Affinity of Ionic Species of Nucleoside Transport Protein Inhibitors

Abstract

A class of very potent nucleoside transport inhibitors is present in two molecular forms around physiological pH. We investigated whether the monoprotonated or the unionized species of these molecules binds to this camer protein with higher affinity.     

THE EFFECTS OF INJURY PREVENTION WARM-UP PROGRAMMES ON KNEE STRENGTH IN MALE SOCCER PLAYERS

The study investigates the effects of the 11+ and HarmoKnee injury prevention programmes on knee strength in male soccer players. Under-21-year-old players (n=36) were divided equally into: the 11+, HarmoKnee and control groups. The programmes were performed for 24 sessions (20-25 min each). The hamstrings and quadriceps strength were measured bilaterally at 60°·s^-1, 180°·s^-1 and 300°·s^-1. The concentric quadriceps peak torque (PT) of the 11+ increased by 27.7% at 300°·s^-1 in the dominant leg (p<0.05). The concentric quadriceps PT of HarmoKnee increased by 36.6%, 36.2% and 28% in the dominant leg, and by 31.3%, 31.7% and 20.05% at 60°·s^-1, 180°·s^-1 and 300°·s^-1 in the non-dominant leg respectively. In the 11+ group the concentric hamstring PT increased by 22%, 21.4% and 22.1% at 60°·s^-1, 180°·s^-1 and 300°·s^-1, respectively in the dominant leg, and by 22.3%, and 15.7% at 60°·s^-1 and 180°·s^-1, in the non-dominant leg. In the HarmoKnee group the hamstrings in the dominant leg showed an increase in PT by 32.5%, 31.3% and 14.3% at 60°·s^-1, 180°·s^-1 and 300°·s^-1, and in the non-dominant leg hamstrings PT increased by 21.1% and 19.3% at 60°·s^-1 and 180°·s^-1 respectively. The concentric hamstrings strength was significantly different between the 11+ and control groups in the dominant (p=0.01) and non-dominant legs (p=0.02). The HarmoKnee programme enhanced the concentric strength of quadriceps. The 11+ and HarmoKnee programmes are useful warm-up protocols for improving concentric hamstring strength in young professional male soccer players. The 11+ programme is more advantageous for its greater concentric hamstring strength improvement compared to the HarmoKnee programme.     

Utility of Dexrazoxane for the Attenuation of Epirubicin-Induced Genetic Alterations in Mouse Germ Cells

Dexrazoxane has been approved to treat anthracycline-induced cardiomyopathy and extravasation. However, the effect of dexrazoxane on epirubicin-induced genetic alterations in germ cells has not yet been reported. Thus, the aim of this study was to determine whether dexrazoxane modulates epirubicin-induced genetic damage in the germ cells of male mice. Our results show that dexrazoxane was not genotoxic at the tested doses. Furthermore, it protected mouse germ cells against epirubicin-induced genetic alterations as detected by the reduction in disomic and diploid sperm, spermatogonial chromosomal aberrations, and abnormal sperm heads. The attenuating effect of dexrazoxane was greater at higher dose, indicating a dose-dependent effect. Moreover, sperm motility and count were ameliorated by dexrazoxane pretreatment. Epirubicin induced marked biochemical changes characteristic of oxidative DNA damage including elevated 8-hydroxy-2ʹ-deoxyguanosine levels and reduction in reduced glutathione. Pretreatment of mice with dexrazoxane before epirubicin challenge restored these altered endpoints. We conclude that dexrazoxane may efficiently mitigate the epirubicin insult in male germ cells, and prevent the enhanced risk of abnormal reproductive outcomes and associated health risks. Thus, pretreating patients with dexrazoxane prior to epirubicin may efficiently preserve not only sperm quality but also prevent the transmission of genetic damage to future generations.     

Size and time-dependent induction of proinflammatory cytokines expression in brains of mice treated with gold nanoparticles

Gold nanoparticles (GNPs) are among the ideal nano-sized materials for medical applications such as imaging and drug delivery. Considering the significance of recent reports on acute phase induction of inflammatory mediators by GNPs, we studied the effect of GNPs on proinflammatory cytokines gene expression in mouse brain. Group 1 served as control whereas groups 2–4 were given only one intraperitoneal dose of 5, 20 and 50?nm GNPs, respectively and sacrificed after 24?h. The animals in groups 5–7 also received the same treatment but sacrificed after 7?days. Groups 8–10 received two injections of GNPs (5, 20 and 50?nm, respectively), first at the beginning of study and second on day 6, and sacrificed on day 7. Total RNA was extracted from the cerebral tissue and analyzed for the gene expressions of IL-1β, IL-6 and TNF-α. A single injection of 5?nm diameter GNPs significantly increased the mRNA expression of IL-1β and IL-6 in mouse brain on day 7, which was not augmented by the second dose of the same GNPs. Larger size GNPs (20?nm and 50?nm) did not cause any significant change in the expression of proinflammatory cytokines in mouse brain. In conclusion, systemic administration of small sized GNPs (5?nm) induced a proinflammatory cascade in mouse brain indicating a crucial role of GNPs size on immune response. It is important to use the right sized GNPs in order to avoid an acute phase inflammatory response that could be cytotoxic or interfere with the bioavailability of nanomaterials.     

Anatomical study of the skull of amphisbaenian Diplometopon zarudnyi (Squamata,Amphisbaenia)

This study investigates the amphisbaenian species skull which includes cranium, lower jaw and hyoid apparatus. The medial dorsal bones comprise the premaxilla, nasal, frontal and parietal. The premaxilla carries a large medial tooth and two lateral ones. The nasals are paired bones and separated by longitudinal suture. Bones of circumorbital series are frontal, orbitosphenoid and maxilla. The occipital ring consists of basioccipital, supraoccipital and exooccipital. Supraoccipital and basioccipital are single bones while the exo-occipitals are paired. The bones of the palate comprise premaxilla, maxilla, septomaxilla, palatine, pterygoid, ectopterygoid, basisphenoid, parasphenoid, orbitosphenoid and laterosphenoid. Prevomer and pterygoid teeth are absent. Palatine represent by two separate bones. The temporal bones are clearly visible. The lower jaw consists of the dentary, articular, coronoid, supra-angular, angular and splenial. The hyoid apparatus is represented by a Y-shaped structure. The mandible is long and is suspended from the braincase via relatively short quadrate. There is an extensive contact between the long angular and the large triangular coronoid. Thus inter-mandibular joint is bridged completely by the angular and consequently, the lower jaws are relatively rigid and kinetic. The maxillae are suspended from the braincase largely by ligaments and muscles rather than through bony articulation. In conclusion, the skull shape affects feeding strategy in Diplometopon zarudnyi. The prey is ingested and transported via a rapid maxillary raking mechanism.     

Effect of ninhydrin on the biochemical and histopathological changes induced by ethanol in gastric mucosa of rats

Studies on the effect of ninhydrin in the normal gastric mucosa and against the ethanol induced gastric injury were undertaken in rats in view of the presence of a carbonyl function as well as hydroxyl groups in its chemical structure. In spite of its potentials to generate hydroxyl radicals, it is deemed to possess antioxidant property by virtue of its electrophilic nature. Recent studies have shown gastro-protection to mediate through a reaction between the electrophilic compounds and sulfhydryl groups of the mucosa. Hence it was found worthwhile to evaluate the interaction between the oxidant and antioxidant functions in the structure of the same compound. The effects of ninhydrin pretreatment on gastric mucosal injuries caused by 80% ethanol, 25% NaCl and 0.2M NaOH were investigated in rats. The gastric tissue in ethanol-treated rats was analyzed for different histopathological lesions. In addition, the effects on ethanol-induced changes in the gastric levels of proteins, nucleic acids, non-protein sulfhydryl (NP-SH) and malondialdehyde (MDA) were also evaluated. Ninhydrin, as such, failed to induce any significant changes in normal gastric mucosa, while its pretreatment at oral doses of 5, 10 and 20 mg/kg was found to provide a dose-dependent protection against the ulcers induced by ethanol, NaOH and NaCl. The results of histopathological evaluation revealed a protective effect of ninhydrin on congestion, hemorrhage, edema, erosions and necrosis caused by ethanol. Furthermore, the pretreatment afforded a dose-dependent inhibition of the ethanol-induced depletion of proteins, nucleic acids, NP-SH and increase of MDA in the gastric tissue. The results obtained clearly demonstrate the anti-ulcerogenic activity of ninhydrin. The exact mechanism of action is not known. However, the carbonyl function in ninhydrin appears to achieve antioxidant balance and protect the gastric mucosa from the ethanol-induced gastric injury. Further studies are warranted to investigate the toxicity and detailed mechanism of action of this potent compound before any clinical trials, especially at the effective lower doses.     

Transcriptional profiling of bovine intervertebral disc cells: implications for identification of normal and degenerate human intervertebral disc cell phenotypes

Introduction  

Nucleus pulposus (NP) cells have a phenotype similar to articular cartilage (AC) cells. However, the matrix of the NP is clearly different to that of AC suggesting that specific cell phenotypes exist. The aim of this study was to identify novel genes that could be used to distinguish bovine NP cells from AC and annulus fibrosus (AF) cells, and to further determine their expression in normal and degenerate human intervertebral disc (IVD) cells.