Nitric oxide modulates glutathione synthesis during endotoxemia

Nitric oxide is known to modulate intracellular glutathione levels, but the relationship between nitric oxide synthesis and glutathione metabolism during endotoxemia is unknown. The present study was designed to examine the effects of increased nitric oxide formation on hepatic glutathione synthesis and antioxidant defense in endotoxemic mice. Our results demonstrate that hepatic glutathione synthesis is decreased for 24 h following injection of lipopolysaccharide (LPS). Administration of the cysteine precursor, L-2-oxothiazolidine-4-carboxylic acid (OTZ), failed to normalize hepatic glutathione concentration, and suggests that decreased γ-glutamylcysteine ligase activity is primarily responsible for the decrease in hepatic glutathione levels during endotoxemia. Inhibition of nitric oxide synthesis prevented the endotoxin-induced changes in hepatic and plasma glutathione status and up-regulated liver glutathione and cysteine synthesis pathways at the level of gene expression. Furthermore, whereas the activity of glutathione peroxidase and glutathione S-transferase decreased during endotoxemia, both of these changes were prevented by inhibition of nitric oxide synthesis. In conclusion, increased nitric oxide synthesis during endotoxemia causes marked changes in glutathione flux and defenses against oxidative stress in the liver.     

Impact of Growth Hormone (GH) Deficiency and GH Replacement upon Thymus Function in Adult Patients

Background

Despite age-related adipose involution, T cell generation in the thymus (thymopoiesis) is maintained beyond puberty in adults. In rodents, growth hormone (GH), insulin-like growth factor-1 (IGF-1), and GH secretagogues reverse age-related changes in thymus cytoarchitecture and increase thymopoiesis. GH administration also enhances thymic mass and function in HIV-infected patients. Until now, thymic function has not been investigated in adult GH deficiency (AGHD). The objective of this clinical study was to evaluate thymic function in AGHD, as well as the repercussion upon thymopoiesis of GH treatment for restoration of GH/IGF-1 physiological levels.

Methodology/Principal Findings

Twenty-two patients with documented AGHD were enrolled in this study. The following parameters were measured: plasma IGF-1 concentrations, signal-joint T-cell receptor excision circle (sjTREC) frequency, and sj/β TREC ratio. Analyses were performed at three time points: firstly on GH treatment at maintenance dose, secondly one month after GH withdrawal, and thirdly one month after GH resumption. After 1-month interruption of GH treatment, both plasma IGF-1 concentrations and sjTREC frequency were decreased (p<0.001). Decreases in IGF-1 and sjTREC levels were correlated (r = 0.61, p<0.01). There was also a decrease in intrathymic T cell proliferation as indicated by the reduced sj/β TREC ratio (p<0.01). One month after reintroduction of GH treatment, IGF-1 concentration and sjTREC frequency regained a level equivalent to the one before GH withdrawal. The sj/β TREC ratio also increased with GH resumption, but did not return to the level measured before GH withdrawal.

Conclusions

In patients with AGHD under GH treatment, GH withdrawal decreases thymic T cell output, as well as intrathymic T cell proliferation. These parameters of thymus function are completely or partially restored one month after GH resumption. These data indicate that the functional integrity of the somatotrope GH/IGF-1 axis is important for the maintenance of a normal thymus function in human adults.

Trial Registration

ClinicalTrials.gov NTC00601419     

The Possible Roles of Priming with ZnO Nanoparticles in Mitigation of Salinity Stress in Lupine (Lupinus termis) Plants

To our knowledge, little attention has been paid to evaluating ZnO nanoparticles (ZNPs) roles in plants grown under salinity stress. In this study, seeds of lupine (Lupinus termis) plants were grown in plastic pots and exposed to 0 (control) and 150 (S) mM NaCl with or without priming with different concentrations of ZnO [20 mg L^?1 (ZNPs1), 40 mg L^?1 (ZNPs2), and 60 mg L^?1 (ZNPs3)] for 20 days. Salinized plants showed a reduction in plant growth parameters (root length, shoot length, fresh weight, and dry weight) and in the contents of photosynthetic pigments (chlorophyll a and b, and carotenoids) and Zn, as well as in the activity of catalase (CAT) against control plants. On the other side, salinity stress boosted the contents of organic solutes (soluble sugar, soluble protein, total free amino acids, and proline), total phenols, malondialdehyde (MDA), ascorbic acid and Na, as well as the activities of superoxide dismutase (SOD), peroxidase (POD), and ascorbate peroxidase (APX) in stressed plants over control plants. However, seed-priming with ZNPs mostly stimulated growth of stressed plants, which was accompanied by reinforcement in the levels of photosynthetic pigments, organic solutes, total phenols, ascorbic acid and Zn, as well as in the activities of SOD, CAT, POD, and APX enzymes over stressed plants alone. On the contrary, priming with ZNPs caused a decrement in the contents of MDA and Na in stressed plants relative to salinized plants alone. It is worthy to mention that, this improvement in salt tolerance of plants primed with ZNPs was more obvious in plants primed with ZNPs3 and grown both in unstressed and stressed regimes. Thus, our findings suggest that seed-priming with ZNPs, especially 60 mg L^?1 ZnO is an effective strategy that can be used to enhance salt tolerance of lupine plants.

     

A colorimetric method for the determination of indole, and its application to assay of tryptophanase.

Indole reacts with sodium nitrite and glycine-HCl buffer, pH 2.6, to form a red color that is stable for more than 1 week. The reaction is reproducible and is linear over a wide range of indole concentrations (0.05–1.00 μmol). Twelve indole derivatives, including tryptophan, and 17 protein amine acids do not interfere. Indole-3-acetic acid, indole-3-acrylic acid, indole-3-pyruvic acid, 5-indole carboxylic acid, and 5-hydroxyindole-3-acetic acid interfere to varying extents (16–27%). Free indole was determined in biological material containing tryptophan by the present method. The method is also applicable to the assay of tryptophanase activity without prior indole extraction.     

Morphological plasticity of Parrotia persica leaves in eastern Hyrcanian forests (Iran) is related to altitude

Variation in leaf characters of Parrotia persica in relation to their position in the canopy along an altitudinal gradient were studied. Genetic and phenotypic characters make P. persica one of the most noteworthy plants in the five floristic regions of Iran. It is an endemic species of the Hyrcanian forests, and occurs naturally from sea level to over 900 m a.s.l. on the north side of the Mountain Ranges of Alborz, northern Iran. There was a significant effect of altitude only on few leaf features [width of lamina, base angle (internal angle of lamina), number of pair vein (number of principal veins of lamina) of leaf, top and end of leaf figure]. Among different geographical sides of the crown, there was no significant difference in the plasticity of leaf features, but leaf figure (both top of leaf figure and end of leaf figure) showed the lowest plasticity among the different leaf characters. Of all characters measured, the lowest plasticity among the three populations was found for base angle and number of vein pairs. A PCA analysis showed that leaf petiole and maximum width of lamina in 0.9 of its length, together with leaf figure and width of lamina, accounted for the greatest variation in difference of populations.     

Data on self-medication among healthcare students at Najran University,KSA

The prevalence of self-medication (SM) has increased in health professionals due to awareness of disease and symptoms. Incorrect use of medication caused harmful effects. To assess the knowledge, attitude and practice of health professionals, this survey was conducted. A cross-sectional study was carried out among health professionals of different specialities. Knowledge, attitude and practice-based questions were asked through an electronically distributed questionnaire. Data were statistically tested using the Chi-square test with SPSS. Most of the health professionals were aware with the term of self-medication; however the knowledge about related questions was not satisfactory. Almost half of the participants practiced self-medication. The prevalence of self-medication among participants was high. They need to be trained and educate about the incorrect use of self-medication.     

Antitumor studies. Part 5: Synthesis, antitumor activity, and molecular docking study of 5-(monosubstituted amino)-2-deoxo-2-phenyl-5-deazaflavins

Various novel 5-(monosubstituted amino)-2-deoxo-2-phenyl-5-deazaflavins derivatives have been synthesized by direct coupling of 5-deazaflavins and N-alkyl or aryl amines. The antitumor activities against human tumor cell lines CCRF-HSB-2 and KB cells have been investigated in vitro and many compounds showed promising potential antitumor activities with less cytotoxicities. AutoDock molecular docking into PTK (PDB code: 1t46) has been done for lead optimization of these compounds as potential PTK inhibitors. Some of the synthesized 5-(monosubstituted amino)-2-deoxo-2-phenyl-5-deazaflavins at the 5-position exhibited reasonable binding affinities into PTK with the hydrogen bond through their C(5)-NH moiety.