- 作者列表："Cox SE","Hart E","Kirkham FJ","Stotesbury H
:L-Glutamine is a conditionally essential amino acid required for synthesis of the pyridines for nucleotides, including nicotinamide adenine dinucleotide (NAD) and glutathione, as well as glutamate, and becomes essential during oxidative stress exposure. The NADH:[NAD⁺ + NADH] (redox) ratio in sickle red blood cells (RBCs) is lower than in normal RBCs, consistent with oxidative stress, therefore glutamine availability is important in sickle cell disease (SCD). RBC glutamine levels vary between SCD studies but the ratio glutamine:glutamate was inversely related to tricuspid regurgitant jet velocity in one. Oral L-glutamine was associated with an increase in NADH and reduction in RBC endothelium adhesion in small studies of SCD patients. In a sickle mouse model, glutamine levels were directly related to cerebral blood flow. Phase II and III randomized, double-blind, controlled trials of L-glutamine 0.6 g/kg/day compared with placebo in children and adults with SCD and = 2 episodes of pain in the previous year provide evidence that L-glutamine is safe and associated with a reduction in painful episodes and in hospitalizations. However, L-glutamine was only tolerated in two-thirds of patients, anemia and hemolysis did not improve and there are few data on mortality and organ complications. Future studies should investigate the effect of other amino acids and total protein intake.
L-谷氨酰胺是合成核苷酸的吡啶 (包括烟酰胺腺嘌呤二核苷酸 (NAD) 和谷胱甘肽) 以及谷氨酸所需的条件必需氨基酸，并且在氧化应激暴露期间变得必需。镰状红细胞 (rbc) 中的NADH:[NAD⁺ + NADH] (氧化还原) 比率低于正常rbc，与氧化应激一致，因此谷氨酰胺可用性在镰状细胞病 (SCD) 中很重要。RBC谷氨酰胺水平在SCD研究之间变化，但谷氨酰胺: 谷氨酸的比率与三尖瓣反流射流速度呈负相关。在SCD患者的小型研究中，口服L-谷氨酰胺与NADH的增加和RBC内皮粘附的减少相关。在镰状小鼠模型中，谷氨酰胺水平与脑血流量直接相关。II期和III期随机，双盲，L-谷氨酰胺0.6g/kg/天与安慰剂相比，在儿童和成人SCD患者中进行的对照试验提供了证据，证明L-谷氨酰胺是安全的，并且与疼痛发作和住院治疗的减少相关。然而，L-谷氨酰胺仅在3分之2的患者中耐受，贫血和溶血没有改善，并且关于死亡率和器官并发症的数据很少。未来的研究应该调查其他氨基酸和总蛋白摄入量的影响。
METHODS:BACKGROUND:Thalassemia is one of the most common monogenetic diseases in the south of China and Southeast Asia. Hemoglobin Bart's hydrops fetalis syndrome was caused by a homozygous Southeast Asian deletion (-/-) in the HBA gene. Few studies have proved the potential of screen for Bart's hydrops fetalis using fetal cell-free DNA. However, the number of cases is still relatively small. Clinical trials of large samples would be needed. OBJECTIVE:In this study, we aimed to develop a noninvasive method of target-captured sequencing and genotyping by the Bayesian method using cell-free fetal DNA to identify the fetal genotype in pregnant women who are at risk of having hemoglobin Bart hydrops fetalis in a large-scale study. STUDY DESIGN:In total, 192,173 couples from 30 hospitals were enrolled in our study and 878 couples were recruited, among whom both the pregnant women and their husbands were detected to be carriers of Southeast Asian type (-/αα) of α-thalassemia. Prenatal diagnosis was performed by chorionic villus sampling, amniocentesis, or cordocentesis using gap-polymerase chain reaction considered as the golden standard. RESULTS:As a result, we found that the sensitivity and specificity of our noninvasive method were 98.81% and 94.72%, respectively, in the training set as well as 100% and 99.31%, respectively, in the testing set. Moreover, our method could identify all of 885 maternal samples with the Southeast Asian carrier and 36 trisomy samples with 100% of sensitivity in T13, T18, and T21 and 99.89% (1 of 917) and 99.88% (1 of 888) of specificity in T18 and T21, respectively. CONCLUSION:Our method opens the possibility of early screening for maternal genotyping of α-thalassemia, fetal aneuploidies in chromosomes 13/18/21, and hemoglobin Bart hydrops fetalis detection in 1 tube of maternal plasma.
METHODS:OBJECTIVES:Sickle cell disease (SCD) is a serious illness with disabling acute and chronic pain that needs better therapies, but insufficient patient participation in research is a major impediment to advancing SCD pain management. The purpose of this article is to discuss the challenges of conducting an SCD study and approaches to successfully overcoming those challenges. DESIGN:In a repeated-measures, longitudinal study designed to characterize SCD pain phenotypes, we recruited 311 adults of African ancestry. Adults with SCD completed 4 study visits 6 months apart, and age- and gender-matched healthy controls completed 1 visit. RESULTS:We recruited and completed measures on 186 patients with SCD and 125 healthy controls. We retained 151 patients with SCD with data at 4 time points over 18 months and 125 healthy controls (1 time point) but encountered many challenges in recruitment and study visit completion. Enrollment delays often arose from patients' difficulty in taking time from their complicated lives and frequent pain episodes. Once scheduled, participants with SCD cancelled 49% of visits often because of pain; controls canceled 30% of their scheduled visits. To facilitate recruitment and retention, we implemented a number of strategies that were invaluable in our success. CONCLUSION:Patients' struggles with illness, chronic pain, and their life situations resulted in many challenges to recruitment and completion of study visits. Important to overcoming challenges was gaining the trust of patients with SCD and a participant-centered approach. Early identification of potential problems allowed strategies to be instituted proactively, leading to success.
METHODS:OBJECTIVES:Sickle cell anemia is the commonest genetic disorder in India, and the frequency of the sickle cell gene is very high in the remote tribal areas where facilities are generally limited. Therefore, a rapid and affordable point-of-care test for sickle cell disease is needed. METHODS:The diagnostic accuracy of HemoTypeSC was evaluated against automated high-performance liquid chromatography (HPLC) as the gold standard for its efficacy in a newborn screening program. RESULTS:A total of 1,559 individuals (980 newborns and 579 adults) from four participating centers were analyzed by both methods. HemoTypeSC correctly identified 209 of 211 total hemoglobin (Hb) SS cases, for a 99.1%/99.9% total HbSS sensitivity/specificity. Overall, HemoTypeSC exhibited sensitivity and specificity of 98.1% and 99.1% for all possible phenotypes (HbAA, HbAS, and HbSS) detected. HPLC is relatively expensive and not available in most laboratories in remote tribal areas. CONCLUSIONS:We conclude that the rapid, point-of-care testing device HemoTypeSC test is suitable for population and newborn screening for the HbS phenotype.