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Josefina Castro-Fornieles,Ramón Deulofeu,Immaculada Baeza,Vanessa Casulà,Begoña Saura,Luisa Lázaro,Josefina Puig,Josep Toro,Miquel Bernardo Dopaminergic abnormalities have been described in anorexia nervosa but studies about plasma level of homovanillic acid (pHVA) have yielded conflicting results probably due to the small number and the heterogeneity of patients. Plasma HVA, nutritional and hormonal parameters and several scales - the... ( view more ) Eating Attitudes Test (EAT), the Beck Depression Inventory (BDI), the Leyton Obsessional Inventory-child version (LOI-C) and the State and Trait Anxiety Inventory (STAI) - were assessed in 44 adolescent anorexia nervosa patients (mean age 14.7 years, SD 1.7) consecutively admitted to an Eating Disorder Unit. They were evaluated at admission, at discharge and, in 34 cases, after 9 months of follow-up. pHVA was also assessed in 16 control adolescents. Patients had significantly higher pHVA than controls (p = .002). About 31% of patients had a very high level of pHVA, a significantly higher (p = .006) mean score in the BDI and a non significantly higher mean score in the EAT. After weight recovery some laboratory parameters improved as well as the EAT (p = .019), the BDI (p = 001) and the Interference score of the LOI-C (p = .004). Moreover, pHVA decreased significantly (p=.036). At follow-up, patients with normal weight had lower (p = .037) pHVA than patients with low weight. The conclusion would be that there is a dopaminergic dysfunction in anorexic patients, specially in a subgroup with high depressive and anorexic symptomatology. With weight recovery and psychopathological improvement, pHVA tends to normalization. ( view less ) Enrique Lerma,Marisa Romero,Alberto Gallardo,Cristina Pons,Josefina Muñoz,Josefina Fuentes,Belen Lloveras,Lluis Catasus,Jaime Prat We studied whether Fas-receptor (Fas-R; CD95) expression, single-nucleotide polymorphisms (SNPs) in the Fas promoter region, and/or Fas-ligand (Fas-L) production could determine individual susceptibility to cervical cancer progression. The clinicopathologic features of 38 patients with cervical squ... ( view more )amous carcinomas (22 stage I, 8 stage II, and 8 stage III+) were reviewed and related with: (a) Fas-R expression by immunohistochemistry; (b) Fas-R SNPs at -670 and -1377 locations by restriction fragment length polymorphism and DNA sequencing; and (c) Fas-L expression by immunohistochemistry. Overall and disease-free survival curves showed significant differences in relation to stage (p < 0.001). Fas-R was identified in 20 of 38 (52.6%) tumors without statistical differences in survival, stage, or Fas-L overproduction. Fas-R GG genotype was more common than expected in advanced tumors (p = 0.065). The Fas-R-1377A allele and AA genotype were unrelated with survival, stage, or Fas-R expression. Fas-L overproduction was detected in 20 of 38 (52.6%) tumors; it was more frequent in advanced-stage tumors and was inversely related to survival (p = 0.03) and decrease in host inflammatory response (p = 0.01). Fas-R expression by tumor cells seems unrelated to stage or lymphoid infiltrate. Tumor production of Fas-L may represent an attempt to destroy the host's lymphocytic reaction. ( view less ) Josefina Castro,Ramón Deulofeu,Araceli Gila,Josefina Puig,Josep Toro OBJECTIVES: To study nutritional abnormalities in adolescent anorexia nervosa and to establish whether certain abnormalities persist after short-term refeeding. METHOD: Sixty-one patients (10-19 years old) admitted to a reference unit for eating disorders between 1999 and 2000 with a diagnosis of a... ( view more )norexia nervosa were evaluated at admission and at discharge. A range of biochemical, nutritional, and hormonal parameters were determined. RESULTS: At admission, no protein or lipid deficiencies were found, although many patients presented with hormonal abnormalities and red blood cell folate and zinc deficiencies. Hormonal abnormalities reverted significantly (p <.000) after renutrition. There were decreases in erythrocytes and in levels of hemoglobin (p <.000) and folic acid (p <.05). Red blood cell folate and zinc increased but did not reach normal levels. CONCLUSIONS: In a large proportion of adolescent anorexic patients, supplementation of folic acid and zinc is recommended although protein or hormonal replacement does not seem to be necessary. ( view less ) José María Casellas,Gabriella Tomé,Carlos Bantar,Pamela Bertolini,Néstor Blázquez,Noemí Borda,Elsa Couto,Norma Cudmani,Josefina Guerrera,María Josefina Juárez,Teresa López,Ana Littvik,Emilce Méndez,Rodolfo Notario,Graciela Ponce,Mirta Quinteros,Francisco Salamone,Mónica Sparo,Emma Sutich,Susana Vaylet,Lidia Wolff The in vitro activity of piperacillin-tazobactam and several antibacterial drugs commonly used in Argentinean hospitals for the treatment of severe infections was determined against selected but consecutively isolated strains from clinical specimens recovered from hospitalized patients at 17 differ... ( view more )ent hospitals from 9 Argentinean cities from different geographic areas during the period November 2001-March 2002. Out of 418 Enterobacteriaceae included in the Study 84% were susceptible to piperacillin-tazobactam. ESBLs putative producers were isolated at an extremely high rate since among those isolates obtained from patients with hospital acquired infections 56% of Klebsiella pneumoniae, 32% of Proteus mirabilis and 25% Escherichia coli were phenotypically considered as ESBLs producers Notably P.mirabilis is not considered by for screening for ESBL producers. ESBLs producers were 100% susceptible to imipenem and 70% were susceptible to piperacillin-tazobactam whereas more than 50% were resistant to levofloxacin. The isolates considered as amp C beta lactamase putative producers showed 99% susceptibility to carbapenems while 26.7% were resistant to piperacillin-tazobactam and 38.4% to levofloxacin. Noteworthy only 4% of the Enterobacteriaceae isolates were resistant to amikacin. Piperacillin-tazobactam was the most active agent against Pseudomonas aeruginosa isolates (MIC(90): 128 microg/ml; 78% susceptibility) but showed poor activity against Acinetobacter spp (MIC(90):>256 microg/ml; 21.7% susceptibility). Only 41.7% Acinetobacter spp isolates were susceptible to ampicillin-sulbactam. Piperacillin-tazobactam inhibited 100% of Haemophilus influenzae isolates (MIC(90) < 0.25 microg/ml) but only 16.6% of them were ampicillin resistant. The activity of piperacillin-tazobactam against oxacillin susceptible Staphylococcus aureus or coagulase negative staphylococci was excellent (MIC(90) 2 microg/ml; 100% susceptibility). Out of 150 enterococci 12 isolates (8%) were identified as E.faecium and only three isolates (2%), 2 E.faecium and 1 E.faecalis were vancomycin resistant. All the enterococci isolates were susceptible to linezolid. Piperacillin-tazobactam showed excellent activity (MIC(90) 2 microg/ml; 92% susceptibility). Regarding pneumococci all the isolates showed MICs of 16 microg/ml for piperacillin-tazobactam. Among 34 viridans group streptococci only 67% were penicillin susceptible and 85.2% ceftriaxone susceptible whereas piperacillin-tazobactam was very active (MIC(90) 4 microg/ml).Piperacillin-tazobactam is therefore a very interesting antibacterial drug to be used, preferably in combination (IE: amikacin-vancomycin) for the empiric treatment of severe infections occurring in hospitalized patients in Argentina. Caution must be taken for infections due to ESBL producers considering that the inoculum effect MICs can affect MIC values. ( view less ) Rose M Snopko,Josefina Ramos-Franco,Alessandro Di Maio,Kimberly L Karko,Christopher Manley,Erika Piedras-Rentería,Rafael Mejía-Alvarez Although abundant ryanodine receptors (RyRs) exist in cardiomyocytes from newborn (NB) rat and despite the maturity of their single-channel properties, the RyR contribution to excitation-contraction (E-C) coupling is minimal. Immature arrangement of RyRs in the Ca(2+) release site of the sarcoplasm... ( view more )ic reticulum and/or distant RyRs location from the sarcolemmal Ca(2+) signal could explain this quiescence. Consequently, Ca(2+) sparks and their cellular distribution were studied in NB myocytes and correlated with the formation of dyads and transverse (T) tubules. Ca(2+) sparks were recorded in fluo-4-loaded intact ventricular myocytes acutely dissociated from adult and NB rats (0-9 days old). Sparks were defined/compared in the center and periphery of the cell. Co-immunolocalization of RyRs with dihydropyridine receptors (DHPR) was used to estimate dyad formation, while the development of T tubules was studied using di-8-ANEPPS and diIC12. Our results indicate that in NB cells, Ca(2+) sparks exhibited lower amplitude (1.7+/-0.5 vs. 3.6+/-1.7 F/F(0)), shorter duration (47+/-3.2 vs. 54.1+/-3 ms), and larger width (1.7+/-0.8 vs. 1.2+/-0.4 microm) than in adult. Although no significant changes were observed in the overall frequency, central sparks increased from approximately 60% at 0-1 day to 82% at 7-9 days. While immunolocalization revealed many central release sites at 7-8 days, fluorescence labeling of the plasma membrane showed less abundant internal T tubules. This could imply that although during the first week, release sites emerge forming dyads with DHPR-containing T tubules; some of these T tubules may not be connected to the surface, explaining the RyR quiescence during E-C coupling in NB. ( view less ) Jose M Munoz-Olaya,Xavier Matabosch,Carmen Bedia,Meritxell Egido-Gabás,Josefina Casas,Amadeu Llebaria,Antonio Delgado,Gemma Fabriàs A novel mechanism-based dihydroceramide desaturase inhibitor (XM462) in which the substrate C5 methylene group is replaced by a sulfur atom is reported. Dihydroceramide desaturase inhibition occurred both in vitro and in cultured cells with IC(50) values of 8.2 and 0.78 microM, respectively, at a s... ( view more )ubstrate concentration of 10 microM. In vitro experiments showed that XM462 produced a mixed-type inhibition (K(i)=2 microM, alpha=0.83). LC-MS analyses showed that accumulation of endogenous dihydroceramides occurred in cells upon treatment with XM462 in serum-free medium, whereas ceramides built up in controls. In addition, XM462 was found to be metabolised to its 1-glucosyl and 1-phosphocholine derivatives, and to the products of N-deacylation and reacylation with palmitoyl and stearoyl groups. In Jurkat A3 cells cultured in serum-free medium, viability, as the percentage of trypan blue unstained cells in total cells, was reduced upon XM462 treatment (5 microM, 24 h), but not in controls. The interest of this compound is discussed. ( view less ) Ramiro J Gómez-Villa,Andreu Comas-García,Vicente López-Rojas,Luis F Pérez-González,Josefina Sánchez-Alvarado,Rocío Salazar-Zaragoza,Juana M Ruiz-González,Angel G Alpuche-Solís,Daniel E NoyolaWe determined the rate of nosocomial viral respiratory infection in infants and the effect of an infection control program during 4 winter seasons. The rate of nosocomial viral respiratory infection decreased from 6.09 episodes per 100 patients admitted during the first study year to 1.46 episodes ... ( view more )per 100 patients admitted during the last study year. ( view less ) Maria Rosario Capeding,Josefina Cadorna-Carlos,May Book-Montellano,Esteban Ortiz OBJECTIVE: To determine seroprotection and vaccine response rates produced by a diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type-b conjugate (DTaP-IPV//PRP approximately T) vaccine containing a polyribosyl-ribitol-phosphate (PRP)-tetanus toxoid conjugate (Pe... ( view more )ntaxim) and given with a hepatitis B vaccine. METHODS: In this multicentre open-label trial, 424 infants who received DTaP-IPV//PRP approximately T at 6, 10 and 14 weeks of age were also randomized to receive hepatitis B vaccine at either 6, 10 and 14 weeks or 0, 6 and 14 weeks of age. Antibody levels were determined at 6 and 18 weeks of age, and reactogenicity was monitored using parental reports. FINDINGS: Immunogenicity was high for all vaccine antigens and was similar to that in a historical control study. After primary vaccination, 98.7% of all infants had an anti-PRP antibody titre > 0.15 microg/ml. Seroprotection against poliovirus type-1, -2 and -3 and tetanus was obtained in all infants, and against diphtheria, in 97.1%. Pertussis seroconversion, defined as a > fourfold increase in antibody titre, occurred in 95.3% for anti-pertussis toxoid antibody and in 89.0% for anti-filamentous haemagglutinin antibody. The hepatitis B seroprotection rate was 99.5% with administration at 0, 6 and 14 weeks, and 97.8%, at 6, 10 and 14 weeks. However, the antibody titre was higher with the 0, 6 and 14-week schedule (601 mIU/ml versus 207 mIU/ml). The reactogenicity of both vaccines was low. CONCLUSION: The DTaP-IPV//PRP approximately T vaccine was highly immunogenic. The anti-hepatitis B antibody response was seroprotective with both schedules, though the antibody titre was higher with the 0, 6 and 14-week schedule. ( view less ) Eduard Vieta,Nuria Cruz,Javier García-Campayo,Rosario de Arce,Jose Manuel Crespo,Vicens Vallès,Josefina Pérez-Blanco,Ernesto Roca,Jose Manuel Olivares,Angel Moríñigo,Raul Fernández-Villamor,Merce Comes We evaluated the prophylactic efficacy and the long-term tolerability of oxcarbazepine administration in the treatment of bipolar I and II disorder as an adjunctive therapy to lithium. We conducted a 52-wk, double-blind, randomized, placebo-controlled, parallel-group, multicentre, clinical trial. B... ( view more )ipolar I and II DSM-IV outpatients, having had two or more episodes in the last year, but currently being in remission, were randomly assigned on a 1:1 ratio to oxcarbazepine (n=26) or placebo (n=29) as adjuncts to ongoing treatment with lithium. The primary efficacy variable was the length of the remission period assessed by means of the Young Mania Rating Scale (YMRS) and Montgomery-Asberg Depression Rating Scale (MADRS). Other assessments were the Clinical Global Impression (CGI-BP-M), functional activity (GAF), anxiety (HAMA) and impulsiveness (BIS-11). The average time until first recurrence of any type was 19.2+/-13.9 wk and 18.6+/-17.0 wk for oxcarbazepine and placebo respectively (p=0.315). Ten (38.46%) patients had a recurrence of any kind in the oxcarbazepine group vs. 17 (58.62%) in the placebo group (p=0.1354). There was a trend for depressive episodes being less likely in the oxcarbazepine group compared to the placebo group (11.54% and 31.03% respectively, p=0.085), and for better functionality with the GAF (p=0.074). Impulsivity was significantly better prevented by oxcarbazepine (p=0.0443). Overall, oxcarbazepine was well tolerated. This pilot, randomized clinical trial, suggests that oxcarbazepine might have some prophylactic efficacy with regards to impulsivity and perhaps mood episodes in patients taking lithium, although further, adequately powered controlled trials are needed to confirm these findings. ( view less ) Susana Andrés,Luisa Lázaro,Manel Salamero,Teresa Boget,Rafael Penadés,Josefina Castro-Fornieles The majority of follow-up studies show stability of deficits after treatment in adults with obsessive-compulsive disorder (OCD), regardless of improvement in symptomatology, and this suggests a possibly chronic dysfunction of the dorsolateral-striatal circuit. To our knowledge, this is the first st... ( view more )udy to explore the evolution of cognitive dysfunction in children and adolescents with OCD after treatment. A neuropsychological battery designed for this study was administered to 29 OCD patients aged between 7 and 18 years before and after 6 months of naturalistic treatment, and to 22 healthy subjects of similar age, sex and intellectual level. In the first assessment, the OCD group performed worse on some tests of memory, speed of information processing and executive functions, this being similar to the cognitive dysfunction described in adult patients. After treatment the cognitive profile of the OCD group was normalized, and many of the significant differences present in the first assessment disappeared. Children and adolescents did not show the stability in cognitive dysfunction described in studies with adults. Six months of effective treatment normalized cognitive performance in young patients, who showed an important response to treatment. ( view less ) Rodrigo González-Romero,Juan Ausió,Josefina Méndez,José M Eirín-López The study of histone evolution has experienced a rebirth, for two main reasons: the identification of new essential histone variants responsible for regulating chromatin dynamics and the subsequent contradictions posed by this variability as it pertains to their long-term evolution process. Althoug... ( view more )h different evolutionary models (e.g., birth-and-death evolution, concerted evolution) may account for the observed divergence of histone genes, conclusive evidence is lacking (e.g., histone H1) or totally nonexistent (e.g., histone H2A). While most of the published work has focused on deuterostomes, very little is known about the diversification and functional differentiation mechanisms followed by histone protein subtypes in protostomes, for which histone variants have only been recently described. In this study, we identify linker and core histone genes in three clam species. Our results demonstrate the prevalence of an 'orphon' H1 lineage in molluscs, a group in which the protostome H1 and sperm nuclear basic proteins are on the verge of diversification. They share an early monophyletic origin with vertebrate-specific variants prior to the differentiation between protostomes and deuterostomes. Given the intringuing evolutionary features of the histone H1 family, we have evaluated the relative importance of gene conversion, point mutation, and selection in maintaining the diversity found among H2A subtypes in eukaryotes. We show evidence for the first time that the long-term evolution of this family is not subject to concerted evolution but, rather, to a gradual evolution following a birth-and-death model under a strong purifying selection at the protein level. ( view less ) Antonio J Herrera,Rocío M de Pablos,Eloisa Carreño-Müller,Ruth F Villarán,José L Venero,Mayka Tomás-Camardiel,Josefina Cano,Alberto Machado We have performed intrastriatal injection of thrombin and searched for distant effects in the cell body region. In striatum, thrombin produced a slight loss of striatal neurons as demonstrated by neural nuclei immunostaining - a non-specific neuronal marker - and the expression of glutamic acid dec... ( view more )arboxylase 67 mRNA, a specific marker for striatal GABAergic interneurons, the most abundant phenotype in this brain area. Interestingly, striatal neuropil contained many boutons immunostained for synaptic vesicle protein 2 and synaptophysin which colocalize with tyrosine hydroxylase (TH), suggesting a degenerative process with pre-synaptic accumulation of synaptic vesicles. When we studied the effects on substantia nigra, we found the disappearance of dopaminergic neurons, shown by loss of TH immunoreactivity, loss of expression of TH and dopamine transporter mRNAs, and disappearance of FluoroGold-labelled nigral neurons. The degeneration of substantia nigra dopaminergic neurons was produced through up-regulation of cFos mRNA, apoptosis and accumulation of alpha-synuclein shown by colocalization experiments. Thrombin effects could be mediated by protease-activated receptor 4 activation, as protease-activated receptor 4-activating peptide mimicked thrombin effects. Our results point out the possible relationship between synapse elimination and retrograde degeneration in the nigral dopaminergic system. ( view less ) Rodrigo González-Romero,Josefina Méndez,Juan Ausió,José M Eirín-López Histone H2A.Bbd (Barr body-deficient) is a novel histone variant which is largely excluded from the inactive X chromosome of mammals. Discovered only 6 years ago, H2A.Bbd displays very unusual structural and functional properties, for instance, it is relatively shorter and only 48% identical compar... ( view more )ed to H2A, lacking both the typical C-terminal tail of the H2A family and the very last sequence of the docking domain, making it the most specialized among all histone variants known to date. Indeed, molecular evolutionary analyses have shown that H2A.Bbd is a highly hypervariable and quickly evolving protein exclusive to mammalian lineages, in striking contrast to all other histones. Different studies have described a deposition pattern of H2A.Bbd in the chromatin that overlaps with regions of histone H4 acetylation suggesting its association with transcriptionally active euchromatic regions of the genome. In this regard, it is believed that this histone variant plays an important role in determining such regions by destabilizing the nucleosome and locally unfolding the chromatin fiber. This review provides a concise, comprehensive and timely summary of the work published on H2A.Bbd structure and function. Special emphasis is placed on its chromatin deposition patterns in relation to gene expression profiles and its evolutionary history, as well as on the dynamics of H2A.Bbd-containing nucleosomes. ( view less ) Marcelo Cantarovich,Heather Ross,José M Arizón,Miguel A Gómez,Lynn Straatman,Josefina Orús,Luis Alonso-Pulpón,Beatriz Díaz Molina,Shaohua Wang,Ernesto Lage,María G Crespo,Nicolás Manito,Jonathan Howlett,Haissam Haddad,Motown Study Group  BACKGROUND: For cyclosporine (CsA), 2-hr postdose level (C2) is the best single time point predictor of the area under the curve and a critical measure for effective dosing. The therapeutic CsA microemulsion (Neoral) C2 range in de novo heart transplant patients remains to be determined. PURPOSE: T... ( view more )he purpose of this study was to determine the efficacy of CsA C2 monitoring in de novo heart transplant patients receiving basiliximab induction. METHODS: This prospective, multicenter, randomized study enrolled 87 adult heart transplant recipients stratified according to 4 to 6 hrs posttransplant serum creatinine less than or equal to 170 micromol/L (cohort A) or more than 170 micromol/L (cohort B). Patients in cohort A were randomized into three C2 ranges (A1: "high" n=25, 1600-1800 ng/mL; A2: "intermediate" n=27, 1400-1600 ng/mL; and A3: "low" n=24, 1200-1400 ng/mL). Patients in cohort B were randomized into intermediate (n=5) and low C2 (n=6). Target ranges were progressively lowered after 1 month. Immunosuppression included basiliximab, Neoral, mycophenolate mofetil, and corticosteroids. Endpoints were acute rejection and renal function. RESULTS: The incidence of acute rejection at 12 months was 44% in group A1, 41% in group A2, 33% in group A3, and 27% in cohort B. Pretransplant and 12-month creatinine clearance (mL/min) were group A1, 72+/-25 and 64+/-24; group A2, 81+/-32 and 68+/-25; group A3, 91+/-28 and 86+/-26; and cohort B, 62+/-28 and 79+/-37. CONCLUSION: These results suggest that C2 monitoring is safe in de novo heart transplant patients. A low Neoral C2 range in combination with basiliximab induction resulted in preserved renal function without increased risk of acute rejection. ( view less ) Irmeli Roine,Heikki Peltola,Josefina Fernández,Inés Zavala,Antonio González Mata,Silvia González Ayala,Antonio Arbo,Rosa Bologna,Greta Miño,José Goyo,Eduardo López,Solange Dourado de Andrade,Seppo SarnaA post hoc analysis of 654 children with bacterial meningitis showed that the level of consciousness is the most important predictor of death and/or neurological sequelae, more than is etiology per se. This finding emphasizes the need of including a measurement of the presenting status in all studi... ( view more )es examining treatment efficacy. ( view less ) Josefina Sala-Roca,Eva Estebanez-Perpina,Ferran Balada,Adriana Garau,Maria Assumpció Martí-Carbonell This study investigates the effect of thyroid hormones on the morphology of hippocampal neurons in adult rats. Hypo- and hyperthyroidism were induced by adding 0.02% methimazole and 1% l-thyroxine, in drinking water from 40 days of age, respectively. When the rats were 89 days old their brains were... ( view more ) removed and stained by a modified Golgi method and blood samples were collected in order to measure T4 serum levels. Neurons were selected and drawn using a camera lucida. Our results show that methimazole administration reduces the dendritic branching of the apical shafts of CA3 and CA1 pyramidal neurons mainly by increasing the distance to the first branch point in both types of neurons, and reducing branch points in the radius of 50 microm from the soma in CA1 neurons. Nevertheless, it was observed an increase of apical spine density in CA3 neurons from this group. Thyroxine reduces apical and basal tree of CA3 pyramidal neurons increasing the distance to the first branch point, reducing branch points in the radius of 50 microm from the soma and increases their apical and basal spine density. In CA1 field, thyroxine reduces the number of basal branch points. Both treatments seems to provoke alterations in the same direction reducing the dendritic branching and increasing spine density, although no significances appeared in some of the parameters analyzed. The effects are more evident in thyroxine than methimazole group; and in CA3 neurons than in CA1 neurons. In discussion it is pointed that the increase of spine density could be a mechanism to compensate the functionality reduction that can be provoke by the treatment effect on dendritic branching. ( view less ) María del Carmen Hernández-Romero,Sandro Argüelles,Ruth F Villarán,Rocío M de Pablos,María José Delgado-Cortés,Marti Santiago,Antonio J Herrera,Josefina Cano,Alberto Machado Anti-inflammatory strategies have attracted much interest for their potential to prevent further deterioration of Parkinson's disease. Recent experimental and clinical evidence indicate that statins - extensively used in medical practice as effective lipid-lowering agents - have also anti-inflammat... ( view more )ory effects. In this study, we investigated the influence of simvastatin on the degenerative process of the dopaminergic neurons of the rat following intranigral injection of lipopolysaccharide (LPS), a potent inductor of inflammation that we have previously used as an animal model of Parkinson's disease. We evaluated TH positive neurons, astroglial, and microglial populations and found that simvastatin prevented the inflammatory processes, as the induction of interleukin-1beta, tumor necrosis factor-alpha, and iNOS and the consequent dopaminergic degeneration induced by LPS. Moreover, simvastatin produced the activation of the neurotrophic factor BDNF, along with the prevention of the oxidative damage to proteins. Moreover, it also prevents the main changes produced by LPS on different mitogen-activated protein kinases, featured as increases of P-c-Jun N-terminal protein kinase, P-extracellular signal-regulated kinase, p-38, and P-glycogen synthase kinase and the decrease of the promotion of cell survival signals such as cAMP response element-binding protein and Akt. Our results suggest that statins could delay the progression of dopaminergic degeneration in disorders involving inflammatory processes. ( view less ) Teresa Jiménez,Ignacio Martín,Josefina Hernández-Nistal,Emilia Labrador,Berta Dopico Here, we report the identification and characterization of CaTPI-2, which is a member of a Cicer arietinum gene family encoding Kunitz-type proteinase inhibitors with at least two members -CaTPI-1 and CaTPI-2. The widespread mRNA accumulation of CaTPI-2 in all the different organs of 4-day-old etio... ( view more )lated seedlings and in stem internodes differs from the more specific Cicer arietinum Trypsin Proteinase Inhibitor-1 (CaTPI-1) transcription. After the generation of polyclonal antibodies against the recombinant Trypsin Proteinase Inhibitor-2 (TPI-2) protein, the protein was located in the cell walls of vegetative organs. The decrease found in both transcription and TPI-2 protein levels when the epicotyls aged, together with the wider and more intensive immunostaining of the protein in apical zones of epicotyls and radicles, in consonance with their higher elongation rate, indicated a relationship of the TPI-2 protein with the elongation process. CaTPI-2 mRNA levels were increased by wounding in both epicotyls and leaves. The accumulation of CaTPI-2 mRNA in seedlings, which was further amplified by mechanical wounding in epicotyls and leaves, suggests the involvement of TPI-2 in the response to wounds. Our results indicate that TPI-2 protein has features different from those of the former characterized Trypsin Proteinase Inhibitor-1 (TPI-1), such as its different gene regulation under light, a different cellular location and its upregulation by wounding, which implies a function different from that of TPI-1 in chickpea metabolism. ( view less ) Yaniris R Avellanet,Ana Patricia Ortiz,José R Pando,Josefina Romaguera Female sexual dysfunction is a multi-causal and multidimensional problem combining sexual, physiological, physical, psychological, and interpersonal determinants. Loss of libido or loss of sexual desire, as a symptom of one of the primary sexual dysfunctions described in females, is highly prevalen... ( view more )t in the general female population. Research on the psychological aspect associated with loss of libido among Hispanic female populations is limited. The objective of this study was to determine how the loss of libido is affected by signs and symptoms of depression, once potential confounders are controlled. Nine-hundred and nineteen Puerto Rican women ages 40 to 59 years living in Puerto Rico participated in health-fairs conducted in twenty-two municipalities between May 2000 and November 2001. Contingency tables and chi-square statistics were used to evaluate the bivariate associations of loss of libido with demographic and lifestyle characteristics, symptom experience and obstetric and gynecologic histories. A logistic regression model was used to estimate the magnitude of the association between loss of libido and signs and symptoms of depression, after controlling for confounders. The overall prevalence of loss of libido in this population was 40.8%. Loss of libido was significantly associated with depressive symptoms (p < 0.05) after adjusting for age, educational attainment, employment status, physical activity, menopausal status/ hormone therapy use and genitourinary symptoms. Women reporting 1-2 depressive symptoms were 67% (95% CI = 1.08-2.60) more likely than women reporting no symptomatology to report loss of libido. The odds of loss of libido increased as the number of depressive symptoms increased [(3-4 symptoms: POR = 3.67, 95% CI = 2.16-5.56); (5-6 symptoms: POR = 5.52, 95% CI = 3.16-9.66)]. Consistent with previous studies, signs and symptoms of depression were significantly associated with loss of libido. Future longitudinal studies should further elucidate the temporal sequence between depression and sexual dysfunctions in this population. ( view less ) Susana Beatriz Etcheverry,Evelina Gloria Ferrer,Luciana Naso,Josefina Rivadeneira,Victoria Salinas,Patricia Ana María Williams Vanadium compounds are known for a variety of pharmacological properties. Many of them display antitumoral and osteogenic effects in several cell lines. Free radicals induce the development of tumoral processes. Natural polyphenols such as flavonoids have antioxidant properties since they scavenge ... ( view more )different free radicals. For these reasons it is interesting to investigate the effects of a new complex generated between the vanadyl(IV) cation and the flavonoid hesperidin. The complex has been synthesized and characterized by physicochemical methods. Spectroscopic analysis revealed a 1:1 stoichiometry of ligand:VO and coordination by deprotonated cis-hydroxyl groups to the disaccharide moiety of the ligand. The complex improves the superoxide dismutase (SOD)-like activity of the ligand, but the scavenging of other radicals tested does not change upon complexation. When tested on two tumoral cell lines in culture (one of them derived from a rat osteosarcoma UMR106 and the other from human colon adenocarcinoma Caco-2), the complex enhanced the antiproliferative effects of the free ligand, and this effect correlated with the morphological alterations toward apoptosis. Also, on the osteoblastic cell line the complex stimulated cell proliferation and collagen type I production at low concentrations. At higher doses the complex behaved as a cytotoxic compound for the osteoblasts. ( view less ) Beatriz Pérez-Cadahía,Blanca Laffon,Miquel Porta,Anunciación Lafuente,Teresa Cabaleiro,Tomàs López,Ana Caride,José Pumarega,Alejandro Romero,Eduardo Pásaro,Josefina Méndez The sinking of the 'Prestige' oil tanker in front of the Galician coast (NW of Spain) in November 2002 offered a unique opportunity to analyze intermediate cytogenetic and endocrine effects among people exposed to the complex mixture of substances that oil constitutes, including several toxic heavy... ( view more ) metals. In this work we evaluated the relationship between exposure to heavy metals (blood concentrations of aluminium, cadmium, nickel, lead and zinc) and genotoxic parameters (sister chromatid exchanges, micronucleus test and comet assay) or endocrine parameters (plasmatic concentrations of prolactin and cortisol) in subjects exposed to 'Prestige' oil during cleaning tasks developed after the spillage. Concentrations of lead were significantly related to the comet assay even after adjusting by age, sex and smoking. Cortisol concentrations were significantly influenced by aluminium, nickel (both, inversely) and cadmium (positively). Women had clearly higher concentrations of prolactin and cortisol, even when adjusting by age, smoking, cadmium, aluminium or nickel. Plasmatic cortisol was jointly influenced by gender, smoking and aluminium or nickel (all p<0.05). In women there was a strong relationship between concentrations of cadmium and prolactin (beta=0.37, p=0.031). When the effects of cadmium, aluminium and nickel on cortisol were simultaneously assessed, only the latter two metals remained statistically significant. Among parameters analysed, cortisol appeared to be the most sensitive to the effects of metal exposure. Plasma levels of cortisol deserve further evaluation as a potentially relevant biomarker to assess the effects of exposure to heavy metals. ( view less ) Ruth F Villarán,M Tomás-Camardiel,Rocío M de Pablos,Marti Santiago,Antonio J Herrera,Ana Navarro,Alberto Machado,Josefina Cano 3-Nitropropionic acid (3-NP), an inhibitor of the mitochondrial enzyme succinate dehydrogenase, induces neuronal degeneration in the striatum. It is known that dopamine (DA) enhances this toxic effect. In this work, we study how the increase of DA influences the toxic effect of 3-NP on DAergic term... ( view more )inals, GABAergic neurons, astroglia and microglia in the striatum. We increased the content of DA through the inhibition of its uptake by nomifensine or the inhibition of its catabolism by deprenyl. We found that although nomifensine and deprenyl enhanced the DA overflow produced by 3-NP perfusion, they protected against the damage induced by 3-NP in the DAergic terminals and the GABAergic neurons in the striatum. Moreover, there was a decrease of apoptotic cells, astrogliosis and activation of microglia as index of damage. We also found that depletion of DA by reserpine and alpha-methyl-p-tyrosine produced a significant reduction of the inhibition of the respiratory rate and of the production of superoxide radical induced by 3-NP in synaptosomes from the striatum. All these results suggest that endogenous dopamine within the dopaminergic terminals of the striatum enhances the mitochondrial production of radical oxygen species along with the respiratory inhibition produced by 3-NP and thus increases the toxicity produced by 3-NP in the striatum. ( view less ) Gary H Posner,Wonsuk Chang,Lindsey Hess,Lauren Woodard,Sandra Sinishtaj,Aimee R Usera,William Maio,Andrew S Rosenthal,Alvin S Kalinda,John G D'Angelo,Kimberly S Petersen,Remo Stohler,Jacques Chollet,Josefina Santo-Tomas,Christopher Snyder,Matthias Rottmann,Sergio Wittlin,Reto Brun,Theresa A Shapiro In four or five chemical steps from the 1,2,4-trioxane artemisinin, a new series of 23 trioxane dimers has been prepared. Eleven of these new trioxane dimers cure malaria-infected mice via oral dosing at 3 x 30 mg/kg. The clinically used trioxane drug sodium artesunate prolonged mouse average survi... ( view more )val to 7.2 days with this oral dose regimen. In comparison, animals receiving no drug die typically on day 6-7 postinfection. At only 3 x 10 mg/kg oral dosing, seven dimers prolong the lifetime of malaria-infected mice to days 14-17, more than double the chemotherapeutic effect of sodium artesunate. Ten new trioxane dimers at only a single oral dose of 30 mg/kg prolong mouse average survival to days 8.7-13.7, and this effect is comparable to that of the fully synthetic trioxolane drug development candidate OZ277, which is in phase II clinical trials. ( view less ) Maria P Garcia-Portilla,Pilar A Saiz,Antonio Benabarre,Pilar Sierra,Josefina Perez,Alfonso Rodriguez,Lorenzo Livianos,Pedro Torres,Julio Bobes BACKGROUND: Previous studies on the prevalence of metabolic syndrome (MetS) in patients with bipolar disorder have reported rates 11% and 79% higher than in their respective general populations. This study evaluates the prevalence of MetS in a group of 194 Spanish patients with bipolar disorder. ME... ( view more )THODS: Naturalistic, multicentre, cross-sectional study. Patients were evaluated for presence of MetS according to modified NCEP ATP III criteria. RESULTS: Mean age was 46.6 (SD 13.9); 49.2% were male. Forty-six percent were in remission. Patients were receiving 2.9 (SD 1.3) drugs. Overall prevalence of MetS was 22.4%. Fifty-four percent met the criterion for abdominal obesity, 36.1% for hypertriglyceridemia, 38.2% for low HDL cholesterol, 20.9% for hypertension, and 12.2% for high fasting glucose. The multivariate analysis for MetS retained only the BMI variable in the model. LIMITATIONS: Cross-sectional study design. CONCLUSIONS: The prevalence of MetS in patients with bipolar disorder is 58% higher than that reported for the general Spanish population. MetS is associated with BMI. Clinicians should be aware of this issue and appropriately monitor patients with bipolar disorder for MetS as part of the standard of care for these patients. ( view less ) André Laranjeira de Carvalho,Luiz Fernando Ferraz da Silva,Sandra Josefina Ferraz Ellero Grisi,Ana Maria de Ulhôa Escobar OBJECTIVE: Evaluating the interaction between mother or caregiver and infant through the Clinical Indicators of Risks in Infant Development and investigating whether local and cultural influences during infant development affect these clinical indicators. INTRODUCTION: The Clinical Indicators of Ri... ( view more )sks in Infant Development was created in order to fully assess infants' development and the subjective relationship between the babies and their caregivers. The absence of two or more Clinical Indicators of Risks in Infant Developments suggests a possibly inadequate mental development. Given the continental size of Brazil and its accentuated cultural differences, one might question how trustworthy these indicators can be when applied to each of the geographical regions of the country. METHODS: This was a cross-sectional study with 737 infants from the capitals of 9 Brazilian states. The size of the initial sample population was based on a pilot study carried out in the cities of São Paulo and Brasília. The ages of children were grouped: 0-3 months, 4-7 months, 8-11 months and 12-18 months. The chi-square test was used together with analyses by the statistical software SPSS 13.0. RESULTS: Statistical analysis of results from the different municipalities against the total sample did not reveal any statistically significant differences. Municipalities represented were Belém (p=0.486), Brasília (p=0.371), Porto Alegre (p=0.987), Fortaleza (p=0.259), Recife (p=0.630), Salvador (0.370), São Paulo (p=0.238), Curitiba (p=0.870), and Rio de Janeiro (p= 0.06). DISCUSSION: Care for mental development should be considered a public health issue. Its evaluation and follow-up should be part of the already available mother-child assistance programs, which would then be considered to provide "full" care to children. CONCLUSIONS: Local habits and culture did not affect the results of the Clinical Indicators of Risks in Infant Development indicators. Clinical Indicators of Risks in Infant Development proved to be robust despite the specificities of each region. ( view less )
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