A comparison of melatonin and α-lipoic acid in the induction of antioxidant defences in L6 rat skeletal muscle cells.

Aging is characterized by a progressive deterioration in physiological functions and metabolic processes. The loss of cells during aging in vital tissues and organs is related to several factors including oxidative stress and inflammation. Skeletal muscle degeneration is common in elderly people; in fact, this tissue is particularly vulnerable to oxidative stress since it requires large amounts of oxygen, and thus, oxidative damage is abundant and accumulates with increasing age. Melatonin (N-acetyl-5-methoxytryptamine) is a highly efficient scavenger of reactive oxygen species and it also exhibits beneficial anti-inflammatory and anti-aging effects. This study investigated the susceptibility of rat L6 skeletal muscle cells to an induced oxidative stress following their exposure to hydrogen peroxide (50 μM) and evaluating the potential protective effects of pre-treatment with melatonin (10 nM) compared to the known beneficial effect of alpha-lipoic acid (300 μM). Hydrogen peroxide-induced obvious oxidative stress; it increased the expression of tumour necrosis factor-alpha and in turn promoted nuclear factor kappa-B and overrode the endogenous defence mechanisms. Conversely, pre-treatment of the hydrogen peroxide-exposed cells to melatonin or alpha-lipoic acid increased endogenous antioxidant enzymes, including superoxide dismutase-2 and heme oxygenase-1; moreover, they ameliorated significantly oxidative stress damage and partially reduced alterations in the muscle cells, which are typical of aging. In conclusion, melatonin was equally effective as alpha-lipoic acid; it exhibited marked antioxidant and anti-aging effects at the level of skeletal muscle in vitro even when it was given in a much lower dose than alpha-lipoic acid

PENGARUH DOSIS PUPUK KOMPOS DAN NPK TERHADAP PERTUMBUHAN DAN HASIL BAWANG MERAH (ALLIUM ASCOLANICUM L.) VARIETAS BREBES

Penelitian ini bertujuan untuk mengetahui pengaruh kompos dan NPK pupuk terhadap pertumbuhan dan produksi tanaman bawang Brebes dan interaksi antara kedua faktor. Percobaan ini menggunakan Faktorial Rancangan Acak Pola. Faktor-faktor yang mempengaruhi dosis diuji kompos terdiri dari 4 tingkatan, yaitu: kontrol, 10, 20 dan 30 faktor ton / ha dan NPK dosis pupuk yang terdiri dari 4 tingkatan, yaitu: kontrol, 100, 200 dan 300 kg / ha, sehingga bahwa ada 16kombinasi perlakuan dengan 3 ulangan dan 48 unit percobaan, setiap unit terdiri dari 5 tanaman sampel percobaan.Hasil penelitian menunjukkan bahwa dosis kompos cenderung lebih baik pada dosis pengobatan 30 ton / ha untuk pertumbuhan dan hasil bawang. Sementara itu, NPK dosis pupuk untuk pertumbuhan dan hasil tanaman bawang merah cenderung lebih baik pada dosis pengobatan 200 kg NPK / ha. Tidak ada interaksi yang nyata antara perlakuan dosis pupuk NPK untuk kompos dengan semua variabel yang diamati pada pertumbuhan dan hasil bawang.Kata kunci: bawang, kompos, NPKBanda Ace

Epithelial expression of vanilloid and cannabinoid receptors: a potential role in burning mouth syndrome pathogenesis

Burning mouth syndrome is an intraoral burning sensation in which the oral mucosa has a normal appearance and no medical or dental causes can be found. It remains an unknown disease for which long-term treatment is still lacking. The aim of this study is to assess in epithelial human tongue the expression of three receptors involved in pain transmission, such as a transient receptor potential vanilloid receptor type 1 (TRPV1) which mediates the sensation produced by chilli peppers, cannabinoid receptors type 1 (CB1) and type 2 (CB2), which are pathway-related to TRPV1. Epithelial cells express TRPV1, CB1 and CB2 receptors suggesting a role for these cells in sensory transduction. The study was performed on 8 healthy and 9 BMS patients. All patients underwent a 3-mm punch biopsy at the anterolateral aspect of the tongue close to the tip. Specimens were included in paraffin and serially cut to obtain 6um thick sections. The sections were processed for TRPV1, CB1 and CB2 immunohistochemistry. The analysis showed an altered expression of the studied receptors. In particular we observed an increase of TRPV1, a decrease of CB1 and an increase of CB2 expression in epithelial cells of the tongue with a change in morphological localization. So, these receptors seem to be correlated with BMS. These data could be useful for future characterization of BMS markers and specific therapies

Stem cell transplantation in neuropathic pain

The neuropathic pain is a disabling condition which occurs secondarily to injury of peripheral or central nervous system. To date, the neuronal basis are poorly understood and effective treatments with long lasting relief are not available. Stem cells represent a more innovative and interesting therapeutic approach for tissue damage restoration. This study evaluates the effect of intravenous administration of murine adult neuronal stem cells and the administration in the lateral cerebral ventricle of human mesenchymal stem cells in two animal models of peripheral mononeuropathy: the chronic constriction injury and the spared nerve injury of the sciatic nerve. Pain related behaviour evaluation, morphofunctional alterations and the stem cell localization in brain, spinal cord and sciatic nerve were studied using respectively behavioural tests and immunohistochemical techniques. Stem cells were able to reduce pain-like behaviours, such as mechanical allodynia and thermal hyperalgesia, and to decrease the activation of nociceptive neurons at central level. The stem cells injected intravenously homed in the injured nerve site, while when injected in the cerebral ventricle was localized near the injection site. These data suggest that the stem cells administered intravenously influence directly the damaged area, whereas the cells injected in the cerebral ventricle could modulate the central neuronal pathway, responsible of neuropathic pain. The administration of stem cells in neuropathic pain syndromes may be a more suitable therapy than ‘’classical’’ drugs to decrease the unpleasant related symptoms

Peripheral Purinergic Modulation in Pediatric Orofacial Inflammatory Pain Affects Brainstem Nitroxidergic System: A Translational Research

Physiology of orofacial pain pathways embraces primary afferent neurons, pathologic changes in the trigeminal ganglion, brainstem nociceptive neurons, and higher brain function regulating orofacial nociception. The goal of this study was to investigate the nitroxidergic system alteration at brainstem level (spinal trigeminal nucleus), and the role of peripheral P2 purinergic receptors in an experimental mouse model of pediatric inflammatory orofacial pain, to increase knowledge and supply information concerning orofacial pain in children and adolescents, like pediatric dentists and pathologists, as well as oro-maxillo-facial surgeons, may be asked to participate in the treatment of these patients. The experimental animals were treated subcutaneously in the perioral region with pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS), a P2 receptor antagonist, 30 minutes before formalin injection. The pain-related behavior and the nitroxidergic system alterations in the spinal trigeminal nucleus using immunohistochemistry and western blotting analysis have been evaluated. The local administration of PPADS decreased the face-rubbing activity and the expression of both neuronal and inducible nitric oxide (NO) synthase isoforms in the spinal trigeminal nucleus. These results underline a relationship between orofacial inflammatory pain and nitroxidergic system in the spinal trigeminal nucleus and suggest a role of peripheral P2 receptors in trigeminal pain transmission influencing NO production at central level. In this way, orofacial pain physiology should be elucidated and applied to clinical practice in the futur

Importance of Different Types of Prior Knowledge in Selecting Genome‐Wide Findings for Follow‐Up

Biological plausibility and other prior information could help select genome‐wide association ( GWA ) findings for further follow‐up, but there is no consensus on which types of knowledge should be considered or how to weight them. We used experts’ opinions and empirical evidence to estimate the relative importance of 15 types of information at the single‐nucleotide polymorphism ( SNP ) and gene levels. Opinions were elicited from 10 experts using a two‐round Delphi survey. Empirical evidence was obtained by comparing the frequency of each type of characteristic in SNP s established as being associated with seven disease traits through GWA meta‐analysis and independent replication, with the corresponding frequency in a randomly selected set of SNP s. SNP and gene characteristics were retrieved using a specially developed bioinformatics tool. Both the expert and the empirical evidence rated previous association in a meta‐analysis or more than one study as conferring the highest relative probability of true association, whereas previous association in a single study ranked much lower. High relative probabilities were also observed for location in a functional protein domain, although location in a region evolutionarily conserved in vertebrates was ranked high by the data but not by the experts. Our empirical evidence did not support the importance attributed by the experts to whether the gene encodes a protein in a pathway or shows interactions relevant to the trait. Our findings provide insight into the selection and weighting of different types of knowledge in SNP or gene prioritization, and point to areas requiring further research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96262/1/gepi21705.pd

SNP Prioritization Using a B ayesian Probability of Association

Prioritization is the process whereby a set of possible candidate genes or SNP s is ranked so that the most promising can be taken forward into further studies. In a genome‐wide association study, prioritization is usually based on the P ‐values alone, but researchers sometimes take account of external annotation information about the SNP s such as whether the SNP lies close to a good candidate gene. Using external information in this way is inherently subjective and is often not formalized, making the analysis difficult to reproduce. Building on previous work that has identified 14 important types of external information, we present an approximate B ayesian analysis that produces an estimate of the probability of association. The calculation combines four sources of information: the genome‐wide data, SNP information derived from bioinformatics databases, empirical SNP weights, and the researchers’ subjective prior opinions. The calculation is fast enough that it can be applied to millions of SNPS and although it does rely on subjective judgments, those judgments are made explicit so that the final SNP selection can be reproduced. We show that the resulting probability of association is intuitively more appealing than the P ‐value because it is easier to interpret and it makes allowance for the power of the study. We illustrate the use of the probability of association for SNP prioritization by applying it to a meta‐analysis of kidney function genome‐wide association studies and demonstrate that SNP selection performs better using the probability of association compared with P ‐values alone.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96317/1/gepi21704.pd