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ObjectiveTo explore the clinical efficacy of Huanglian Jiedutang as an adjunctive treatment for acute cerebral infarction complicated with gastric motility disorder. MethodSixty patients with acute cerebral infarction complicated with gastric motility disorder with fire toxin syndrome were randomly divided into a western medicine control group （control group） and a traditional Chinese medicine （TCM） combined treatment group （observation group）， with 30 cases in each group. The control group received basic treatment for cerebral infarction and relevant western medical symptomatic treatment based on the patients' gastrointestinal symptoms. The observation group received Huanglian Jiedutang in addition to the treatment provided to the control group. The treatment course was 7 days. Neurological deficit scores and gastrointestinal dysfunction scores were assessed in both groups before treatment and on the 4th and 7th days of treatment. Gastrointestinal electrographic parameters， serum citrulline （CIT）， and motilin （MTL） levels were measured in both groups before treatment and on the 7th day of treatment. Clinical efficacy was compared between the two groups. ResultCompared with the baseline in both groups， the neurological deficit scores and gastrointestinal dysfunction scores were significantly reduced on the 4th and 7th days of treatment （P<0.05）. The reductions in these scores were more significant on the 7th day compared with those on the 4th day of treatment （P<0.05）. On the 4th and 7th days of treatment， the observation group showed a significantly greater reduction in neurological deficit scores and gastrointestinal dysfunction scores compared with the control group （P<0.05）. On the 7th day of treatment， compared with the baseline， both groups showed a significant increase in gastric antral and gastric body electric wave amplitudes as well as serum CIT and MTL levels （P<0.05）， and there were no statistically significant differences in the frequency of gastric antral and gastric body electric waves. On the 7th day of treatment， compared with the control group， the observation group had a significant increase in gastric antral and gastric body electric wave amplitudes as well as serum CIT and MTL levels （P<0.05）， and there were no statistically significant differences in the frequency of gastric antral and gastric body electric waves. After 7 days of treatment， the total effective rate in the observation group was 90.00% （27/30）， higher than 76.67% （23/30） in the control group， but the difference was not statistically significant. ConclusionAdjunctive treatment with Huanglian Jiedutang can effectively improve the symptoms of neurological function impairment and gastrointestinal dysfunction in patients with acute cerebral infarction complicated with gastric motility disorder， increase gastric antral and gastric body electric wave amplitudes， improve gastric motility disorder， and increase serum CIT and MTL levels， thereby improving the imbalanced secretion function of the gastrointestinal tract.
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Rheumatoid arthritis (RA) is a group of heterogeneous autoimmune diseases with erosive arthritis as the main clinical feature. The pathogenesis of RA remains unclear. Autoantibodies can be detected in blood or synovial fluid in approximately 70% of patients with RA in the early stage of the disease. Anti-citrullinated protein antibody (ACPA) is the most commonly used autoantibody in the diagnosis of RA. However, ACPA is not a specific antibody for RA. The discovery and clinical application of serum ACPA-negative RA biomarkers is of positive significance for the early diagnosis and prognosis improvement of RA. This paper reviews the research progress of ACPA-negative RA biomarkers.
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Background & objectives: Malaria affects around 228 million people all over the globe. Malaria causing parasite Plasmodium infection leads to activation of immune responses. The growth of parasite and immune activation requires semi essential amino acids like L-arginine. Malaria infection leads to condition of hyperargininemia and low availability of nitric oxide. However, the effect of L-arginine supplementation in malaria infected mice has not been explored in in-vivo studies. In this study we have compared the effect of oral supplementation of nitric oxide donor, L-arginine and L-citrulline, in malaria infected mice Methods: To examine the effect of oral supplementation of L-arginine and L-citrulline, Plasmodium berghei infected mice were divided in different groups and respective groups were fed with L- arginine and L-citrulline, parasitemia was measured on different days. Mice was sacrificed and immunophenotyping was done on 10 days post infection. Results: our results show that supplementation of L-arginine induces conducive environment for Plasmodium growth due to which the infected mice dies earlier than control wild type infected mice whereas L-citrulline supplementation inhibits parasite growth and mice survives for longer period of time. Flow cytometric analysis shows that supplementation of L-arginine increases cTLA-4 on T cell population, increases Treg cells leading to immunosuppression while supplementation of L-citrulline does not have effect on T cells population and number of Treg cell decrease compared to P. berghei infected mice. Interpretation & conclusion: our results show that L-citrulline can be a better alternative than L-arginine because of lower expression of inhibitory molecules and lower parasitemia as well as increased survival of infected mice.
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Objective:To study the expression and significance of neutrophil extracellular traps (NETs) in neonatal sepsis.Methods:Prospective research were used in this study. Term infants with neonatal sepsis hospitalized for the first time in the Department of Neonatology, Children's Hospital of Soochow University from June 2020 to November 2020 were selected as the sepsis group. According to a ratio of about 1∶1, term infants with mild hyperbilirubinemia who were admitted in the same period, with gestational age difference less than 1 week from those in the sepsis group, and whose parents agreed to participate in the study were selected as the control group. On admission, clinical data as well as blood samples of the two groups were collected. Levels of NETs marker citrulline histone H3-DNA (CitH3-DNA) were detected by Enzyme-linked immunosorbent assay, and circulating cell-free DNA (cfDNA) was tested by the fluorescence microplate reader. General data, white blood cell (WBC), neutrophil count (NE), platelet (PLT), C- reactive protein (CRP), blood culture, CitH3-DNA and cfDNA were compared between the two groups. The diagnostic value of CITH3-DNA and cfDNA in neonatal septicemia was analyzed by the receiver operating characteristic (ROC) curve.Results:A total of 74 infants were included in the study, including 39 cases in the sepsis group and 35 cases in the control group. CitH3-DNA and cfDNA in the sepsis group were significantly higher than those in the control group [CitH3-DNA (optical density): 0.85±0.05 vs. 0.48±0.03, cfDNA (mg/L): 0.90±0.05 vs. 0.56±0.03] ( P<0.01). There was no significant correlation between CitH3-DNA and cfDNA. The level of CitH3-DNA had no correlation with gender, gestational age, age, birth weight, WBC, NE, PLT and CRP ( P>0.05). cfDNA was positively correlated with age and NE ( P<0.05), and negatively correlated with PLT ( P<0.05). Combined with CRP, the area under the ROC curve of CitH3-DNA+CRP, cfDNA+CRP, and CitH3-DNA+cfDNA+CRP were 0.947, 0.947 and 0.970 respectively, and the sensitivity to predict neonatal sepsis were 92.3%, 84.6% and 94.9% respectively, the specificity were 94.3%, 97.1% and 100% respectively, all higher than the predictive value of each index alone. Conclusions:The plasma NETs levels increase significantly in neonatal sepsis patients, especially CitH3-DNA with a strong specificity, and can be considered as a biomarker for early diagnosis of neonatal sepsis. NETs together with CRP, could drastically improve the predictive value of neonatal sepsis.
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The aim of this study was to evaluate the effects of citrulline malate (CIT) supplementation on aerobic and muscular endurance in young adult males. Eighteen young adult men (age: 21.5 ± 2.7 years) were randomized into two groups (Citrulline malate - CIT and Placebo - PLA; N = 9/ group ) and received the respective supplements for 7 days. The CIT group was supplemented with 6 g CIT + 6 g dextrose (total: 12 g), while the PLA group received the same amount (12 g) of dextrose. At the pre- and post-supplementation, the following variables were analyzed: aerobic (maximal treadmill test, Tmax) and muscle (repetitions maximum test, Rmax) endurance tests, as well as mean and maximum heart rate (HR) in Tmax and ratings of perceived exertion (PSE) in Rmax. No significant (P > 0.05) differences were found between CIT and PLA groups in time until exhaustion in Tmax, total repetitions in Rmax, maximal HR and PSE from pre- to post-supplementation. The mean HR was statistically lower (P < 0.05) in the CIT group compared to the PLA in the Tmax. In conclusion, supplementation of CIT (6 g / day) does not improve aerobic and muscular endurance, as well as maximal HR or PSE in healthy young adults, despite reducing the mean HR during the maximal incremental test. (AU)
O objetivo deste estudo foi avaliar os efeitos da suplementação de citrulina malato (CIT) sobre a resistência aeróbica e muscular em homens adultos jovens. Em um desenho experimental randomizado, duplo-cego e controlado com placebo, dezoito homens adultos jovens (idade: 21,5 ± 2,7 anos) foram randomizados em dois grupos (Citrulina malato CIT e Placebo PLA; N = 9/grupo) e receberam os respectivos suplementos por um período de 7 dias. O grupo CIT foi suplementado com 6 g de CIT + 6 g de dextrose (total: 12 g), enquanto o grupo PLA recebeu a mesma quantidade (12 g) de dextrose. Nos momentos pré e pós suplementação as seguintes variáveis foram analisadas: resistência aeróbia (teste incremental máximo em esteira rolante, Tmáx) e muscular (teste de repetições máximas, Rmáx), bem como a frequência cardíaca (FC) média e máxima no Tmáx e a análise da percepção subjetiva de esforço (PSE) no Rmáx. Nenhuma diferença significante (P > 0,05) foi encontrada entre os grupos CIT e PLA no tempo até a exaustão no Tmáx, total de repetições no Rmáx, FC máxima e PSE do momento pré para o pós suplementação. A FC média foi estatisticamente (P < 0,05) menor no grupo CIT comparado ao PLA no Tmáx. Em conclusão, a suplementação de CIT (6 g/dia) não melhora a resistência aeróbica e muscular, bem como a FC máxima ou PSE em adultos jovens saudáveis, apesar de reduzir a FC média durante o teste incremental máximo. (AU)
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Abstract Citrulline is a non-essential amino acid, involved in key biological functions in plants and humans. Rootstocks have a major impact on citrulline accumulation in grafted watermelon. Information regarding rootstock induced changes in citrulline metabolism is elusive. To understand the regulatory mechanism, parallel changes in the expression profiles of citrulline metabolic genes and citrulline content of watermelon were monitored during the development of self-rooted watermelon and watermelon grafted onto pumpkin, wild and bottle gourd rootstocks. Results demonstrated that rootstocks regulated the expression profiles in different ways to influence the citrulline content. GAT, NAGPR, ASS3 ASS2 and Asl2 showed the negative correlation with citrulline content in pumpkin grafted watermelon. Pumpkin rootstock promoted the citrulline content by high down-regulation and synergistic effect of ASS2, ASS3, ASL1 and ASl2 genes. In wild grafted watermelon, citrulline was accumulated as a result of down regulation of GAT, NAGS and ASL2 genes, which showed an inverse correlation with citrulline. In gourd grafted watermelon, changes in citrulline content were observed to be linked with lower expressions of GAT, NAGK, ASS2, ASS3, ASL1 and ARG which were negatively correlated with citrulline content. Our study will provide the basis to understand the molecular mechanism of citrulline accumulation in various rootstocks.
Resumo A citrulina é um aminoácido não essencial, envolvida em importantes funções biológicas de plantas e seres humanos. Os porta-enxertos têm um grande impacto no acúmulo de citrulina na melancia enxertada. Informações sobre alterações induzidas por porta-enxertos no metabolismo da citrulina ainda não foram descritas. Para entender o mecanismo regulatório, foram monitoradas mudanças paralelas nos perfis de expressão dos genes metabólicos de citrulina e no teor de citrulina da melancia durante o desenvolvimento da melancia e da melancia enxertada em porta-enxertos de abóbora, silvestre e cabaça. Os resultados demonstraram que o porta-enxerto regulou os perfis de expressão de diferentes maneiras para influenciar no conteúdo de citrulina. GAT, NAGPR, ASS3, ASS2 e ASL2 apresentaram correlação negativa com o teor de citrulina em melancia enxertada de abóbora. O porta-enxerto de abóbora promoveu o conteúdo de citrulina por meio de baixa regulação e efeito sinérgico de duas famílias de genes ASS e ASL. Na melancia enxertada, a acumulação de citrulina resultou na regulação negativa de GAT, NAGS e ASL2, que mostraram uma correlação inversa com a citrulina. Na melancia enxertada, observou-se que as alterações no conteúdo de citrulina foram associadas a menores expressões de GAT, NAGK, ASS2, ASS3, ASL1 e ARG, que foram negativamente correlacionadas com o conteúdo de citrulina. Esses resultados fornecem a base para identificar o mecanismo molecular do acúmulo de citrulina em vários porta-enxertos.
Subject(s)
Humans , Citrullus/genetics , Citrulline , Plant RootsSubject(s)
Humans , Post-Exercise Hypotension , Citrulline/analogs & derivatives , Dietary Supplements , MalatesABSTRACT
Intestinal failure (IF) is the critical reduction of the gut mass or its function below the minimum needed to absorb nutrients and fluids required for adequate growth in children. Severe IF requires parenteral nutrition (PN). Pediatric IF is most commonly due to congenital or neonatal intestinal diseases or malformations divided into 3 groups: 1) reduced intestinal length and consequently reduced absorptive surface, such as in short bowel syndrome (SBS) or extensive aganglionosis; 2) abnormal development of the intestinal mucosa such as congenital diseases of enterocyte development; 3) extensive motility dysfunction such as chronic intestinal pseudo-obstruction syndromes. The leading cause of IF in childhood is the SBS. In clinical practice the degree of IF may be indirectly measured by the level of PN required for normal or catch up growth. Other indicators such as serum citrulline have not proven to be highly reliable prognostic factors in children. The last decades have allowed the development of highly sophisticated nutrient solutions consisting of optimal combinations of macronutrients and micronutrients as well as guidelines, promoting PN as a safe and efficient feeding technique. However, IF that requires long-term PN may be associated with various complications including infections, growth failure, metabolic disorders, and bone disease. IF Associated Liver Disease may be a limiting factor. However, changes in the global management of IF pediatric patients, especially since the setup of intestinal rehabilitation centres did change the prognosis thus limiting “nutritional failure” which is considered as a major indication for intestinal transplantation (ITx) or combined liver-ITx.
Subject(s)
Child , Humans , Bone Diseases , Citrulline , Enterocytes , Intestinal Diseases , Intestinal Mucosa , Intestinal Pseudo-Obstruction , Liver Diseases , Micronutrients , Parenteral Nutrition , Parenteral Nutrition, Home , Prognosis , Rehabilitation , Short Bowel SyndromeABSTRACT
Objective To observe the effects of Lianggesan on serum citrulline and intestinal fatty acid binding protein (IFABP) levels in patients with mechanical ventilation and acute gastrointestinal injury (AGI). Methods Eighty patients with mechanical ventilation and AGI admitted to Tianjin First Center Hospital from May to December 2017 were divided into a conventional treatment group and a traditional Chinese medicine (TCM) treatment group according to different treatment methods, 40 cases in each group; 10 patients with mechanical ventilation but without AGI were selected as a control group. All patients were given invasive mechanical ventilation after admission, and the gastrointestinal tract intervention was carried out according to AGI grading treatment process; Lianggesan (compositions:forsythia suspensa 30 g, scutellaria 10 g, gardenia 10 g, bamboo leaf 10 g, rhubarb 10 g, mint 6 g, mirabilite 6 g, licorice 15 g) was added to the TCM treatment group on the basis of the conventional treatment. The above TCM drug used was a single Chinese medicine granule produced by Jiangyin Tianjiang Pharmaceutical Co., Ltd. Each single Chinese herbal granule was proportionally poured into 200 mL boiling water at 80-100 ℃, 100 mL each time, twice daily nasal feeding for one week. The changes of serum citrulline and IFABP levels were observed before and 1, 3, 5 and 7 days after treatment in the three groups. Results Before treatment, serum citrulline levels in the conventional treatment group and the TCM treatment group were significantly lower than those in the control group (μmol/L: 19.84±4.74, 20.84±4.65 vs. 28.89±2.18, both P < 0.05), and IFABP levels were significantly higher than those in the control group (ng/L:571.89±42.89, 552.49±44.78 vs. 155.68±22.95, both P < 0.05), there were no significant differences between the conventional treatment group and the TCM treatment group (P > 0.05); with the extension of treatment time, the levels of citrulline in the conventional and TCM treatment groups were decreased first and then increased gradually, reaching the valley value on the first day of treatment [the two groups were (16.12±4.44), (18.49±4.59) μmol/L] respectively, and then increased gradually, reaching the peak value on the 7th day of treatment, the increased range of citrulline in the TCM treatment group was more obvious than that in the conventional treatment group (μmol/L: 26.77±4.18 vs. 22.75±3.07, P < 0.05), and the treatment lasted for 5 days, and 7 days, the level of citrulline in the TCM treatment group was close to that in the control group; the IFABP levels in the conventional treatment group and the TCM treatment group were increased first and then decreased gradually, reaching the peak value on the first day of treatment [the two groups were (654.23±63.24), (630.32±49.11) ng/L] respectively, and then decreased gradually, reaching the trough value on the 7th day of treatment, the degree of decrease in the TCM treatment group was more obvious than that in the conventional treatment group (ng/L: 262.21±30.89 vs. 375.43±44.43, P < 0.05), but the level of IFABP in the TCM treatment group was still significantly higher than that in the control group (ng/L: 262.21±30.89 vs. 158.95±29.34, P < 0.05). Conclusion Lianggesan can elevate the serum citrulline level, reduce the serum IFABP level, and effectively improve the intestinal function of patients with mechanical ventilation and AGI.
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Objective To investigate the clinical significance of serum citrulline levels in evaluating the remnant bowel absorptive function with enterostomy in the neonatal period by means of tandem mass spectrum so as to guide clinical treatment with parenteral nutrition(PN) or not.Methods The serum amino acid profiles of 30 enterostomy infants including small intestinal enterostomy 17 cases of enterostomy and 13 cases of colon enterostomy and 20 cases of control infants in Wuhan Children's Hospital,Tongji Medical College University of Science & Technology from January 2016 to June 2018 were performed by using tandem mass spectrum,and the related amino acid with the bowel absorbing ability-citrulline was screened out.The Pearson correlation of the serum citrulline levels with the gain weight of the infants was studied.Results The weight of small intestinal enterostomy was significantly lower than colon enterostomy and control infants [(3.22 ± 1.00) kg vs.(5.63 ± 0.66) kg and (6.09 ± 0.85) kg],and there was statistical significance (F =57.23,P ＜ 0.05).Serum citrulline levels were significantly lower in small intestinal enterostomy compared with colon enterostomy and controls [(10.65 ± 5.82) μmol/L vs.(16.57 ± 4.33) μmol/L and (16.52 ± 4.20) μmol/L],and there was statistical significance (F =8.29,P ＜ 0.05).In enterostomy infants serum citrulline was positively correlated with gain weight everyday(r =0.65,P ＜ 0.05).Serum citrulline level ＜ 12 μmol/L had 81.3％ sensitivity and 71.4％ specificity for underweight.Conclusions Serum citrulline is a simple and accurate biomarker for evaluation of the absorptive function and adaptation of the enterostomy infants.Serum citrulline level ＜ 12 μmol/L is a strong predictor of PN-dependence in infants with temporary enterostomy.
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Objective To investigate the early diagnostic value of intra-abdominal pressure (IAP) combined with intestinal fatty acid binding protein (IFABP) for patients with mechanical ventilation complicated with acute gastrointestinal injury (AGI).Methods From August 2015 to December 2015,1 19 patients with mechanical ventilation were admitted to ICU in our hospital,with 78 cases of AGI patients and 41 cases of non-AGI patients.Multiple physiological indexes and laboratory indexes of the two groups were recorded and compared.Results There was no statistical difference in sex,age,APACHE Ⅱ score,BMI index,Lac and mean arterial pressure (MAP) between the two groups (P ＞0.05);the OR values of mechanical ventilation time,oxygenation index,end-expiratory positive pressure (PEEP),CIT,IFABP and IAP were more than 1,so these indicators were all risk factors for AGI in patients with mechanical ventilation.The area under the curve of IAP,IFABP,mechanical ventilation and PEEP were more than 0.5,indicating that these indicators have a certain predictive value for AGI patients with mechanical ventilation.The sensitivity and specificity of IAP were 95％ and 80％ respectively,and the sensitivity and specificity of IFABP were 87.5％ and 50％,respectively.IAP was correlated with IFABP (r =0.621,P =0.031).Conclusions Mechanical ventilation time,oxygenation index,PEEP,CIT,IFABP,and IAP are risk factors for AGI patients with mechanical ventilation.IAP,IFABP,mechanical ventilation time and PEEP have a certain predictive value for AGI patients with mechanical ventilation.The diagnostic value of IAP and IFABP is high,and the two are closely related.Combined application can provide a certain objective basis for clinical AGI diagnosis.
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Damage control and gastrointestinal surgery have come a long way from the first reported case of an enterocutaneous fistula to advances in Intestinal transplant and vacuum assisted therapy. Everything we have known in between such as intestinal resections, enteral/parenteral nutrition, delayed abdominal wall closure and intestinal reconstruction have all lead to an exponential increase in our knowledge of gastrointestinal surgery. One area that still remains a significant challenge and clinical dilemma to the general surgeon is intestinal failure in short bowel syndrome. Not only does the anatomical complexity of short bowel syndrome offer difficulties in the definite reconstruction, but also the accompanying intestinal failure increases patient morbidity and mortality. There are no current algorithms or systematic approaches to these daunting clinical scenarios and although surgery has come a long way, there is still room for determining optimal approaches. Therefore, it is critical to keep researching new ways to treat these patients. A relatively new horizon in managing intestinal failure in short bowel syndrome is the use of biomarkers. Here we present a short review on the possible future treatment. The aim of this paper is to provide a pathway for future research into the treatment of this complex area of general surgery
La cirugía gastrointestinal y de control de daños ha tenido un recorrido amplio desde el primer caso reportado de fístula entero-cutánea, hasta llegar al uso de presión subatmosférica para el cierre asistido y el trasplante intestinal. Todos los avances propuestos en el intermedio, como las resecciones intestinales, los planes de nutrición entérica y parenteral, el cierre postergado de la pared abdominal y la reconstrucción intestinal, han llevado a un aumento exponencial del conocimiento de la cirugía gastrointestinal. A pesar de esto, hay un área que permanece como un reto significativo y un dilema clínico para el cirujano general: la falla intestinal en el síndrome de intestino corto. En esta, su complejidad anatómica presenta dificultades a la hora de su reconstrucción, y su alteración funcional aumenta la morbimortalidad del paciente. Así como sucede en la mayoría de las fallas específicas de órganos, esta se caracteriza por cambios en los marcadores séricos que ya han sido bien descritos en la literatura médica. En la falla cardiaca hay elevación del péptido natriurético auricular; en la falla renal, elevación de la creatinina sérica; en la falla hepática, elevación de las transaminasas, y así sucesivamente. Estos marcadores no solo indican la gravedad de la situación, sino que se relacionan con la suficiencia del órgano en cuanto a su función y su mejoría con la rehabilitación. Ahora, ¿cuáles son los marcadores del sistema gastrointestinal? Recientemente, la seriedad de la falla intestinal y su solución han sido objeto de la observación clínica y sintomática con el fin de determinar la orientación de la rehabilitación intestinal y el momento ideal para el inicio de la vía oral. En los últimos años han surgido biomarcadores pertinentes al estudio del sistema digestivo. En esta revisión se discuten los aspectos relacionados con el presente y el futuro de los marcadores serológicos intestinales en el síndrome de intestino corto
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Humans , Short Bowel Syndrome , Biomarkers , Citrulline , Apoprotein(a)ABSTRACT
ABSTRACT Objective To investigate whether acute citrulline supplementation might influence post-exercise hypotension in normotensive and hypertensive individuals. Methods Following a randomized double-blind design, twenty normotensive (28±7 years, 74±17kg, 1.7±0.09m) and 20 hypertensive individuals (55±12 years, 76±15kg, 1.59±0.09m) were randomly assigned to one of the four experimental groups (Normotensive-Placebo; Normotensive-Citrulline; Hypertensive-Placebo; Hypertensive-Citrulline). The placebo groups ingested 6g of corn starch and the citrulline groups ingested 6g of citrulline dissolved in water. The participants performed 40 minutes of walking/running on a treadmill at 60-70% heart rate reserve. Blood pressure was measured immediately after a 60-min exercise session using an oscillometric device and 24-h ambulatory monitoring. Results The post-exercise hypotension was more pronounced in hypertensives and the Hypertensive-Citrulline group showed a consistent systolic blood pressure reduction during the laboratorial phase, which can be seen by looking at the mean of 60 minutes (-15.01mmHg vs -3.14mmHg [P=0.005]; -4.16mmHg [P=0.009]; -6.30mmHg [P=0.033] in comparison with the Normotensive-Placebo, Normotensive-Citrulline, and Hypertensive-Placebo groups, respectively). During ambulatory blood pressure monitoring, the Hypertensive-Citrulline group showed a significant reduction in systolic blood pressure (-21.05mmHg) in the awake period compared with the Normotensive-Citrulline group (-3.17mmHg [P=0.010]). Conclusion Acute citrulline oral supplementation can induce greater post-exercise hypotension response in hypertensive than normotensive individuals.
RESUMO Objetivo Investigar se a suplementação aguda de citrulina pode influenciar a hipotensão pós-exercício em indivíduos normotensos e hipertensos. Métodos Seguindo delineamento duplo-cego randomizado, vinte indivíduos normotensos (28±7 anos, 74±17kg, 1,7±0,09m) e 20 hipertensos (55±12 anos, 76±15kg, 1,59±0,09m) foram randomizados e distribuídos em um dos quatro grupos experimentais (Normotenso-Placebo; Normotenso-Citrulina; Hipertenso-Placebo; Hipertenso--Citrulina). Os grupos placebo ingeriram 6g de amido de milho e os grupos citrulina 6g de citrulina, dissolvidos em água. Os participantes realizaram 40 minutos de caminhada/corrida em esteira a uma intensidade entre 60-70% da frequência cardíaca de reserva. A pressão arterial foi aferida imediatamente após a sessão de exercício por 60 minutos usando um equipamento oscilométrico, e durante 24 horas por monitorização ambulatorial. Resultados A hipotensão pós-exercício foi mais pronunciada nos hipertensos e o grupo Hipertenso-Citrulina mostrou uma redução consistente da pressão arterial sistólica durante a fase laboratorial, o que pode ser visto pela média de 60 minutos (-5,01mmHg vs -3,14mmHg [P=0,005]; -4,16mmHg [P=0,009]; -6,30mmHg [P=0,033] em comparação com o Normotenso-Placebo, Normotenso-Citrulina e Hipertenso-Placebo, respectivamente). Durante a monitorização ambulatorial da pressão arterial, o Hipertenso-Citrulina demonstrou uma redução significativa na pressão arterial sistólica (-21,05mmHg) durante a vigília em comparação com o Normotenso-Citrulina (-3,17mmHg [P=0,010]). Conclusão A suplementação oral aguda de citrulina induz maior resposta hipotensiva pós-exercício em indivíduos hipertensos do que normotensos.
Subject(s)
Humans , Male , Female , Dietary Supplements , Exercise , Citrulline , Blood Pressure Monitoring, Ambulatory , Post-Exercise Hypotension , Arterial Pressure , HypertensionABSTRACT
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 in food supplements and concentrations in energy drinks given by NFSA. These risk assessments will provide NFSA with the scientific basis while regulating the addition of “other substances” to food supplements and other foods. "Other substances" are described in the food supplement directive 2002/46/EC as substances other than vitamins or minerals that have a nutritional and/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-citrulline, and it is based on a previous risk assessment and articles retrieved from a literature search. According to information from NFSA, L-citrulline is an ingredient in food supplements sold in Norway. NFSA has requested a risk assessment of 1000, 1500 and 2000 mg/day of L-citrulline in food supplements. The intake of L-citrulline was estimated for the age groups children (10 to <14 years), adolescents (14 to <18 years) and adults (≥18 years). Other sources of L-citrulline, such as foods and cosmetics, have not been included in the present risk assessment. The natural isoform of citrulline is the L-form. In mammals, it is found in all organisms and tissues. L-Citrulline is not part of the amino acids that are incorporated into proteins by the standard genetic code; therefore it is classified as a non-protein amino acid. Thus, its presence in a protein always results from a post-translational modification of the protein. L-citrulline is found in high levels in certain Cucurbitacea, including watermelon, cucumber, pumpkin and courgette, and in certain algae such as Grateloupia vulgaris. It is also present in fish, meat, pulses and milk, and in vegetables such as onions and garlic. Following oral intake of L-citrulline, plasma L-citrulline concentration increases rapidly but returns to baseline values within 5-8 hours post-exposure. There are three interconnected metabolic pathways for L-citrulline: 1) arginine biosynthesis, 2) nitric oxide (NO) cycle, and 3) the complete urea cycle. Renal L-citrulline reabsorption appears very efficient because urinary loss is very low even at high (up to 15 g) L-citrulline intake. No adverse health effects of L-citrulline were observed in six human studies covering the ages 12 months to 56 years, with L-citrulline exposure lengths varying from less than one day (acute doses) to 2 years. The doses varied from 2.1-179 mg/kg bw per day for children. (<14 years), 1.5-175 mg/kg bw per day for adolescents (14 to <18 years) and 21-214 mg/kg bw per day in adults. The human studies available had low number of participants and, with exception of one study, included non-healthy populations. In a 2-year study by Rajantie et al. (1980), 19 patients with lysinuric protein intolerance, ages 1.9-32.7 years, were included. No adverse effects were reported from daily intakes of 65 mg/kg bw in children (10 to <14 years), 46 mg/kg bw in adolescents (14 to <18 years) and 40 mg/kg bw in adults (highest doses applied). These age-specific reference points were used for comparisons with the estimated exposures in the risk characterization. For children, from a daily intake of 1000, 1500 and 2000 mg the estimated exposures are 23.0, 34.6 and 46.1 mg/kg bw per day, respectively. These intake values are below 65 mg/kg bw per day. VKM therefore considers it unlikely that a daily intake of 1000, 1500 or 2000 mg L-citrullline from food supplements causes adverse health effects in children (10 to <14 years). For adolescents, from a daily intake of 1000, 1500 and 2000 mg the estimated exposures are 16.3, 24.5 and 32.6 mg/kg bw per day, respectively. These intake values are below 46 mg/kg bw per day. VKM therefore considers it unlikely that a daily intake of 1000, 1500 or 2000 mg L-citrullline from food supplements causes adverse health effects adolescents (14 to <18 years). For adults, from a daily intake of 1000, 1500 and 2000 mg the estimated exposures are 14.3, 21.4 and 28.6 mg/kg bw per day, respectively. These intake values are below 40 mg/kg bw per day. VKM therefore considers it unlikely that a daily intake of 1000, 1500 or 2000 mg L-citrullline from food supplements causes adverse health effects in adults (≥18 years). Since LPI patients have a different intestinal absorption, renal reabsorption and reduced intracellular efflux of cationic amino acids compared to healthy individuals, it is uncertain whether doses given to LPI patients can be directly extrapolated to healthy individuals. Persons with citrullinemia caused by mutations in enzymes involved in citrulline metabolism are potentially vulnerable to intake of additional L-citrulline from supplements. In addition, humans with chronic renal failure and/or mutations in renal citrulline transporters are potentially vulnerable to supplementation of L-citrulline.
ABSTRACT
L-arginine (L-Arg) is an alkaline amino acid that possesses various function groups and acts as an important precursor for useful chemical synthesis. L-Arg derivatives are widely applied in pharmaceutical, food and cosmetic industries. Environment friendly and cost-effective production of L-Arg derivatives by enzymatic catalysis provides significant advantages over chemical synthesis and microbial fermentation. In this article, several typical L-Arg derivatives and their enzymatic production processes are highlighted. Furthermore, prospect is also addressed about enzymatic production of L-Arg derivatives.
ABSTRACT
Abstract Citrulline is a non-essential amino acid, involved in key biological functions in plants and humans. Rootstocks have a major impact on citrulline accumulation in grafted watermelon. Information regarding rootstock induced changes in citrulline metabolism is elusive. To understand the regulatory mechanism, parallel changes in the expression profiles of citrulline metabolic genes and citrulline content of watermelon were monitored during the development of self-rooted watermelon and watermelon grafted onto pumpkin, wild and bottle gourd rootstocks. Results demonstrated that rootstocks regulated the expression profiles in different ways to influence the citrulline content. GAT, NAGPR, ASS3 ASS2 and Asl2 showed the negative correlation with citrulline content in pumpkin grafted watermelon. Pumpkin rootstock promoted the citrulline content by high down-regulation and synergistic effect of ASS2, ASS3, ASL1 and ASl2 genes. In wild grafted watermelon, citrulline was accumulated as a result of down regulation of GAT, NAGS and ASL2 genes, which showed an inverse correlation with citrulline. In gourd grafted watermelon, changes in citrulline content were observed to be linked with lower expressions of GAT, NAGK, ASS2, ASS3, ASL1 and ARG which were negatively correlated with citrulline content. Our study will provide the basis to understand the molecular mechanism of citrulline accumulation in various rootstocks.
Resumo A citrulina é um aminoácido não essencial, envolvida em importantes funções biológicas de plantas e seres humanos. Os porta-enxertos têm um grande impacto no acúmulo de citrulina na melancia enxertada. Informações sobre alterações induzidas por porta-enxertos no metabolismo da citrulina ainda não foram descritas. Para entender o mecanismo regulatório, foram monitoradas mudanças paralelas nos perfis de expressão dos genes metabólicos de citrulina e no teor de citrulina da melancia durante o desenvolvimento da melancia e da melancia enxertada em porta-enxertos de abóbora, silvestre e cabaça. Os resultados demonstraram que o porta-enxerto regulou os perfis de expressão de diferentes maneiras para influenciar no conteúdo de citrulina. GAT, NAGPR, ASS3, ASS2 e ASL2 apresentaram correlação negativa com o teor de citrulina em melancia enxertada de abóbora. O porta-enxerto de abóbora promoveu o conteúdo de citrulina por meio de baixa regulação e efeito sinérgico de duas famílias de genes ASS e ASL. Na melancia enxertada, a acumulação de citrulina resultou na regulação negativa de GAT, NAGS e ASL2, que mostraram uma correlação inversa com a citrulina. Na melancia enxertada, observou-se que as alterações no conteúdo de citrulina foram associadas a menores expressões de GAT, NAGK, ASS2, ASS3, ASL1 e ARG, que foram negativamente correlacionadas com o conteúdo de citrulina. Esses resultados fornecem a base para identificar o mecanismo molecular do acúmulo de citrulina em vários porta-enxertos.
ABSTRACT
Objective To investigate the diagnostic significance of combined detection of rheumatoid factor (RF),anti-cyclic cit-rullinated antibody (anti-CCP antibody),glucose-6-phosphatase (GPI)and anti-RA33 antibody in rheumatoid arthritis (RA).Meth-ods One hundred and twenty-six patients with RA,60 patients with other autoimmune diseases and 60 healthy subjects undergoing physical examination were selected as the research subjects.The singled detection of RF,anti-CCP antibody,GPI and anti-RA33 an-tibody,and their combined detection were used to analyze their roles in RA diagnosis.Results Compared with the healthy control group,the four indexes in the RA group were increased,the difference was statistically significant (P<0.05),the RF level in the autoimmune diseases group was increased compared with the control group,the difference was statistically significant(P<0.05). Compared with the the autoimmune diseases group,the four indexes in the RA group were increased,the difference was statistically significant (P<0.05).The sensitivity and specificity of RF to RA were 77.77% and 63.33%;the sensitivity and specificity of anti-CCP antibody to RA were 69.04% and 95.00%;the sensitivity and specificity of GPI antibody to RA were 25.40% and 100.00%;the sensitivity and specificity of anti-RA33 antibody were 27.77% and 99.16%,respectively.The specificity of combined 2 indica-tors was increased from 63.33% to 85.00%,which of combined 3 indicators was increased to 93.33% and which of combined 4 in-dicators even reached to 100.00%.Conclusion The combination of RF,anti-CCP antibody,GPI and anti-RA33 antibody indicators greatly increases with the sensitivity and specificity for diagnosing RA and has clinical significance.
ABSTRACT
Objective To explore the role of the changes in endogenous L-citrulline levels and arginases expression in erectile dysfunction of diabetic rats,and investigate the effect of L-citrulline incubation ex vivo on the erectile dysfunction.Methods Type 2 diabetic rats were induced by high fat diet plus a single intraperitoneal injection of small dose streptozotocin (30 mg/kg),followed by high fat diet for 8 weeks.The erectile function of rats was reflected by the relaxation response to acetylcholine (ACh) of corpus cavernosum detected by isometric tension measurement.Levels of endogenous nitric oxide inhibitor asymmetric dimethylarginine (ADMA) and cyclic guanosine monophosphate (cGMP) were measured by enzyme-linked immunosorbent assay (ELISA).The content of L-citrulline,nitric oxide (NO) and the activity of nitric oxide synthase (NOS) were determined with colorimetric method.Western blotting was applied to detect the protein expression of NOS,arginases and phosphodiesterase 5 (PEDS).Results The relaxation response to ACh of corpus cavernosum from diabetic rats was significantly lower than that of control rats (P ＜ 0.01),indicating the erectile dysfunction of diabetic rats.This erectile dysfunction was companied by the decreases of L-citrulline levels in serum and corpus cavernosum as well as up-regulation of arginaseⅠ & Ⅱ expression in the corpus cavernosum of diabetic rats.Incubation with L-citrulline (3 mmol/L) for 45 min ex vivo improved the relaxation function of corpus cavernosum from diabetic rats (P ＜ 0.05),while incubation with PED5 inhibitor silaenafil (3 μmoL/L) had no significant effect.Furthermore,the ADMA level was increased,while the NOS activity,cGMP and NO contents were decreased in corpus cavernosum of diabetic rats compared to control rats.Down-regulation of endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) protein expression as well as up-regulation of inducible nitric oxide synthase (iNOS) and PDE5 protein expression were also observed in the corpus cavernosum of diabetic rats.Conclusions The decreased endogenous L-citrulline levels and upregulated arginases expression was closely related to erectile dysfunction of diabetic rats,and the mechanism is associated to the up-regulation of arginase activity and decrease of NO synthesis in corpus cavernosum.L-citrulline incubation ex vivo exerted therapeutic effect on the relaxation dysfunction of corpus cavernosum from diabetic rats.
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Objective To observe the incidence of acute gastrointestinal injury (AGI) in intensive care unit (ICU) patients, and to approach the value of serum citrulline and intestinal fatty acid binding protein (IFABP) on diagnosis of AGI in critical patients. Methods A prospective study was conducted. 576 critical patients admitted to ICU of Yantai Yuhuangding Hospital from February 2016 to February 2017 were enrolled. According to the AGI classification proposed by European Society of Intensive Care Medicine (ESICM) in 2012, the AGI and severity of the patients were observed. The general data, severity and prognosis of patients with different AGI grades were recorded. According to the random number table, 20 patients with normal kidney function from AGI Ⅰ to Ⅳ were selected. The femoral artery blood was collected within 12 hours of ICU admission, and serum citrulline level was detected by high performance liquid chromatography (HPLC). Serum IFABP level was determined by enzyme-linked immunosorbent assay (ELISA). Twenty healthy subjects were selected as controls. The receiver operating characteristic curve (ROC) was drawn, and the predictive values of citrulline and IFABP for AGI diagnosis were evaluated. Results ① 576 patients were enrolled in the analysis. Of which 530 patients (92.0%) had AGI, and 289 patients with gradeⅠ (54.5%), 154 with grade Ⅱ (29.1%),64 with grade Ⅲ (12.1%), and 23 with grade Ⅳ (4.3%). With the increase in AGI classification, acute physiology and chronic health evaluation system Ⅱ (APACHE Ⅱ) score, sequential organ failure score (SOFA), the length of ICU stay and 28-day mortality were gradually increased. ② Compared with health control group, the levels of serum citrulline in patients with different AGI grades were significantly decreased, and IFABP was significantly increased. With the increase in AGI classification, the citrulline level was gradually decreased, and IFABP level was gradually increased [citrulline levels (μmol/L) in AGIⅠ,Ⅱ,Ⅲ,Ⅳ groups were 14.1±3.6, 12.7±3.1, 8.3±2.7, and 5.6±3.4, F = 3.287, P = 0.027, and IFABP levels (ng/L) were 526.7±204.9, 698.4±273.8, 894.7±455.9, and 1 062.8±532.2, F = 2.903, P = 0.043]. ROC curve analysis showed that citrulline had a higher predictive value for AGI diagnosis. The area under the ROC curve (AUC) was 0.927. When the cut-off value of citrulline was 9.7 μmol/L, the sensitivity and specificity were 87.5% and 87.5%, respectively. The AUC of IFABP was 0.043, which has no predictive value for the diagnosis of AGI. Conclusions The AGI is extremely common in ICU. The higher the AGI grade is, the worse the prognosis is. Citrulline has high diagnostic value for AGI in critical patients, but IFABP has no predictive value on the diagnosis of AGI.
ABSTRACT
Arginine deiminase (ADI) was first high-efficient expressed in Corynebacterium crenatum SYPA 5-5. The ADI was purified by Ni-NTA affinity chromatography and SDS-PAGE analysis showed the molecular weight (MW) was 46.8 kDa. The optimal temperature and pH of ADI were 37 ℃ and 6.5 respectively. The Michaelis constant was 12.18 mmol/L and the maximum velocity was 0.36 μmol/(min·mL). Under optimal conditions, 300 g/L of arginine was transformed and the productivity reach 8 g/(L·h). The recombinant strain was cultivated in a 5-L fermentor and used for whole-cell transformation of 300 g/L arginine, under repeated-batch bioconversion, the cumulative production reached 1 900 g/L.