Evolución clínico funcional de pacientes con fibrosis quística tratados con lumacaftor/ivacaftor en un centro pediátrico. Serie de casos / Clinical and functional course of patients with cystic fibrosis treated with lumacaftor/ivacaftor at a children's hospital. A case series

Los moduladores de la proteína reguladora transmembrana de fibrosis quística (CFTR) tratan el defecto de esta proteína. El objetivo es describir la evolución de niños con fibrosis quística tratados con lumacaftor/ivacaftor. Se trata de una serie de 13 pacientes de 6 a 18 años con ≥ 6 meses de tratamiento. Se analizaron el volumen espiratorio forzado en el primer segundo (VEF1), puntaje Z del índice de masa corporal (IMC), antibioticoterapia/año, antes del tratamiento y durante 24 meses posteriores. A los 12 meses (9/13) y 24 meses (5/13), la mediana de cambio del porcentaje del predicho VEF1 (ppVEF1) fue de 0,5 pp [-2-12] y 15 pp [8,7-15,2], y del puntaje Z de IMC de 0,32 puntos [-0,2-0,5] y 1,23 puntos [0,3-1,6]. El primer año (11/13) la mediana de días de uso de antibiótico disminuyó de 57 a 28 (oral) y de 27 a 0 (intravenoso). Dos niños evidenciaron eventos adversos asociados.

Cystic fibrosis transmembrane regulator (CFTR) modulators treat defective CFTR protein. Our objective is to describe the course of children with cystic fibrosis treated with lumacaftor/ivacaftor. This is a case series of 13 patients aged 6 to 18 years with ≥ 6 months of treatment. Forced expiratory volume in the first second (FEV1), body mass index (BMI) Z-score, antibiotic therapy/year, before treatment and for 24 months after treatment were analyzed. At 12 months (9/13) and 24 months (5/13), the median change in the percent predicted FEV1 (ppFEV1) was 0.5 pp (-2­12) and 15 pp (8.7­15.2) and the BMI Z-score was 0.32 points (-0.2­0.5) and 1.23 points (0.3­1.6). In the first year, in 11/13 patients, the median number of days of antibiotic use decreased from 57 to 28 (oral) and from 27 to 0 (intravenous). Two children had associated adverse events.

Actualización en fibrosis quística: uso de exacaftor/tezacaftor/ivacaftor/en pacientes con fibrosis quística port-trasplante pulmonar / Use of exacaftor/tezacaftor/ivacaftor in cystic patients post lung transplantation

El uso de moduladores de CFTR en pacientes con fibrosis quística post trasplante pulmonar es un tema todavía controversial. Varias publicaciones reportan los beneficios del modulador elexacaftor/tezacaftor/ivacaftor en los síntomas extrapulmonares de la fibrosis quística, especialmente enfermedad sinusal, síntomas gastrointestinales y diabetes. Un número alto de pacientes debe discontinuar el tratamiento por mala tolerancia, sin embargo, no se describen interacciones de importancia con el tratamiento inmunosupresor. Se debe considerar para su uso los riesgos versus beneficios en forma individual en cada paciente.

The use of CFTR modulators in patients with cystic fibrosis after lung transplantation is still a controversial issue. Several publications report the benefits of the use of the modulator elexacaftor/tezacaftor/ivacaftor on extrapulmonary symptoms of cystic fibrosis, especially sinus disease, gastrointestinal symptoms and diabetes. A high number of patients must discontinue treatment due to poor tolerance; however, no significant interactions with immunosuppressive treatment have been described. The individual risk-benefit of each patient should be considered for its use.

Simultaneous determination of paracetamol, dextromethorphan, chlorpheniramine, pseudoephedrine and major impurities of paracetamol and pseudoephedrine by using capillary electrophoresis

Abstract A capillary electrophoresis method was developed for the first time and optimized for the determination of paracetamol, pseudoephedrine, dextromethorphan, chlorpheniramine, 4-aminophenol and ephedrine in tablet formulation. Optimum electrophoretic conditions were achieved by using a background electrolyte of 75 mmol L-1 sodium borate buffer at pH 8.0, a capillary temperature of 30°C, a separation voltage of 30 kV and a pressure injection of the sample at 50 mbar for 10 s. Calibration graphs showed a good linearity with a coefficient of determination (R2) of at least 0.999 for all compounds. Intraday and interday precision (expressed as relative standard deviation (RSD) %) were lower than 1.39% for capillary electrophoresis method. The developed method was demonstrated to be simple and rapid for the determination of paracetamol, pseudoephedrine, dextromethorphan, chlorpheniramine, 4-aminophenol and ephedrine in tablet formulation providing recoveries in the range between 99.62 and 100.57% for all analytes.

Electrochemical DNA Biosensor for Mycobacterium leprae Identification

Abstract Nowadays, a prompt and reliable diagnosis is one of the most critical measures for leprosy control. The current diagnostic is based on clinical exams by a health care professional, and it may not recognize early signs of the disease. Therefore, other leprosy diagnosis methods are needed that are sensitive, disease-specific, and easy to deliver to the end-user. This study describes the construction of an electrochemical DNA biosensor to detect PCR products of Mycobacterium leprae using methylene blue as an indicator of the hybridization. The capture probe was immobilized on the graphite electrode modified with poly(4-aminophenol). The electrode surface was morphologically characterized by atomic force microscopy. Linear voltammetry was used to monitor the concentration of methylene blue on the DNA biosensor, which indicated a limit detection of 1 x 10-10 mol/L. The biosensor showed selective when placed to hybridize with a non-complementary sequence. This study suggests that the electrochemical DNA biosensor developed is promising for detecting DNA of Mycobacterium leprae.

Moduladores mejoran la función pulmonar en la mutación más frecuente de la fibrosis quística / Proteine modulators improve pulmonary function in the most common cystic fibrosis mutation

Un tópico de análisis crítico es un resumen estandarizado que se organiza en torno a una pregunta clínica estructurada, realiza una revisión crítica y resalta la relevancia de sus resultados aplicados a nuestra realidad. El estudio analizado evalúa en 1100 pacientes de 12 años o más portadores de fibrosis quística (FQ) homocigotos para la mutación más frecuente phe508del CFTR, la terapia combinada de dos moduladores de la proteína CFTR, comparado con placebo, la que mostró mejoría significativa de la función pulmonar (VEF1) de 2.6 a 4 puntos porcentuales 1. Estos resultados proponen un tratamiento curativo al 50 por ciento de los pacientes en USA y al 15 por ciento en nuestro país, una vez superado los costos.

A CAT is a standardized summary of research evidence organized around a clinical question, aimed to provide a critique of the research and a statement of the clinical relevance of results. In the analyzed paper, the authors evaluated 1100 patients with cystic fibrosis (CF) 12 years and older with two copies of phe508del CFTR genetic mutation, the combination therapy of two CFTR modulators led to mean absolute improvements in lung function (VEF1) between 2.6 and 4 percentage points, which was statistically significant. These results are promising for the 50 percent of the USA CF population and 15 percent of the CF Chilean population.

Moduladores mejoran la función pulmonar en la mutación más frecuente de la fibrosis quística / Proteine modulators improve pulmonary finction in the most common cystic fibrosis mutation

Un tópico de análisis crítico es un resumen estandarizado que se organiza en torno a una pregunta clínica estructurada, realiza una revisión crítica y resalta la relevancia de sus resultados aplicados a nuestra realidad. El estudio analizado evalúa en 1100 pacientes de 12 años o más portadores de fibrosis quística (FQ) homocigotos para la mutación más frecuente phe508del CFTR, la terapia combinada de dos moduladores de la proteína CFTR, comparado con placebo, la que mostró mejoría significativa de la función pulmonar (VEF1) de 2.6 a 4 puntos porcentuales1. Estos resultados proponen un tratamiento curativo al 50% de los pacientes en USA y el 15% en nuestro país, una vez superado los costos. (AU)

A CAT is a standardized summary of research evidence organized around a clinical question, aimed to provide a critique of the research and a statement of the clinical relevance of results. In the analyzed paper, the authors evaluated 1100 patients with cystic fibrosis (CF) 12 years and older with two copies of phe508del CFTR genetic mutation, the combination therapy of two CFTR modulators led to mean absolute improvements in lung function (VEF1) between 2.6 and 4 percentage points, which was statistically significant. These results are promising for the 50% of the USA CF population and 15% of the CF Chilean population. (AU)

Determination of serum acetaminophen based on the diazo reaction and its application in the evaluation of gastric emptying / 药学学报

This study aims to establish a method to determine the serum acetaminophen concentration based on diazo reaction, and apply it in the gastric emptying evaluation. Theoretically, acetaminophen could take hydrolysis reaction in hydrochloric acid solution to produce p-aminophenol, which could then take diazo reaction resulting in a product with special absorption peak at 312 nm. Then the serum acetaminophen concentration and recovery rate were calculated according to the standard curve drawn with absorbance at 312 nm. ICR mice were given a dose of acetaminophen (500 mg x kg(-1)) by gavage and the serum acetaminophen was dynamically measured through the diazo reaction. Besides, ICR mice were subcutaneously injected with the long-acting GLP-1 analog GW002 before the gavage of acetaminophen, and serum acetaminophen concentration was measured as above to study how GW002 could influence the gastric emptying. The data showed acetaminophen ranging from 0 to 160 μg x mL(-1) could take diazo reaction with excellent linear relationship, and the regression equation was y = 0.0181 x +0.0104, R2 = 0.9997. The serum acetaminophen was also measured with good linear relationship (y = 0.0045 x + 0.0462, R = 0.9982) and the recovery rate was 97.4%-116.7%. The serum concentration of acetaminophen reached peak at about 0.5 h after gavage, and then gradually decreased. GW002 could significantly lower the serum acetaminophen concentration and make the area under the concentration-time curve (AUC) decrease by 28.4%. In conclusion, a method for the determination of serum acetaminophen based on the diazo reaction was established with good accuracy and could be used in the evaluation of gastric emptying.

Glycogen Synthase Kinase 3 Inactivation Induces Cell Senescence through Sterol Regulatory Element Binding Protein 1-Mediated Lipogenesis in Chang Cells

BACKGROUND: Enhanced lipogenesis plays a critical role in cell senescence via induction of expression of the mature form of sterol regulatory element binding protein 1 (SREBP1), which contributes to an increase in organellar mass, one of the indicators of senescence. We investigated the molecular mechanisms by which signaling molecules control SREBP1-mediated lipogenesis and senescence. METHODS: We developed cellular models for stress-induced senescence, by exposing Chang cells, which are immortalized human liver cells, to subcytotoxic concentrations (200 microM) of deferoxamine (DFO) and H2O2. RESULTS: In this model of stress-induced cell senescence using DFO and H2O2, the phosphorylation profile of glycogen synthase kinase 3alpha (GSK3alpha) and beta corresponded closely to the expression profile of the mature form of SREBP-1 protein. Inhibition of GSK3 with a subcytotoxic concentration of the selective GSK3 inhibitor SB415286 significantly increased mature SREBP1 expression, as well as lipogenesis and organellar mass. In addition, GSK3 inhibition was sufficient to induce senescence in Chang cells. Suppression of GSK3 expression with siRNAs specific to GSK3alpha and beta also increased mature SREBP1 expression and induced senescence. Finally, blocking lipogenesis with fatty acid synthase inhibitors (cerulenin and C75) and siRNA-mediated silencing of SREBP1 and ATP citrate lyase (ACL) significantly attenuated GSK3 inhibition-induced senescence. CONCLUSION: GSK3 inactivation is an important upstream event that induces SREBP1-mediated lipogenesis and consequent cell senescence.

Glycogen Synthase Kinase 3 Inactivation Induces Cell Senescence through Sterol Regulatory Element Binding Protein 1-Mediated Lipogenesis in Chang Cells

BACKGROUND: Enhanced lipogenesis plays a critical role in cell senescence via induction of expression of the mature form of sterol regulatory element binding protein 1 (SREBP1), which contributes to an increase in organellar mass, one of the indicators of senescence. We investigated the molecular mechanisms by which signaling molecules control SREBP1-mediated lipogenesis and senescence. METHODS: We developed cellular models for stress-induced senescence, by exposing Chang cells, which are immortalized human liver cells, to subcytotoxic concentrations (200 microM) of deferoxamine (DFO) and H2O2. RESULTS: In this model of stress-induced cell senescence using DFO and H2O2, the phosphorylation profile of glycogen synthase kinase 3alpha (GSK3alpha) and beta corresponded closely to the expression profile of the mature form of SREBP-1 protein. Inhibition of GSK3 with a subcytotoxic concentration of the selective GSK3 inhibitor SB415286 significantly increased mature SREBP1 expression, as well as lipogenesis and organellar mass. In addition, GSK3 inhibition was sufficient to induce senescence in Chang cells. Suppression of GSK3 expression with siRNAs specific to GSK3alpha and beta also increased mature SREBP1 expression and induced senescence. Finally, blocking lipogenesis with fatty acid synthase inhibitors (cerulenin and C75) and siRNA-mediated silencing of SREBP1 and ATP citrate lyase (ACL) significantly attenuated GSK3 inhibition-induced senescence. CONCLUSION: GSK3 inactivation is an important upstream event that induces SREBP1-mediated lipogenesis and consequent cell senescence.

Antidotes of cyanide intoxication

Cyanide poisoning can occur from industrial disasters, smoke inhalation from fire, food, and multiple other sources. Cyanide inhibits mitochondrial oxidative phosphorylation by blocking mitochondrial cytochrome oxidase, which in turn results in anaerobic metabolism and depletion of adenosine triphosphate in cells. Rapid administration of antidote is crucial for life saving in severe cyanide poisoning. Multiple antidotes are available for cyanide poisoning. The action mechanism of cyanide antidotes include formation of methemoglobin, production of less or no toxic complex, and sulfane sulfur supplementation. At present, the available antidotes are amyl nitrite, sodium nitrite, sodium thiosulfate, hydroxocobalamin, 4-dimethylaminophenol, and dicobalt edetate. Amyl nitrite, sodium nitrite, and 4-dimethylaminophenol induce the formation of methemoglobin. Sodium thiosulfate supplies the sulfane sulfur molecule to rhodanese, allowing formation of thiocyanate and regeneration of native enzymes. Hydroxocobalamin binds cyanide rapidly and irreversibly to form cyanocobalamin. Dicobalt edetate acts as a chelator of cyanide, forming a stable complex. Based on the best evidence available, a treatment regimen of 100% oxygen and hydroxocobalamin, with or without sodium thiosulfate, is recommended for cyanide poisoning. Amyl nitrite and sodium nitrite, which induce methemoglobin, should be avoided in victims of smoke inhalation because of serious adverse effects.

Progress in the study of allergic disease drugs targeting on IgE/FcepsilonRI signaling pathway / 药学学报

Allergic diseases have become global social health problems. The binding of IgE with its high affinity receptor FcepsilonRI plays a key step in I-type allergy. Recently, more and more key molecules on the IgE/FcepsilonRI signaling transduction pathway were to be the drug candidates against allergic diseases, with in-depth study of FcepsilonRI signal pathway gradually. The main drugs include molecule antibodies, peptides, vaccines, fusion proteins, small molecules, and other drugs related to IgE/FcepsilonRI. The recent progress in the study of mechanisms of representative drugs targeting on IgE/FcepsilonRI signaling pathway was reviewed in this article.

Biodegradation of aromatic amine compounds using moving bed biofilm reactors

Three moving bed biofilm reactors were used to treat synthesized wastewater of aromatic amine compounds including aniline, para-diaminobenzene and para-aminophenol that are found in many industrial wastewaters. The reactors with cylindrical shape had an internal diameter and an effective depth of 10 and 60 cm, respectively. The reactors were filled with light expanded clay aggregate as carriers and operated in an aerobic batch and continuous conditions. Evaluation of the reactors' efficiency was done at different retention time of 8, 24, 48 and 72 h with an influent COD from 100 to 3500 mg/L [filling ratio of 50%]. The maximum obtained removal efficiencies were 90% [influent COD=2000 mg/L], 87% [influent COD=1000 mg/L] and 75% [influent COD=750 mg/L] for aniline, para-diaminobenzene and para-aminophenol, respectively. In the study of decrease in filling ratio from 50 to 30 percent, 6% decrease for both para-diaminobenzene and para-aminophenol and 7% increase for aniline degradation were obtained. The removal efficiency was decreased to about 10% after 15 days of continuous loading for each of the above three substrates. In the shock loading test, initially the COD removal rate was decreased in all reactors, but after about 10 days, it has been approached to the previous values. Finally, biodegradability of aromatic amines has been proved by nuclear magnetic resonance system

Spectrophotometric determination of phenylephrine using P-aminophenol and potassium periodate

A fast and sensitive method has been developed for the determination of Phenylephrine hydrochloride [PE] in pharmaceutical preparations. The method is based on the reaction between PE and p-aminophenol [PAP] in presence of KIO[4] at pH 10. The absorbance of solution is measured at [lambda [max]] 640 nm. Beer's law is obeyed over the concentration range from 15 to 100 micro g ml[-1], and the extinction coefficient was calculated to be 1.01 x 10[3] 1 mol[-1] cm[-1]. The different analytical parameters have been investigated. The method has been successfully applied to determine PE in some pharmaceutical preparations

Microdetermination of aminophenols and cresols via their reactions with bromine

The oxidation of aminophenols [APs] and cresols [CRs] with bromine in aqueous solution was investigated and used for microdetermination of these reductants under selected optimum conditions of pH, temperature, catalyst, time of contact of reactants and concentration ratios. The potentiometric-argentimetric titration of the librated bromide using silver amalgam electrode was found to be independent of the bromine concentration. Possible schemes, for the course of these reactions were simply suggested. The reactions were quantitative at concentration ranges of APs, 9.80 to 22.24 mg, percent recovery 98 to 103 percent and SD = 0.11 to 0.023 at [Br[2]]/[APs] ratio 2 to 4 and CRs in the concentration range 3.24 to 25.95 mg, percent recovery = 96.6 to 104.8 percent and SD = 0.19 to 0.03 at Br[2]]/[APs] ratio 2 to 6. The reaction between Br[2] and APs was fast in the order p-AP > o-AP > m-AP and with CRs it was in the order O-CR > m-CR > P-CR under the selected optimum conditions

Reaction kinetics of bromine and aminophenols

The kinetics of reactions of bromine and aminophenols has been studied at different temperatures. The overall order of the reactions determined from the half-life times was found to be 2.1, 2.12 and 2.4 for, 0-, m- and p-aminophenol, respectively. The thermodynamic parameters of activations were calculated and discussed. The final products of the reactions were investigated by elemental analysis, IR and mass spectra. Proposed schemes for these reactions were presented

Antipyretic activity of diacetyl para-amino phenol.

Diacetyl para-amino phenol (DAPAP) was generated by interaction between aspirin and paracetamol in a mechanical shaker. It revealed antipyretic activity in albino rats. The antipyretic action was found to be having the same onset of action and duration as that of aspirin. This compound lacked ulcerogenic and analgesic activity. DAPAP therefore may have safety as an antipyretic drug in patients with history of peptic ulcer.

Paracetamol: estudo cromatográfico (CCD) de soluçöes semi-aquosas e demonstraçäo da interferência do P-Aminofenol sobre as análises quantitativas realizadas por espectrofotometria U.V / Paracetamol: chromatographic (TLC) studies of the semi-aqueous solutions and p-aminophenol interfering on spectrophotometric quantitative analysis

Soluçöes de paracetamol 100mg/ml, constituídas por misturas binárias água/polietilenoglicol 400 e água/álcool etílico absoluto, submetidas e näo submetidas a tratamento térmico, foram analisadas através de cromatografia em camada delgada. Tais estudos, acrescidos de varredura do espectro de absorçäo U.V., confirmaram a interferência exercida pelo p-aminofenol sobre as análises quantitativas, realizadas através de espectrofotometria U.V. a 244nm

Manejo de afecciones musculoesqueleticas en pacientes deportistas, con una nueva asociacion (naproxen + carisoprodol). Estudio abierto comparativo. / Management of muskleskeletal lesions in sportive patients, with a new association (naproxen + carisoprodol). Open comparative study

En esta comunicacion se reportan los resultados de la experiencia con 25 pacientes deportistas, los cuales fueron separados al azar en dos grupos, bajo un diseno obierto comparativo: I) naproxen + carisoprodol (NC) y II) N-acetil-p aminofenol + metocarbamol (NAPAF).Los pacientes incluidos en el estudio presentaban fases agudas de diversos padecimientos del aparato musculoesqueletico. El tratamiento asignado a cada paciente se administro cada 6 horas durante tres dias, con evaluaciones periodicas de las mediciones usuales en este tipo de estudio. La asociacion NC demostro poseer mayor eficacia terapeutica en los indices evaluados en este estudio comparativo con la asociacion NAPAF