Guía internacional para una dosificación más segura de la clozapina en adultos mediante el uso de 6 titulaciones personalizadas de dosis basados en la etnicidad, la proteína C reactiva y los niveles de clozapina / An international adult guideline for making clozapine titration safer by using six ancestry-based personalized dosing titrations, CRP, and clozapine levels

Esta guía internacional propone mejorar los prospectos de la clozapina en todo el mundo mediante la inclusion de información sobre la titulación del fármaco en función de la ascendencia del paciente. Las bases de datos de reacciones adversas a medicamentos (RAM) sugieren que la clozapina es el tercer fármaco más tóxico en los Estados Unidos de América (EE. UU.) y que produce una mortalidad por neumonía en todo el mundo 4 veces mayor que la correspondiente a la agranulocitosis o la miocarditis. El rango terapéutico de referencia para las concentraciones séricas estables de clozapina es estrecho, de 350 a 600 ng/ml, con potencial de toxicidad y reacciones adversas más fecuentes a medida que aumentan las concentraciones. La clozapina se metaboliza principalmente por CYP1A2 (las mujeres no fumadoras requieren la dosis más baja y los hombres fumadores la dosis más alta). A través de la conversión fenotípica, la prescripción conjunta de inhibidores del metabolismo de la clozapina (incluidos los anticonceptivos orales y el valproato), la obesidad o la inflamación con elevaciones de la proteína C reactiva (PCR), pueden convertir al paciente en un metabolizador lento/pobre (MP). Las personas de ascendencia asiática (de Pakistán a Japón) o los habitantes originarios de las Américas tienen menor actividad de CYP1A2 y requieren dosis más bajas de clozapina para alcanzar concentraciones de 350 ng/ml. En los EE. UU. se recomiendan dosis diarias de 300-600 mg/día. La dosificación personalizada lenta puede prevenir RAM tempranas (incluidos el síncope, la miocarditis y la neumonía). La esencia de esta guía se fundamenta en 6 esquemas de titulaciones personalizadas para pacientes hospitalizados...(AU)

This is the Spanish translation of an international guideline which proposes improving clozapine package inserts worldwide by using ancestry-based: 1) dosing and 2) titration. Adverse drug reaction (ADR) databases suggest clozapine: 1) is the third most toxic drug in the United States (US), and 2) produces worldwide pneumonia mortality four times greater than that of agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers require the lowest dose and male smokers the highest dose). Poor metabolizer (PM) status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity or inflammation with C-reactive protein (CRP) elevations. People with ancestry from Asia (Pakistan to Japan) or the Americas’ original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/ml. Daily doses of 300-600 mg/day are recommended in the US. Slow personalized titration may prevent early ADRs (including syncope, myocarditis and pneumonia). The core of this guideline consists of six personalized titration schedules for inpatients...(AU)

François-Antoine-Henri Descroizilles (1781-1825), demostrador real de química, boticario, inventor y químico industrial: padre del análisis volumétrico". Parte 1 / François-Antoine-Henri Descroizilles (1781-1825), démonstrateur royal de chimie, apothecary, inventor and industrial chemist: the father of titrimetric analysis. Part I

En esta contribución se pasa revista a la vida y obra de François-Antoine-Henry Descroizilles, personaje polifacético, reconocido como un químico hábil y sabio por eminentes científicos de su época, que ejerce como profesor de química, boticario, y químico industrial. Descroizilles contribuye a dar una solución al problema de la sidra latente en Normandía primero y al blanqueo de los tejidos por el nuevo método de Berthollet en la zona de Rouen después. A este último respecto propone un método de determinar la concentración de cloro, nudo gordiano del problema. Descroizilles puede considerarse con todo justicia como padre del análisis volumétrico, pero su ingenio va mucho más allá y su nombre puede asociarse a una variedad de inventos. En la aproximación que se realiza se hace hincapié en el contexto del nuevo proceso de blanqueo por cloro, aspecto no contemplado siempre con suficientemente profundidad en trabajos previos sobre Descroizilles. En la primera parte de esta contribución vamos a situar y estudiar las condiciones de contorno de este tema, en una época en la que se despierta en las mentes el interés por las artes químicas. Sin embargo, en el desarrollo de la industria del blanqueo con cloro no solo ejercen influencia los aspectos técnicos de los procesos involucrados, sino también los factores sociales y económicos. Aspectos de la vida y obra de Descroizilles, incluyendo temas tales como la problemática de la sidra, inventos, polvos de gas, alumbre, y la contribución de Gay Lussac a la volumetría, serán objeto de un posterior estudio (segunda parte)

In this contribution the life and work of François-Antoine-Henry Descroizilles is reviewed. He is recognized as a multifaceted person, and as a skilled and wise chemist by eminent scientists of his time. Descroizilles developed his professional career as a chemistry teacher, apothecary, and industrial chemist, contributing firstly to give a solution to the latent problem of cider in Normandy, and to the bleaching of tissues by the new method of Berthollet in the area of Rouen later. He proposes on this respect a (redox) titrimetric method of determining the concentration of chlorine, Gordian knot of the problem. Descroizilles can rightly on this way be considered as the father of titrimetric analysis, but his ingenuity goes much further, and his name can be associated to a variety of inventions. In the approach that is carried out here, emphasis is previously placed on the context of the new chloric bleaching, aspect that might not be always treated with enough depth in previous papers on Descroizilles. In the first part of this paper the boundary conditions of this topic will be located and studied, in a time, in which the intent of the study of the chemical arts rapidly acquires great importance. The development of the chlorine bleaching industry is influenced by the technical aspects of the processes involved, but also by the social and economic factors. Aspects of the life and work of Descroizilles, including topics such as the problem of cider, inventions, bleaching power and alum, as well as the contributions of Gay Lussac to titrimetry will be the subject of a future report (second part)

Estimativa do tempo de reparo ósseo em dentes com lesão periapical tratados endodonticamente utilizando modelagem matemática / Estimation of bone repair time in teeth with periapical lesion treated endodontically using mathematical modeling

Os objetivos deste estudo foram avaliar, com a ajuda de um modelo matemático, o tempo estimado para ocorrer reparo ósseo em dentes com lesão periapical tratados endodonticamente e comparar o volume da lesão periapical (em mm3 ) após a utilização de dois tipos de medicação intracanal. Para isso, foram selecionados 34 dentes unirradiculares com lesão periapical de pacientes da Disciplina de Endodontia do ICT/SJC-UNESP que necessitavam de tratamento endodôntico. Após a seleção dos dentes, foram obtidas radiografias periapicais (RP) e tomografias computadorizadas de feixe cônico (TCFC) antes de iniciar o tratamento endodôntico (T0). Os dentes foram divididos em dois grupos de acordo com a medicação intracanal utilizada (n=17): G1 ­ Hidróxido de cálcio associado à Clorexidina Gel 2% e G2 ­ Ultracal XS®. Foram obtidas novas radiografias periapicais e tomografias (TCFC) após o término do tratamento endodôntico (T1), sendo outras após 3 meses (T2) e também após 6 meses (T3). Os arquivos das tomografias foram exportados no formato DICOM (Digital Imaging and Communications in Medicine) para avaliar a volumetria das lesões pré e pós tratamento (em voxel/mm3 ) pelo processo de segmentação semiautomático em todos os períodos de tempo pré-estabelecidos (T0, T1, T2 e T3), por meio do software de livre acesso ITK-SNAP1.4.1 (University of North Carolina, Chapel Hill, NC, USA). Após a análise da volumetria das lesões periapicais em todos os períodos de tempo, os dados obtidos foram utilizados para construir um modelo matemático que foi empregado para estimar o tempo de reparo ósseo das lesões. Os dados obtidos foram analisados estatisticamente pelo Teste t - Student de amostras independentes (p<0,05). Houve diminuição do volume da lesão periapical nos casos tratados endodonticamente e a medicação intracanal utilizada, seja Hidróxido de cálcio + Clorexidina gel 2% ou Ultracal®, não apresentou diferença significativa no tempo de reparo ósseo nem no volume da lesão periapical nos períodos pré-determinados. Não houve diferença na estimativa de tempo de reparo ósseo entre os grupos avaliados, sendo, em média, 249 dias para o G1 e 245 dias para o G2. A utilização de um modelo matemático para estimativa de reparo ósseo pode ser uma alternativa viável na previsão do tempo de reparo dos casos tratados endodonticamente(AU)

The objectives of this study were to evaluate the estimated time for bone repair in teeth with periapical lesions treated endodontically and to compare the volume of the periapical lesion (in mm3) with the help of a mathematical model after the use of two types of intracanal medication. For this, 34 single rooted teeth with periapical lesion were selected from patients of the Endodontic Discipline of the ICT/SJC-UNESP who needed endodontic treatment. After the teeth were selected, periapical radiography (RP) and cone-beam computed tomography (CBCT) were obtained before starting the endodontic treatment. The teeth were divided into two groups according to the intracanal medications used (n=17): G1 - Calcium hydroxide associated with 2% chlorhexidine gel and G2 ­ Ultracal XS®. New periapical radiographs and tomographys (CBCT) were obtained after endodontic treatment (T1), others after 3 months (T2) and after 6 months (T3). The files of CBCT were exported in DICOM (Digital Imaging and Communications in Medicine) format to evaluate the volumetry of pre and post-treatment lesions (voxel/mm3 ) by the semi-automatic segmentation process at all the pre-established time periods (T0, T1, T2, T3) through the free access software ITK SNAP-1.4.1 (University of North Carolina, Chapel Hill, NC, USA). After the analysis of the periapical lesion volume in all time periods, the data were used to construct a mathematical model that was used to estimate the bone repair time of the lesion. The data obtained were statistically analyzed by Student's t - test of independent samples (p <0.05). ). There was a decrease in the volume of the periapical lesion in endodontically treated cases and the intracanal medication used, whether calcium hydroxide + chlorhexidine gel 2% or Ultracal®, did not present a significant difference in bone repair time nor in the periapical lesion volume in the predetermined periods. There was no difference in the estimated bone repair time between the groups evaluated, being, on average, 249 days for G1 and 245 days for G2. The use of a mathematical model for estimation of bone repair may be a viable alternative in predicting the repair time of endodontically treated cases(AU)