scholarly journals Kinetic and Cross-Sectional Studies on the Genesis of Hypoargininemia in Severe PediatricPlasmodium falciparumMalaria

2019 ◽  
Vol 87 (4) ◽  
Author(s):  
Matthew P. Rubach ◽  
Haoyue Zhang ◽  
Salvatore M. Florence ◽  
Jackson P. Mukemba ◽  
Ayam R. Kalingonji ◽  
...  

ABSTRACTThe low bioavailability of nitric oxide (NO) and its precursor, arginine, contributes to the microvascular pathophysiology of severe falciparum malaria. To better characterize the mechanisms underlying hypoargininemia in severe malaria, we measured the plasma concentrations of amino acids involved inde novoarginine synthesis in children with uncomplicated falciparum malaria (UM;n = 61), children with cerebral falciparum malaria (CM;n = 45), and healthy children (HC;n = 109). We also administered primed infusions ofl-arginine uniformly labeled with13C6and15N4to 8 children with severe falciparum malaria (SM; age range, 4 to 9 years) and 7 healthy children (HC; age range, 4 to 8 years) to measure the metabolic flux of arginine, hypothesizing that arginine flux is increased in SM. Using two different tandem mass spectrometric methods, we measured the isotopic enrichment of arginine in plasma obtained at 0, 60, 90, 120, 150, and 180 min during the infusion. The plasma concentrations of glutamine, glutamate, proline, ornithine, citrulline, and arginine were significantly lower in UM and CM than in HC (P ≤ 0.04 for all pairwise comparisons). Of these, glutamine concentrations were the most markedly decreased: median, 457 μM (interquartile range [IQR], 400 to 508 μM) in HC, 300 μM (IQR, 256 to 365 μM) in UM, and 257 μM (IQR, 195 to 320 μM) in CM. Arginine flux during steady state was not significantly different in SM than in HC by the respective mass spectrometric methods: 93.2 μmol/h/kg of body weight (IQR, 84.4 to 129.3 μmol/h/kg) versus 88.0 μmol/h/kg (IQR, 73.0 to 102.2 μmol/h/kg) (P = 0.247) by the two mass spectrometric methods in SM and 93.7 μmol/h/kg (IQR, 79.1 to 117.8 μmol/h/kg) versus 81.0 μmol/h/kg (IQR, 75.9 to 88.6 μmol/h/kg) (P = 0.165) by the two mass spectrometric methods in HC. A limited supply of amino acid precursors for arginine synthesis likely contributes to the hypoargininemia and NO insufficiency in falciparum malaria in children.

2015 ◽  
Vol 308 (9) ◽  
pp. H1171-H1176 ◽  
Author(s):  
Jennifer C. Sullivan ◽  
Paula Rodriguez-Miguelez ◽  
Margaret A. Zimmerman ◽  
Ryan A. Harris

In experimental animal models of hypertension, angiotensin (1–7) [ANG-(1–7)] is higher in females compared with males; however, it is less clear whether the same applies to humans. Therefore, this study sought to compare circulating concentrations of ANG-(1–7) in apparently healthy men and women under normal physiological conditions. With the use of a cross-sectional experimental design, blood was collected in EDTA anticoagulant from 42 volunteers (21 men and 21 women; and age range, 19–48 yr) for analysis of plasma concentrations of ANG-(1–7) and ANG II. Blood pressure was measured and vascular endothelial function was determined ( n = 25) using the brachial artery flow-mediated dilation (FMD) test. As a result, women exhibited a higher circulating concentration of ANG-(1–7) ( P = 0.04) compared with men, whereas values of ANG II were similar between groups. Baseline arterial diameter, peak diameter, and shear rate were significantly greater ( P < 0.02) in men compared with women. No significant differences in FMD, FMD normalized for shear, or time to peak dilation were observed between men and women. In addition, a positive correlation between ANG-(1–7) and FMD ( P = 0.04) and negative association between ANG-(1–7) with ANG II ( P = 0.01) were only identified in men, whereas a positive relationship between ANG-(1–7) and diastolic blood pressure ( P = 0.03) was observed in women. In conclusion:, women exhibit significantly higher plasma concentrations of ANG-(1–7) compared with men. In addition, this study describes a relationship between ANG-(1–7), vascular function, and diastolic blood pressure that appears to be sex dependent.


1992 ◽  
Vol 82 (1) ◽  
pp. 63-70 ◽  
Author(s):  
S. Pukrittayakamee ◽  
N.J. White ◽  
T. M. E. Davis ◽  
S. Looareesuwan ◽  
W. Supanaranond ◽  
...  

1. Hypoglycaemia and lactic acidosis are important manifestations of severe falciparum malaria. To investigate hepatic gluconeogenesis in acute falciparum malaria, liver blood flow and galactose clearance were estimated in seven adult patients with moderately severe infection and seven patients with severe infection (three of whom died later). Nine patients were restudied in convalescence. 2. Liver blood flow, determined from the plasma clearance of Indocyanine Green, was lower in acute illness than in convalescence [16.1 (7.0) versus 23.9 (7.2) ml min−1 kg−1, mean (sd)], but this difference was not statistically significant (P= 0.15). There was a significant inverse correlation between admission venous plasma lactate concentrations and the liver blood flow estimated from the clearance of Indocyanine Green (rs = 0.71, P = 0.004). 3. The plasma clearance of galactose after intravenous injection was similar in the acute [15.4 (4.90) ml min−1 kg−1] and convalescent study [12.8 (2.1) ml min−1 kg−1]. The ratio of galactose clearance to Indocyanine Green clearance was significantly higher in acute disease [1.41 (0.51)] than in convalescence [0.70 (0.34)], largely because of the elevated ratios in severely ill patients [1.48 (0.50)]. 4. The rise in blood glucose concentration after galactose administration was significantly higher during acute illness [1.48 (0.72) mmol/l] than in convalescence [0.67 (0.41) mmol/l, P = 0.022], but the insulin response was similar, indicating reduced tissue insulin sensitivity. There was no significant change in the plasma concentrations of other metabolites (lactate, pyruvate, alanine and triacylglycerol) in either study. 5. These results suggest that the segment of the glycolytic pathway between galactose and glucose is unimpaired in patients with severe falciparum malaria. Since galactose does not stimulate insulin secretion directly and does not appear to increase plasma lactate concentrations, this simple sugar may be an alternative to glucose in the treatment of malaria-associated hypoglycaemia.


2005 ◽  
Vol 123 (3) ◽  
pp. 119-123 ◽  
Author(s):  
Neuseli Marino Lamari ◽  
Alceu Gomes Chueire ◽  
José Antonio Cordeiro

CONTEXT AND OBJECTIVE: Standardization of normal joint mobility criteria is complex, especially for preschool children, for whom differentiation from hypermobility (JH) is even more difficult. This study aimed to investigate joint mobility of the fifth finger, wrist, elbow, knee and trunk among preschool children, estimate the incidence of JH and evaluate the effect of gender and age and the applicability of standard criteria for identifying JH among preschool children. DESIGN AND SETTING: Cross-sectional descriptive and quantitative study, at São José do Rio Preto medical school. METHODS: 1,120 healthy children (534 boys, 47.7%; 586 girls, 52.3%; age range: 4-7 years) were evaluated using Beighton scores. Passive extension of fifth finger (> 90º), passive apposition of thumb to forearm, active extension of elbow and knee (> 10º) and anterior trunk flexion placing flat hand on ground were assessed. One point was scored for each positive result (maximum: 9). Scores > 4 were considered to be JH. Student’s t test and variance analysis were used for statistical analysis. RESULTS: JH was observed in 80% of wrists, 53.3% of fifth fingers, 36.6% of elbows, 14% of trunks and 12.5% of knees. Scores > 4 were found for 64.6% of the children. Females had higher angular values. Lower scores were associated with greater age. CONCLUSIONS: JH is a common condition among preschool children and currently available methods are inadequate. New parameters and criteria should be developed for identifying JH among these children.


Author(s):  
Khalid Abdelsamea Mohamedahmed ◽  
Zeinab Abdalmalik Ahmed ◽  
Bakri Yousif Mohammed Nour ◽  
Adam Dawoud Abakar ◽  
Asaad Ma. Babker

Background: Falciparum malaria remains one of the most global infection among children particularly in communities with poor resources. Falciparum malaria associated with several hematological changes that affect the major blood cell lines such as platelets lead to platelets parameters (platelets count and indices) abnormalities. Objectives: The aim of this study was to evaluate the effects of falciparum malaria on platelets parameters (platelets count and indices) among Sudanese children. In addition to study relationships and correlation between platelets parameters and malaria parasitemia and parasite count. Materials and Methods: A case control study was conducted in Wad Medani Pediatric Hospital in collaboration with Faculty of Medical laboratory Sciences, University of Gezira, Sudan among 100 children with severe falciparum malaria (mean age 8.63 ± 3.40 years; 61% males), 100 children with uncomplicated falciparum malaria (mean age 8.83 ± 4.20 years; 45% males) and 100 children with normal healthy children controls (mean age 10.08 ± 3.58 years; 50% males). Parasitemia and parasite count (%) was determined directly from thick and thin blood films respectively. The platelets parameters (platelets count and indices) measured by using Sysmex XP 300 N automated analyzer, and platelets count was confirmed and assessed using stained thin blood film. SPSS software (V 20.0) and Stat disk software (V 13.0) were used for data analysis. Results: 72 % of severe falciparum malaria (SM) have hyperparasitemia, while 18 % among uncomplicated falciparum malaria (UM). The thrombocytopenia account for 43 % (SM: 30.5 %; UM: 12.5 %), low PCT account for 35.5 % (SM: 27 %; UM: 8.5 %) and high PDW account for 46.5 % (SM: 23.5 %; UM: 23 %) in falciparum malaria cases. The mean PLTs count and PDW were statistically significantly differences between falciparum malaria cases and normal healthy control (P value 0.000 and 0.008 respectively). The mean PLTs count and PCT in severe falciparum malaria cases were lower than uncomplicated falciparum malaria cases (P value 0.005 and 0.000 respectively). The PLTs count and PCT had significant negative correlation within malaria parasitemia (P value 0.000; r -0.286; P value 0.004; r -0.205 respectively) and malaria parasite count (P value 0.000; r -0.450; P value 0.000; r -0.270 respectively). Conclusion: The study concluded that thrombocytopenia, low PCT and high PDW were observed as most platelets parameters changes in falciparum malaria. PLTs count along with PCT to be recommended as hematological diagnostic markers and prognostic tool to assess the disease severity and to improve the management of falciparum malaria among patients.


1995 ◽  
Vol 73 (01) ◽  
pp. 039-048 ◽  
Author(s):  
A Bierhaus ◽  
Ch J Hemmer ◽  
N Mackman ◽  
R Kutob ◽  
R Ziegler ◽  
...  

SummarySerum from patients with P. falciparum malaria at day 1 (pretherapy) induces tissue factor (TF) in cultured endothelial cells. TF induction depends on de novo transcription as shown in Nuclear Run On assays. Electrophoretic mobility shift assays demonstrated binding of AP-1 and NF- κB/Rel proteins to their recognition sites in the TF promotor. After therapy (day 28), stimulation of TF antigen by patient serum is reduced by 70%. When serum obtained before and after therapy was compared, a decrease of NF-κB activation was evident. Activation of NF-κB-like proteins was in part dependent on TNFα in patient serum, since a TNFα neutralizing antibody reduced induction of TF transcription and translation and induction of NF-κB-like proteins. Induction of TF activity was suppressed by pDTC, an inhibitor of NF-κB activation. When different promotor constructs of the TF gene were tested, induction was dependent upon the presence of the intact NF-κB-like binding site in the TF promotor. A mutant with deleted NF-κB, but intact AP-1 sites was not inducible. Mutation of the AP-1 sites did not prevent induction, but reduced inducibility by pretherapy serum. Therefore, NF-κB/Rel proteins are responsible for induction of TF transcription by pretherapy serum, but AP-1 is needed for highest inducibility. The effect of antiparasitic therapy on the induction of TF by serum from patients with complicated P. falciparum malaria is dependent on a therapy-mediated loss of activation of NF-κB-like proteins in post-treatment patient serum.


1970 ◽  
Vol 6 (1) ◽  
pp. 184-193
Author(s):  
Ольга Віговська

У статті теоретично обґрунтовано феномен конструктивного самозбереження особистості як ознаки самоактуалізації, розкриття власного потенціалу і побудови перспективи розвитку особистості та емпірично виявлено ознаки психологічної детермінації домінуючого інстинкту у конструктивній самореалізації жінок з різним соціальним статусом. Зазначено, що проблема самозбереження асоціюється з особливостями прояву інстинкту самозбереження людини, але потреби вищого порядку зумовлюють соціальну природу її поведінки, яка локалізована у найвищій точці самореалізації. Теоретично обгрунтовано, що самореалізація визначає тенденцію раціональної організації життя людини та проявляється у її почутті задоволеністю життям. З’ясовано, що психологічну основу конструктивного самозбереження становлять індивідуально-типологічні характеристики людини, які відображають психофізіологічні та психосоціальні резерви самореалізації особистості. Розроблена програма емпіричного дослідження, а також комплекс використаних методів математичної обробки результатів дослідження дає змогу конкретизувати психологічний зміст детермінації домінуючого інстинкту у конструктивній самореалізації жінок вікового діапазону 35-45 років та з різним соціальним статусом. У жінок, які виховують проблемну (хвору) дитину, домінує інстинкт "егофільного типу", що виражається у їх надмірному егоцентризмі і супроводжується низькими показниками самоактуалізації, на відміну від досліджуваних жінок, які виховують здорових дітей і у яких на фоні вираженої тенденції до самоактуалізації домінує базовий інстинкт "дослідницького типу" та "лібертофільного типу". This article theoretically proves constructive phenomenon of self identity as signs of self-disclosure own potential and prospects of development of individual construction. In addition, it empirically showes signs of psychological determination of the dominant instinct in a constructive self-determination of women with different social statuses. It was noted that the issue of self-preservation is associated with the peculiarities of manifestation of self-preservation instinct of man, but it needs higher-order cause social nature of the behavior that is localized at the highest point of self-realization. It theorized that self-realization determines the trend of rational organization of human life and manifests itself in its sense of life satisfaction. It was found that the psychological basis of constructive self-preservation of the individual make individually-typological characteristics of a person that reflect physiological and psychosocial reserves of self-realization. The developed program of empirical research, as well as the methods used complex mathematical processing of results of research allows to specify the content of the psychological determination of the dominant instinct of constructive self-realization а women age range of 35-45 years and with different social status. Women who bring up the problem child dominates the instinct of self-preservation, which is reflected in their excessive self-centeredness, and is accompanied by low levels of self-actualization, as opposed to the study of women who are raising healthy children and that against the backdrop of a pronounced tendency to self-actualization, dominated by basic instinct "research type" and "independent type."


2017 ◽  
Author(s):  
Xueming Dong

Catalytic deoxygenation of coal enhances the stability and combustion performance of coal-derived liquids. However, determination of the selectivity of removal of oxygen atoms incorporated in or residing outside of aromatic rings is challenging. This limits the ability to evaluate the success of catalytic deoxygenation processes. A mass spectrometric method, in-source collision-activated dissociation (ISCAD), combined with high resolution product ion detection, is demonstrated to allow the determination of whether the oxygen atoms in aromatic compounds reside outside of aromatic rings or are part of the aromatic system, because alkyl chains can be removed from aromatic cores via ISCAD. Application of this method for the analysis of a subbituminous coal treated using a supported catalyst revealed that the catalytic treatment reduced the number of oxygen-containing heteroaromatic rings but not the number of oxygen atoms residing outside the aromatic rings.<br>


2017 ◽  
Author(s):  
Xueming Dong

Catalytic deoxygenation of coal enhances the stability and combustion performance of coal-derived liquids. However, determination of the selectivity of removal of oxygen atoms incorporated in or residing outside of aromatic rings is challenging. This limits the ability to evaluate the success of catalytic deoxygenation processes. A mass spectrometric method, in-source collision-activated dissociation (ISCAD), combined with high resolution product ion detection, is demonstrated to allow the determination of whether the oxygen atoms in aromatic compounds reside outside of aromatic rings or are part of the aromatic system, because alkyl chains can be removed from aromatic cores via ISCAD. Application of this method for the analysis of a subbituminous coal treated using a supported catalyst revealed that the catalytic treatment reduced the number of oxygen-containing heteroaromatic rings but not the number of oxygen atoms residing outside the aromatic rings.<br>


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