Vitamin C May Help to Reduce the Knee's Arthritic Symptoms. Outcomes Assessment of Nutriceutical Therapy.

INTRODUCTION: Osteoarthritis (OA) is a chronic joint disease characterized by degeneration of the articular cartilage, changes in the physico-chemical properties of the synovial fluid and macroscopical modifications of the joint. Patients with Classes I and II of Knee OA can be treated with pharmacologic therapy. Vitamin C is key for both preventing inflammatory arthritis and maintaining healthy joints with OA. AIM: The aim of our paper is to verify the effectiveness of the addition of vitamin c in nutriceutical drugs for the therapy of the knee arthritis in the young adult. RESULTS: Group B has a lower VAS score at 6 and 12 months with p<0.05. Not statistical difference we found in KSS during all follow up. A better quality of life was founded in Group B at 12 months in group B(p<0.05) and less use of pain killers/monthly(p<0.05). CONCLUSION: There is no denying that vitamin C benefits everybody, whether they have arthritis or not. Therefore, it is a good idea to maintain a healthy balance of vitamin C. Without a doubt, vitamin C benefits most people with early OA.

Case-control study on the risks of BSE infections in Northern Germany.

This study was to identify risk factors for bovine spongiform encephalopathy (BSE) by means of individual case-control data. 43 BSE cases in a defined region in Lower Saxony and Schleswig-Holstein were compared with 84 control animals. Purchase of new breeding stock and cross contamination between feed on the farm did not seem to have influence on the BSE incidence in these regions. The results indicate independent risk patterns. Pattern 1: Cows with high milk yield seemed to be at risk on big farms with adjacent pig production and when they were not fed milk replacer. Pattern 2: Milk replacer (esp. from certain producers) is a risk factor for Non-Red Holstein cattle, low yielding cows and farms without pig production. Pattern 3: Red Holstein cattle not being fed milk replacer have a higher BSE risk than other breeds when they have a low milk yield and live on small farms with pig production. This study, like findings in Bavaria, Lower Saxony and Schleswig-Holstein, strengthens the hypothesis that BSE in Germany was caused by a feed mediated ubiquitous exposure to PrP(sc) during a confined time period. Producers, in need of buying animal derived feed components during that time slot, were more likely to spread the PrP(sc) than others. Their increased risk is not necessarily due to an inadequate purchasing policy, but can also be coincidental. The breed Red Holstein is not the risk factor itself but represents the risk from concentrated feed for animals during a susceptible age period (calves). Therefore, the authors suggest a continuous exclusion of animal-derived fat components from milk replacers.

Haploinsufficiency of VGluT1 but not VGluT2 impairs extinction of spatial preference and response suppression.

The excitatory neurotransmitter l-glutamate is transported into synaptic vesicles by vesicular glutamate transporters (VGluTs) to transmit glutamatergic signals. Changes in their expression have been linked to various brain disorders including schizophrenia, Parkinson's, and Alzheimer's disease. Deleting either the VGluT1 or VGluT2 gene leads to profound developmental and neurological complications and early death, but mice heterozygous for VGluT1 or VGluT2 are viable and thrive. Acquisition, retention and extinction of conditioned visuospatial and emotional responses were compared between VGluT1(+/-) and VGluT2(+/-) mice, and their wildtype littermates, using different water maze procedures, appetitive scheduled conditioning, and conditioned fear protocols. The distinct brain expression profiles of the VGluT1 and -2 isoforms particularly in telencephalic structures, such as neocortex, hippocampus and striatum, are reflected in very specific behavioral changes. VGluT2(+/-) mice were unimpaired in spatial learning tasks and fear extinction. Conversely, VGluT1(+/-) mice displayed spatial extinction learning deficits and markedly impaired fear extinction. These data indicate that VGluT1, but not VGluT2, plays a role in the neural processes underlying inhibitory learning.

Exploring the role of nociceptor-specific sodium channels in pain transmission using Nav1.8 and Nav1.9 knockout mice.

Two voltage gated sodium channels, Na(v)1.8 and Na(v)1.9, are exclusively expressed in primary sensory neurons and are suggested to play a role in different pain conditions, including chronic inflammatory and neuropathic pain states. Since no selective pharmacological tools are available, we investigated the involvement of Na(v)1.8 and Na(v)1.9 in pain transmission by the phenotypic characterization of Na(v)1.8 and Na(v)1.9 knockout mice and their wild-type littermates in models of acute nociception, peripheral inflammation and neuropathic pain. The present study provides evidence for a modulatory role of Na(v)1.9, and to a lesser extent Na(v)1.8 in the development of cold, but not mechanical allodynia in neuropathic pain conditions. Moreover, our results also indicate that Na(v)1.9 signaling might be involved in visceral pain. In contrast, the presumed critical role of these two sodium channel subtypes to inflammatory pain hypersensitivity seem, according to our results, to be limited and temporarily.

Impairment of VGLUT2 but not VGLUT1 signaling reduces neuropathy-induced hypersensitivity.

Glutamate is the major excitatory neurotransmitter in the central nervous system with an important role in nociceptive processing. Storage of glutamate into vesicles is controlled by vesicular glutamate transporters (VGLUT). Null mutants for VGLUT1 and VGLUT2 were poorly viable, thus, pain-related behavior was presently compared between heterozygote VGLUT1 and VGLUT2 mice and their respective wild-type littermates using a test battery that included a variety of assays for thermal and mechanical acute nociception, and inflammatory and neuropathic pain syndromes. Behavioral analysis of VGLUT1 mutant mice did not show important behavioral changes in the pain conditions tested. Reduction of VGLUT2 also resulted in unaltered acute nociceptive and inflammatory-induced pain behavior. Interestingly, VGLUT2 heterozygote mice showed an attenuation or absence of some typical neuropathic pain features (e.g., absence of mechanical and cold allodynia after spared nerve injury). Chronic constriction injury in VGLUT2 heterozygote mice showed also reduced levels of cold allodynia, but had no impact on mechanical thresholds. Together, these data suggest that VGLUT2, but not VGLUT1, plays a role in neuropathy-induced allodynia and hypersensitivity, and might be a therapeutic target to prevent and/or treat neuropathic pain.

Opioid-induced proliferation of vascular endothelial cells.

Angiogenesis is an important issue in cancer research and opioids are often used to treat pain in cancer patients. Therefore it is important to know if the use of opioids is associated with an aberrant stimulation of tumor growth triggered by the stimulation of angiogenesis in cancer patients. Some studies in the literature have suggested the presence of the µ3 opioid receptor, known as the receptor for many opioids, on endothelial cells, which are key players in the process of angiogenesis. In this study we used endothelial cells known to express the µ3 opioid receptor (MOR3), to evaluate the effects of morphine on angiogenesis. We first investigated the effect of morphine on the proliferation of endothelial cells. We showed that morphine is able to stimulate vascular endothelial cell proliferation in vitro. This effect of morphine is mediated by the mitogen-activated protein kinase (MAPK) pathway as pre-treatment with PD98059 inhibited this excessive proliferation. Because previous studies indicated nitric oxide (NO) as a downstream messenger we investigated the role of NO in the aberrant proliferation of endothelial cells. Our data could not confirm these findings using intracellular NO measurements and quantitative fluorescence microscopy. The potential use and pitfalls of opioids in cancer patients is discussed in light of these negative findings.

La accesibilidad al servicio público de transporte aéreo en Bolivia

Se busca que la autoridad de regulación del transporte aéreo realice actividades tendientes a promover y desarrollar el acceso mayoritario de la población al servicio de transporte aéreo en condiciones justas y razonables, expresadas a través de las tarifas que inciden en el uso masivo o disminución del uso del servicio aéreo antes citado

Differences in nociceptive behavioral performance between C57BL/6J, 129S6/SvEv, B6 129 F1 and NMRI mice.

The interpretation of knockout and transgenic mouse studies in pain research critically depends on detailed knowledge of the performance profile of the background strains. Pain-related behavior was compared between four relevant mouse strains (C57BL/6J, 129S6/SvEv, B6 129 F1 and NMRI mice of both sexes) using an extended test battery that included an unusual variety of assays for thermal and mechanical acute nociception, and inflammatory and neuropathic pain. Strain- and gender-dependent differences were demonstrated in many of these nociceptive assays. Particularly, C57BL and 129 mice, which serve as the default genetic backgrounds for experiments in genetically altered mice, display quite different patterns of nociceptive performance. Compared to C57BL/6J mice, 129S6/SvEv animals are less sensitive to inflammatory pain conditions (thermal sensitivity after carrageenan subplantar injection; flinch behavior after formalin injection), while the opposite is observed in the neuropathic pain condition and the visceral pain model. These data may be of special interest for genetic studies, where issues related to the background phenotype may confound their interpretation.

Vesicular glutamate transporter VGLUT2 expression levels control quantal size and neuropathic pain.

Uptake of L-glutamate into synaptic vesicles is mediated by vesicular glutamate transporters (VGLUTs). Three transporters (VGLUT1-VGLUT3) are expressed in the mammalian CNS, with partial overlapping expression patterns, and VGLUT2 is the most abundantly expressed paralog in the thalamus, midbrain, and brainstem. Previous studies have shown that VGLUT1 is necessary for glutamatergic transmission in the hippocampus, but the role of VGLUT2 in excitatory transmission is unexplored in glutamatergic neurons and in vivo. We examined the electrophysiological and behavioral consequences of loss of either one or both alleles of VGLUT2. We show that targeted deletion of VGLUT2 in mice causes perinatal lethality and a 95% reduction in evoked glutamatergic responses in thalamic neurons, although hippocampal synapses function normally. Behavioral analysis of heterozygous VGLUT2 mice showed unchanged motor function, learning and memory, acute nociception, and inflammatory pain, but acquisition of neuropathic pain, maintenance of conditioned taste aversion, and defensive marble burying were all impaired. Reduction or loss of VGLUT2 in heterozygous and homozygous VGLUT2 knock-outs led to a graded reduction in the amplitude of the postsynaptic response to single-vesicle fusion in thalamic neurons, indicating that the vesicular VGLUT content is critically important for quantal size and demonstrating that VGLUT2-mediated reduction of excitatory drive affects specific forms of sensory processing.

Differences in behavioural test battery performance between mice with hippocampal and cerebellar lesions.

Effects of hippocampal or cerebellar lesions have been described extensively, but the ability of behavioural tests for laboratory mice to distinguish between such lesions has not been studied in detail. We compared the behavioural consequences of large bilateral hippocampal and hemispheric cerebellar lesions with eight commonly used tests that included elements of neuromotor performance, exploratory behaviour, and learning and memory ability. Dissociation between the effects of the different lesions was most obviously demonstrated by neuromotor impairment in cerebellum-lesioned mice (typically in the rotarod task) and hyperactivity in hippocampus-lesioned mice (typically in cage activity recordings). Several of the behavioural variables derived from the test battery correlated differently with the size of the hippocampal and cerebellar lesions. In contrast, no absolute dissociation between the effects of these lesions was found in the Morris maze, a reportedly hippocampus-dependent learning and memory task. The contextual fear conditioning task, on the other hand, did reveal a selective decrease of context-dependent freezing in hippocampus-lesioned mice, whereas cerebellum-lesioned animals displayed an increase in freezing responses. By and large, the present battery of tests does allow differentiation between the effects of cerebellar and hippocampal lesions in laboratory mice.