Hvidingram2944

In both cases, patients experienced partial or complete loss of smell. This paper is the first one to analyze zinc salts and concentrations of those two epidemiological adversities and directly compare formulations distributed to the public with animal toxicity data. The information gained from animal and epidemiological data provides a foundation for the formation of opinion given in this paper regarding safety of intranasal zinc in emerging clinical trials with intranasal insulin.Recent studies suggest a possible link between type 2 diabetes and Alzheimer's disease (AD). Glucogan-like peptide 1 (GLP-1) facilitates insulin release from pancreas under hyperglycemic conditions. In addition to its metabolic effects, GLP-1 and its long-lasting analogs, including exenatide can stimulate neurogenesis and improve cognition in rodent AD model. The aim of the present study was to investigate the effects of exenatide on hippocampal cellularity, cognitive performance and inflammation response in a rat model of AD. Fourteen rats were used to create AD model using intracerebroventricular (ICV) streptozotocin (STZ) infusion while 7 rats were administered 0.9% NaCl only (sham-operated group). Following stereotaxic surgery, STZ received rats were randomly distributed into two groups, and treated with either saline or exenatide 20 µgr/kg/day through intraperitoneally for two weeks. Erastin2 Then, cognitive performance (passive avoidance learning), brain tumor necrosis factor alpha (TNF-α) levels, choline acetyltransferase (ChAT) activity and hippocampal neuronal count were determined. While the brain TNF-α levels were significantly high in the saline-treated STZ group, exenatide treatment suppressed the increase in TNF-α levels. Saline-treated STZ group showed reduced ChAT activity compared to sham group. However, exenatide significantly preserved brain ChAT activity. The cognitive performance was also impaired in saline group while exenatide improved memory in rats. Moreover, exenatide treatment significantly prevented the decrease in hippocampal neurons. Overall, the results of the present study clearly indicated exenatide might have beneficial effects on impaired cognitive performance and hippocampal neuronal viability in AD by suppressing the inflammation response and increasing cholinergic activity.Atorvastatin has protective effects against myocardial ischemia-reperfusion injuries and ischemia-reperfusion arrhythmia. This study was designed to investigate whether atorvastatin is able to protect against myocardial ischemia-reperfusion injury by enhancing the expression of Connexin 43 (Cx43) via the activation of the phosphatidylinositol-3-kinase (PI3K)/Akt pathway and mitochondrial ATP-sensitive potassium (K(ATP)) channels. Isolated perfused rat hearts were treated with classic ischemia postconditioning (IPOST), atorvastatin, and atorvastatin combined with inhibitor of PI3K and K(ATP) channels, respectively, after 30min of LAD ischemia and then subjected to reperfusion for 120min. The QRS duration and the ischemia-reperfusion ventricular arrhythmia were assessed. The lactate dehydrogenase (LDH) and creatine kinase isoenzyme (CK-MB) levels were measured and the Cx43 expression was assessed by immunoblotting and immunohistochemistry. After 120min of reperfusion, atorvastatin and IPOST significantly decreased the QRS duration and inhibited ventricular arrhythmia. They also decreased the levels of LDH and CK-MB. Meanwhile, atorvastatin and IPOST also significantly enhanced the Cx43 expression and the phosphorylation of Cx43. Such protective effects were abolished in the presence of the inhibitor of PI3K or the inhibitor of mitochondrial K(ATP) channels. This study suggests that atorvastatin protected against myocardial ischemia-reperfusion injury and enhanced the expression of Cx43 by activating the PI3K/Akt pathway and mitochondrial K(ATP) channels.The ATP-gated ion channel P2X7 has emerged as a potential central nervous system (CNS) drug target based on the hypotheses that pro-inflammatory cytokines such as IL-1β that are released by microglia, may contribute to the etiology of various disorders of the CNS including depression. In this study, we identified two closely related P2X7 antagonists, JNJ-54232334 and JNJ-54140515, and then tritium labeled the former to produce a new radioligand for P2X7. JNJ-54232334 is a high affinity ligand for the rat P2X7 with a pKi of 9.3±0.1. In rat cortical membranes, [3H] JNJ-54232334 reached saturable binding with equilibrium dissociation (Kd) constant of 4.9±1.3 nM. The compound displayed monophasic association and dissociation kinetics with fast on and off rates. In rat brain sections, specific binding of [3H] JNJ-54232334 was markedly improved compared to the previously described P2X7 radioligand, [3H] A-804598. In P2X7 knockout mouse brain sections, [3H] A-804598 bound to non-P2X7 binding sites in contrast to [3H] JNJ-54232334. In rat or wild type mouse brain sections [3H] JNJ-54232334 bound in a more homogenous and region independent manner. The ubiquitous expression of P2X7 receptors was confirmed with immunohistochemistry in rat brain sections. The partial displacement of [3H] A-804598 binding resulted in the underestimation of the level of ex vivo P2X7 occupancy for JNJ-54140515. Higher levels of P2X7 ex vivo occupancy were measured using [3H] JNJ-54232334 due to less non-specific binding. In summary, we describe [3H] JNJ-54232334 as a novel P2X7 radioligand, with improved properties over [3H] A-804598.Condensed catechins are commonly present in fermented tea, and are produced by the oxidation of monomeric catechins. Due to their auto-oxidation, catechins have diverse structural features, including different binding modes and degrees of polymerization. Because of their structural complexity, their physiological functions and possible health-benefits have not yet been fully investigated. This review focuses on the physiological potentials of dimeric and trimeric catechins in the intestine (regulation of absorption across the intestinal membrane), blood vessels (vasorelaxation in vessel regulation), and muscle organs (promotion of glucose uptake resulting in an anti-diabetic effect). Furthermore, the roles of non-absorbable theaflavins (dimeric catechins), absorbable theasinensins (dimeric catechins), and absorbable procyanidins (dimeric and trimeric catechins) on target organs are discussed.Quinones are highly reactive molecules that readily undergo either one- or two-electron reduction. One-electron reduction of quinones or their derivatives by enzymes such as cytochrome P450 reductase or other flavoproteins generates unstable semiquinones, which undergo redox cycling in the presence of molecular oxygen leading to the formation of highly reactive oxygen species. Quinone reductases 1 and 2 (QR1 and QR2) catalyze the two-electron reduction of quinones to form hydroquinones, which can be removed from the cell by conjugation of the hydroxyl with glucuronide or sulfate thus avoiding its autoxidation and the formation of free radicals and highly reactive oxygen species. This characteristic confers a detoxifying enzyme role to QR1 and QR2, even if this character is strongly linked to the excretion capacity of the cell. Using EPR spectroscopy and confocal microscopy we demonstrated that the amount of reactive oxygen species (ROS) produced by Chinese hamster ovary (CHO) cells overexpressing QR1 or QR2 compared to naive CHO cells was determined by the quinone structural type. Indeed, whereas the amount of ROS produced in the cell was strongly decreased with para-quinones such as menadione in the presence of quinone reductase 1 or 2, a strong increase in ROS was recorded with ortho-quinones such as adrenochrome, aminochrome, dopachrome, or 3,5-di-tert-butyl-o-benzoquinone in cells overexpressing QR, especially QR2. These differences could originate from the excretion process, which is different for para- and ortho-quinones. These results are of particular interest in the case of dopamine considering the association of QR2 with various neurological disorders such as Parkinson disease.Aim of this study was to induce a single-sided deafness (SSD) in rats before hearing onset. Rats were operated at postnatal day 10 by approaching the tympanic cavity along a retroauricular path without manipulating ossicles or tympanic membrane. The ototoxic aminoglycoside neomycin was injected intracochlearly through the round window membrane on one side. When the animals have reached young adult stages, their hearing threshold was determined by their auditory brainstem response (ABR). Monaural deafening was considered successful when the hearing threshold was at least 95 dB above the threshold of the normal hearing ear. Growing up with one non-functional ear, rats developed a striking anatomical asymmetry of their cochlear nuclei (CN). The CN from age-matched normal hearing brains and from both sides of single-sided deaf brains were cut into series of frontal sections and their volumes calculated. No difference was detected between the volume of the normal hearing CN and the contralateral CN in SSD rats. By contrast, growth retardation was found for the ventral CN on the deaf side to result in a volume of only 57% compared to the normal hearing side. Marginal growth retardation was also observed for the dorsal CN on the deaf side. Thus, loss of sensory activation leads mainly, but not exclusively, to a reduction of tissue volume in the ventral CN of the deaf side, leaving the contralateral side apparently unaffected.

Long-term motor outcome of acute stroke patients with severe motor impairment is difficult to predict. While measure of corticospinal tract (CST) injury based on diffusion tensor imaging (DTI) in subacute stroke patients strongly predicts motor outcome, its predictive value in acute stroke patients is unclear. Using a new DTI-based, density-weighted CST template approach, we demonstrated recently that CST injury measured in acute stroke patients with moderately-severe to severe motor impairment of the upper limb strongly predicts motor outcome of the limb at 6 months.

The current study compared the prognostic strength of CST injury measured in 10 acute stroke patients with moderately-severe to severe motor impairment of the upper limb by the new density-weighted CST template approach versus several variants of commonly used DTI-based approaches.

Use of the density-weighted CST template approach yielded measurements of acute CST injury that correlated most strongly, in absolute magnitude, with 6-month upper limb strength (rs=0.93), grip (rs=0.94) and dexterity (rs=0.89) compared to all other 11 approaches. Formal statistical comparison of correlation coefficients revealed that acute CST injury measured by the density-weighted CST template approach correlated significantly more strongly with 6-month upper limb strength, grip and dexterity than 9, 10 and 6 of the 11 alternative measurements, respectively.

Measurements of CST injury in acute stroke patients with substantial motor impairment by the density-weighted CST template approach may have clinical utility for anticipating healthcare needs and improving clinical trial design.

Measurements of CST injury in acute stroke patients with substantial motor impairment by the density-weighted CST template approach may have clinical utility for anticipating healthcare needs and improving clinical trial design.