A novel long non-coding RNA in the rheumatoid arthritis risk locus TRAF1-C5 influences C5 mRNA levels.

Long non-coding RNAs (lncRNAs) can regulate the transcript levels of genes in the same genomic region. These locally acting lncRNAs have been found deregulated in human disease and some have been shown to harbour quantitative trait loci (eQTLs) in autoimmune diseases. However, lncRNAs linked to the transcription of candidate risk genes in loci associated to rheumatoid arthritis (RA) have not yet been identified. The TRAF1 and C5 risk locus shows evidence of multiple eQTLs and transcription of intergenic non-coding sequences. Here, we identified a non-coding transcript (C5T1lncRNA) starting in the 3' untranslated region (UTR) of C5. RA-relevant cell types express C5T1lncRNA and RNA levels are further enhanced by specific immune stimuli. C5T1lncRNA is expressed predominantly in the nucleus and its expression correlates positively with C5 mRNA in various tissues (P=0.001) and in peripheral blood mononuclear cells (P=0.02) indicating transcriptional co-regulation. Knockdown results in a concurrent decrease in C5 mRNA levels but not of other neighbouring genes. Overall, our data show the identification of a novel lncRNA C5T1lncRNA that is fully located in the associated region and influences transcript levels of C5, a gene previously linked to RA pathogenesis.

Antinociceptive effect on mice of the hydroalcoholic fraction and (-) epicatechin obtained from Combretum leprosum Mart & Eich.

Previous studies on Combretum leprosum, a tree growing in the Northeastern states of Brazil, have shown antinociceptive effects of the ethanol extract of its leaves and bark, but studies examining its constituents are rare. The objective of this study was to evaluate the antinociceptive effect of the hydroalcoholic fraction (HF) of one of its constituents, the flavonoid (-) epicatechin (EPI), administered orally to mice (20-30 g) in models of chemical nociception, and the possible mechanisms involved. Different doses of HF (62.5 to 500 mg/kg) and EPI (12.5 to 50 mg/kg) were evaluated in models of abdominal writhing, glutamate, capsaicin, and formalin in animals pretreated with different antagonists: naloxone, ondansetron, yohimbine, ketanserin, pindolol, atropine, and caffeine in the abdominal writhing test. To determine the role of nitric oxide, the animals were pretreated with L-arginine (600 mg/kg, ip) in the glutamate test. The HF was effective (P < 0.05) in all protocols at different doses and EPI was effective in the abdominal writhing, capsaicin and glutamate tests (P < 0.05) at doses of 25 and 50 mg/kg. However, in the formalin test it was only effective in the second phase at a dose of 25 mg/kg. The antinociceptive effect of HF was inhibited when HF was associated with yohimbine (0.15 mg/kg), ketanserine (0.03 mg/kg), and L-arginine (600 mg/kg), but not with the other antagonists. HF and EPI were effective in models of chemical nociception, with the suggested participation of the adrenergic, serotonergic and nitrergic systems in the antinociceptive effect of HF.

Antinociceptive effect on mice of the hydroalcoholic fraction and (-) epicatechin obtained from Combretum leprosum Mart & Eich

Previous studies on Combretum leprosum, a tree growing in the Northeastern states of Brazil, have shown antinociceptive effects of the ethanol extract of its leaves and bark, but studies examining its constituents are rare. The objective of this study was to evaluate the antinociceptive effect of the hydroalcoholic fraction (HF) of one of its constituents, the flavonoid (-) epicatechin (EPI), administered orally to mice (20-30 g) in models of chemical nociception, and the possible mechanisms involved. Different doses of HF (62.5 to 500 mg/kg) and EPI (12.5 to 50 mg/kg) were evaluated in models of abdominal writhing, glutamate, capsaicin, and formalin in animals pretreated with different antagonists: naloxone, ondansetron, yohimbine, ketanserin, pindolol, atropine, and caffeine in the abdominal writhing test. To determine the role of nitric oxide, the animals were pretreated with L-arginine (600 mg/kg, ip) in the glutamate test. The HF was effective (P < 0.05) in all protocols at different doses and EPI was effective in the abdominal writhing, capsaicin and glutamate tests (P < 0.05) at doses of 25 and 50 mg/kg. However, in the formalin test it was only effective in the second phase at a dose of 25 mg/kg. The antinociceptive effect of HF was inhibited when HF was associated with yohimbine (0.15 mg/kg), ketanserine (0.03 mg/kg), and L-arginine (600 mg/kg), but not with the other antagonists. HF and EPI were effective in models of chemical nociception, with the suggested participation of the adrenergic, serotonergic and nitrergic systems in the antinociceptive effect of HF.

Antinociceptive effect of Zanthoxylum rhoifolium Lam. (Rutaceae) in models of acute pain in rodents.

AIM OF THE STUDY: Zanthoxylum rhoifolium Lam. (Rutaceae) is locally known as "mamica de cadela", and its bark is popularly used for toothache and earache. The objective of this study was to investigate the antinociceptive effect of the ethanolic extract from this species' stem bark (EtOH), its fractions of partition (hexane-HEX, ethyl acetate-AcOEt, aqueous-AQ) and lupeol (a triterpene obtained from HEX) in models of acute pain. MATERIALS AND METHODS: Male and female Swiss mice (25-35 g, n=6-12 animals/group) were used to assess acute toxicity and nociception (Animal Ethics Committee/UFPI, No. 09/2008). Acute toxicity was studied up to 2 g/kg p.o. of EtOH. In the formalin test (2%, 20 microL/paw), the licking time of the stimulated paw was quantified during the first 5 min (first phase) and at 15-30 min (second phase), 1h after oral treatment with EtOH, HEX, AcOEt or saline, and 30 min after use of morphine-MOR (5 mg/kg i.p.). The same response evoked by capsaicin (2 microg/20 microL/paw) was quantified during 5 min, after administration of EtOH, HEX, AcOEt, AQ, saline and MOR. The licking time of the paw that was stimulated with glutamate (10 micromol/20 microL) was measured (15 min) after treatment with EtOH, HEX, AcOEt, AQ, lupeol, saline or MK801 (0.03 mg/kg, i.p.). Mice were submitted to the rota-rod task and open-field test in order to assess any non-specific muscle-relaxant or sedative effects of EtOH (250 mg/kg p.o.) and HEX (500 mg/kg p.o.). RESULTS: The animals did not exhibit any acute toxicity to EtOH (up to 2 g/kg p.o.), so it was not possible to calculate the LD50. EtOH, HEX and AcOEt (62.5-250 mg/kg) produced a significant antinociceptive effect in the formalin and capsaicin tests. However, AQ was ineffective. EtOH, HEX, AcOEt and lupeol reduced the glutamate-evoked nociceptive response, but AQ had no effect. EtOH and HEX did not alter the locomotion of animals in the open-field or rota-rod tests, which suggest a lack of a central depressant effect. CONCLUSION: The results confirm the popular use of Zanthoxylum rhoifolium as an analgesic, and contribute to the pharmacological knowledge of this species because it was shown that EtOH and its less polar partition fractions (HEX, AcOEt) have an antinociceptive effect in models of chemical nociception, and that lupeol appears to be one of the constituents responsible for this effect.

Contribution of Fcgamma receptor IIIA gene 158V/F polymorphism and copy number variation to the risk of ACPA-positive rheumatoid arthritis.

BACKGROUND: Fcgamma receptors (FcgammaRs) are potent immune modulators. FcgammaR genes encompass a complex region, polymorphic by both single nucleotide polymorphisms (SNPs) and copy number variation (CNV). The heterogeneity of rheumatoid arthritis (RA) combined with the genetic complexity of FcgammaR genes may be the cause of inconsistent findings in previous RA studies on FcgammaR SNPs. There is increasing evidence that anti-citrullinated peptide antibody (ACPA)-positive RA and ACPA-negative RA have a different genetic background. OBJECTIVE: To investigate whether FcgammaRIIIA 158V/F SNP associates differently with ACPA-positive and ACPA-negative RA and to assess if the FcgammaRIIIA gene CNV affects the association of the FcgammaRIIIA 158V/F SNP with RA and whether the FcgammaRIIIA gene CNV confers risk for RA. METHODS: 945 patients with RA and 388 healthy controls, all Dutch-Caucasians, were included in the study. FcgammaRIIIA 158V/F SNP was genotyped using Sequenom. CNV of the FcgammaRIIIA gene was determined in 456 patients with RA and 285 controls using multiplex ligation-dependent probe amplification. Associations between genotypes and RA were analysed, stratifying for the presence/absence of ACPA and CNV. RESULTS: In all patients with RA the FcgammaRIIIA 158V/F SNP was not associated with RA. In ACPA-positive RA (n = 358), the VV genotype was more prevalent in cases than in controls (18.4% vs 13.2%, OR = 1.5, p = 0.05). After stratification for CNV the VV genotype was associated with RA in general (n = 426) (OR = 1.6, 95% CI 0.97 to 2.6, p = 0.05) and with ACPA-positive RA (n = 135) (OR = 2.1, 95% CI 1.2 to 3.8, p = 0.009) but not with ACPA-negative RA. The distribution of CNV was not significantly different between patients with RA and controls. CONCLUSION: The FcgammaRIIIA 158 VV genotype confers risk for ACPA-positive RA; this association increased slightly after correction for CNV of the FcgammaRIIIA gene. CNV itself is not associated with RA susceptibility.

[Remuneration and productivity: the case of the Minas Gerais Hospital Foundation, Brazil, 1992-1995]. / Remuneración y productividad: el caso de la Fundación hospitalaria del Estado de Minas Gerais, Brasil, 1992-1995.

This article presents an analysis of the Minas Gerais State Hospital Foundation immediately after the introduction in its health services units in early 1993 of a new system of rewards for good performance and productivity, as a complement to salaried remuneration. Analysis was based on a cross-sectional study of changes in indicators of production and productivity in the Foundation during the 1992-1995 period. Data were obtained from hospitalization authorization forms, payment authorization guides, and bulletins from the Human Resource Administration. The strategy of conditional remuneration and incentives was adopted not only to step up production and productivity, but also to increase the employees' commitment to the institution. Analysis of the selected indicators appears to confirm other study results in that remuneration based on results (conditional incentives) leads to a positive change in the production level of services and productivity, even if it does not last for the long term. Study results also support the notion that such alternatives may be deliberately used as part of a more general strategy of organizational development and not only as an isolated element for concrete improvements in productivity.

[Lipoprotein(a) concentrations in type I diabetes mellitus]. / Concentraciones de la lipoproteína (a) en la diabetes mellitus tipo I.

OBJECTIVES: To determine the distribution of lipoprotein(a) levels and prevalence of hyperLp(a) in diabetes mellitus type I (IDDM). To analyze the effect of glycemic control and microalbuminuria on Lp(a) levels. METHODS: Cross-sectional study of 263 subjects with IDDM with a mean age of 19.2 +/- 11.6 years and an evolutive course of 6.3 +/- 6.5 years. Apart from Lp(a), measurements were obtained from serum levels of lipids, apolipoproteins AI and B, fructosamine, glycosilated hemoglobin (HbA1c), and albuminuria in all patients. RESULTS: Mean serum concentrations of Lp(a) were 16.5 +/- 18.1 mg/dl and 18.5% of patients had Lp(a) levels > 30 mg/dl [hyperLp(a)]. With a multivariate regression analysis, the only variable correlated with Lp(a) levels was cholesterol LDL (p < 0.001). Patients with hyperLp(a) did not differ from the other patients in any of the other variables analyzed, and patients with HbA1c higher and lower than 8% had similar mean serum Lp(a) concentrations (14.0 +/- 16 vs. 17.9 +/- 20). Lp(a) concentration was also similar among patients with albuminuria higher and lower than 20 micrograms/min (16.6 +/- 20 vs. 17.7 +/- 16). CONCLUSIONS: Control of glycemia and microalbuminuria have no effect on Lp(a) concentrations in diabetes mellitus type I. HyperLp(a) is not indicative of a poor glycemic control.

Avaliacao do cateter de subclavia como acesso vascular para hemodialise. / Evaluation of the subclavian catheter as a vascular access for hemodialysis

Os autores relatam a experiencia de 7 meses com o uso do cateter de subclavia como acesso vascular para hemodialise. Foram realizadas 81 sessoes em 11 pacientes, utilizando-se 15 cateteres colocados segundo tecnica de Seldinger pela via subclavicular. O tempo de permanencia variou de 3 a 44 dias (media 15,4). A recirculacao media, calculada em 3 pacientes, foi 11,2% e nao houve divergencia entre as diferencas pre e pos-dialise de ureia, creatinina e acido urico, quando comparados aos valores obtidos em 3 pacientes em dialise com dupla puncao de fistula de Cimino. Nao foram observadas complicacoes na puncao, sendo a dobra do cateter responsavel pelo baixo fluxo e coagulacao em 2 casos. Registrou-se apenas 1 episodio de infeccao com hemocultura e cultura da ponta do cateter positivas

Perspectivas no tratamento da insuficiencia renal cronica em nosso meio. / Treatment of the chronic renal insufficiency in our milieu

Os autores analisam em varias linhas de pesquisas desenvolvidas no Centro de Pesquisas em Doencas Hepato-Renais, ate alcancar a fase de transplante renal humano. A tecnica do autotransplante em caes e descrita com detalhes Na preservacao renal, enfantizam o uso das substancias ricas em K e Mg, tendo o dextran 70 ou haemacell como coloide a 4oC. As alteracoes histopatologicas em 17 rins de caes autotransplantados foram analisadas, tendo sido estes animais divididos em tres grupos, segundo o tempo de preservacao. Em 42 animais divididos em tres grupos, estudamos o uso da ciclofosfamida e metilprednisolona no pre-tratamento do animal doador. As drogas eram feitas por via endovenosa 6 e 2 horas antes da nefrectomia. Finalmente, analisamos o desenvolvimento do transplante renal humano no Estado do Ceara