Routine therapeutic drug monitoring in patients treated with 10-360 mg/day citalopram

From data collected during routine TDM, plasma concentrations of citalopram (CIT) and its metabolites demethylcitalopram (DCIT) and didemethylcitalopram (DDCIT) were measured in 345 plasma samples collected in steady-state conditions. They were from 258 patients treated with usual doses (20-60 mg/d) and from patients medicated with 80-360 mg/d CIT. Most patients had one or several comedications, including other antidepressants, antipsychotics, lithium, anticonvulsants, psychostimulants and somatic medications. Dose-corrected CIT plasma concentrations (C/D ratio) were 2.51 +/- 2.25 ng mL-1 mg-1 (n = 258; mean +/- SD). Patients >65 years had significantly higher dose-corrected CIT plasma concentrations (n = 56; 3.08 +/- 1.35 ng mL-1 mg-1) than younger patients (n = 195; 2.35 +/- 2.46 ng mL-1 mg-1) (P = 0.03). CIT plasma concentrations in the generally recommended dose range were [mean +/- SD, (median)]: 57 +/- 64 (45) ng/mL (10-20 mg/d; n = 64), 117 +/- 95 (91) ng/mL (21-60 mg/d; n = 96). At higher than usual doses, the following concentrations of CIT were measured: 61-120 mg/d CIT, 211 +/- 103 (190) ng/mL (n = 93); 121-200 mg/d: 339 +/- 143 (322) ng/mL (n = 70); 201-280 mg/d: 700 +/- 408 (565) ng/mL (n = 18); 281-360 mg/d: 888 +/- 620 (616) ng/mL (n = 4). When only one sample per patient (at the highest daily dose if repeated dosages) is considered, there is a linear and significant correlation (n = 48, r = 0.730; P < 0.001) between daily dose (10-200 mg/d) and CIT plasma concentrations. In experiments with dogs, DDCIT was reported to affect the QT interval when present at concentrations >300 ng/mL. In this study, DDCIT concentration reached 100 ng/mL in a patient treated with 280 mg/d CIT. Twelve other patients treated with 140-320 mg/d CIT had plasma concentrations of DDCIT within the range 52-73 ng/mL. In a subgroup comprised of patients treated with > or =160 mg/d CIT and with CIT plasma concentrations < or =300 ng/mL, and patients treated with < or =200 mg/d CIT and CIT plasma concentrations > or = 600 ng/mL, the enantiomers of CIT and DCIT were also analyzed. The highest S-CIT concentration measured in this subgroup was 327 ng/mL in a patient treated with 140 mg/d CIT, but the highest S-CIT concentration (632 ng/mL) was measured in patient treated with 360 mg/d CIT. In conclusion, there is a highly linear correlation between CIT plasma concentrations and CIT doses, well above the usual dose range.

Hydroxyapatite coatings grown by pulsed laser deposition with a beam of 355 nm wavelength

Calcium phosphate coatings, obtained at different deposition rates by pulsed laser deposition with a Nd:YAG laser beam of 355-nm wavelength, were studied. The deposition rate was changed from 0.043 to 1.16 /shot by modification of only the ablated area, maintaining the local fluence constant to perform the ablation process in similar local conditions. Characterization of the coatings was performed by scanning electron microscopy, x-ray diffractometry, and infrared, micro-Raman, and x-ray photoelectron spectroscopy. The coatings showed a compact surface morphology formed by glassy gains with some droplets on them. Only hydroxyapatite (HA) and alpha-tricalcium phosphate (alpha-TCP) peaks were found in the x-ray diffractograms. The relative content of alpha TCP diminished with decreasing deposition rates, and only HA peaks were found for the lowest rate. The origin of alpha TCP is discussed.

Nimistöntutkimus ja lähdekritiikki

Vastine Ritva Korhosen artikkeliin Tutkimus teilasi aineistonsa // Virittäjä 4/2000, s. 616-618

A validated assay by liquid chromatography-tandem mass spectrometry for the simultaneous quantification of elvitegravir and rilpivirine in HIV positive patients.

Because of the large variability in the pharmacokinetics of anti-HIV drugs, therapeutic drug monitoring in patients may contribute to optimize the overall efficacy and safety of antiretroviral therapy. An LC-MS/MS method for the simultaneous assay in plasma of the novel antiretroviral agents rilpivirine (RPV) and elvitegravir (EVG) has been developed to that endeavor. Plasma samples (100 μL) extraction is performed by protein precipitation with acetonitrile, and the supernatant is subsequently diluted 1:1 with 20-mM ammonium acetate/MeOH 50:50. After reverse-phase chromatography, quantification of RPV and EVG, using matrix-matched calibration samples, is performed by electrospray ionization-triple quadrupole mass spectrometry by selected reaction monitoring detection using the positive mode. The stable isotopic-labeled compounds RPV-(13) C6 and EVG-D6 were used as internal standards. The method was validated according to FDA recommendations, including assessment of extraction yield, matrix effects variability (<6.4%), as well as EVG and RPV short and long-term stability in plasma. Calibration curves were validated over the clinically relevant concentrations ranging from 5 to 2500 ng/ml for RPV and from 50 to 5000 ng/ml for EVG. The method is precise (inter-day CV%: 3-6.3%) and accurate (3.8-7.2%). Plasma samples were found to be stable (<15%) in all considered conditions (RT/48 h, +4°C/48 h, -20°C/3 months and 60°C/1 h). Selected metabolite profiles analysis in patients' samples revealed the presence of EVG glucuronide, that was well separated from parent EVG, allowing to exclude potential interferences through the in-source dissociation of glucuronide to parent drug. This new, rapid and robust LCMS/MS assay for the simultaneous quantification of plasma concentrations of these two major new anti-HIV drugs EVG and RPV offers an efficient analytical tool for clinical pharmacokinetics studies and routine therapeutic drug monitoring service. Copyright © 2013 John Wiley & Sons, Ltd.

A Y-like social chromosome causes alternative colony organization in fire ants.

Intraspecific variability in social organization is common, yet the underlying causes are rarely known. In the fire ant Solenopsis invicta, the existence of two divergent forms of social organization is under the control of a single Mendelian genomic element marked by two variants of an odorant-binding protein gene. Here we characterize the genomic region responsible for this important social polymorphism, and show that it is part of a pair of heteromorphic chromosomes that have many of the key properties of sex chromosomes. The two variants, hereafter referred to as the social B and social b (SB and Sb) chromosomes, are characterized by a large region of approximately 13 megabases (55% of the chromosome) in which recombination is completely suppressed between SB and Sb. Recombination seems to occur normally between the SB chromosomes but not between Sb chromosomes because Sb/Sb individuals are non-viable. Genomic comparisons revealed limited differentiation between SB and Sb, and the vast majority of the 616 genes identified in the non-recombining region are present in the two variants. The lack of recombination over more than half of the two heteromorphic social chromosomes can be explained by at least one large inversion of around 9 megabases, and this absence of recombination has led to the accumulation of deleterious mutations, including repetitive elements in the non-recombining region of Sb compared with the homologous region of SB. Importantly, most of the genes with demonstrated expression differences between individuals of the two social forms reside in the non-recombining region. These findings highlight how genomic rearrangements can maintain divergent adaptive social phenotypes involving many genes acting together by locally limiting recombination.

ESTUDIO PREDICA: Prevalencia de desnutrición y caquexia en pacientes ambulatorios con insuficiencia cardíaca crónica. Comparación de dos métodos de cribaje nutricional

La prevalencia de desnutrición y caquexia en pacientes ambulatorios con Insuficiencia Cardíaca Crónica es muy variable dependiendo del método utilizado para el diagnóstico. Este estudio observacional transversal pretende identificar cual de los diversos métodos de cribaje nutricional es el más sensible y específico para su detección, respecto a la Valoración Global Subjetiva. Se analizaron 48 pacientes dónde la prevalencia de desnutrición fue del 18,8%, y la de caquexia varió según el método (7,3-9,8%). La sensibilidad y especificidad del Mini Nutritional Assessment fueron elevadas en comparación con los otros métodos. Por lo tanto, puede ser el método más recomendado para el cribado nutricional.

Estudio Clínico aleatorio, controlado, paralelo, para evaluar la eficacia del ejercicio físico progresivo como tratamiento en los pacientes diagnosticados del Síndrome de Fatiga Crónica

Antecedentes: El Síndrome de Fatiga Crónica (SFC) es una enfermedad que presenta disfunción multidimensional. Se recomienda tratamiento multidisciplinario que incluya el ejercicio. Material y métodos: Diseñamos un proyecto unicéntrico, experimental, prospectivo partiendo de la hipótesis siguiente: El ejercicio físico progresivo (EFP) enseñado por fisioterapeutas, puede beneficiar a los enfermos de SFC mejorando sus síntomas. Resultados: Evidencian la eficacia del EFP con SFC valorando las variables sintomáticas con escalas y cuestionarios. Conclusiones: El estudio, valora sintomatología relevante antes de iniciar el tratamiento para comparar los resultados obtenidos, mediante tres seguimientos, constatando la eficacia del tratamiento multidisciplinar con EFP a corto y largo plazo.

Tratamiento con acupuntura en pacientes diagnosticados del Síndrome de Fatiga Crónica

El Síndrome de Fatiga Crónica presenta muchas perturbaciones *multidimensionales que afectan de forma *holística a las personas que sufren esta enfermedad y que el tratamiento actual de la fatiga, dolor, ansiedad-depresión y alteraciones del sueño, presentes en esta entidad clínica, es insatisfactorio. La hipótesis de partida de este ensayo consiste a contrastar que la acupuntura resulta más útil que el placebo. Proponemos la realización de un estudio clínico, aleatorio y controlado con placebo, de la técnica de acupuntura, orientado al aumento de la sensación del paciente de bienestar, al alivio del dolor y de la rigidez, la acupuntura es eficaz para reducir la fatiga, ansiedad-depresión y alteraciones del sueño, en el paciente diagnosticado, del Síndrome de Fatiga Crónica.

Biologia e tabela de vida de fertilidade de Agrotis ipsilon em dieta artificial

O objetivo deste trabalho foi desenvolver uma dieta artificial para criação de Agrotis ipsilon em laboratório com base em parâmetros biológicos e na tabela de vida de fertilidade. A dieta artificial utilizada continha feijão, caseína, proteína de soja, levedura e germe de trigo como fontes protéicas. Os parâmetros biológicos duração e viabilidade das fases larval e pupal, peso de pupas, de ambos os sexos, com 24 horas de idade, razão sexual, longevidade dos adultos, período de pré-oviposição e número de ovos produzidos por fêmea e a tabela de vida de fertilidade foram avaliados. Foram observados seis ínstares larvais com duração de 25,4 dias e viabilidade de 93%. A duração da fase pupal foi de 12,4 dias e viabilidade de 96%. A viabilidade de ciclo total foi 72%. O peso de pupas foi 387 mg (machos) e 484 mg (fêmeas). A razão sexual foi 0,46. O período de pré-oviposição foi de um dia, com 1.806 ovos por fêmea. Na tabela de vida verificou-se que a taxa líquida de reprodução e a razão finita de aumento foram 616,9 e 1,14, respectivamente. A dieta artificial é adequada à manutenção da criação de A. ipsilon, em laboratório.