Multiple sclerosis prevalence in Salta City, Argentina.

INTRODUCTION: Multiple Sclerosis (MS) is one of the leading causes of disability in young adults. Its prevalence varies according to different countries. In Argentina there is a wide heterogeneity regarding data published in different areas of the country. Prevalence established in most studies is 17 cases per 100,000 inhabitants; however, most of the available data comes from studies that took place in Buenos Aires. There is little or no information from other provinces, especially from Northwest of Argentina (NOA), where there are no studies of the disease prevalence. The aim of this study is to investigate MS prevalence, phenotypes and epidemiological characteristics in Salta, Argentina, in order to contribute to the current knowledge of MS epidemiology and distribution in our country. METHODS: A descriptive, observational, transversal study was carried out in the capital city of Salta. Researchers from all public and private hospitals with a Neurology Department have participated. Private researchers who are well known leaders in demyelinating diseases in the city provided valuable information. Patients who did not have medical control for the past two years as well as patients whose last address was not registered in Salta were excluded. RESULTS: 120 registries were obtained from the four hospitals that participated and from the 12 private researchers. Ten patients were excluded due to overlapping data. The population of the area based on 2010 census was 535,310, so we estimated an MS prevalence 23.8 cases per 100,000 inhabitants (95% CI 20.1-27.4), 24.1 cases per 100,000 inhabitants in female population (95% CI 21.2-28.6) and 18.2 cases per 100,000 inhabitants (95% CI 15.2-21.1) in male population. In our analysis, 64 (58.2%) were female and the average age was 42.1 years. 81.8% are recurrent remitting forms, 16.4% secondary progressive and 1.8% primary progressive. CONCLUSION: This is the first study that provides epidemiological data on the prevalence and clinical forms of MS in Salta City as well as in the entire Northwest Region of Argentina(NOA). We estimate a prevalence of 23.8 cases per 100,000 inhabitants, which establishes a moderate risk area for MS.

Stereotactic body radiation therapy and intensity modulated radiation therapy induce different plasmatic cytokine changes in non-small cell lung cancer patients: a pilot study.

PURPOSE: To assess kinetics of plasmatic cytokines during radiation therapy (RT) for locally advanced and early-stage non-small cell lung cancer (NSCLC). METHODS: This prospective study was conducted on 15 early-stage NSCLC underwent to extreme hypofractionated regimen (52 Gy in 8 fractions) with stereotactic body RT (SBRT), and 13 locally advanced NSCLC underwent to radical moderated hypofractionated regimen (60 Gy in 25 fractions) with intensity modulated RT (IMRT). For patients undergoing SBRT, peripheral blood samples were collected on the first day of SBRT (TFd), the last day (TLd) and 45 days (T45d) after the end of SBRT. For patients undergoing IMRT, blood samples were collected at: TFd, 2 weeks (T2w), 4 weeks (T4w), TLd, and T45d. The following cytokines were measured: IL-1, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17A, EGF, FGF-2, INF-γ, MIP-1α, MIP-1ß, TGF-α, TNF-α, and VEGF. Cytokine levels measured in different RT time and compared. RESULTS: No difference in baseline levels of cytokines was documented between patient radiation approaches (except for MIP-1α). For SBRT patients, a mean reduction of IL-10 and IL-17 plasma level was documented between TLd and TFd, respectively (p < 0.05). For IMRT patients, a statistically significant (p < 0.05) mean plasma level reduction was documented between T4w and TFd for all the following cytokines: IL-1, IL-1ra, IL-2, IL-12, FGF-2, MIP-1α, MIP-1ß, TGF-α, TNF-α, VEGF. CONCLUSIONS: SBRT and IMRT induce different plasmatic cytokine changes in NSCLC patients, supporting hypothesis that RT regimes of dose schedules and techniques have different impacts on the host immune response.

Autoantibodies to beta1-adrenoceptors in human chronic periodontitis induce overexpression of fibroblast CD40 and trigger prostaglandin E2 generation.

BACKGROUND AND OBJECTIVE: Autoimmune mechanisms may contribute to the pathogenesis of periodontal disease. Autoantibodies with the potential to bind and activate beta(1)-adrenoceptors (beta(1)-AR) of human gingival fibroblasts were studied to provide evidence of altered humoral immune response in chronic periodontal disease. MATERIAL AND METHODS: Flow cytometry and enzyme-linked immunosorbent assay using cell culture-adherent gingival fibroblasts and/or their purified membranes and/or a synthetic peptide corresponding to the second extracellular loop of human beta(1)-AR were used to detect serum antibodies. The effects of antibodies from chronic periodontal disease patients on PGE(2) generation and CD40 expression were also tested. RESULTS: Circulating immunoglobulin G (IgG) from chronic periodontal disease patients (but not from normal individuals) interacted with the fibroblast surface, activating beta(1)-AR. Atenolol or CGP 20712 (beta 1-AR antagonists) and beta(1) synthetic peptide inhibited the interaction of IgG with beta(1)-AR. Immunoglobulin G from chronic periodontal disease patients also displayed agonist-like activity associated with specific beta(1)-AR activation, increasing PGE(2) generation and CD40 overexpression. The corresponding affinity-purified anti-beta(1)-AR peptide IgG mimicked these effects. Both effects were prevented by inhibition of cyclo-oxygenase. CONCLUSION: This article supports the participation of humoral immune alterations in chronic periodontal disease resulting in postsynaptic functional deregulation. Overproduction of proinflammatory mediators (PGE(2) and CD40 expression) is induced as a consequence of antibody-beta(1)-AR interaction. The PGE(2)-CD40-IgG axis may play a part in the pathophysiological mechanisms underlying the inflammatory process in chronic periodontal disease.

Differential signalling pathways involved in cholinoceptor-dependent stimulation of nitric oxide isoforms in dental pulp.

AIM: To investigate the role of muscarinic acetylcholine receptor (mAChR) subtype activity in the regulation of endothelial- (e) and neuronal- (n) nitric oxide synthase (NOS) expression and activity. METHODOLOGY: Rat dental pulp tissue was used throughout the study. The e-nos and n-nos mRNA levels were specifically measured using reverse transcriptase polymerase chain reaction procedures that involve simultaneous co-amplification of both target cDNA and a reference template with a single set of primers. NOS activity was measured by the production of [U-(14)C]-citrulline from [U-(14)C]-arginine. RESULTS: Stimulation of M(1)/M(2) and M(3)/M(4) mAChRs with pilocarpine caused an increase in e-nos and n-nos mRNA levels and NOS activity in the dental pulp. The specific mAChR subtype antagonists, L-NMMA, l-NIO and N(2)-propyl-L-arginine but not aminoguanidine attenuated all these effects. Inhibitors of phospholipase C (PLC), protein kinase C (PKC) and calcium/calmodulin (CaM) prevented the pilocarpine-dependent increase in n-nos and e-nos mRNA levels and NOS activity. CONCLUSIONS: Activation of mAChR subtypes stimulated NOS activity by increasing the production of NO through e-nos and n-nos gene expression and NOS activity. The mechanism appears to occur secondarily to stimulation of CaM and PKC enzymatic activity.

Psidium guajava 'Paluma' (the guava plant) as a new bio-indicator of ozone in the tropics.

Psidium guajava 'Paluma' saplings were exposed to carbon filtered air (CF), ambient non-filtered air (NF), and ambient non-filtered air+40ppb ozone (NF+O(3)) 8h per day during two months. The AOT40 values at the end of the experiment were 48, 910 and 12 895ppbh(-1), respectively for the three treatments. After 5 days of exposure (AOT40=1497ppbh(-1)), interveinal red stippling appeared in plants in the NF+O(3) chamber. In the NF chamber, symptoms were observed only after 40 days of exposure (AOT40=880ppbh(-1)). After 60 days, injured leaves per plant corresponded to 86% in NF+O(3) and 25% in the NF treatment, and the average leaf area injured was 45% in NF+O(3) and 5% in the NF treatment. The extent of leaf area injured (leaf injury index) was explained mainly by the accumulated exposure of ozone (r(2)=0.91; p<0.05).

Nucleotide-sugar transporters: structure, function and roles in vivo.

The glycosylation of glycoconjugates and the biosynthesis of polysaccharides depend on nucleotide-sugars which are the substrates for glycosyltransferases. A large proportion of these enzymes are located within the lumen of the Golgi apparatus as well as the endoplasmic reticulum, while many of the nucleotide-sugars are synthesized in the cytosol. Thus, nucleotide-sugars are translocated from the cytosol to the lumen of the Golgi apparatus and endoplasmic reticulum by multiple spanning domain proteins known as nucleotide-sugar transporters (NSTs). These proteins were first identified biochemically and some of them were cloned by complementation of mutants. Genome and expressed sequence tag sequencing allowed the identification of a number of sequences that may encode for NSTs in different organisms. The functional characterization of some of these genes has shown that some of them can be highly specific in their substrate specificity while others can utilize up to three different nucleotide-sugars containing the same nucleotide. Mutations in genes encoding for NSTs can lead to changes in development in Drosophila melanogaster or Caenorhabditis elegans, as well as alterations in the infectivity of Leishmania donovani. In humans, the mutation of a GDP-fucose transporter is responsible for an impaired immune response as well as retarded growth. These results suggest that, even though there appear to be a fair number of genes encoding for NSTs, they are not functionally redundant and seem to play specific roles in glycosylation.

Nucleotide-sugar transporters: structure, function and roles in vivo

The glycosylation of glycoconjugates and the biosynthesis of polysaccharides depend on nucleotide-sugars which are the substrates for glycosyltransferases. A large proportion of these enzymes are located within the lumen of the Golgi apparatus as well as the endoplasmic reticulum, while many of the nucleotide-sugars are synthesized in the cytosol. Thus, nucleotide-sugars are translocated from the cytosol to the lumen of the Golgi apparatus and endoplasmic reticulum by multiple spanning domain proteins known as nucleotide-sugar transporters (NSTs). These proteins were first identified biochemically and some of them were cloned by complementation of mutants. Genome and expressed sequence tag sequencing allowed the identification of a number of sequences that may encode for NSTs in different organisms. The functional characterization of some of these genes has shown that some of them can be highly specific in their substrate specificity while others can utilize up to three different nucleotide-sugars containing the same nucleotide. Mutations in genes encoding for NSTs can lead to changes in development in Drosophila melanogaster or Caenorhabditis elegans, as well as alterations in the infectivity of Leishmania donovani. In humans, the mutation of a GDP-fucose transporter is responsible for an impaired immune response as well as retarded growth. These results suggest that, even though there appear to be a fair number of genes encoding for NSTs, they are not functionally redundant and seem to play specific roles in glycosylation.

Muscarinic cholinoceptor activation modulates DNA synthesis and CD40 expression in fibroblast cells.

1 The aim of the present work was to examine the role of muscarinic acetylcholine receptors (mAChR) on DNA synthesis and CD40 expression in human fibroblast cells. Neonatal human skin fibroblast cultures were stimulated with carbachol in presence or absence of specific antagonists and the following parameters were measured: identification of mAChR subtypes, DNA synthesis, inositol phosphates (InsP) production and CD40 expression. 2 Human fibroblasts express mAChR with Kd 0.47 +/- 0.11 nm and Bmax 236 +/- 22 fmol mg protein(-1). Carbachol stimulates DNA synthesis, InsP and the expression of CD40. All these effects were inhibited by atropine, mustard hydrochloride (4-DAMP) and pirenzepine but not by AF-DX 116 and tropicamide, indicating that M3 and M1 mAChR are implicated in carbachol action. The relative Ki of the antagonists obtained by competition binding assay was in parallel to the relative potency for blocking both carbachol-stimulated InsP accumulation and DNA synthesis. 3 The intracellular pathway leading to carbachol-induced biological effects involved phospholipase C and calcium/calmodulin, as U-73122 and trifluoroperazine blocked carbachol effects, respectively. Calphostin C, a protein kinase C inhibitor, had no effect, indicating that this enzyme does not participate in the system. 4 These results may contribute to a better understanding of the modulatory role of the parasympathetic muscarinic system on normal human fibroblast function.

Tropical fruit trees as bioindicators of industrial air pollution in southeast Brazil.

Psidium guajava L., Psidium cattleyanum Sabine and Mangifera indica L. were tested under field conditions as possible tropical bioindicators of industrial air pollution. The study was performed around the industrial complex of Cubatão, SE Brazil, which comprises 23 industries, including fertilizer, cement, chemical, petrochemical, and steel plants, with 110 production units and 260 emission sources of pollutants. Saplings were exposed to environmental conditions during four periods of 16 weeks each (September 1994-September 1995), at four different sites in the coastal mountains near the industrial complex: the Valley of Pilões River (VP), the reference area; the Valley of Mogi River (VM), with high contamination of particulate matter, fluorides (F), sulfur (S) and nitrogen (N) compounds; Caminho do Mar (CM1, CM2), mainly affected by organic pollutants, S and N compounds, and secondary pollutants; and Paranapiacaba (PP), affected by secondary pollutants, such as ozone. M. indica did not adapt to the climatic conditions at the exposure sites. In the two Psidium species, the presence of visible symptoms, root/shoot ratio, foliar contents of F, S and N, amounts of ascorbate (AA) and water-soluble thiols (-SH), as well as peroxidase activity (POD) were determined. P. guajava showed higher foliar accumulation of F, S and N, more pronounced alterations of biochemical indicators, and less visible leaf injury than P. cattleyanum. P. guajava may be used as an accumulative indicator in tropical climates, while further studies will be needed before P. cattleyanum might be applied as a sensitive species in biomonitoring programs.

Response of stress indicators and growth parameters of Tibouchina pulchra Cogn. exposed to air and soil pollution near the industrial complex of Cubatão, Brazil.

The present study was performed in the vicinity of the industrial complex of Cubatão, São Paulo, Brazil, in order to evaluate the response of 'manaca da serra' Tibouchina pulchra Cogn. (Melastomataceae), a common species of secondary Atlantic Rain Forest vegetation, to the impact of complex air pollution. Emphasis was given to changes of biochemical parameters such as ascorbic acid concentration, peroxidase activity, contents of water-soluble thiols, pH of leaf extract and buffering capacity. These plant factors are often used as early indicators of air pollution stress. Field experiments included sampling of leaves from mature trees in areas with different air pollution load (passive monitoring), exposure of saplings cultivated in uniform soil at these areas (active monitoring) and a study on the combined effects of contaminated soil and air pollution. In general, metabolic response of saplings was more accentuated than that of mature trees. Leaf extract pH and buffering capacity showed no or only small alterations in plants exposed to industrial emissions. In contrast, air pollution resulted in a distinct decrease in ascorbic acid contents and an increase in peroxidase activity and thiol concentrations in leaves. Cultivation of saplings in soil types from contaminated regions frequently caused the same modifications or enhanced the effects produced by air pollution. Growth analysis of exposed saplings demonstrated that a change of the relationship between above-ground and below-ground plant parts was the most obvious effect of air pollution and soil contamination. The experiments showed that even T. pulchra, a species considered resistant to air pollution, suffers metabolic disturbances by the present ambient air and soil quality. Although biochemical and physiological alterations were not related to a certain air pollution type, they could be used to estimate the overall pollution load and to map zones with different air quality.