Cisteína oral N-Acetyl versus indometacina retal para prevenção de pancreatite pós-CPRE: um ensaio controlado randomizado multinacional multicêntrico / Oral n-acetyl cysteine versus rectal indomethacin for prevention of post ercp pancreatitis: a multicenter multinational randomized controlled trial

ABSTRACT Background This multicenter multinational RCT designed to compare the efficacy of suppository indomethacin and NAC for prevention of PEP. Methods: During a 6-month period, all of the ERCP cases in seven referral centers were randomly assigned to receive either 1200 mg oral NAC, indomethacin suppository 100 mg, 1200 mg oral NAC plus indomethacin suppository 100 mg or placebo 2 hours before ERCP. The primary outcomes were the rate and severity of any PEP. Results: A total of 432 patients included (41.4% male). They were originally citizens of 6 countries (60.87% Caucasian). They were randomly allocated to receive either NAC (group A, 84 cases), rectal indomethacin (group B, 138 cases), NAC + rectal indomethacin (group C, 115 cases) or placebo (group D, 95 cases). The rate of PEP in groups A, B and C in comparison with placebo were 10.7%, 17.4%, 7.8% vs 20% (P=0.08, 0.614 & 0.01 respectively). The NNT for NAC, indomethacin and NAC + indomethacin was 11, 38 and 8 respectively. Conclusion: Oral NAC is more effective than rectal indomethacin when compared to placebo for prevention of PEP and the combination of NAC and Indomethacin had the lowest incidence of PEP and may have synergistic effect in preventing of PEP (IRCT20201222049798N1; 29/12/2020).

RESUMO Contexto: Este estudo randomizado, controlado multicêntrico e multinacional foi projetado para comparar a eficácia da indometacina supositório e N-acetil cisteína (NAC) para prevenção de pancreatite pós colangiografia endoscópica. Métodos: Durante um período de 6 meses, todos os pacientes submetidos à CPRE em sete centros de referência foram aleatoriamente atribuídos para receber 1200 mg de NAC oral, supositório de indometacina 100 mg, 1200 mg de NAC oral mais supositório de indometacina 100 mg ou placebo 2 horas antes do procedimento. Os resultados primários foram a taxa e a gravidade de qualquer pancreatite pós procedimento (PPP). Resultados: Um total de 432 pacientes foram incluídos (41,4% do sexo masculino). Eram originalmente cidadãos de seis países (60,87% caucasianos). Foram alocados aleatoriamente para receber NAC (grupo A, 84 casos), indometacina retal (grupo B, 138 casos), NAC + indometacina retal (grupo C, 115 casos) ou placebo (grupo D, 95 casos). A taxa de PPP nos grupos A, B e C em comparação com o placebo foi de 10,7%, 17,4%, 7,8% vs 20% (P=0,08, 0,614 e 0,01, respectivamente). Conclusão A NAC oral é mais eficaz do que a indometacina retal quando comparado ao placebo para prevenção de PPP e a combinação de NAC e indometacina teve a menor incidência de PPP e pode ter efeito sinérgico na sua prevenção de PPP. (IRCT20201222049798N1; 29/12/2020).

Indicación de N-acetilcisteína en distintas formas de toxicidad por paracetamol / Indication of n-acetylcysteine in differents forms of paracetamol toxicity

Introducción: la hepatotoxicidad por paracetamol está relacionada con la formación del metabolito N-acetil-parabenzoquinoneimina (NAPQI) y su falta de detoxificación a través del glutatión, cuyas reservas se deplecionan en el contexto de una sobredosis. La administración de N-acetilcisteína (NAC) como sustancia dadora de grupos tioles (-SH) contribuye a la prevención del daño hepático que puede desarrollarse con dosis terapéuticas o tóxicas. Métodos: se comentan 5 casos de exposición a paracetamol en los cuales se administró NAC por alteración de la función hepática. La gravedad de los cuadros varió en función de las dosis y del tiempo de latencia hasta la consulta. Resultados: cuatro pacientes ingirieron una única dosis tóxica y una paciente recibió la dosis diaria máxima de paracetamol de 4000 mg/día durante 5 días. La paciente que consultó dentro de las 4 horas posteriores a la ingesta no presentó elevación de transaminasas. Todas las pacientes recibieron NAC y sus valores de enzimas hepáticas se normalizaron al momento del alta. Conclusión: la administración temprana de NAC puede ser útil para prevenir daño hepático tanto en ingestas de dosis tóxicas, como en casos de utilización de dosis terapéuticas máximas durante varios días. (AU)

Introduction: paracetamol hepatotoxicity is related to the formation of the metabolite N-acetyl-parabenzoquinoneimine (NAPQI) and its lack of detoxification through glutathione, whose reserves are depleted in paracetamol overdose. The administration of N-acetylcysteine (NAC) as a donor of sulfhydryl groups (-SH) can prevent liver damage that could even occur with therapeutic or toxic doses. Methods: 5 cases of exposure to paracetamol are discussed, in which NAC was administered due to impaired liver function. These manifestations presented different severity depending on the drug doses and the time until medical consultation. Results: four patients ingested single toxic doses and one patient received the maximum daily dose of paracetamol of 4000 mg/day for 5 days. The patient who consulted within 4 hours after ingestion did not present elevation of transaminases. All patients received NAC, with normal liver enzymes at discharge. Conclusion: the early administration of NAC may be useful to prevent liver damage both in toxic dose intakes and in cases of use of maximum therapeutic doses for several days. (AU)

A Study Of N-Acetyl Cysteine On Clinical, Metabolic Parameter And Hormonal Profile In Women With Polycystic Ovarian Syndrome

Background:Polycystic ovary disease (PCOD) isacommon endocrine disorder, whichis mainlycharacterized by infertility,anovulation, hyperinsulinemia, dyslipidaemia, biochemical imbalance. In our present study we have evaluated the effect of NAC in womensuffering from PCOD in terms oftheir clinical, metabolic and hormonal parameters. Material And Methods:We conducted this prospective study for a period of 5 months on 60 women who are affected with PCOD (diagnosed by Rotterdam criteria) of age group 18–30 year, visiting OPD of obstetrics and gynaecology department of Acharya Vinobha Bhave Rural Hospital (AVBRH) Jawaharlal Nehru Medical College (J.N.M.C) located in Sawangi (Meghe), Wardha. Patients who had oligo/amenorrhoea, hirsutism (hyperandrogenism) and ultrasound finding (Polycystic ovaries) were included in this study. Clinical, metabolicparameter and hormonal profile were measured pre and post treatment with NAC. Result:Fifty-six patients who received tab N acetylcysteine 600 mg three times a day, shown improvement in BMI, waist circumference, WHR, fasting glucose, fasting insulin and total testosterone level after a period of 3 months but no significant reduction in weight. Conclusion:It has been concluded that longer treatment with N-acetyl cysteine may result in more desirable outcomes and more effective control of clinical symptoms of PCOS, hyperandrogenism, and carbohydrate parameters. So, NAC can be used as a insulin sensitizer drug for PCOS women.

Can paricalcitol increase the effectiveness of n-acetylcysteine in contrast induced acute kidney prophylaxis in rats? A biochemical and histopathological study / ¿Puede el paricalcitol aumentar la eficacia de la n-acetilcisteína en la profilaxis renal aguda inducida por contraste en ratas? Un estudio bioquímico e histopatológico

SUMMARY: N-Acetylcysteine (NAC) is used for contrast induced acut kidney injury (CI-AKI) prophylaxis because of its antioxidant effects. Paricalcitol, which has reno-protective effects, is likely to provide a more effective prophylaxis when added to NAC treatment. The study was designed based on this hypothesis. The study was organised to include 4 groups each consisting of 7 rats. Group 1 was the control group, and Group 2 included rats with CI-AKI. Rats in Group 3 were administered NAC at a dose of 100 mg/kg via oral gavage once a day for 5 days. Rats in group 4 were administered paricalcitol at a dose of 0.4 mcg/kg once a day for 5 days in addition to NAC. CI-AKI was induced after the treatments in both groups. The study was terminated on the sixth day. Samples were collected from the rats' sera and kidney tissues to study oxidant and antioxidant parameters; kidney function tests were also studied. There were significant differences between the contrast nephropathy group (Group 2) and NAC and NAC+paricalcitol groups with respect to serum urea and creatinine levels. When the same groups were compared regarding oxidant (TOS-MDA) and antioxidant (TAC-Paraoxonase) parameters, we observed that the oxidant parameters increased in serum and kidney tissue samples with NAC use, and that effect was strengthened by the addition of paricalcitol to NAC treatment. However, despite increased antioxidant effectiveness, we observed no decrease in urea and creatinine levels when paricalcitol was added for CI-AKI in rats. There was no significant difference between Group 3 and Group 4. Paricalcitol provides a more potent antioxidant effect in both serum and kidney tissue samples when added to NAC treatment in rats with CI-AKI. Despite increased antioxidant parameters, however, paricalcitol does not provide a significant decrease in urea and creatinine levels.

RESUMEN: Debido a sus efectos atioxidantes la N- acetilcisteína (NAC) se usa para la profilaxis de la lesión renal aguda inducida por contraste (CI-AKI). Es probable que el paricalcitol, que tiene efectos renoprotectores, proporcione una profilaxis más eficaz cuando se agrega al tratamiento con NAC. En base a esta hipótesis el estudio fue diseñado para incluir cuatro grupos cada uno compuesto por siete ratas. El grupo 1 fue el grupo control y el grupo 2 incluyó ratas con CI-AKI. A las ratas del Grupo 3 se les administró NAC con una dosis de 100 mg/kg por sonda oral una vez al día, durante 5 días. A las ratas del grupo 4 se les administró paricalcitol a una dosis de 0,4 mcg/kg una vez al día durante 5 días, además de NAC. Se indujo CI-AKI después de los tratamientos en ambos grupos. El estudio finalizó el sexto día. Se recolectaron muestras de suero y tejidos renales de ratas para estudiar los parámetros oxidantes y antioxidantes; También se estudiaron las pruebas de función renal. Hubo diferencias significativas entre el grupo de nefropatía por contraste (Grupo 2) y los grupos NAC y NAC+paricalcitol con respecto a los niveles séricos de urea y creatinina. Cuando se compararon los mismos grupos con respecto a los parámetros oxidantes (TOS-MDA) y antioxidantes (TAC-Paraoxonase), observamos que los parámetros oxidantes aumentaron en muestras de suero y tejido renal con el uso de NAC, y ese efecto se vio reforzado por la adición de paricalcitol a tratamiento NAC. Sin embargo, a pesar de una mayor eficacia antioxidante, no observamos una disminución en los niveles de urea y creatinina cuando se agregó paricalcitol para CI-AKI en ratas. No hubo diferencias significativas entre el Grupo 3 y el Grupo 4. El paricalcitol proporciona un efecto antioxidante más potente tanto en muestras de suero como de tejido renal cuando se agrega al tratamiento con NAC en ratas con CI-AKI. Sin embargo, a pesar del aumento de los parámetros antioxidantes, el paricalcitol no proporciona una disminución sig- nificativa en los niveles de urea y creatinina.

Adecuación al flujograma PROA de neumonía aguda comunitaria en la emergencia del Hospital de Clínicas en 2019, Uruguay / Adaptation to the PROA flowchart for community acute pneumonia in the Hospital de Clínicas emergency in 2019, Uruguay / Adaptação ao fluxograma PROA para pneumonia aguda comunitária na emergência do Hospital de Clínicas em 2019, Uruguai

Resumen: Introducción: La resistencia antimicrobiana es uno de los principales problemas de salud pública mundial. Representa una causa importante de morbilidad en la población general y un elevado costo para los sistemas sanitarios. La Neumonía Aguda Comunitaria (NAC) representa una de las principales infecciones bacterianas en nuestro medio. Objetivo general: Evaluar la adecuación al flujograma del Programa de Optimización de Antimicrobianos (PROA) para el manejo de NAC en Departamento de Emergencia del Hospital de Clínicas (HC) entre julio y agosto de 2019. Materiales y métodos: Se realizó un estudio observacional, transversal, en el período de julio-agosto de 2019, en Departamento de Emergencia del Hospital de Clínicas. Se incluyeron pacientes mayores de 18 años, que firmaron el consentimiento informado, diagnosticados con NAC, cumpliendo criterios clínicos e imagenológicos establecidos en el flujograma del PROA del Hospital de Clínicas. Se elaboró una base de datos diseñada a partir del flujograma. Resultados: Se incluyeron 51 pacientes para el análisis. La edad promedio fue 54 años, 28 eran mujeres. Las comorbilidades más prevalentes fueron: tabaquismo, consumo de pasta base de cocaína y alcoholismo, presentes en 51% de la muestra. Treinta y cinco pacientes presentaron criterios de severidad, predominando insuficiencia respiratoria en 71%. Un 43 % presentaron factores de riesgo para microorganismos multirresistentes. Se observó una adecuación al PROA de 41%. Discusión: La adecuación al tratamiento recomendado fue inferior a la descrita en otros trabajos. El principal problema fue una errónea clasificación en los grupos de riesgo propuestos en el flujograma, ocasionando la hospitalización de pacientes que debieron recibir tratamiento ambulatorio, recibiendo antibioticoterapia de mayor espectro. Conclusiones: La existencia de PROA hospitalarios permite realizar monitoreo de prácticas diagnósticas y prescripción de antimicrobianos. Se observó una inadecuada aplicación del flujograma, lo que determinó el uso de antibióticos de mayor espectro con riesgo potencial del desarrollo de resistencia.

Abstract: Introduction: Antimicrobial resistance is one of the main world public health problems. It represents an important cause of morbidity in general population and a high cost for health systems. Community Acquired Pneumonia (CAP) represents one of the main bacterial infections in our midst. Objective: To evaluate the adequacy of the Antimicrobial Stewardship (AMS) in the management of CAP in the Emergency Department of Hospital de Clínicas (HC) between July and August 2019. Materials and methods: An observational, cross-sectional study was conducted from July-August 2019, in the Emergency Department of Hospital de Clínicas. Patients older than 18 years old were included, who signed the informed consent, diagnosed with CAP, fulfilling clinical and imaging criteria established in the flowchart. A database designed from the AMS flow chart of the Hospital de Clínicas was developed. Results: 51 patients were included for the analysis. The average age was 54 years, 28 were women. The most prevalent comorbidities were smoking, consumption of cocaine paste or alcoholism, present in 51% of the sample. Thirty-five patients presented severity criteria, prevailing respiratory failure in 71%. Risk factors for multiresistant microorganisms was 43%. PROA adequacy of 41.2% was observed. Discussion: The adequacy to the recommended treatment was lower than that described in other papers. The main problem was an erroneous classification in the risk groups proposed in the flowchart, causing hospitalization of patients who had to receive treatment at home, receiving broader spectrum antibiotic therapy. Conclusions: The existence of hospital stewardships allows monitoring of diagnostic practices and antimicrobial prescription. Inadequate application of the flow chart was observed, which determined the use of broader spectrum antibiotics with potential risk of developing resistance.

Resumo: Introdução: A resistência antimicrobiana é um dos principais problemas de saúde pública global. Representa uma das principais causas de morbidade na população em geral e um alto custo para os sistemas de saúde. A Pneumonia Aguda Comunitária (PAC) representa uma das principais infecções bacterianas em nosso meio. Objetivo: Avaliar a adequação do fluxograma do Programa de Otimização de Antimicrobianos (PROA) para o gerenciamento do PAC no Pronto Atendimento do Hospital de Clínicas (HC) entre julho e agosto de 2019. Materiais e métodos: Foi realizado um estudo observacional, transversal, no período de julho a agosto de 2019, no Pronto-Socorro do Hospital de Clínicas. Foram incluídos pacientes maiores de 18 anos, que assinaram o termo de consentimento livre e esclarecido, com diagnóstico de PAC, que preenchessem os critérios clínicos e de imagem estabelecidos no fluxograma do PROA do Hospital de Clínicas. Um banco de dados projetado a partir do fluxograma foi desenvolvido. Resultados: 51 pacientes foram incluídos para análise. A idade média era de 54 anos, 28 eram mulheres. As comorbidades mais prevalentes foram: tabagismo, consumo de pasta base de cocaína e etilismo, presentes em 51% da amostra. Trinta e cinco pacientes apresentaram critérios de gravidade, predominando insuficiência respiratória em 71%. 43% apresentaram fatores de risco para microrganismos multirresistentes. Observou-se adequação ao PROA de 41%. Discussão: A adequação ao tratamento recomendado foi inferior ao descrito em outros estudos. O principal problema era uma classificação errônea nos grupos de risco propostos no fluxograma, ocasionando a internação de pacientes que precisavam receber tratamento ambulatorial, recebendo antibioticoterapia de maior espectro. Conclusões: A existência de PROAs hospitalares permite o monitoramento das práticas diagnósticas e prescrição de antimicrobianos. Observou-se uma aplicação inadequada do fluxograma, que determinou o uso de antibióticos de maior espectro e com potencial risco de desenvolvimento de resistência.

Identification and expression analysis of the DaNAC transcription factor family in Dipsacus asper / 药学学报

italic>NAC transcription factor genes play an important role in regulating plant adversity stress tolerance and secondary metabolism. To explore DaNAC transcription factor participation in the synthesis of asperosaponin Ⅵ in Dipsacus asper, we analyzed the expression of DaNAC genes based on full-length transcriptome data from different tissues (root, stem, leaf, flower, seed) to provide a theoretical foundation for regulating the metabolism of D. asper. RNA-seq data was used to identify open reading frames. Bioinformatic methods were used to identify the conserved domain motifs and construct an evolutionary tree. qRT-PCR was carried out to analyze tissue-specific and adversity-stressed expression. Twenty-nine DaNAC sequences were identified, all of which contain the conserved NAM domain and conserved motif 1 and motif 2 at the N terminal. Five DaNAC genes are closely related to the NAC genes in Arabidopsis thaliana and rice that are involved in adversity stress and are clustered in the Group Ⅰ subfamily. qRT-PCR revealed that DaNAC genes are differentially expressed between tissues. The expression levels were highest in leaves, followed by roots, stems and petioles, and the lowest in flowers and seeds. Compared with normal growth conditions, the expression of four NAC genes was up-regulated by treatment with low temperature (15 ℃). The expression of three genes (34564NAC2, 33883NAC48, 6727NAC14) was up-regulated and one gene (34480NAC22) was down-regulated by 150 μmol·L-1 MeJA. The results illustrate that the expression of NAC genes is induced by adversity stress, which provides a foundation for further study on the role of NAC family members in adversity stress in D. asper.

Melatonin can be, more effective than N-acetylcysteine, protecting acute lung injury induced by intestinal ischemia-reperfusion in rat model

OBJECTIVES: The current study compared the impact of pretreatment with melatonin and N-acetylcysteine (NAC) on the prevention of rat lung damage following intestinal ischemia-reperfusion (iIR). METHODS: Twenty-eight Wistar rats were subjected to intestinal ischemia induced by a 60 min occlusion of the superior mesenteric artery, followed by reperfusion for 120 min. Animals were divided into the following groups (n=7 per group): sham, only abdominal incision; SS+iIR, pretreated with saline solution and iIR; NAC+iIR, pretreated with NAC (20 mg/kg) and iIR; MEL+iIR, pretreated with melatonin (20 mg/kg) and iIR. Oxidative stress and inflammatory mediators were measured and histological analyses were performed in the lung tissues. RESULTS: Data showed a reduction in malondialdehyde (MDA), myeloperoxidase (MPO), and TNF-alpha in the animals pretreated with NAC or MEL when compared to those treated with SS+iIR (p<0.05). An increase in superoxide dismutase (SOD) levels in the NAC- and MEL-pretreated animals as compared to the SS+iIR group (34±8 U/g of tissue; p<0.05) was also observed. TNF-α levels were lower in the MEL+iIR group (91±5 pg/mL) than in the NAC+iIR group (101±6 pg/mL). Histological analysis demonstrated a higher lung lesion score in the SS+iIR group than in the pretreated groups. CONCLUSION: Both agents individually provided tissue protective effect against intestinal IR-induced lung injury, but melatonin was more effective in ameliorating the parameters analyzed in this study.

Bioinformatics analysis and expression pattern of NAC transcription factor family of Angelica dahurica var. formosana from Sichuan province / 中国中药杂志

NAC(NAM/ATAF/CUC) protein plays an important role in plant growth and development, secondary cell wall formation and stress response. In this study, based on the sequencing data of Angelica dahurica, the NAC family was systematically analyzed using bioinformatics methods and its expression pattern was analyzed. Studies showed that 75 candidate genes had been selected from the NAC transcription factor family of A. dahurica, with the protein size of 148-641, all of which were unstable hydrophilic proteins. Most NAC proteins were localized in the nucleus, and had complete NAC domain. Phylogenetic analysis of NAC family proteins of A.dahurica and Arabidopsis thaliana showed that among the 17 subfamilies, NAC members were unevenly distributed in each subfamily, indicating that the evolution of species is developing in multiple directions. Among them, ANAC063 subfamily contained no NAC sequence of A. dahurica, which might be due to the functional evolution of the species. Analysis of protein transmembrane structure and signal peptide showed that NAC transcription factor could carry out transmembrane transportation, but its signal peptide function had not been found. Expression analysis showed that most transcription factors responded to abiotic stress and hormones to varying degrees, and the effects of hormones were obvious, especially ABA and IAA. In different organs of A. dahurica, most members of the NAC family had higher expression in root phloem, followed by root xylem. This study lays a foundation for further research on the function of A. dahurica NAC transcription factor and for solving the biological problems of A. dahurica.

Molecular Speciation and Antifungal Susceptibility Profile of Candida Species in a Tertiary Care Centre in Central Kerala.

Candidiasis is a common life-threatening condition with various clinical manifestations. It can cause significant morbidity and mortality, especially in critically ill patients. Though mainly caused by C. albicans, it has shown a change in the epidemiological pattern with an increase in the prevalence of non albicans Candida (NAC) in the recent years. This change has also reflected in the profile of antifungal susceptibility since many of these species show high level of antifungal resistance associated with treatment failures. Thus, it is important to know the regional distribution of Candida species and also find their antifungal susceptibility profile to the commonly used antifungal agents.METHODSThis is a descriptive study conducted for a period of two years on the clinical isolates of Candida species which satisfied the inclusion and exclusion criteria. Speciation was done by phenotypic methods which include germ tube test, chromogenic medium, corn meal agar and VITEK-2 system and by molecular methods using multiplex PCR. Antifungal susceptibility testing was done using automated method by VITEK-2 compact system.RESULTSAmong the 80 isolates studied, on speciation C .albicans 25(31.25%) was the most common, followed by C. tropicalis 23 (28.75%), C. parapsilosis 13 (16.25%), C. krusei 12 (15%), C. pelliculosa 4 (5%), C. auris 2 (2.5%) and C. glabrata 1 (1.25%). Most isolates were susceptible to almost all the antifungal agents tested, but C. krusei showed high level of resistance.CONCLUSIONSC. albicans was the commonest individual species, but there was an overall predominance of non-albicans Candida (NAC). Speciation of Candida isolates is important as there is wide variation in their antifungal resistance pattern. Knowledge about the prevalent species and their antifungal susceptibility will help in early initiation of appropriate treatment, thus reducing the morbidity and mortality associated with Candida infections.

Factores de Riesgo asociados a la severidad en Neumonía adquirida en la comunidad

RESUMEN Introducción: La neumonía constituye la principal causa infecciosa de hospitalización y muerte entre los adultos. Varios factores han sido asociados con la ocurrencia de la NAC, como ser la edad, el tabaquismo, la exposición ambiental, la malnutrición, NAC previa, asma, higiene bucal inadecuada, terapia inmunosupresora y esteroides orales. El objetivo general del estudio fue determinar las características clínicas y evolución de la neumonía adquirida en la comunidad en pacientes hospitalizados en la III Cátedra de Clínica, durante el periodo comprendido entre enero de 2013 a diciembre 2015. Metodología: Se realizó un estudio observacional, descriptivo, retrospectivo, de corte transversal en pacientes con NAC hospitalizados en la III Cátedra del Hospital de Clínicas, durante el periodo enero de 2013 a diciembre de 2015, en pacientes >15 con Neumonía Adquirida de la Comunidad con síntomas, signos y radiografía compatibles, hospitalizados en la III Cátedra del Hospital de Clínicas. Resultados: Durante el periodo de estudio, 70 pacientes con NAC fueron hospitalizados en la III Cátedra de Clínica Médica, La edad media de los pacientes fue de 59 ± 18,1 años, con predominio del sexo femenino 52,8% (37/70). El 81,8% fueron NAC de base derecha, siendo el 63% (44/70) unilateral y el 16% (11/70) con derrame pleural. El 98.5% (69/70) de los pacientes presentaron 1 o más factores de riesgo; la Hipertensión arterial fue la patología más frecuente 64.3% (45/70), seguido de la Insuficiencia Cardíaca Congestiva Global (ICCG) 44% (31/10) y la diabetes 37% (26/70). Las neumonías severas (bilateral con o sin derrame y unilateral con derrame), fueron más frecuentes en los pacientes con diabetes, enfermedad renal, obesidad y asma, siendo esta frecuencia significativamente superior en los pacientes con diabetes. Conclusiones: El estudio demostró que los pacientes con diabetes presentaron un riesgo significativamente superior comparados con aquellos que no presentaron esta patología, para el desarrollo de NAC grave.

ABSTRACT Community Acquired Pneumonia (CAP) is the leading infectious cause of hospitalization and death among adults. Several factors have been associated with the occurrence of NAC, such as age, smoking, environmental exposure, malnutrition, previous CAP, asthma, inadequate oral hygiene and immunosuppressive therapy. The general objective of the study was to determine the clinical characteristics and evolution of CAP in patients hospitalized in the III Cátedra de Clínica Médica - Hospital de Clínicas, during the period January 2013 to December 2015. Methodology: An observational, descriptive, retrospective, cross-sectional study was conducted in patients with CAP hospitalized in the III Cátedra de Clínica Médica - Hospital de Clínicas, during the period January 2013 to December 2015, in patients> 15 with CAP with compatible symptoms, signs and radiography. Results: During the study period, 70 patients with CAP were hospitalized in the III Chair of Medical Clinic, the average age of the patients was 59 ± 18.1 years, with a predominance of the female sex 52.8% (37/70), 81.8% were right-sided CAP, 63% (44/70) unilateral and 16% (11/70) with pleural effusion. The 98.5% (69/70) of the patients presented one or more risk factors; hypertension was the most frequent pathology 64.3% (45/70), followed by Global Congestive Heart Failure (GCHF) 44% (31/10) and diabetes 37% (26/70). Severe pneumonias (bilateral with or without effusion and unilateral with effusion) were more frequent in patients with diabetes, kidney disease, obesity and asthma, this frequency was significantly higher in patients with diabetes. Conclusions: The study showed that patients with diabetes presented a significantly higher risk compared to those who did not present this pathology, for the development of severe CAP.

OsNAC-like transcription factor involved in regulating seed-storage protein content at different stages of grain filling in rice under aerobic conditions

In this study, we show that NAC-like transcription factor (TF) has 90% sequence similarity with cDNA of the OsNac5 gene present in the NCBI database. Phylogenetic analysis of the NAC gene family was performed with inclusion of the highly diverse C-terminal sequences. We report that this gene is also found to be orthologous to Glycine max NAC8, NAC2, Triticum aestivum NAC6 and paralogous to OsNAC6. mRNA was purified from five recombinant inbred lines (RILs) and parents of rice at three different stages of grain filling under aerobic conditions, with grain protein content (GPC) spanning from 4 to 14%. TheNAC-like TF encoding a protein was found to be upregulated at the S2 stage in the leaf (3.9-fold) and panicle (1.84-fold) of parent HPR14 and in five RILs (1.9 to 4.51-fold in leaves and 0.47 to 3.2-fold in panicles). Expression analysis of the NAC-like TF encoding a protein for the rice gene was found to be upregulated at the S2 stage in the leaf and panicle of parental line HPR14 and RILs with high protein content.

Nac-1 is required for maintenance of multipotency in neural stem/progenitor cells / 西安交通大学学报(医学版)

Objective: To study the regulatory mechanism of Nac-1 on the self-renewal of neural stem/progenitor cells (NSPCs). Methods: The expression level of Nac-1 was detected by using ESCs-derived NSPCs as the cell model. RNA interference was used to reduce the expression of Nac-1; the interference efficiency was detected by quantitative RT-PCR and Western blot. The proliferation and apoptosis of NSPCs were detected by cell counting and flow cytometry. Luciferase assay was used to detect the transcriptional regulation of Nac-1 on c-Myc. Results: Nac-1 was highly expressed in NSPCs, and its mRNA level decreased by 77% after differentiation. Compared with that in the control group, the mRNA level of Nac-1 in the NSPCs of the experimental group was significantly decreased, and the interference efficiency was 69% and 66%, respectively. NSPCs with Nac-1 knockdown showed slow proliferation, increased apoptosis and tended to differentiate, and the mRNA level of c-Myc decreased by 46% and 57% in two Nac-1 knockdown groups, respectively. Luciferase assay showed that the transcriptional activity of c-Myc promoter decreased by 24% and 36%, respectively, suggesting that Nac-1 could regulate the promoter activity of c-Myc gene. Conclusion: Nac-1 can promote the proliferation of NSPCs and inhibit their differentiation by regulating the transcription of c-Myc.

Risk Assessment of “Other Substances” - L-cysteine and L-cystine

The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), assessed the risk of “other substances” in food supplements and energy drinks sold in Norway. VKM has assessed the risk of doses given by NFSA. These risk assessments will provide NFSA with the scientific basis while regulating the addition of “other substances” to food supplements. “Other substances” are described in the food supplement directive 2002/46/EC as substances other than vitamins or minerals that have a nutritional or physiological effect. It is added mainly to food supplements, but also to energy drinks and other foods. VKM has not in this series of risk assessments of “other substances” evaluated any claimed beneficial effects from these substances, only possible adverse effects. The present report is a risk assessment of L-cysteine and L-cystine, and is based on previous risk assessments of these amino acids and articles retrieved from a comprehensive literature search. In this report L-cysteine and L-cystine are often termed merely cysteine and cystine, respectively. L-cysteine is a central compound in sulphur metabolism in the human body. L-cysteine is a conditionally essential sulphur-containing amino acid, obtained from L-methionine and from serine. Sulphur-containing amino acids are mainly found in cereal proteins and animal proteins, and less abundantly in pulses. Cysteine may occur in proteins either as cysteine itself or as cystine. Cystine is the disulphide dimer of cysteine, and is a more stable compound than cysteine. According to information from the Norwegian Food Safety Authority (NFSA), cysteine and cystine are ingredients in food supplements purchased in Norway and NFSA has requested a risk assessment of the following doses of cysteine and cystine in food supplements: L-cysteine 10 mg/day and L-cystine 250, 500, 750 and 1000 mg/day. The mean usual daily intake of cysteine in the USA for all life stage- and gender groups is 1.0 g/day (NHANES II, USA). Because there are few intervention studies with cysteine or cystine, studies with N-acetylcysteine (or N-acetyl-L-cysteine, NAC), which is readily converted to cysteine, is included in this risk assessment. NAC is used as a pharmaceutical drug for various conditions, mainly as mucolytic agent, as paracetamol antidote, and has been included in numerous clinical trials. Most of the cited studies have tested NAC in doses of about 600-1200 mg/day. The study groups have been various patient groups which included children, adolescents, adults and elderly, however relatively few studies have been conducted in children. In the randomised controlled trials there have been no differences in severe adverse events between the placebo and NAC-groups. The adverse effects reported are generally limited to mild gastrointestinal symptoms. The dose 1200 mg of NAC yields maximum 900 mg of L-cysteine or L-cystine. In adults, it is well documented that doses up to 900 mg per day for one year (corresponding to 13 mg/kg bw/day in a 70 kg adult) is without appreciable health risk. The data for doses above 900 mg/day are more scarce. There are no data indicating that children and adolescent are more vulnerable than adults for L-cysteine or L-cystine. No tolerance level is set for cysteine or cystine specifically for children or adolescents, but an assumption is made that these age groups have similar tolerance per kg body weight as adults. VKM concludes that: In adults (≥18 years), the specified doses 10 mg/day L-cysteine and 250, 500 and 750 mg/day L-cystine in food supplements are considered to be unlikely to cause adverse health effects, whereas the dose 1000 mg L-cystine per day may represent a risk of adverse health effects. In adolescents (14 to <18 years), the specified doses 10 mg/day L-cysteine and 250, 500 and 750 mg/day L-cystine in food supplements are considered to be unlikely to cause adverse health effects in adolescents, whereas the dose 1000 mg L-cystine per day may represent a risk of adverse health effects. In children (10 to <14 years), the specified doses 10 mg/day L-cysteine and 250 and 500 mg/day L-cystine in food supplements are considered to be unlikely to cause adverse health effects, whereas the doses 750 and 1000 mg L-cystine per day may represent a risk of adverse health effects. Children below 10 years were not included in the terms of reference.

Transcriptome profiling and digital gene expression analysis of genes associated with salinity resistance in peanut

Background: Soil salinity can significantly reduce crop production, but the molecular mechanism of salinity tolerance in peanut is poorly understood. A mutant (S1) with higher salinity resistance than its mutagenic parent HY22 (S3) was obtained. Transcriptome sequencing and digital gene expression (DGE) analysis were performed with leaves of S1 and S3 before and after plants were irrigated with 250 mM NaCl. Results: A total of 107,725 comprehensive transcripts were assembled into 67,738 unigenes using TIGR Gene Indices clustering tools (TGICL). All unigenes were searched against the euKaryotic Ortholog Groups (KOG), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, and these unigenes were assigned to 26 functional KOG categories, 56 GO terms, 32 KEGG groups, respectively. In total 112 differentially expressed genes (DEGs) between S1 and S3 after salinity stress were screened, among them, 86 were responsive to salinity stress in S1 and/or S3. These 86 DEGs included genes that encoded the following kinds of proteins that are known to be involved in resistance to salinity stress: late embryogenesis abundant proteins (LEAs), major intrinsic proteins (MIPs) or aquaporins, metallothioneins (MTs), lipid transfer protein (LTP), calcineurin B-like protein-interacting protein kinases (CIPKs), 9-cis-epoxycarotenoid dioxygenase (NCED) and oleosins, etc. Of these 86 DEGs, 18 could not be matched with known proteins. Conclusion: The results from this study will be useful for further research on the mechanism of salinity resistance and will provide a useful gene resource for the variety breeding of salinity resistance in peanut.

Sub-cytotoxic concentrations of ionic silver promote the proliferation of human keratinocytes by inducing the production of reactive oxygen species / 医学前沿

Silver-containing preparations are widely used in the management of skin wounds, but the effects of silver ions on skin wound healing remain poorly understood. This study investigated the effects of silver ions (Ag) on the proliferation of human skin keratinocytes (HaCaT) and the production of intracellular reactive oxygen species (ROS). After treating HaCaT cells with Ag and/or the active oxygen scavenger N-acetyl cysteine (NAC), cell proliferation and intracellular ROS generation were assessed using CCK-8 reagent and DCFH-DA fluorescent probe, respectively. In addition, 5-bromo-2-deoxyUridine (BrdU) incorporation assays, cell cycle flow cytometry, and proliferating cell nuclear antigen (PCNA) immunocytochemistry were conducted to further evaluate the effects of sub-cytotoxic Ag concentrations on HaCaT cells. The proliferation of HaCaT cells was promoted in the presence of 10 and 10 mol/L Ag at 24, 48, and 72 h. Intracellular ROS generation also significantly increased for 5-60 min after exposure to Ag. The number of BrdU-positive cells and the presence of PCNA in HaCaT cells increased 48 h after the addition of 10 and 10 mol/L Ag, with 10 mol/L Ag markedly increasing the cell proliferation index. These effects of sub-cytotoxic Ag concentrations were repressed by 5 mmol/L NAC. Our results suggest that sub-cytotoxic Ag concentrations promote the proliferation of human keratinocytes and might be associated with a moderate increase in intracellular ROS levels. This study provides important experimental evidence for developing novel silver-based wound agents or dressings with few or no cytotoxicity.

Identification and analysis of NAC family in ginger(Zingiber officinale) based on RNA-seq data / 中国中药杂志

The NAC family is an important transcription factor which regulate plant growth and development， signal transduction， and stress response.In this study， the protein identification， subfamily classification， the determination of physical and chemical properties， protein structure， and expression pattern of NAC family were performed using bioinformatic methods based on the RNA-seq data of ginger. The results showed that a total of 72 NAC transcription factors were identified in 271.1 Mb total nucleotides， and they could be clustered into 13 subfamilies according to the phylogenetic tree.The physical and chemical properties， structure analysis revealed that the amino acid number and isoelectric point were different among 13 NAC subfamilies; the secondary structure of NACs transcription factors mainly consist of random coil， and the tertiary structure is similar.In addition，the expression patterns of genes under different soil moisture and Ralstonia solanacearum infection showed that 23 NACs were differentially expressed， which were mainly distributed in Ⅷ，Ⅶ， and ⅩⅤ subfamilies related to plant senescence， hormone metabolism and cell wall metabolism.The results provide some valuable information for the research and development of NAC transcription factors in ginger.

Klebsiella pneumoniae aisladas de pacientes con neumonía adquirida en la comunidad / Klebsiella pneumoniae isolada de pacientes com pneumonia adquirida na comunidade / Klebsiella pneumoniae isolated from patients with community-acquired pneumonia

Introducción: la neumonía adquirida en la comunidad (NAC) constituye un importante problema de salud en el ámbito mundial y en Cuba. Su incidencia y letalidad hacen de esta afección un verdadero reto para los servicios asistenciales. Objetivo: identificar la incidencia de Klebsiella pneumoniae aislada de muestras de esputo en pacientes con neumonía adquirida en la comunidad. Método: se realizó un estudio descriptivo y trasversal en el laboratorio de microbiología del Centro Provincial de Higiene, Epidemiología y Microbiología de Guantánamo de enero a junio del 2016. El universo de estudio estuvo formado por 88 pacientes. Se aplicó el procedimiento de laboratorio propuesto por Expósito et al. Resultados: se identificaron 72 muestras de esputo productivo, de las cuales fueron positivas al cultivo bacteriológico 56 muestras, de ellas en 34 se aísló Klebsiella pneumoniae, que resultaron la muestra en estudio, mostrando resistencia marcada a amoxicilina y ceftriaxona. Se enmarcó este microorganismo como un patógeno que emergió como responsable de la etiología de infecciones respiratorias adquiridas en la comunidad. Conclusiones: Klebsiella pneumoniae por su frecuencia de aislamiento, por los mecanismos patogénicos y de resistencia que presenta, se considera un patógeno oportunista que emerge como responsable de la etiología de infecciones respiratorias adquiridas en la comunidad(AU)

Introduction: Community-acquired pneumonia (CAP) is a major health problem worldwide and in Cuba. Its incidence and lethality make this desease a real challenge for healthcare services. Objective: to identify the incidence of Klebsiella pneumoniae isolated from sputum samples in patients with community-acquired pneumonia. Method: a descriptive and cross-sectional study was carried out in the microbiology laboratory of the Provincial Hygiene, Epidemiology and Microbiology Center of Guantanamo from January to June 2016. The universe of study consisted of 88 patients. The laboratory procedure proposed by Expósito et al. Results: 72 samples of productive sputum were identified, of which 56 samples were positive for bacterial culture, Klebsiella pneumoniae was isolated in 34, which resulted in the study sample, showing marked resistance to amoxicillin and ceftriaxone. This microorganism was framed as a pathogen that emerged as responsible for the etiology of respiratory infections acquired in the community. Conclusions: Klebsiella pneumoniae, due to its frequency of isolation, due to its pathogenic and resistance mechanisms, is considered an opportunistic pathogen that emerges as responsible for the etiology of respiratory infections acquired in the community(AU)

Introdução: A pneumonia adquirida na comunidade (PAC) é um grande problema de saúde em todo o mundo e em Cuba. Sua incidência e letalidade tornam essa doença um verdadeiro desafio para os serviços de saúde. Objetivo: identificar a incidência de Klebsiella pneumoniae isolada de amostras de escarro em pacientes com pneumonia adquirida na comunidade. Método: um estudo descritivo e transversal foi realizado no laboratório de microbiologia do Centro Provincial de Higiene, Epidemiologia e Microbiologia em Guantánamo, de janeiro a junho de 2016. O grupo de estudo consistiu de 88 pacientes. O procedimento laboratorial proposto por Expósito et al. Resultados: 72 amostras de expectoração, que eram positivos para a cultura bacteriana 56 amostras, 34 deles em Klebsiella pneumoniae, que estavam a amostra em estudo, mostrando marcada resistência à amoxicilina e ceftriaxona foi isolado identificado. Esse microrganismo foi enquadrado como um patógeno que emergiu como responsável pela etiologia das infecções respiratórias adquiridas na comunidade. Conclusões: Klebsiella pneumoniae por isolamento frequência por mecanismos patogénicos e de resistência presente, é considerado um agente patogénico oportunista que surge como responsável pela etiologia das infecções respiratórias adquiridas na comunidade(AU)

Research progress of Akt in drug addiction mechanism / 中国药理学通报

Akt is the downstream target protein of phosphatidylinositol 3-kinase(PI3K),and PI3K/Akt signaling pathway is involved in cell proliferation,differentiation,apoptosis and metabolism.The activities of Akt in the central nervous system is also regulated by the neurotransmitter dopamine(DA),therefore Akt mediates multiple drug addiction process.This article reviews the structural characteristics and activity regulation of Akt,as well as the related research in drug addiction of this signal molecule.

Pro-inflammatory mechanism of lectin from Pinellia pedatisecta on macrophage / 中国中药杂志

To investigate the mechanism of lectin from Pinellia pedatisecta(PPL) on macrophage-induced inflammation and its association with inflammatory corpuscles NLRP3. Lectin from P. pedatisecta was isolated and purified by gel chromatography, and its purity was analyzed by using SDS-PAGE gel electrophoresis. ELISA was used to investigate the effect of PPL on inflammatory cytokines released by macrophages, with IL-1β as indicators;and fluorescence probe DCFH-DA fluorometer was used to determine changes in active oxygen ROS of macrophages after application of lectin from P. pedatisecta.RAW264.7 cells were pre-treated with ROS inhibitor N-acetylcysteine (NAC) to investigate the effect on ROS and the release of inflammatory factor IL-1β from macrophages to research the relationship between them. The protein levels of NLRP3, Caspase-1 p20, ASC and TXNIP were determined by Western blot.The results showed that isolated and purified PPL could reach electrophoretic purity; PPL stimulated macrophages and induced the excessive release of ROS, leading to strong oxidative stress reaction, and the levels of intracellular inflammatory factorsIL-1β were significantly increased. NAC could inhibit PPL-induced ROS excessive production and significantly reduce the release of IL-1β. In addition, PPL could induce the increase in protein expression levels of Caspase-1 p20, NLRP3 and ASC, and significantly reduce TXNIP expression. The results showed that PPL could cause a strong oxidative stress response by stimulating macrophages, activate inflammatory corpuscles NLRP3, and result in large amount of IL-1β release. That is, PPL could lead to inflammatory cascade reaction by promoting the maturation and secretion of IL-1β through ROS-TXNIP-NLRP3-IL-1β signaling pathway.

Cloning, subcellular localization, and heterologous expression of ApNAC1 gene from Andrographis paniculata / 中国中药杂志

Andrographis paniculata is widely used as medicinal herb in China for a long time and andrographolide is its main medicinal constituent. To investigate the underlying andrographolide biosynthesis mechanisms, RNA-seq for A. paniculata leaves with MeJA treatment was performed. In A. paniculata transcriptomic data, the expression pattern of one member of NAC transcription factor family (ApNAC1) matched with andrographolide accumulation. The coding sequence of ApNAC1 was cloned by RT-PCR, and GenBank accession number was KY196416. The analysis of bioinformatics showed that the gene encodes a peptide of 323 amino acids, with a predicted relative molecular weight of 35.9 kDa and isoelectric point of 6.14. To confirm the subcellular localization, ApNAC1-GFP was transiently expressed in A. paniculata protoplast. The results indicated that ApNAC1 is a nucleus-localized protein. The analysis of real-time quantitative PCR revealed that ApNAC1 gene predominantly expresses in leaves. Compared with control sample, its expression abundance sharply increased with methyl jasmonate treatment. Based on its expression pattern, ApNAC1 gene might involve in andrographolide biosynthesis. ApNAC1 was heterologously expressed in Escherichia coli and recombinant protein was purified by Ni-NTA agarose. Further study will help us to understand the function of ApNAC1 in andrographolide biosynthesis.