Bio-energetic impairment in human calf muscle in thyroid disorders: a P MRS study

Mitochondrial metabolism particularly oxidative phosphorylation is greatly influenced by thyroid hormones. Earlier studies have described neuromuscular symptoms as well as impaired muscle metabolism in hypothyroid and hyperthyroid patients. In this study, we intend to look in to the muscle bioenergetics including phosphocreatine recovery kinetics based oxidative metabolism in thyroid dysfunction using in vivo ³¹P nuclear magnetic resonance spectroscopy (MRS). ³¹P MRS was carried out at resting state on 32 hypothyroid, 10 hyperthyroid patients and 25 control subjects. Nine out of 32 hypothyroid patients and 17 out of 25 control subjects under went exercise protocol for oxidative metabolism study and performed plantar flexion exercise while lying supine in 1.5 T magnetic resonance scanner using custom built exercise device. MRS measurements of inorganic phosphate (Pi), phosphocreatine (PCr), phosphodiesters (PDE) and adenosine triphosphate (ATP) of the calf muscle were acquired during rest, exercise and recovery phase. PCr recovery rate constant (k_PCr) and oxidative capacity were calculated by monoexponential fit of PCr versus time (t) at the beginning of recovery. During resting condition in hypothyroid patients, PCr/Pi ratio was reduced whereas PDE/ATP and Pi/ATP were increased. However, in case of hyperthyroidism, an increased PCr/Pi ratio and reduced PDE/ATP and Pi/ATP were observed. The results confirmed differential energy status of the muscle due to increased or decreased levels of thyroid hormone. Our results also demonstrate reduced oxidative metabolism in hypothyroid patients based on PCr recovery kinetics. PCr recovery kinetics study after exercise revealed decreased PCr recovery rate constant (k_PCr) in hypothyroid patients compared to controls that resulted in decrease in oxidative capacity of muscle by 50% in hypothyroids. These findings are consistent with a defect of high energy phosphate mitochondrial metabolism in thyroid dysfunction.     

Radioaktive und stabile Isotope bei der Lösung pflanzenphysiologischer Probleme

Es werden neuere Ergebnisse von Untersuchungen zur Biosynthese einiger Alkaloide und zum Stoffwechsel von Herbiziden mitgeteilt und diskutiert, die unter Verwendung von ¹⁴C, ³H und ¹⁵N durchgeführt wurden.     

Compartmental Approach for Evaluation of Plasma Kinetics and 13Co2-Exhalation after Oral Loading with L-[1-13C]Leucine

Abstract

A seven compartment model was applied for evaluation of oral L-[1-¹³C]leucine loading tests (38 μmol/kg body wt.) in healthy volunteers. The model comprises transport and absorption in stomach and gut into a central L-leucine-compartment which is connected to a protein compartment and to the compartment of the corresponding 2-oxo acid. CO₂ release from the latter occurs in a fast and a slow compartment into the central CO₂ compartment for exhalation. Using the fmins routine of MATLAB for parameter estimation, a good agreement was obtained between calculated and actually measured kinetics of ¹³C-labelled metabolites and a mean in vivo L-leucine oxidation of 0.365 ± 0.071 μmol/kg per min (n = 5) was computed. Plausibility of the model was checked by predicting in vivo leucine oxidation rates from primed continuous infusion tests (priming: L-[1-¹³C]leucine, 5 μmol/kg; NaH¹³CO₂, 1.2 μmol/kg; infusion: L-[1-¹³C]leucine, 5 μmol/kg per h). In 5 tested volunteers, the experimental L-leucine oxidation rate amounted to 0.358 ± 0.105 μmol/kg per min versus predicted 0.324±0.099 μmol/kg per min. Possible causes for some observed intraindividual variations are discussed.     

Theoretische Aspekte der Untersuchung des Stickstoffmetabolismus mit 15N beim Menschen II. Probleme der Auswertung und Interpretation klinischer Untersuchungen

Klinische Untersuchungen zum menschlichen Stickstoffmetabolismus, die unter Verwendung des stabilen Stickstoffisotops ¹⁵N durchgeführt wurden, werden mit Hilfe eines 3-Compartmentmodells ausgewertet und interpretiert. Möglichkeiten zur Erweiterung dieses Modells werden diskutiert, und durch Computerstudien wird die Aussagekraft der aus Modellen gewonnenen Resultate überprüft.     

Tumor Metabolism‐Engineered Composite Nanoplatforms Potentiate Sonodynamic Therapy via Reshaping Tumor Microenvironment and Facilitating Electron–Hole Pairs’ Separation

Reactive oxygen species (ROS) depletion and low ROS production that result from the intratumoral redox metabolism equilibrium and low energy conversion efficiency from ultrasound mechanical energy to ROS‐represented chemical energy, respectively, are two vital inhibitory factors of sonodynamic therapy (SDT). To address the two concerns, a tumor metabolism‐engineered composite nanoplatform capable of intervening intratumoral ROS metabolism, breaking the redox equilibrium, and reshaping the tumor microenvironment is constructed to reinforce SDT against tumors. In this metabolism‐engineered nanoplatform, Nb₂C nanosheets serve as the scaffold to accommodate TiO₂ sonosensitizers and l ‐buthionine‐sulfoximine. Systematic experiments show that such nanoplatforms can reduce ROS depletion via suppressing glutathione synthesis and simultaneously improving ROS production via the Nb₂C‐enhanced production and separation of electron–hole pairs. Contributed by the combined effect, net ROS content can be significantly elevated, which results in the highly efficient anti‐tumor outcomes in vivo and in vitro. Moreover, the combined design principles, that is, tumor metabolism modulation for reducing ROS depletion and electron–hole pair separation for facilitating ROS production, can be extended to other ROS‐dependent therapeutic systems.     

Antiproliferative effect of millimeter radiation on human erythromyeloid leukemia cell line K562 in culture: ultrastructural- and metabolic-induced changes

In the present study we compared the proliferation behavior, the ultrastructural morphology and the glycolitic metabolism of K562 cells irradiated by low-power wide-band millimeter waves, with those of sham-exposed K562 cells (control), maintained in the same culture conditions. The gigaHertz radiation treatments, performed between 53-78 10(9) Hz, induced a noticeable inhibition of the cell proliferation that could be related to relevant ultrastructural changes. Such effects brought the irradiated cell system to lose the homeostasis and to trigger defense/reparatory mechanisms in order to reestablish a new steady state. (13)C-Nuclear magnetic resonance data on the kinetic of glucose metabolism demonstrated that the irradiated cells enhanced the glycolitic aerobic pathway, indicating that such system need to produce an extra-bioenergy. Most of the ATP synthesized served probably to perform the above processes resulting in a significant decrease of the proliferation rate without significant cell death increment.     

Simultaneous determination of allantoin, hypoxanthine, xanthine, and uric acid in serum/plasma by CE

Allantoin (All) is an oxidative end product of purines in mammals. The small amount of All present in human plasma or serum results from free radical action on urate and may provide a stable marker of in vivo free radical activity. Because free radicals have been implicated in the development and progression of atherosclerosis, this study focused on the metabolic compounds of the All pathway. We propose a new fast CE (CE/UV) method for the simultaneous determination of All, uric acid (UA), hypoxanthine (HX), and xanthine (X) in human plasma. These products were quantified in the plasma of patients with chronic renal failure before hemodialysis (n = 6), patients with chronic heart failure (n = 6) and controls (n = 6). The filtered plasma were diluted ten-fold before the direct injection in CE/UV (195 nm), which allows separating the four compounds in less than 13 min. The metabolites were detectable at concentrations of 0.3-0.6 micromol/L. The method was linear over the range 0.5-150 micromol/L for All, HX, and X and 10-1500 micromol/L for UA (r > 0.99). The analytical performance of this method is satisfactory with intra-assay CV < 3.4%, inter-assay CV < 5% (HX and X < 7%), and recovery (93-101%). The proposed CE-UV method appears to be a useful tool for studying physiological and pathological changes of HX, UA, and All levels in plasma samples, the latter being a possible indicator of free radical damage in vivo.     

Growth, biochemical modifications and proline metabolism in Helianthus annuus L. as induced by drought stress

In the present investigation, two watering treatments, viz., 100% and 60% field capacity (FC) were used to understand the effects of water deficit on early growth, biomass allocation, pigment and biochemical constituents and proline metabolism of five varieties of Sunflower (Helianthus annuus L.) plants. We found that there was a significant difference in early growth, dry matter accumulation, pigment, biochemical constituents and proline metabolism among the five varieties. The root length, shoot length, total leaf area, fresh and dry weight, chlorophyll a, b, total chlorophyll and carotenoid were significantly reduced under water stress treatments. Water stress increased the proline, free amino acid and glycinebetaine contents along with increased activity of γ-glutamyl kinase but the activity of proline oxidase reduced as a consequence of water stress.     

硼的生物必需性及人体健康效应

长期以来人们一直认为硼仅是植物必需的微量元素,但近年来的研究证明,硼可能也是动物和人的必需营养素,其证据涉及硼对矿物质的电介质、能量底物、氮、活性氧类等代谢以及红血球生成和血细胞生成的影响。许多发现提示,硼缺乏损伤钙代谢、能量代谢、脑功能和免疫功能,硼也有助于预防炎症性疾病。急性和慢性毒理观察表明,人体摄入１ｇ硼酸／ｄ（２．５ｍｇ Ｂ／ｋｇ／ｄ）不会产生任何毒性症状;慢性有害作用水平为５ｍｇ／ｋｇ     

口服ALA在正常小鼠胃中的代谢

目的:探求光敏剂5-氨基酮戊酸(ALA)口服后在小鼠胃中的代谢,寻求光敏诊断最佳的剂量及时间.方法:昆明小鼠口服不同剂量的ALA(20mg/kg、40mg/kg、60mg/kg、80mg/kg 4个组别),不同时间(1小时、2小时、4小时、6小时、8小时、10小时、12小时、24小时、48小时.)以激光诱导荧光OMA检测系统测定胃卟啉和组织荧光强度,并经数据处理观察ALA不同时间在胃中的代谢状态.结果:胃卟啉荧光峰值除以组织荧光峰值的比值在口服ALA40 mg/kg后1小时最大.结论:从实验数据分析口服ALA作OMA荧光光谱分析以40mg/kg为最佳检测剂量,最佳检测时间为口服ALA后1小时.