RÉSUMÉ
A new composite organic oscillating reaction system based on BrO₃-Ce(SO₄)₂-H₂SO₄-malonic acid/tartaric acid was proposed in this paper. On the basis of the influence of the concentration of each component on the stability and characteristic parameters of the blank system, the electrochemical fingerprints of 30 kinds of traditional Chinese medicines (TCM) were obtained. The results showed that the electrochemical fingerprint can be used for the identification of TCMs, the distinguishment of different parts and the appraisal of genuineness, which is fast, sensitive and accurate. At the same time, we explored and verified the mechanism of oscillation and the formation mechanism of TCM fingerprint.
Sujet(s)
Médicaments issus de plantes chinoises , Chimie , Techniques électrochimiques , Malonates , Chimie , Médecine traditionnelle chinoise , Composés phytochimiques , Tartrates , ChimieRÉSUMÉ
As a newly-identified protein post-translational modification, malonylation is involved in a variety of biological functions. Recognizing malonylation sites in substrates represents an initial but crucial step in elucidating the molecular mechanisms underlying protein malonylation. In this study, we constructed a deep learning (DL) network classifier based on long short-term memory (LSTM) with word embedding (LSTM) for the prediction of mammalian malonylation sites. LSTM performs better than traditional classifiers developed with common pre-defined feature encodings or a DL classifier based on LSTM with a one-hot vector. The performance of LSTM is sensitive to the size of the training set, but this limitation can be overcome by integration with a traditional machine learning (ML) classifier. Accordingly, an integrated approach called LEMP was developed, which includes LSTM and the random forest classifier with a novel encoding of enhanced amino acid content. LEMP performs not only better than the individual classifiers but also superior to the currently-available malonylation predictors. Additionally, it demonstrates a promising performance with a low false positive rate, which is highly useful in the prediction application. Overall, LEMP is a useful tool for easily identifying malonylation sites with high confidence. LEMP is available at http://www.bioinfogo.org/lemp.
Sujet(s)
Animaux , Séquence d'acides aminés , Génétique , Acides aminés , Apprentissage profond , Prévision , Méthodes , Lysine , Chimie , Apprentissage machine , Malonates , Chimie , Maturation post-traductionnelle des protéines , GénétiqueSujet(s)
Animaux , Mâle , Rats , /génétique , Foie/effets des médicaments et des substances chimiques , Foie/enzymologie , Thiazoles/pharmacologie , Séquence nucléotidique , /biosynthèse , /génétique , /biosynthèse , /génétique , /biosynthèse , /génétique , /biosynthèse , Expression des gènes/effets des médicaments et des substances chimiques , Techniques in vitro , Foie/traumatismes , Malonates/pharmacologie , Microsomes du foie/effets des médicaments et des substances chimiques , Microsomes du foie/enzymologie , Sondes oligonucléotidiques/génétique , ARN messager/génétique , ARN messager/métabolisme , Rat Sprague-DawleyRÉSUMÉ
This study was carried out to verify if composites could be bleached using chlorine dioxide as compared with hydrogen peroxide. 3M ESPE Filtek Z350 Universal Restorative discs were prepared (n=40), with dimensions 5 mm diameter x 2 mm thickness. The discs were divided into 4 groups of 10 discs each. Color assessment was performed by CIEDE2000. The discs were stained with coffee, tea, wine and distilled water (control) solutions for 14 days, 5 hours daily. Color assessment was repeated on stained discs and followed by bleaching of 5 discs from each group using chlorine dioxide and hydrogen peroxide in-office systems. Finally, a last color assessment was performed and compared statistically. DE2000 after bleaching was very close to baseline for both the bleaching agents, although chlorine dioxide showed better results than hydrogen peroxide. After staining, there was a clinically significant discoloration (∆E2000≥3.43) for the tea, coffee and wine groups, and discoloration (∆E2000) was seen more in the wine group as compared to tea and coffee. Overall, the control group (distilled water) had the least color change in the three intervals. After bleaching, the color in all specimens returned close to the baseline. The color differences between bleaching and baseline were less than 3.43 for all groups. The obtained results show that chlorine dioxide is slightly superior to hydrogen peroxide in the bleaching of composites, while maintaining the shade of the composite close to the baseline.
Este estudo foi realizado para verificar se resinas compostas podem ser clareadas com uso do dióxido de cloro, em comparação com peróxido de hidrogênio. Foram preparados discos com resina restauradora Filtek Z350 3M ESPE (n=40), com dimensões 5 mm de diâmetro × 2 mm de espessura. Os discos foram divididos em 4 grupos de 10 discos cada. A avaliação da cor foi realizada por meio do CIEDE2000. Os discos foram manchados com soluções de café, chá, vinho e água destilada (controle) por 5 h diárias durante 14 dias. A avaliação da cor foi repetida nos discos manchados e seguida por clareamento de 5 discos de cada grupo, utilizando dióxido de cloro ou peróxido de hidrogênio pela técnica de consultório. Finalmente, uma última avaliação da cor foi realizada e as técnicas comparadas estatisticamente. DE2000 após o clareamento foi muito próxima ao baseline, para ambos os agentes clareadores, embora o dióxido de cloro tenha mostrado melhores resultados do que o peróxido de hidrogênio. Após o manchamento, houve uma descoloração clinicamente significativa (ΔE2000≥3,43) para os grupos de chá, café e vinho, sendo que o clareamento (ΔE2000) foi melhor obtido com o grupo do vinho, em comparação com chá e café. No geral, o grupo controle (água destilada) teve a menor mudança de cor nos três intervalos. Após o clareamento, a cor em todos os espécimes voltou próxima ao baseline. As diferenças de cor entre o clareamento e o baseline foram inferiores a 3,43 para todos os grupos. Os resultados indicam que o dióxido de cloro é ligeiramente superior ao peróxido de hidrogênio no clareamento de resinas compostas, mantendo a cor próxima à escala do baseline.
Sujet(s)
Humains , Autoanticorps/analyse , Immunoglobuline G/immunologie , L-Lactate dehydrogenase/immunologie , Malonates/effets indésirables , Nicardipine/effets indésirables , Maladie chronique , Défaillance cardiaque/traitement médicamenteux , Défaillance cardiaque/immunologie , Hépatite/traitement médicamenteux , Hépatite/immunologie , L-Lactate dehydrogenase/sang , Malonates/administration et posologie , Nicardipine/administration et posologieRÉSUMÉ
Unilocular bone cysts are the most common entities affecting the maxillofacial region. The mechanism of proliferation and expansion remains unclear. Metalloproteinases (MMPs) are associated to diverse pathological conditions. The aim of the present study was to correlate the radiographic aspect (area) and the presence of MMP-2 and MMP-9 in dentigerous cysts, radicular cysts and keratocystic odontogenic tumors. The radiographic area of each lesion was calculated using the mathematical formula of the ellipse area. All specimens were subjected to immunohistochemical analysis for these enzymes. The average radiographic area was 284.17 mm2, 235.81 mm2 and 381.81 mm2, respectively. Statistical analyses revealed no association between the immunoreactivity of MMPs and radiographic area of the lesions in all pathologies studied, except for MMP-2 and radicular cysts, for which smaller lesions had increased immunostaining for this enzyme. The results demonstrate that quantities of MMP-2 and MMP-9 are especially involved with dentigerous and radicular cysts in expansion, whereas these enzymes seem to be related to the biological behavior of keratocystic odontogenic tumors, indicating invasion and cell proliferation. Moreover, there is an inverse association between MMP-2 and MMP-9 in keratocystic odontogenic tumors (p=0.03; rs=-0.660), indicating activity in different regions.
Cistos ósseos uniloculares são as entidades mais comuns que afetam a região maxilofacial. O mecanismo de proliferação e expansão permanece obscuro. As metaloproteinases (MMPs) estão associadas a diversas condições patológicas. O objetivo do presente estudo foi correlacionar o aspecto radiográfico (área) e a presença de MMP-2 e MMP-9 em cistos dentígeros, cistos radiculares e tumores odontogênicos queratocísticos. A área radiográfica de cada lesão foi calculada usando a fórmula matemática da área de elipse. Todas as amostras foram submetidas à análise imunoistoquímica para estas enzimas. A área radiográfica média foi de 284,17 mm2, 235,81 mm2 e 381,81 mm2, respectivamente. As análises estatísticas não mostraram associação entre a imunorreatividade de MMPs e área radiográfica das lesões em todas as patologias estudadas, exceto para MMP-2 e cistos radiculares, nas quais as lesões menores tinham maior imunomarcação para esta enzima. Os resultados demonstraram que a quantidade de imunomarcação da MMP-2 e MMP-9 estão envolvidos com cistos dentígeros e radiculares na expansão óssea, ao passo que estas enzimas parecem estar relacionados com o comportamento biológico dos tumores odontogénicos queratocísticos, indicando invasão e proliferação celular. Além disso, há uma relação inversa entre a MMP-2 e MMP-9 em tumores odontogénicos queratocísticos (p=0,03; rs= -0,660), indicando atividade em diferentes regiões.
Sujet(s)
Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Maladies alcooliques du foie/traitement médicamenteux , Malonates/usage thérapeutique , Maladies alcooliques du foie/métabolisme , Fragments peptidiques/sang , Procollagen-Proline Dioxygenase/sang , Procollagène/sang , Protéines/métabolismeRÉSUMÉ
Após algumas décadas de batalha, a geriatria e a gerontologia se tornaram as legítimas ciências do envelhecimento. Hoje surge uma contestação a tal condição. Em sua breve história, a medicina antienvelhecimento se afirmou como prática médica que questiona o modo de se endereçar o envelhecimento biológico. Com isso, toda a medicina é questionada. Aqui, exploramos especialmente como essa controvérsia se estrutura em torno dos fundamentos das ciências do envelhecimento. Há bases para esses questionamentos? Como eles foram tratados por aqueles que os receberam? Tendo em vista uma perspectiva sociotécnica, é interessante pensar que, para geriatras e gerontólogos, a necessária crítica à medicina antienvelhecimento também traz uma importante reflexão sobre o modo como as ciências do envelhecimento vêm tratando seu objeto.
After some decades of struggle, geriatrics and gerontology have become the legitimate sciences of aging. Today, their status is being questioned. In its short history, anti-aging medicine has taken root as a medical practice that questions how to address biological aging. In so doing, all medicine is questioned. Here, we explore in particular how this controversy is structured around the founding principles of the sciences of aging. Is there any basis for these questionings? How have they been treated by those who have received them? Taking a socio-technical viewpoint, it is worth considering that for geriatricians and gerontologists, the need to criticize anti-aging medicine also raises some important reflections about how the sciences of aging address their subject.
Sujet(s)
Animaux , Mâle , Rats , Antiulcéreux/pharmacologie , Malonates/pharmacologie , Ulcère gastrique/prévention et contrôle , Anti-inflammatoires non stéroïdiens , Éthanol , Muqueuse gastrique/anatomopathologie , Indométacine , Prostaglandines/métabolisme , Rat Wistar , Ulcère gastrique/induit chimiquement , Ulcère gastrique/anatomopathologie , Sucralfate/pharmacologieRÉSUMÉ
Estudo descritivo cujos objetivos foram elaborar títulos diagnósticos de enfermagem segundo a CIPE®, realizar mapeamento cruzado entre as formulações diagnósticas e os títulos diagnósticos da NANDA-I, identificar dentre os títulos diagnósticos formulados os constantes e não constantes na NANDA-I e realizar mapeamento dos títulos formulados com as Necessidades Humanas Básicas. Utilizou-se técnica de oficina, com 32 enfermeiros de unidades de terapia intensiva, de mapeamento cruzado e de validação por concordância com peritos. Na oficina foram elaborados 1.665 títulos diagnósticos submetidos a processo de refinamento que resultou em 120 títulos, submetidos a mapeamento cruzado com títulos diagnósticos da NANDA-I e com as necessidades humanas básicas. Os produtos do mapeamento foram submetidos à validação de conteúdo por dois enfermeiros peritos, obtendo-se índices de concordância de 92% e 100%. Constatou-se que 63 títulos constavam na NANDA-I e 47 não.
This descriptive study aimed at elaborating nursing diagnostic labels according to ICNP®; conducting a cross-mapping between the diagnostic formulations and the diagnostic labels of NANDA-I; identifying the diagnostic labels thus obtained that were also listed in the NANDA-I; and mapping them according to Basic Human Needs. The workshop technique was applied to 32 intensive care nurses, the cross-mapping and validation based on agreement with experts. The workshop produced 1665 diagnostic labels which were further refined into 120 labels. They were then submitted to a cross-mapping process with both NANDA-I diagnostic labels and the Basic Human Needs. The mapping results underwent content validation by two expert nurses leading to concordance rates of 92% and 100%. It was found that 63 labels were listed in NANDA-I and 47 were not.
Estudio descriptivo cuyos objetivos fueron la elaboración de etiquetas de diagnósticos de enfermería según la CIPE®, para llevar a cabo lo mapeo cruzado entre el diagnóstico formulado y las etiquetas de los diagnósticos NANDA-I, para identificar entre los títulos de diagnósticos formulados los que eran constantes y no constantes en NANDA-I y asignarlos a las necesidades humanas básicas. Fueron conducidas técnica de oficina con 32 enfermeros de las unidades de cuidados intensivos, mapeo cruzado y validación de acuerdo con los expertos. Se elaboró 1665 títulos diagnósticos en la oficina sometidos a un proceso de refinamiento. El resultado fue de 120 títulos que se presentaron a un proceso de mapeo con los títulos de diagnósticos de la NANDA-I y con las necesidades humanas básicas. Validación de contenido se realizó con los productos de lo mapeo por dos enfermeras expertas y las tasas de concordancia del 92% y 100% fueron obtenidas. Se encontró que 63 títulos estaban contenidos en la NANDA-I y 47 no lo hicieron.
Sujet(s)
Animaux , Mâle , Rats , Malonates/métabolisme , Microsomes du foie/métabolisme , Toluène/analogues et dérivés , Phénomènes chimiques , Chimie , Relation dose-effet des médicaments , Chromatographie gazeuse-spectrométrie de masse , Glucuronates/métabolisme , Injections veineuses , Microsomes du foie/effets des médicaments et des substances chimiques , Lignées consanguines de rats , Toluène/administration et posologie , Toluène/métabolisme , XénobiotiqueRÉSUMÉ
OBJECTIVE: to investigate the burnout syndrome and its relationship with demographic and academic variables among undergraduate nursing students at a public university in Southern Brazil. METHOD: a quantitative study with 168 students, by applying an adaptation of the Maslach Burnout Inventory - Student Survey, validated for this study. We used descriptive and variance analysis of the data analysis. RESULTS: we found that students do not have the burnout syndrome, manifesting high average scores in Emotional Exhaustion, low in Disbelief and high in Professional Effectiveness; that younger students who perform leisure activities have greater Professional Effectiveness, unlike students in early grades with no extracurricular activities; combining work and studies negatively influenced only the Professional Effectiveness factor, while the intention of giving up influenced negatively Disbelief and Professional Effectiveness factors. CONCLUSION: the situations that lead students to Emotional Exhaustion need to be recognized, considering the specificity of their study environments. .
OBJETIVO: investigar a síndrome de Burnout e sua relação com variáveis sociodemográficas e acadêmicas, entre estudantes de graduação em enfermagem de uma universidade pública do Sul do Brasil. MÉTODO: estudo quantitativo, realizado com 168 estudantes, mediante a aplicação de uma adaptação do Maslach Burnout Inventory - Student Survey, validada para este estudo. Utilizou-se a análise descritiva e de variância para análise dos dados. RESULTADOS: constatou-se que os estudantes não apresentam a síndrome de Burnout, manifestando médias altas em exaustão emocional, baixas em descrença e altas em eficácia profissional; que estudantes mais jovens e que realizam atividades de lazer apresentam maior eficácia profissional, diferentemente de estudantes das séries iniciais e que não realizam atividades extracurriculares; conciliar trabalho e estudos influenciou negativamente apenas o fator eficácia profissional, enquanto a intenção de desistir do curso influenciou negativamente os fatores descrença e eficácia profissional. CONCLUSÃO: faz-se necessário o reconhecimento das situações que levam os estudantes à exaustão emocional, considerando a especificidade de seus ambientes de formação. .
OBJETIVO: investigar la síndrome de burnout y su relación con variables sociodemográficas y académicas, entre estudiantes de pregrado en enfermería de una universidad pública del Sur de Brasil. MÉTODO: estudio cuantitativo, desarrollado con 168 estudiantes, mediante la aplicación de una adaptación del Maslach Burnout Inventory - Student Survey, validada para fines de ese estudio. Fueron utilizados los análisis descriptivo y de variancia para analizar los datos. RESULTADOS: se constató que los estudiantes no presentan la síndrome de burnout, manifestando altos promedios en Agotamiento Emocional, bajos en Descreencia y altos en Eficacia Profesional; que estudiantes más jóvenes y que practican actividades de ocio presentan mayor Eficacia Profesional, diferentemente de estudiantes de los años iniciales sin actividades extracurriculares; conciliar trabajo y estudios influyó negativamente apenas el factor Eficacia Profesional, mientras la intención de desistir del curso influyó negativamente los factores Descreencia y Eficacia Profesional. CONCLUSIÓN: es necesario reconocer las situaciones que llevan a los estudiantes al Agotamiento Emocional, considerando la especificidad de sus ambientes de formación. .
Sujet(s)
Animaux , Mâle , Rats , Chromatographie en phase liquide à haute performance/méthodes , Glucuronates/analyse , Malonates/métabolisme , Microsomes du foie/analyse , Sulfures/analyse , Glucuronates/métabolisme , Glucuronosyltransferase/métabolisme , Microsomes du foie/métabolisme , Lignées consanguines de rats , Thiols/métabolisme , Sulfures/métabolismeRÉSUMÉ
Objective. To estimate the annual cost of the National Cervical Cancer Screening Program (CCSP) of the Mexican Institute of Social Security (IMSS). Materials and methods. This cost analysis examined regional coverage rates reported by IMSS. We estimated the number of cytology, colposcopy, biopsy and pathology evaluations, as well as the diagnostic test and treatment costs for cervical intraepithelial neoplasia grade II and III (CIN 2/3) and cervical cancer. Diagnostic test costs were estimated using a micro-costing technique. Sensitivity analyses were performed. Results. The cost to perform 2.7 million cytology tests was nearly 38 million dollars, which represents 26.1% of the total program cost (145.4 million). False negatives account for nearly 43% of the program costs. Conclusion. The low sensitivity of the cytology test generates high rates of false negatives, which results in high institutional costs from the treatment of undetected cervical cancer cases.
Objetivo. Estimar el costo anual del Programa Nacional de Detección Oportuna de Cáncer Cervical en el Instituto Mexicano del Seguro Social (IMSS). Material y métodos. Este análisis de costos examinó las distintas coberturas por región reportadas por el IMSS. Se estimó el número de citologías, colposcopías, biopsias y evaluaciones de patología y los costos de pruebas de diagnóstico y de tratamientos por neoplasia cervical intraepitelial de grado II y III (NIC 2/3) y cáncer cervical. Los costos de las pruebas de diagnóstico se estimaron utilizando una técnica de microcosteo. Se llevó a cabo un análisis de sensibilidad. Resultados. El costo de realizar 2.7 millones de citologías fue de 38 millones de dólares, lo que representa 26.1% del costo total del programa (145.4 millones). Los falsos negativos corresponden a casi 43% de los costos del programa. Conclusiones. La baja sensibilidad de la citología genera un alto número de falsos negativos que resultan en costos elevados para la institución por el tratamiento de estos casos no detectados.
Sujet(s)
Animaux , Femelle , Rats , Collagène/métabolisme , Fibronectines/métabolisme , Laminine/métabolisme , Cirrhose expérimentale/métabolisme , Malonates/pharmacologie , Spécificité des anticorps , N-Méthyl-N-nitroso-méthanamine , Études d'évaluation comme sujet , Matrice extracellulaire/métabolisme , Techniques immunoenzymatiques , Cirrhose expérimentale/induit chimiquement , Rat Sprague-DawleyRÉSUMÉ
Lysophosphatidic acid (LPA) is an important bioactive phospholipid involved in cell signaling through Gprotein-coupled receptors pathways. It is also involved in balancing the lipid composition inside the cell, and modulates the function of lipid rafts as an intermediate in phospholipid metabolism. Because of its involvement in these important processes, LPA degradation needs to be regulated as precisely as its production. Lysophosphatidic acid phosphatase type 6 (ACP6) is an LPA-specific acid phosphatase that hydrolyzes LPA to monoacylglycerol (MAG) and phosphate. Here, we report three crystal structures of human ACP6 in complex with malonate, L-(+)-tartrate and tris, respectively. Our analyses revealed that ACP6 possesses a highly conserved Rossmann-foldlike body domain as well as a less conserved cap domain. The vast hydrophobic substrate-binding pocket, which is located between those two domains, is suitable for accommodating LPA, and its shape is different from that of other histidine acid phosphatases, a fact that is consistent with the observed difference in substrate preferences. Our analysis of the binding of three molecules in the active site reveals the involvement of six conserved and crucial residues in binding of the LPA phosphate group and its catalysis. The structure also indicates a water-supplying channel for substrate hydrolysis. Our structural data are consistent with the fact that the enzyme is active as a monomer. In combination with additional mutagenesis and enzyme activity studies, our structural data provide important insights into substrate recognition and the mechanism for catalytic activity of ACP6.
Sujet(s)
Humains , Séquence d'acides aminés , Domaine catalytique , Cristallographie aux rayons X , Malonates , Métabolisme , Modèles moléculaires , Données de séquences moléculaires , Nitrophénols , Métabolisme , Composés organiques du phosphore , Métabolisme , Phosphoric monoester hydrolases , Chimie , Classification , Métabolisme , Tartrates , Métabolisme , Eau , MétabolismeRÉSUMÉ
Protein tyrosine phosphatase (PTP) 1B is a potential target for the treatment of diabetes and obesity. Phosphotyrosine (pTyr) is the substrate for PTP1B dephosphorylation. Malonic acid moiety was used herein as a mimic of the phosphate group in pTyr, and novel malonic acid derivatives 1-7 were designed, synthesized and evaluated as PTP1B inhibitors. Results from enzymatic assays indicated that compounds 3 and 4 exhibited potent inhibition against human recombinant PTP1B with IC50 values of 7.66 and 1.88 micromol x L(-1), respectively.
Sujet(s)
Humains , Conception de médicament , Antienzymes , Chimie , Pharmacologie , Concentration inhibitrice 50 , Malonates , Chimie , Pharmacologie , Structure moléculaire , Protein Tyrosine Phosphatase, Non-Receptor Type 1 , Métabolisme , Relation structure-activitéRÉSUMÉ
<p><b>OBJECTIVE</b>To observe abnormal metabolic changes caused by ischemic cerebral apoplexy and the regulating action of Tongsaimai pellets on abnormal metabolism by analyzing the change of small molecules in plasma of ischemic cerebral apoplexy rat. To find the potential biomarkers, and to explore metabolic mechanisms of Tongsaimai pellets.</p><p><b>METHOD</b>Rat models of middle cerebral artery occlusion was established with electric coagulation, and rats were divided into 4 groups, model group, sham-operation group, Tongsaimai pellets group and positive control group. Tongsaimai pellets and positive control group were orally administrated by 13.2 g x kg(-1) x d(-1) of crude drugs and 32 mg x kg(-1) x d(-1) of Nimodipine respectively, m odel and sham-operation group by equal volume of distilled water for a week. Plasma of model and sham-operation group were collected, and plasma of Tongsaimai pellets and positive control group were collected on the 1st, 3rd , 7th day after administration. Endogenous metabolites of four groups were determined with GC-MS. Partial least squares discriminant analysis (PLS-DA) was applied to analyze multivariate data and set up model, and T-test was used in significant statistical analysis.</p><p><b>RESULT</b>Compared with sham-operation group rats, pyruvic acid, taurine and hydroxyproline obviously increased in model group rats, while lactic acid, glyceric acid, aminomalonic acid, fructose, tryptophan and leucine significantly decreased, so these metabolites were potential metabolic biomarkers. These endogenous metabolites except taurine got restoration in Tongsaimai group rats.</p><p><b>CONCLUSION</b>Abnormal metabolite level in plasma can be certainly recovered by Tongsaimai pellets, and the treatment of Tongsaimai pellets can be connected with the regulation of related metabolic pathways.</p>
Sujet(s)
Animaux , Mâle , Rats , Encéphalopathie ischémique , Sang , Traitement médicamenteux , Médicaments issus de plantes chinoises , Utilisations thérapeutiques , Fructose , Sang , Acides glycériques , Sang , Hydroxyproline , Sang , Acide lactique , Sang , Leucine , Sang , Malonates , Sang , Métabolomique , Méthodes , Acide pyruvique , Sang , Rat Sprague-Dawley , Accident vasculaire cérébral , Sang , Traitement médicamenteux , Taurine , Sang , Tryptophane , SangRÉSUMÉ
Short-chain acyl-CoA dehydrogenase deficiency (SCADD; OMIM # 201470) is an autosomal recessive inborn error of mitochondrial fatty acid beta-oxidation, presenting with a variety of clinical signs and symptoms. Developmental delay, hypertonia or hypotonia, ketotic hypoglycemia, and epilepsy are most frequently reported. In general, patients diagnosed through newborn screening have shown normal growth and development in contrast to those diagnosed as a result of clinically initiated evaluations. Here, the case of an asymptomatic Korean newborn with SCADD identified by tandem mass spectrometry is reported. The patient showed an elevated concentration of butyrylcarnitine detected on newborn screening. Urinary excretion of ethylmalonic acid was elevated by urine organic acid analysis. To confirm the diagnosis of SCADD, a direct sequencing analysis of 10 coding exons and the exon-intron boundaries of the ACADS gene were performed. Genetic analysis of ACADS showed the following novel compound heterozygous missense mutations: c.277C>A (p.Leu93Ile) on exon3 and c.682G>A (p.Glu288Lys) on exon6. These results will provide further evidence of mutational heterogeneity for SCADD.
Sujet(s)
Humains , Nouveau-né , Acyl-CoA dehydrogenase , Butyryl-CoA dehydrogenase , Carnitine , Codage clinique , Bases de données génétiques , Épilepsie , Exons , Croissance et développement , Hypoglycémie , Malonates , Dépistage de masse , Hypotonie musculaire , Caractéristiques de la population , Spectrométrie de masse en tandemRÉSUMÉ
<p><b>AIM</b>Malonyl-CoA is regarded as a key signaling molecule in mammalian cells. It is converted to acetyl-CoA, and to a lesser extent, to malonyl acid and malonylcarnitine (C3DC). Availability of carnitine has been reported to be essential for the developing fetus. The objectives of the present study were to analyze associations of malonylcarnitine, acetylcarnitine (C2), and free carnitine (CO) in subjects with orofacial clefts.</p><p><b>METHODOLOGY</b>We performed a retrospective analysis of carnitine concentration obtained from a newborn screening program carried out in our institution. Concentrations of whole blood malonylcarnitine, acetylcarnitine, and free carnitine were measured using tandem mass spectrometry. The study group consisted of 51 children with nonsyndromic cleft lip with or without cleft palate. In total, 106 healthy children without congenital anomalies served as controls. Cut-off points were established using likelihood ratio values.</p><p><b>RESULTS</b>The mean concentration of malonylcarnitine in the cleft group was lower than that of the control group, 0.048 micromol x L(-1) vs. 0.058 micromol x L(-1), respectively (P = 0.009). In patients with orofacial cleft, low malonylcarnitine levels (< or = 0.047 micromol x L(-1)) were 1.7 times more predominant than in healthy individuals (P = -0.03). The mean concentration of acetylcarnitine was also lower in affected newborns in comparison to controls, 33.8 micromol x L(-1) vs. 37.8 micromol x L(-1), respectively (P = 0.026). After analysis of acetylcarnitine and free carnitine concentrations, the likelihood ratio test did not indicate valuable cut-offpoints.</p><p><b>CONCLUSION</b>The study provides initial data indicating a potential association between decreased malonylcarnitine and abnormal palatogenesis.</p>
Sujet(s)
Femelle , Humains , Nouveau-né , Mâle , Acétyl-carnitine , Sang , Carnitine , Sang , Chromatographie en phase liquide , Bec-de-lièvre , Sang , Fente palatine , Sang , Sang , Fonctions de vraisemblance , Malonates , Sang , Malonyl coenzyme A , Sang , Dépistage néonatal , Études rétrospectives , Spectrométrie de masse en tandemRÉSUMÉ
We report a Kuwaiti girl with ethylmalonic encephalopathy. She presented at the age of 4 months with chronic mucoid diarrhea and delayed psychomotor development, and at 6 months she developed myoclonic epilepsy. She was found to have central hypotonia with pyramidal tract signs, acrocyanosis, and petechiae. Plasma lactate level was elevated. Blood spot and urine for organic acids results were consistent with the diagnosis of ethylmalonic encephalopathy. Cerebral MRI showed basal ganglia and white matter changes. Gene mutation study revealed homozygous deletion of exon 4 of the ETHE1 gene. The patient died at 14 months after extensive bronchopneumonia. Our objective is to alert physicians to the existence of such a devastating disease in our community and their role in the early diagnosis in the index patient for proper genetic counseling
Sujet(s)
Humains , Femelle , Malonates , Protéines mitochondriales , Encéphalopathies/étiologie , Imagerie par résonance magnétiqueRÉSUMÉ
A series of N.N-dimethyl-1-aminoethyl-2-amido-alkyl malonate and N, N-bis-carboxymethyl-1-aminoethyl-2-amido alkyl malonate surfactants based on fatly alcohol have been synthesized. The structure of these compounds was confirmed by elemental and spectroscopic analysis. The critical micelle concentration, efficiency, effectiveness, surface tension reduction at the air/water interface, CmC/C20 ratios. standard free energy of micellization, wetting and foam stability of the surfactants were determined. The results suggested that the minimum area/surfactants molecule [Amin] for the investigated compounds decreased with increasing the incorporated anionic group in the molecule of surfactant. It was shown that wetting and foaming characteristics of amphoteric surfactants were significantly better than those observed for anionic ones
Sujet(s)
Malonates/synthèse chimique , Spectrométrie de masse/méthodes , Spectrophotométrie IR/méthodesRÉSUMÉ
PURPOSE: Heptaplatin (Sunpla) is a cisplatin derivative. A phase IIb trial using heptaplatin resulted in a 34% response rate with mild nephrotoxicity. We conducted a randomized phase III trial of heptaplatin plus 5-FU compared with cisplatin plus 5-FU in patients with advanced gastric cancer. MATERIALS AND METHODS: One hundred seventy-four patients (heptaplatin, n=88; cisplatin, n=86) from 13 centers were enrolled. The eligibility criteria were as follows: patients with pathologically-proven adenocarcinoma, chemonaive patients, or patients who had received only single adjuvant chemotherapy, and who had a measurable or evaluable lesion. On day 1, heptaplatin (400 mg/m2) or cisplatin (60 mg/m2) was given over 1 hour with 5-FU (1 gm/m2) on days 1~5 every 4 weeks. RESULTS: At the time of survival analysis, the median overall survival was 7.3 months in the 5-FU + heptaplatin (FH) arm and 7.9 months in the 5-FU + cisplatin (FP) arm (p=0.24). Of the FH patients, 34.2% (complete response [CR], 1.3%; partial response [PR], 32.9%) experienced a confirmed objective response compared with 35.9% (CR 0%, PR 35.9%) of FP patients (p=0.78). The median-time-to-progression was 2.5 months in the FH arm and 2.3 months in the FP arm. The incidence of neutropenia was higher with FP (28%) than with FH (16%; p=0.06); grade 3~4 nausea and vomiting were more frequent in the FP than in the FH arm (p=0.01 and p=0.05, respectively). The incidence of increased proteinuria and creatininemia was higher with FH than with FP; however, there was no statistical difference. There were no treatment-related deaths. CONCLUSION: Heptaplatin showed similar effects to cisplatin when combined with 5-FU in advanced gastric cancer patients with tolerable toxicities.
Sujet(s)
Humains , Adénocarcinome , Bras , Traitement médicamenteux adjuvant , Cisplatine , Association de médicaments , Fluorouracil , Incidence , Malonates , Nausée , Neutropénie , Composés organiques du platine , Protéinurie , Tumeurs de l'estomac , VomissementRÉSUMÉ
Heptaplatin is a recently developed platinum derivative. This agent has been reported to have a response rate of 17% as a single agent, and tolerable toxicity in the treatment of advanced gastric cancer. The aim of this study was to evaluate the efficacy and toxicity of a combination of 5-fluorouracil (5-FU) and heptaplatin in patients with advanced gastric cancer. Forty-seven chemotherapy-naive patients with advanced or recurred gastric cancer were recruited. 5-FU was administered over 120 hr by continuous intravenous infusion from day 1 to 5, at a daily dose of 1,000 mg/m2 and heptaplatin was administered over 1 hr by intravenous infusion on day 1 at 400 mg/m2, and this cycle was repeated every 4 weeks. The response rate was 21%, median progression-free survival was 1.9 months (95% CI, 1.6 to 2.2 months). Median overall survival was 6.2 months (95% CI, 4 to 8.4 months) and the 1-yr survival rate was 29% for all patients. The most frequent toxicity was proteinuria. Toxicities were generally mild and reversible. This study demonstrates that the combination of 5-FU/heptaplatin combination is less active but tolerated in patients with advance gastric cancer.
Sujet(s)
Adulte , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Survie sans rechute , Fluorouracil/administration et posologie , Études de suivi , Malonates/administration et posologie , Composés organiques du platine/administration et posologie , Tumeurs de l'estomac/traitement médicamenteux , Facteurs temps , Résultat thérapeutiqueRÉSUMÉ
A existência de cepas de plasmódio resistentes aos fármacos utilizados no tratamento da malária é uma das causas da gravidade e aumento da incidência desta doença infecciosa no mundo. Por esta razão, muitas pesquisas estão sendo feitas visando à síntese de compostos novos que atuem por mecanismos de ação diferentes aos fármacos já tradicionais. Considerando que mefloquina e artemisinina são utilizadas como associação no tratamento da malária, este trabalho teve como objetivo o planejamento, síntese e avaliação biológica de novos antimaláricos estruturalmente relacionados com estes fármacos...
Sujet(s)
Antipaludiques/synthèse chimique , Paludisme , Malonates , Méfloquine , Plasmodium falciparum , Chimie pharmaceutique , Analyse coût-bénéfice , Évaluation de médicament , Planification , Résultat thérapeutiqueRÉSUMÉ
A purple non-sulfur bacterium isolated from dairy effluent was identified as Rps. palustris JA1. This organism was able to grow on pyridine as sole source of carbon in a light dependent anaerobic process with a doubling time of 30 h. Intermediates of pyridine photobiodegradation were identified as glycine and malonate, produced in stoichiometric molar ratios with simultaneous utilization, yielding biomass.