Plasma micronutrient concentrations in infants undergoing therapy for phenylketonuria

Twenty-seven infants with classical phenylketonuria were evaluated longitudinally for 6 mo while ingesting Phenex^TM -1 Amino Acid Modified Medical Food With Iron as their primary protein source. Intake of selected nutrients and biochemical indices of trace and ultratrace mineral status and plasma retinol and α-tocopherol concentrations were evaluated. The means of iron status indices (complete blood count, plasma ferritin, iron, transferrin saturation, total iron binding capacity) and the plasma concentrations of trace and ultratrace minerals (copper, manganese, molybdenum, selenium, zinc) and plasma retinol and α-tocopherol were in the reference ranges. Vitamin A intakes (r = 0.49,p < 0.05) and plasma retinol-binding protein concentrations (r = 0.42,p < 0.05) were positively correlated with plasma retinol concentrations at 3 mo of study. At 6 mo, concentrations of plasma transthyretin (r = 0.72,p < 0.01) and retinolbinding protein (r = 0.48,p < 0.05) were positively correlated with plasma retinol concentrations. At 6 mo, concentrations of plasma transthyretin (r = 0.52,p < 0.05) were positively correlated with retinol-binding protein concentrations. Phenex-1 supports normal mean iron status indices and mean concentrations of trace and ultratrace minerals, retinol, and α-tocopherol when fed in adequate amounts.     

Plasma zinc and copper in Paris area preschool children with growth impairment

Plasma zinc, copper, and parameters of growth were measured in a group of 116 French preschool children, 2–5 yr-old from low-income households. Participants were selected on the basis of Z-scores of weight for height (WHZ) and height for age (HAZ). Zinc and copper concentrations of children with growth impairment (GI), defined by a WHZ and/or HAZ< −1 Z-score, were compared to those of age, sex, and ethnic origin matched controls (WHZ and HAZ >−1 Z-score). Mean (±SD) plasma zinc concentration was 12.58±1.84 μmol/L in the GI group, and 13.27±1.98 μmol/L in the controls. The difference of the means of paired samples was 0.69±2.34, and by pairedt-test the significance reachedp=0.028. This effect was primarily a result of the weight retarded group (WHZ <−1 Z-score,p<0.009) and to the girls (p<0.05). There were no significant differences in plasma copper concentrations between groups. These results suggest the presence of marginal zinc deficiency in French preschool children with low weight for height Z-scores.     

Mutations of the phenylalanine hydroxylase gene in patients with phenylketonuria in Shanxi,China

The variation in mutations in exons 3, 6, 7, 11 and 12 of the phenylalanine hydroxylase (PAH) gene was investigated in 59 children with phenylketonuria (PKU) and 100 normal children. Three single nucleotide polymorphisms were detected by sequence analysis. The mutational frequencies of cDNA 696, cDNA 735 and cDNA 1155 in patients were 96.2%, 76.1% and 7.6%, respectively, whereas in healthy children the corresponding frequencies were 97.0%, 77.3% and 8.3%. In addition, 81 mutations accounted for 61.0% of the mutant alleles. R111X, H64 > TfsX9 and S70 del accounted for 5.1%, 0.8% and 0.8% mutation of alleles in exon 3, whereas EX6-96A > G accounted for 10.2% mutation of alleles in exon 6. R243Q had the highest incidence in exon 7 (12.7%), followed by Ivs7 + 2 T > A (5.1%) and T278I (2.5%). G247V, R252Q, L255S, R261Q and E280K accounted for 0.8% while Y356X and V399V accounted for 5.9% and 5.1%, respectively, in exon 11. R413P and A434D accounted for 5.9% and 2.5%, respectively, in exon 12. Seventy-two variant alleles accounted for the 16 mutations observed here. The mutation characteristics and distributions demonstrated that EX6-96A > G and R243Q were the hot regions for mutations in the PAH gene in Shanxi patients with PKU.     

Mutational landscape of phenylketonuria in Iran

To date more than 1000 different variants in the PAH gene have been identified in patients with phenylketonuria (PKU). In Iran, several studies have been performed to investigate the genetics bases of the PKU in different parts of the country. In this study, we have analysed and present an update of the mutational landscape of the PAH gene as well as the population genetics and frequencies of detected variants for each cohort. Published articles on PKU mutations in Iran were identified through a comprehensive PubMed, Google Scholar, Web of Science (ISI), SCOPUS, Elsevier, Wiley Online Library and SID literature search using the terms: “phenylketonuria”, “hyperphenylalaninemia”, and “PKU” in combination with “Iran”, “Iranian population”, “mutation analysis”, and “Molecular genetics”. Among the literature-related to genetics of PKU, 18 studies were on the PKU mutations. According to these studies, in different populations of Iran 1497 patients were included for mutation detection that resulted in detection of 129 different mutations. Results of genetic analysis of the different cohorts of Iranian PKU patients show that the most prevalent mutation in Iran is the pathogenic splice variant c.1066-11G > A, occurring in 19.54% of alleles in the cohort. Four other common mutations were p.Arg261Gln, p.Pro281Leu, c.168 + 5G > C and p.Arg243Ter (8.18%, 6.45%, 5.88% and 3.7%, respectively). One notable feature of the studied populations is its high rate of consanguineous marriages. Considering this feature, determining the prevalent PKU mutations could be advantageous for designing screening and diagnostic panels in Iran.     

Plasma zinc concentrations of mothers and the risk of oral clefts in their children in Utah

BACKGROUND: The role of maternal zinc nutrition in human oral clefts (OCs) is unclear. We measured plasma zinc concentrations (PZn) of case and control mothers to evaluate the associations between PZn and risk of OCs with and without other malformations. METHODS: Case mothers were ascertained by the Utah Birth Defects Network and control mothers were selected from Utah birth certificates by matching for child gender and delivery month and year. Maternal blood was collected >1 year after the last pregnancy. PZn was available for 410 case mothers who were divided into four subgroups: isolated cleft lip with or without cleft palate (CL/P‐I, n = 231), isolated cleft palate (CP‐I, n = 74), CL/P with other malformations (CLP‐M, n = 42), and CP with other malformations (CP‐M, n = 63). PZn was available for 447 control mothers. The mean age of children at blood sampling was 3.7 years for all cases combined and 4.3 years for controls. RESULTS: Mean PZns of all groups were similar, and low PZn (<11.0 μmol/L) was found in 59% of cases and 62% of controls. Risk of OCs did not vary significantly across PZn quartiles for the four subgroups individually and all OC groups combined. CONCLUSIONS: We previously reported that poor maternal zinc status was a risk factor for OCs in the Philippines, where OC prevalence is high and maternal PZn is low. In Utah, however, no such association was found, suggesting that poor maternal zinc status may become a risk factor only when zinc status is highly compromised. Birth Defects Research (Part A), 2009. © 2008 Wiley‐Liss, Inc.     

Plasma active and inactive renin concentrations in children

Plasma active and inactive renin concentrations (PARC and PIRC) were measured by immunoradiometric assay. Age-related changes in PARC, PIRC and the ratio of PARC/PIRC were studied in 78 normal children, age 1 month to 15 years. The effects of upright position for 15 min were also investigated in 7 postmenarcheal girls. PARC and PIRC in infants were significantly higher than in older children and their ratio of PARC/PIRC was significantly lower than in prepubertal children. During puberty, PARC, PIRC and their ratio were higher in premenarcheal girls than in postmenarcheal girls. In the upright position, PARC, PIRC and the ratio were increased significantly. These finding suggest that: (1) the production of inactive renin is increased but the activation of renin may be lowered in infants; (2) the activation of renin is affected by the menstrual cycle, and (3) the production and activation of renin are increased during short term standing.     

Plasma nitric oxide and iron concentrations in exercised rats are negatively correlated

The aim of this study was to investigate the effect of strenuous exercise on plasma nitric oxide and iron (PI) concentrations in rats. The rats were divided into six groups: 3, 6 and 12 months of the exercise (swimming) groups and their corresponding controls. At the end of experimental periods, blood samples were collected to measure plasma NOx (nitrate and nitrite) and iron concentrations and other hematological indices. The correlative analysis of plasma NOx with PI in the exercised and the control rats was performed. The results showed that plasma NOx concentration was significantly greater and PI lower in the 3, 6, and 12 months of the exercise groups compared to their sedentary controls (p < 0.01). However, the duration of strenuous exercise had no significant effect on plasma NOx or PI contents. A negative correlation between plasma NOx and PI levels was found in all three exercise groups (r = -0.750, -0.578, and -0.808 and p < 0.01, 0.05, 0.01 respectively), but not in the sedentary control groups. These results imply that strenuous exercise may lead to an increase in plasma NOx concentration as well as a low iron level. They also suggest the possibility that the increased NO production might be associated with the development of the lower iron status in exercise.     

Plasma chromium concentrations in normal infants and cystic fibrosis patients

Plasma Cr concentrations have been studied in normal children aged 0–14 yr. Levels ranged from 0.65 to 0.88 μg/1 and did not change with age. Plasma concentrations of CF patients given 0.5–0.75 μg Cr/kg/d in addition to their diet were similar to normal values. There was no correlation between these plasma values and growth retardation.     

Plasma proteomics and the paediatric patient

Introduction: Plasma proteomics has been extensively utilized for studies that investigate various disease settings (e.g. cardiovascular disease), as well as to monitor the effect of pharmaceuticals on the plasma proteome (e.g. chemotherapy). However, plasma proteomic studies focusing on children represent a very small proportion of the plasma proteomic studies completed to date. Early disease detection and prevention is critical in pediatrics, as children must live with the disease outcomes for many years and often carry negative outcomes into adulthood. Pediatrics represents an area of plasma proteomics that is about to undergo a significant expansion.

Areas covered: This review is based on a PubMed search focusing on five keywords that are plasma, biomarkers, pediatric, proteomics, and children. It is a comprehensive summary of plasma proteomic studies specific to the pediatric patient and discusses aspects such as the clinical setting, sample size, methodological approaches and outlines the significance of the findings.

Expert commentary: Plasma proteomics is expanding significantly as a result of major advancements in proteomic technology. This is in synergy with the growing focus on true early disease detection and prevention in early life. We are about to see a new era of advanced medical science built from pediatric proteomics.     

Dermatoglyphics in Phenylketonuria

The dermatoglyphic characteristics on the fingertips, palms and soles of 100 Polish children with proven diagnosis (urine test and blood serum tests) of PKU and of the parents of 23 of them were studied. Our results confirm that PKU is not characterized by dermatoglyphic differences. An apparent diminution in complexity of finger pattern type in patients is shown to be due to the genetic relationship between the parents and their offspring rather than the influence of the PKU disorder itself.     

The essential fatty acid status in phenylketonuria patients under treatment

Phenylketonuric patients are on a special diet that lacks certain essential fatty acids. This study evaluates the essential fatty acid status of a group of phenylketonuric patients in the Netherlands undergoing dietary treatment. To this end, the essential fatty acid status of nine phenylketonuria patients was studied. On the basis of age and gender, two control subjects were selected for each patient. The essential fatty acid composition of duplicate food portions and the essential fatty acid status of plasma and erythrocytes were analyzed. Phenylketonuria subjects had a different essential fatty acid profile from their peers, especially concerning the n-3 fatty acids. N-6 and n-3 fatty long-chain polyenes were hardly consumed by phenylketonuria subjects, in contrast to the control subjects. Linoleic acid, on the other hand, was consumed in significantly higher amounts by phenylketonuria subjects and made up about 40% of their daily fat consumption. The essential fatty acid consumption pattern of the phenylketonuria subjects is mirrored by the essential fatty acid concentrations in blood. The essential fatty acid status of the phenylketonuric diet should be improved in order to prevent deficiency in n-3 fatty acids.     

Reactivity of anhydrous Keggin-type molybdenum heteropolyacids with alkylsilanes: Synthesis and characterization

The reaction of anhydrous molybdenum-based heteropolyacids with diethylmethyl silane has been studied and the reaction products were characterized by various physicochemical methods such as infrared and Raman spectroscopies, XPS and solid-state NMR. The reaction leads to the evolution of hydrogen which reduces partly the polyacid, and to the formation of a [Et₂MeSi] species interacting weakly with the polyoxometalate. Upon reaction with oxygen insertion of oxygen into the Si-C bonds is observed, even at low temperature.     

Platelet selenium in children with normal and low selenium intake

The concentration of selenium was determined by instrumental neutron activation analysis in erythrocytes, platelets, and plasma of eight dietetically treated children with phenylketonuria (n=6) or maple-syrup-urine disease (n=2) with low selenium intake and for ten children with normal selenium intake. The normal selenium concentration in platelets was about 600 ng/g and about five times higher than in erythrocytes of the same children. A decreased selenium concentration in platelets was seen only when the corresponding concentrations in erythrocytes and plasma were very low. This suggests a special role of selenium in platelets.     

Asymmetric dimethylarginine in children with homocystinuria or phenylketonuria

Plasma concentration of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthesis from l-arginine and a cardiovascular risk factor, was found to be elevated in plasma of homocysteinemic adults. Enhanced cardiovascular risk due to homocystinuria and impaired renal function has been found in patients with phenylketonuria (PKU) on protein-restricted diet. However, it is still unknown whether ADMA synthesis is also elevated in children with homocystinuria due to cystathionine beta-synthase deficiency (classical homocystinuria), and whether ADMA may play a role in phenylketonuria in childhood. In the present study, we investigated the status of the l-arginine/NO pathway in six young patients with homocystinuria, in 52 young phenylketonuria patients on natural protein-restricted diet, and in age- and gender-matched healthy children serving as controls. ADMA in plasma and urine was determined by GC–MS/MS. The NO metabolites nitrate and nitrite in plasma and urine, and urinary dimethylamine (DMA), the dimethylarginine dimethylaminohydrolase (DDAH) metabolite of ADMA, were measured by GC–MS. Unlike urine ADMA excretion, plasma ADMA concentration in patients with homocystinuria was significantly higher than in controls (660 ± 158 vs. 475 ± 77 nM, P = 0.035). DMA excretion rate was considerably higher in children with homocystinuria as compared to controls (62.2 ± 24.5 vs. 6.5 ± 2.9 μmol/mmol creatinine, P = 0.068), indicating enhanced DDAH activity in this disease. In contrast and unexpectedly, phenylketonuria patients had significantly lower ADMA plasma concentrations compared to controls (512 ± 136 vs. 585 ± 125 nM, P = 0.009). Phenylketonuria patients and controls had similar l-arginine/ADMA molar ratios in plasma. Urinary nitrite excretion was significantly higher in phenylketonuria as compared to healthy controls (1.7 ± 1.7 vs. 0.7 ± 1.2 μmol/mmol creatinine, P = 0.003). Our study shows that the l-arginine/NO pathway is differently altered in children with phenylketonuria and homocystinuria. Analogous to hyperhomocysteinemic adults, elevated ADMA plasma concentrations could be a cardiovascular risk factor in children with homocystinuria. In phenylketonuria, the l-arginine/NO pathway seems not be altered. Delineation of the role of ADMA in childhood phenylketonuria and homocystinuria demands further investigation.     

The spectrum of mutations and methods for their detection in the phenylalanine hydroxylase gene in phenylketonuria patients from the novosibirsk region

Phenylketonuria (PKU) is a widespread autosome recessive hereditary disease caused by a deficiency of the liver enzyme phenylalanine hydroxylase, which results in distortion of metabolism of phenylalanine and accumulation of toxic metabolites. The knowledge of molecular bases of PKU is of a high social importance as it enables phenotypic correction of the disease in the case of its early diagnostics. This disease is known to be associated with mutations in the phenylalanine hydroxylase gene, the distribution and mutation spectrum having pronounced ethnic and regional features. We studied the spectrum of mutations in the phenylalanine hydroxylase gene in a group of patients with PKU from the Novosibirsk region to reveal 10 missense point mutations, 1 mutation in the splice donor site, and 1 microdeletion. For these mutations, most widely distributed in the region, we used straightforward detection methods basing on the restriction fragment length polymorphism (RFLP), artificial constructed restriction sites (ACRS) PCR, and denaturing gradient gel electrophoresis (DGGE).     

Interaction of phosphorus and molybdenum in relation to uptake and utilization of molybdenum,phosphorus, zinc,copper and manganese by rice

Summary The effect of phosphorus and molybdenum alone and combined, on the uptake and utilization of Mo, Mn, Zn, Cu and P by rice (Var. IR-579) was studied in the greenhouse at varying levels of Mo (0, 2.5 and 5.0 ppm) and (0,100 and 200 ppm). Application of P increased the dry matter yield of shoot and root. Combined application of P and Mo increased the dry matter yield of shoot. Application of Mo increased the concentration of Mo and P in shoot. Applied P caused an increase in the concentration of Mo, Zn and P in shoot. Combined application of P and Mo resulted in an increase in concentration and uptake of Mo in shoot.     

Plasma carnitine status - a prognostic factor in children with dilated cardiomyopathy

Summary Objective - Dilated cardiomyopathy is a rare disorder in childhood that results in a high mortality. The aim of our study was to evaluate the prognostic relevance of the individual plasma carnitine status in children with dilated cardiomyopathy. Methods - In 26 patients plasma carnitine concentrations were determined before and after 6 and 12 months of L-carnitine treatment. According to the plasma short chain acyl-carnitine/free carnitine ratio (AC/FC) at the first presentation children were divided into two groups. Results - In group 1 (AC/FC < 0.4) the median time from diagnosis until death was 35.8 months, the cumulative survival rate was 84% after 2 years. In group 2 (AC/FC > 0.4) median time from diagnosis until death was 8 months, the cumulative survival rate was 50% at 2 years (p < 0.05).Dividing both groups into survivors and nonsurvivors in group 2 a significantly higher AC/FC ratio in the nonsurvivors could be found (survivors 0.78 v 1.3 in nonsurvivors). A significant improvement of left ventricular function 6 and 12 months after presentation and after starting L-carnitine treatment could only be documented in the surviving patients of group 2. Conclusion - The individual plasma carnitine status in children with dilated cardiomyopathy may serve as a risk factor for survival.     

How to Ignite an Atmospheric Pressure Microwave Plasma Torch without Any Additional Igniters

This movie shows how an atmospheric pressure plasma torch can be ignited by microwave power with no additional igniters. After ignition of the plasma, a stable and continuous operation of the plasma is possible and the plasma torch can be used for many different applications. On one hand, the hot (3,600 K gas temperature) plasma can be used for chemical processes and on the other hand the cold afterglow (temperatures down to almost RT) can be applied for surface processes. For example chemical syntheses are interesting volume processes. Here the microwave plasma torch can be used for the decomposition of waste gases which are harmful and contribute to the global warming but are needed as etching gases in growing industry sectors like the semiconductor branch. Another application is the dissociation of CO₂. Surplus electrical energy from renewable energy sources can be used to dissociate CO₂ to CO and O₂. The CO can be further processed to gaseous or liquid higher hydrocarbons thereby providing chemical storage of the energy, synthetic fuels or platform chemicals for the chemical industry. Applications of the afterglow of the plasma torch are the treatment of surfaces to increase the adhesion of lacquer, glue or paint, and the sterilization or decontamination of different kind of surfaces. The movie will explain how to ignite the plasma solely by microwave power without any additional igniters, e.g., electric sparks. The microwave plasma torch is based on a combination of two resonators — a coaxial one which provides the ignition of the plasma and a cylindrical one which guarantees a continuous and stable operation of the plasma after ignition. The plasma can be operated in a long microwave transparent tube for volume processes or shaped by orifices for surface treatment purposes.     

钼靶、多模态MRI对乳腺癌及肿块型浆细胞性乳腺炎的鉴别诊断价值研究

摘要 目的：探讨钼靶、多模态MRI对乳腺癌及肿块型浆细胞性乳腺炎（PCM）的鉴别诊断价值。方法：回顾性分析2017年4月-2021年2月我院经病理证实的98例乳腺癌患者及31例肿块型PCM患者的钼靶和MRI资料,比较乳腺癌和肿块型PCM的钼靶及MRI形态学表现、ADC值、时间-信号强度曲线（TIC）的差异。采用受试者工作特征曲线（ROC）分析钼靶、多模态MRI鉴别诊断乳腺癌及肿块型PCM的效能。结果：钼靶形态学显示：乳腺癌、肿块型PCM在病灶形态及边缘表现上差异有统计学意义（P＜0.05）;乳腺癌、肿块型PCM在密度、伴随征象以及是否有斑点、泥沙样钙化表现上差异无统计学意义（P＞0.05）。多模态MRI形态学显示：乳腺癌、肿块型PCM在形态、边缘、导管扩张、强化方式、TIC曲线类型及ADC信号表现上差异有统计学意义（P＜0.05）;乳腺癌、肿块型PCM在T2WI信号及伴随征象表现上差异无统计学意义（P＞0.05）。ROC曲线分析结果显示：多模态MRI成像检查对乳腺癌及肿块型PCM的鉴别诊断价值明显优于钼靶检查,其曲线下面积（AUC）、准确度、敏感度、特异度及Youden指数分别为0.921、90.63%、100%、89.37%、0.89。结论：钼靶主要通过形态学表现鉴别诊断乳腺癌和肿块型PCM,多模态MRI则可通过病灶形态学表现、ADC值、动态增强表现及TIC客观性判断病灶性质,因此其鉴别诊断价值优于钼靶检查。