroenoxysilanes provided the 10-substituted difluoromethylene ketones in good to moderate yields. Interestingly enough, the course and the stereochemistry of these reactions are highly dependent on the nature of the Lewis acids used; the addition reaction was accompanied by epimerization at C-9, and the stereochemistry at C-10 depends on the difluoroenoxysilane used. The best results were obtained using SnCl(4) to give the 9alpha,10beta-stereoisomer in high stereoselectivity. When 0.4 equiv of SnCl(4) was used for the reaction with the alpha-(4-methoxyphenylenoxysilane)-beta,beta-difluoroenoxysilane, however, a rearrangement of the endoperoxide was observed.

Novel [1,2]- and [2,3]-Wittig rearrangements of alpha-benzyloxy beta-CF(3)-beta-lactam enolates.

[reaction: see text] alpha-Benzyloxy alpha-CF(3)-beta-lactams are shown to offer the first examples of the enolate [1,2]- and enolate ortho-[2,3]-Wittig rearrangements which provide a unique entry to the alpha-benzyl-alpha-hydroxy lactams and the alpha-aryl-alpha-hydroxy lactams, respectively. Both products are potential precursors of new trifluoromethyl isoserines, and the latter is not accessible via the usual alkylation methodology.

1-Trifluoromethyl epoxy ethers. Effect of hexafluoro-2-propanol on reactions with secondary aromatic amines: synthesis of 3-trifluoromethyl indole derivatives.

Trifluoromethyl epoxy ethers 1 and 2 reacted with aromatic amines in hexafluoro-2-propanol at room temperature providing trifluoromethyl indolinols 3 and 4 in excellent isolated yields. 3-Trifluoromethyl indoles 9 and 10 could be prepared by treatment of indolinols with SOCl(2).

Synthesis and antimalarial activities of fluoroalkyl derivatives of dihydroartemisinin.

Fluoroalkyl ethers (4) of dihydroartemisinin (2) have been prepared by reaction of fluoroalkyl alcohols with dihydroartemisinin by different methods (BF3,Et2O or TMSCl catalysis or Mitsunobu reaction). Ethers 4a-d derived from primary fluoroalkyl alcohols were obtained in moderate to good yields by these methods. Ethers 4e-j have been prepared from fluoroalkyl secondary and tertiary alcohols and phenol using the Mitsunobu reaction. Although in vitro antimalarial activities of ethers toward Plasmodium falciparum W-2 asiatic strain are moderate, in vivo activities against Plasmodium berghei (NT 173) are excellent.

Stereoselective synthesis of peptidyl trifluoromethyl alcohols and ketones: inhibitory potency against human leucocyte elastase, cathepsin G, porcine pancreatic elastase and HIV-1 protease.

New fluorinated inhibitors have been designed to target two major proteases-human leucocyte elastase and HIV-1 protease. Two series of beta-peptidyl trifluoromethyl alcohols (TFMAs) Z-L-Val-NH-*CH(Y)*CH(OH)-CF3, where *C is the chiral centre, varied in the nature of the substituent Y, a phenylethyl [-(CH2)2-C6H5] or an isopropyl [-CH(CH3)2] group. These TFMAs were first synthesized as two pairs of the syn and anti diastereoisomers. The inhibitory effects of these mixtures were then assessed on three serine proteases chosen on the basis of the aromatic and aliphatic nature of the substituents-human leucocyte elastase (HLE), human cathepsin G (HCG) and porcine pancreatic elastase (PPE). In the presence of detectable inhibition, each epimer at C2 was separated to determine its inhibition constant (Ki) towards HLE, HCG and PPE. The stereoisomerically pure TFMAs were then oxidized into peptidyl trifluoromethyl ketones (TFMKs) for similar inhibition assays. The absolute configuration of the compounds remained unknown. One epimer at C2 of each syn and anti TFMA with the phenylethyl substituent behaved as a competitive inhibitor towards HLE and HCG with inhibition constants below the millimolar range, whereas their TFMK counterparts were non-inhibitors. In the second series, the two ketones inhibited both elastases with Ki values in the micromolar range, whereas only the syn TFMA was active towards HLE (Ki = 5.65 x 10(-4)M). The tested compounds also had structural properties compatible with recognition by HIV-1 protease. The inhibition of the enzyme was observed with TFMK only (IC50 = 15-200 microM). The phenylethyl substituent promoted inhibition by a factor of 10 (IC50 = 15 microM) compared with the isopropyl substituent (IC50 = 200 microM) leading to selective inhibition of HIV-1 protease. Isomerically pure TFMKs were more potent towards HLE than the alcohols from which they were obtained. However, an enantiomerically pure TFMA selectively inhibited HLE unlike its TFMK analogue which also inhibited PPE. This last result together with the selective inhibition of HIV-1 protease by TFMK with a phenylethyl substituent might be relevant to the design of specific HLE and HIV-1 inhibitors as therapeutic agents.