Analysis of molecular changes induced by mineral trioxide aggregate on spla2

Abstract The aim of this study was to analyze the effects of MTA on the structure and enzymatic activity of sPLA2 in order to provide subsidies for improvement in the formulation of the product. MTA powder was incubated for 60 min in the presence of sPLA2 and was analyzed by chromatography, electrospray mass (ESI-MS) and small-angle X-ray scattering (SAXS). It was find that the elution profile, retention time, and fragmentation of sPLA2 were altered after treatment with MTA. Calcium was the MTA component that most amplified the inflammatory signal. Significant interactions were found between MTA and sPLA2, which could aid in our understanding of the mechanisms of action of MTA during the inflammatory process and it may facilitate the structural modification of MTA, thereby improving its biological safety and consequently the rate of the treatment success.

Resumo O objetivo deste estudo foi analisar os efeitos do MTA na estrutura e atividade enzimática da sPLA2 a fim de fornecer subsídios para melhoria na formulação do produto. O MTA em pó foi incubado por 60 min na presença de sPLA2 e analisado por cromatografia, espectroscopia de massa por eletropulverização (ESI-MS) e espalhamento de raios-X de baixo ângulo (SAXS). Encontrou-se que o perfil de eluição, o tempo de retenção e a fragmentação da sPLA2 foram alterados após o tratamento com MTA. O cálcio foi o componente do MTA que mais ampliou o sinal inflamatório. Encontraram-se interações significativas entre o MTA e o sPLA2, o que poderia auxiliar na compreensão dos mecanismos de ação do MTA durante o processo inflamatório e facilitar a modificação estrutural do MTA, melhorando sua segurança biológica e consequentemente a taxa de sucesso do tratamento.

Effects of artepillin C on model membranes displaying liquid immiscibility

It has been hypothesized that the therapeutic effects of artepillin C, a natural compound derived from Brazilian green propolis, are likely related to its partition in the lipid bilayer component of biological membranes. To test this hypothesis, we investigated the effects of the major compound of green propolis, artepillin C, on model membranes (small and giant unilamelar vesicles) composed of ternary lipid mixtures containing cholesterol, which display liquid-ordered (lo) and liquid-disordered (ld) phase coexistence. Specifically, we explored potential changes in relevant membrane parameters upon addition of artepillin C presenting both neutral and deprotonated states by means of small angle X-ray scattering (SAXS), differential scanning calorimetry (DSC), and confocal and multiphoton excitation fluorescence microscopy. Thermotropic analysis obtained from DSC experiments indicated a loss in the lipid cooperativity of lo phase at equilibrium conditions, while at similar conditions spontaneous formation of unilamellar vesicles from SAXS experiments showed that deprotonated artepillin C preferentially located at the surface of the membrane. Time-resolved experiments using fluorescence microscopy showed that at doses above 100 µM, artepillin C in its neutral state interacted with both liquid-ordered and liquid-disordered phases, inducing curvature stress and promoting dehydration at the membrane interface.

Early onset intellectual disability in chromosome 22q11.2 deletion syndrome / Inicio temprano de discapacidad intelectual en el Síndrome de deleción del cromosoma 22q11.2

Chromosome 22q11.2 deletion syndrome, or DiGeorge syndrome, or velocardiofacial syndrome, is one of the most common multiple anomaly syndromes in humans. This syndrome is commonly caused by a microdelection from chromosome 22 at band q11.2. Although this genetic disorder may reflect several clinical abnormalities and different degrees of organ commitment, the clinical features that have driven the greatest amount of attention are behavioral and developmental features, because individuals with 22q11.2 deletion syndrome have a 30-fold risk of developing schizophrenia. There are differing opinions about the cognitive development, and commonly a cognitive decline rather than an early onset intellectual disability has been observed. We report a case of 22q11.2 deletion syndrome with both early assessment of mild intellectual disabilities and tetralogy of Fallot as the only physic manifestation.

El síndrome del cromosoma 22q11.2, también conocido como supresión o síndrome de DiGeorge o síndrome velocardiofacial, es uno de los síndromes más comunes de anomalías múltiples en los seres humanos. Este síndrome es comúnmente causado por una microdeleción del cromosoma 22 en q11.2 banda. Aunque este trastorno genético muestra varias anomalías clínicas y diferentes grados de compromiso orgánico, las características clínicas que han atraído la mayor atención son el comportamiento y el desarrollo, porque las personas con síndrome de deleción 22q11.2 tienen un riesgo 30 veces mayor de desarrollar esquizofrenia. Hay diferentes opiniones sobre el desarrollo cognitivo, y comúnmente se se ha observado un deterioro cognitivo en lugar de un inicio temprano de discapacidad intelectual. Presentamos un caso de síndrome de deleción 22q11.2 tanto con la evaluación temprana de discapacidades intelectuales leves como con la tetralogía de Fallot como única manifestación física.

Intravenous lidocaine for postmastectomy pain treatment: randomized, blind, placebo controlled clinical trial / Lidocaína intravenosa no tratamento da dor pós-mastectomia: ensaio clínico aleatório encoberto placebo controlado / Lidocaína intravenosa en el tratamiento del dolor posmastectomía: ensayo clínico aleatorizado, encubierto, placebo controlado

BACKGROUND AND OBJECTIVE: Postoperative pain treatment in mastectomy remains a major challenge despite the multimodal approach. The aim of this study was to investigate the analgesic effect of intravenous lidocaine in patients undergoing mastectomy, as well as the postoperative consumption of opioids. METHODS: After approval by the Human Research Ethics Committee of the Instituto de Medicina Integral Prof. Fernando Figueira in Recife, Pernambuco, a randomized, blind, controlled trial was conducted with intravenous lidocaine at a dose of 3 mg/kg infused over 1 h in 45 women undergoing mastectomy under general anesthesia. One patient from placebo group was. RESULTS: Groups were similar in age, body mass index, type of surgery, and postoperative need for opioids. Two of 22 patients in lidocaine group and three of 22 patients in placebo group requested opioid (p = 0.50). Pain on awakening was identified in 4/22 of lidocaine group and 5/22 of placebo group (p = 0.50); in the post-anesthetic recovery room in 14/22 and 12/22 (p = 0.37) of lidocaine and placebo groups, respectively. Pain evaluation 24 h after surgery showed that 2/22 and 3/22 patients (p = 0.50) of lidocaine and placebo groups, respectively, complained of pain. CONCLUSION: Intravenous lidocaine at a dose of 3 mg/kg administered over a period of an hour during mastectomy did not promote additional analgesia compared to placebo in the first 24 h, and has not decreased opioid consumption. However, a beneficial effect of intravenous lidocaine in selected and/or other therapeutic regimens patients cannot be ruled out. .

JUSTIFICATIVA E OBJETIVO: O tratamento da dor pós-operatória em mastectomia continua sendo um grande desafio apesar da abordagem multimodal. O objetivo deste estudo foi investigar o efeito analgésico da lidocaína intravenosa em pacientes submetidas a mastectomia, como também, o consumo de opioide pós-operatório. MÉTODOS: Após aprovação pelo comitê de ética e pesquisa em seres humanos do Instituto de Medicina Integral Prof. Fernando Figueira em Recife - Pernambuco foi realizado ensaio clínico aleatório encoberto placebo controlado com lidocaína intravenosa na dose de 3 mg/kg infundida em uma hora, em 45 mulheres submetidas a mastectomia sob anestesia geral. Excluída uma paciente do grupo placebo. RESULTADOS: Os grupos foram semelhantes quanto à idade, índice de massa corpórea, tipo de intervenção cirúrgica e necessidade de opioide no pós-operatório. Solicitaram opioide 2/22 pacientes nos grupos da lidocaína e 3/22 placebo (p = 0,50). Identificada a dor ao despertar em 4/22 no grupo lidocaína e 5/22 (p = 0,50) no grupo placebo; na sala de recuperação pós-anestésica em 14/22 e 12/22 (p = 0,37) nos grupos lidocaína e placebo respectivamente. Ao avaliar a dor 24 horas após o procedimento cirúrgico 3/22 e 2/22 (p = 0,50) das pacientes relataram dor em ambos os grupos respectivamente. CONCLUSÃO: A lidocaína intravenosa na dose de 3mg/kg administrada em um período de uma hora no transoperatório de mastectomia não promoveu analgesia adicional em relação ao grupo placebo nas primeiras 24 horas e não diminuiu o consumo de opioide. Contudo, um efeito benéfico da lidocaína intravenosa em pacientes selecionadas e/ou em outros regimes terapêuticos não pode ser descartado. .

JUSTIFICACIÓN Y OBJETIVO: El tratamiento del dolor postoperatorio en la mastectomía continúa siendo un gran reto a pesar del abordaje multimodal. El objetivo de este estudio fue investigar el efecto analgésico de la lidocaína intravenosa en pacientes sometidas a mastectomía, así como el consumo postoperatorio de opiáceos. MÉTODOS: Después de la aprobación por el Comité de Ética e Investigación en seres humanos del Instituto de Medicina Integral Prof. Fernando Figueira, en Recife, Pernambuco, se realizó un ensayo clínico aleatorizado, encubierto, placebo controlado con lidocaína intravenosa en una dosis de 3 mg/kg infundida en una hora, en 45 mujeres sometidas a mastectomía bajo anestesia general. Una paciente del grupo placebo fue excluida. RESULTADOS: Los grupos fueron similares en cuanto a la edad, índice de masa corporal, tipo de intervención quirúrgica y necesidad de opiáceos en el postoperatorio. Solicitaron opiáceos 2/22 pacientes en los grupos de la lidocaína y 3/22 placebo (p = 0,50). Fue identificado el dolor al despertar en 4/22 en el grupo lidocaína y 5/22 (p = 0,50) en el grupo placebo; en la sala de recuperación postanestésica en 14/22 y 12/22 (p = 0,37) en los grupos lidocaína y placebo, respectivamente. Al calcular el dolor 24 h después del procedimiento quirúrgico 3/22 y 2/22 (p = 0,50) de las pacientes relataron dolor en ambos grupos respectivamente. CONCLUSIÓN: La lidocaína intravenosa en una dosis de 3 mg/kg administrada en un período de una hora en el transoperatorio de mastectomía no generó analgesia adicional con relación al grupo placebo en las primeras 24 h y no disminuyó el consumo de opiáceos. Sin embargo, no puede ser descartado un efecto beneficioso de la lidocaína intravenosa en pacientes seleccionadas y/o en otros regímenes terapéuticos. .

Preparation and in vitro embolic efficiency evaluation of hydroxycamptothecine-loaded liquid embolic agent / 药学学报

The purpose of this study is to investigate the preparation of hydroxycamptothecine (HCPT)-loaded cubic crystal liquid embolic precursor solution, and evaluate its in vitro embolic efficiency. Phytantriol was used as cubic crystal liquid embolic material, and the optimal formulation was selected according to ternary phase diagram. Polarized light microscopy, differential scanning calorimetry, and small angle X-ray scattering (SAXS) were used to characterize the cubic crystal structure. High performance liquid chromatography and X-ray diffraction analysis were used to investigate the lactone ring of HCPT. In vitro dissolution was preliminary evaluated, and the simulation embolic model was constructed to evaluate the embolic efficiency of precursor solution. Meanwhile, the gelation time and adhesion force were investigated. The results showed that HCPT-loaded precursor solution for embolization had been successfully prepared with low viscosity which was injectable. The precursor solution could transform into Pn3m structure liquid crystal phase gel rapidly when contracting with excess water. The formed HPCT gel remained its lactone form as the same in precursor solution, and expressed the good ability to block the saline flow, and HCPT could keep sustained releasing drug over 30 days. The prepared drug-loaded embolic precursor solution showed a promising potential for vascular embolization and application in clinical treatment of tumor.

Mechanism of the Rpn13-induced activation of Uch37

Uch37 is a de-ubiquitinating enzyme that is activated by Rpn13 and involved in the proteasomal degradation of proteins. The full-length Uch37 was shown to exhibit low iso-peptidase activity and is thought to be auto-inhibited. Structural comparisons revealed that within a homo-dimer of Uch37, each of the catalytic domains was blocking the other's ubiquitin (Ub)-binding site. This blockage likely prevented Ub from entering the active site of Uch37 and might form the basis of auto-inhibition. To understand the mode of auto-inhibition clearly and shed light on the activation mechanism of Uch37 by Rpn13, we investigated the Uch37-Rpn13 complex using a combination of mutagenesis, biochemical, NMR, and small-angle X-ray scattering (SAXS) techniques. Our results also proved that Uch37 oligomerized in solution and had very low activity against the fluorogenic substrate ubiquitin-7-amino-4-methylcoumarin (Ub-AMC) of de-ubiquitinating enzymes. Uch37Δ(Hb,Hc,KEKE), a truncation removal of the C-terminal extension region (residues 256-329) converted oligomeric Uch37 into a monomeric form that exhibited iso-peptidase activity comparable to that of a truncation-containing the Uch37 catalytic domain only. We also demonstrated that Rpn13C (Rpn13 residues 270-407) could disrupt the oligomerization of Uch37 by sequestering Uch37 and forming a Uch37-Rpn13 complex. Uch37 was activated in such a complex, exhibiting 12-fold-higher activity than Uch37 alone. Time-resolved SAXS (TR-SAXS) and FRET experiments supported the proposed mode of auto-inhibition and the activation mechanism of Uch37 by Rpn13. Rpn13 activated Uch37 by forming a 1:1 stoichiometric complex in which the active site of Uch37 was accessible to Ub.

Evaluation de la mobilite active des doigts par la cotation de la distance pulpo-palmaire exprimee en travers de doigts

L'evaluation de la mobilite des doigts est realisee classiquement par des methodes exigeant l'utilisation des instruments comme goniometre; latte graduee et autres. La disponibilite de ces instruments dans les structures medicales non specialisees et la competence des medecins praticiens generalistes a les utiliser correctement ne sont pas evidentes.Le but de la presente etude est de proposer une methode qui utilise les seuls doigts du patient comme outil de mesure; sans aucune intervention instrumentale.Quatre cents sujets de la population de Mbujimayi en R.D. Congo (196 de sexe masculin et 204 de sexe feminin) ont ete examines dans cette etude qui a consiste a mesurer la largeur des doigts et les angles des articulations des doigts a differents degres de flexion.Une echelle simple et pratique est proposee a l'issue de l'etude pour coter les differents degres de flexion des doigts

Methods for grain size analysis of nanomedicines / 药学学报

As nanomedicines are developing fast in both academic and market areas, building up suitable methods for nanomedicine analysis with proper techniques is an important subject, requiring further research. The techniques, which could be employed for grain size analysis of nanomedicines, were reviewed. Several key techniques were discussed with their principles, scope of applications, advantages and defects. Their applications to nanomedine analysis were discussed according to the properties of different nanomedicines, with the purpose of providing some suggestions for the control and administration of nanomedicines.

Preparation, characterization and content determination of cubic phase gel containing capsaicin / 中国中药杂志

<p><b>OBJECTIVE</b>To prepare the cubic phase gel containing capsaicin and characterize its properties.</p><p><b>METHOD</b>The cubic phases gel composed of glycerol monoolein, capsaicin and water was made by self-emulsion technology. The characterization of cubic phase gel was carried out by cross-polarizing light microscopy (CPLM) and Small Angle X-Ray Scattering (SAXS). The capsaicin content was determined by HPLC analysis.</p><p><b>RESULT</b>Under CPLM, cubic phase gel showed dark background. SAXS scattering spectra showed the scattering peaks at 0.1096, 0.1334, 0.1557, 0.1883 A(-1) which was compatible with q1:q2:q3:q4 = mean square root of 2: mean square root of 3: mean square root of 4: mean square root of 6. It was well known that the scattering vector ratio was the characteristic of cubic phase and the internal structure was confirmed to be Pn3m (Q224). The linear range for capsaicin determination was 3.25 x 10(-4) - 2.08 x 10(-2) g x L(-1) (R2 = 1). The average recovery was 97.53% with RSD of 2.9% (n=9).</p><p><b>CONCLUSION</b>CPLM and SAXS technology are suitable to characterize the cubic phase gel The determination of the capsaicin content by HPLC is simple and reproducible.</p>