Anatomic and functional outcome after 23-gauge sutureless transconjunctival vitrectomy, peeling and intravitreal triamcinolone for idiopathic macular epiretinal membranes

Purpose:To report the functional, anatomic outcome and safety profile of 23-gauge pars plana vitrectomy (PPV) combined with peeling and intravitreal injection of triamcinolone acetonide (TA) in eyes with idiopathic epiretinal membranes (ERM). Methods:Retrospective, nonrandomized study of consecutive patients who underwent 23-gauge transconjunctival sutureless PPV with subsequent membrane peeling and intravitreal TA injection for an idiopathic ERM. All patients were operated between February 2007 and February 2008 at the Jules Gonin University Eye Hospital. The minimum follow-up was 6-months. Results:Thirty-nine eyes of 39 patients were included. The mean follow-up was 7 months (SD: 2.2, range: 6-15 months). Twenty-two (56%) eyes were pseudophakic and 17 (44%) were phakic at the time of surgery. Mean preoperative intraocular pressure (IOP) was 14 mmHg (SD: 3.5). At the final follow-up mean IOP was 14.5 (SD: 2.7) that did not differ significantly from the IOP at baseline (P: 0.14- 2-tailed t test). Five patients (13%) needed temporary topical anti-glaucoma treatment.Mean preoperative BCVA was 0.28 decimal equivalent (logMAR 0.54, SD: 0.2, range: 1.0 - 0.2). and improved significantly (P <0.0001, 2-tailed t test) to a mean of 0.6 decimal equivalent (logMAR 0.22, SD: 0.16, range: 0.6 - 0) at the final follow-up. The visual acuity improved by a mean of 3.2 lines (SD 2.1, range 0- 8). Twenty-nine patients (74%) demonstrated a gain of 3 or more lines.Mean central macular thickness (CMT) was 456 µm (SD: 77) at the baseline that reduced significantly (P <0.0001, 2-tailed t test) at the final follow-up to 327µm (SD: 79). Average CMT reduction was 131µm (SD: 77, range: 36- 380 µm). A subgroup analysis of 15 selected cases that had CMT measurement 1 week after surgery demonstrated that 84% of the total final reduction in CMT occurred during the first week. Conclusions:23-gauge sutureless transconjunctival vitrectomy with the concomitant administration of intravitreal TA is a safe and effective technique for the treatment of idiopathic ERM and may speed up anatomical recovery.

WePreserve 2009: DPE/Planets/CASPAR/nestor Joint Training Event: The Preservation challenge: basic concepts and practical applications (Barcelona, 23-27 març 2009)

Reseña del congreso WePreserve 2009 que tuvo lugar los pasados 23 al 27 de marzo en Barcelona, organizadopor la Facultad de Biblioteconomía y Documentación de la Universitat de Barcelona, con la colaboración del Institut d'Estudis Catalans, la Biblioteca de Catalunya y el Consorci de Biblioteques de Barcelona. El seminario 2009 WePreserve se celebra anualmente desde el año 2007 y participan todas las figuras de referencia europeas en materia de investigación en sistemas y metodologías que garantizan la preservación digital de los documentos: Digital Preservation Europe (DPE), Preservation and Long-term Access Through Networked Services (Planets), Cultural Artistic and Scientific Knowledge for Preservation, Access and Retrieval (CASPAR), y Network of expertise in Digital long-term preservation (nestor).

Immunopathology in ocular toxoplasmosis: facts and clues

Although parasite-mediated host cell lysis is deemed to be an important cause of tissue destruction in ocular toxoplasmosis (OT), the severity of the disease is probably correlated with hypersensitivity and inflammation. Notwithstanding, the mechanisms that regulate the inflammatory process in recurrent OT are poorly understood. Recent evidence has identified interleukin (IL) 17 as a marker for disease severity. The ocular and cerebral presence of this cytokine is generally associated with the induction of autoimmune responses in the brain and the eye. Indeed, there are indications that autoimmunity may contribute to clinical variability in the activity of OT. IL-23, which induces the proliferation of IL-17-producing cells and IL-27, which is a counterplayer to IL-17, may regulate T(H)-1-cell-mediated responses in OT. The importance of these cytokines in experimental models of uveitis and encephalitis has been recently reported. CD25(+) regulatory T-cells may control the local inflammatory response and protect the host against collateral inflammatory tissue damage. The responses of these cells to OT may be suitably tailored to cope with either an acquired or a congenital aetiology. Knowledge relating to immunoreactivity in OT has grown impressively during the past few years. Its characteristic and variable features have been identified and the potential relevance of autoimmunity has been assessed. In light of this knowledge, potential future treatment options have been considered.

Association between IL-18 gene polymorphisms and biopsy-proven giant cell

INTRODUCTION: The objective was to investigate the potential implication of the IL18 gene promoter polymorphisms in the susceptibility to giant-cell arteritis GCA). METHODS: In total, 212 patients diagnosed with biopsy-proven GCA were included in this study. DNA from patients and matched controls was obtained from peripheral blood. Samples were genotyped for the IL18-137 G>C (rs187238), the IL18-607 C>A (rs1946518), and the IL18-1297 T>C (rs360719) gene polymorphisms with polymerase chain reaction, by using a predesigned TaqMan allele discrimination assay. RESULTS: No significant association between the IL18-137 G>C polymorphism and GCA was found. However, the IL18 -607 allele A was significantly increased in GCA patients compared with controls (47.8% versus 40.9% in patients and controls respectively; P = 0.02; OR, 1.32; 95% CI, 1.04 to 1.69). It was due to an increased frequency of homozygosity for the IL18 -607 A/A genotype in patients with GCA (20.4%) compared with controls (13.4%) (IL18 -607 A/A versus IL18 -607 A/C plus IL18 -607 C/C genotypes: P = 0.04; OR, 1.59; 95% CI, 1.02 to 2.46). Also, the IL18-1297 allele C was significantly increased in GCA patients (30.7%) compared with controls (23.0%) (P = 0.003; OR, 1.48; 95% CI, 1.13 to 1.95). In this regard, an increased susceptibility to GCA was observed in individuals carrying the IL18-1297 C/C or the IL18-1297 C/T genotypes compared with those carrying the IL18-1297 T/T genotype (IL18-1297 C/C plus IL18-1297 T/C versus IL18-1297 T/T genotype in GCA patients compared with controls: P = 0.005; OR, 1.61; 95% CI, 1.15 to 2.25). We also found an additive effect of the IL18 -1297 and -607 polymorphisms with TLR4 Asp299Gly polymorphism. The OR for GCA was 1.95 for combinations of genotypes with one or two risk alleles, whereas carriers of three or more risk alleles have an OR of 3.7. CONCLUSIONS: Our results show for the first time an implication of IL18 gene-promoter polymorphisms in the susceptibility to biopsy-proven GCA. In addition, an additive effect between the associated IL18 and TLR4 genetic variants was observed.

Association study of genetic variants of pro-inflammatory chemokine and cytokine genes in systemic lupus erythematosus

BACKGROUND. Several lines of evidence suggest that chemokines and cytokines play an important role in the inflammatory development and progression of systemic lupus erythematosus. The aim of this study was to evaluate the relevance of functional genetic variations of RANTES, IL-8, IL-1alpha, and MCP-1 for systemic lupus erythematosus. METHODS. The study was conducted on 500 SLE patients and 481 ethnically matched healthy controls. Genotyping of polymorphisms in the RANTES, IL-8, IL-1alpha, and MCP-1 genes were performed using a real-time polymerase chain reaction (PCR) system with pre-developed TaqMan allelic discrimination assay. RESULTS. No significant differences between SLE patients and healthy controls were observed when comparing genotype, allele or haplotype frequencies of the RANTES, IL-8, IL-1alpha, and MCP-1 polymorphisms. In addition, no evidence for association with clinical sub-features of SLE was found. CONCLUSION. These results suggest that the tested functional variation of RANTES, IL-8, IL-1alpha, and MCP-1 genes do not confer a relevant role in the susceptibility or severity of SLE in the Spanish population.

Inflammatory Markers and Incident Heart Failure Risk in Older Adults: The Health, Aging, and Body Composition Study

Background: Inflammation is associated with heart failure (HF) risk factors and also directly affects myocardial function. However, the association between inflammation and HF risk in older adults has not been adequately evaluated. Methods: The association of baseline serum concentrations of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF- ), and C-reactive protein (CRP) with incident HF was assessed with Cox proportional hazards models among 2610 older persons without prevalent HF enrolled in the Health, Aging, and Body Composition (Health ABC) Study (age, 73.6±2.9 years; 48.3% men; 59.6% white). Results: Median (interquartile range) baseline concentrations of IL-6, TNF- , and CRP were 1.80 (1.23, 2.76) pg/mL, 3.14 (2.41, 4.06) pg/mL, and 1.64 (0.99, 3.04) µg/mL, respectively. On follow-up (median, 9.4 years), 311 participants (11.9%) developed HF. In models controlling for clinical predictors of HF and incident coronary heart disease, doubling of IL-6, TNF- , and CRP concentrations was associated with 34% (95% CI, 18 -52%; P<.001), 33% (95% CI, 9 - 63%; P=.006), and 13% (95% CI, 3-24%; P=.01) increase in HF risk, respectively. In models including all 3 markers, IL-6 and TNF- , but not CRP, remained significant. Findings were similar across sex and race. Post-HF ejection fraction (EF) was available in 239 (76.8%) cases. When only cases with preserved EF were considered (n=105), IL-6 (HR per doubling, 1.57; 95% CI, 1.28 -1.94; P<.001), TNF- (HR per doubling, 1.59; 95% CI, 1.12-2.26; P=.01), and CRP (HR per doubling, 1.23; 95% CI, 1.05-1.44; P=.01) were all associated with HF risk in adjusted models. In contrast, when only cases with reduced EF (n=134) were considered, only IL-6 attained marginal significance in adjusted models (HR per doubling, 1.20; 95% CI, 0.99 -1.46; P=.06). Participants with 2 or 3 markers above median had pronounced HF risk in adjusted models (HR, 1.66; 95% CI, 1.12-2.46; P=.01; and HR, 1.76; 95% CI, 1.16 -2.65; P=.007, respectively). Addition of IL-6 to the clinical Health ABC HF model improved discrimination (C index from 0.717 to 0.734; P=.001) and fit (decreased Bayes information criterion by 17.8; P<.001). Conclusions: Inflammatory markers are associated with HF risk among older adults and may improve HF risk stratification.

“El Mediterráneo en el diálogo Norte-Sur”: III Curso Internacional de Defensa. Jaca (Huesca), 19-23 de septiembre de 1995

Del 19 al 23 de setembre de 1995 es va celebrar a Jaca (Osca) el III Curs Internacional de Defensa, amb el títol específic “ El Mediterrani en el Diàleg Nord Sud”, organitzat per la Càtedra Miguel de Cervantes de l’Acadèmia General Militar i la Universitat de Saragossa. Els objectius assenyalats pels organitzadors es van centrar a potenciar l’intercanvi d’opinions entre especialistes i representants de les institucions sobre aspectes polítics, socials, econòmics i de defensa que afecten l’espai geopolític de les dues riberes del Mediterrani, i a analitzar els mecanismes de cooperació que actuen a l’àrea i la política de la Unió Europea a la zona

Interleukin-15 augments oxidative metabolism and fungicidal activity of human monocytes against Paracoccidioides brasiliensis

Interleukin (IL)-15 is a pleiotropic cytokine that regulates the proliferation and survival of many cell types. IL-15 is produced by monocytes and macrophages against infectious agents and plays a pivotal role in innate and adaptive immune responses. This study analyzed the effect of IL-15 on fungicidal activity, oxidative metabolism and cytokine production by human monocytes challenged in vitro with Paracoccidioides brasiliensis (Pb18), the agent of paracoccidioidomycosis. Peripheral blood monocytes were pre-incubated with IL-15 and then challenged with Pb18. Fungicidal activity was assessed by viable fungi recovery from cultures after plating on brain-heart infusion-agar. Superoxide anion (O2-), hydrogen peroxide (H2O2), tumour necrosis factor-alpha (TNF-α), IL-6, IL-15 and IL-10 production by monocytes were also determined. IL-15 enhanced fungicidal activity against Pb18 in a dose-dependent pattern. This effect was abrogated by addition of anti-IL-15 monoclonal antibody. A significant stimulatory effect of IL-15 on O2- and H2O2 release suggests that fungicidal activity was dependent on the activation of oxidative metabolism. Pre-treatment of monocytes with IL-15 induced significantly higher levels of TNF-α, IL-10 and IL-15 production by cells challenged with the fungus. These results suggest a modulatory effect of IL-15 on pro and anti-inflammatory cytokine production, oxidative metabolism and fungicidal activity of monocytes during Pb18 infection.

Activation of peroxisome proliferator-activated receptor-β/-δ (PPAR-β/-δ) ameliorates insulin signaling and reduces SOCS3 levels by inhibiting STAT3 in interleukin-6-stimulated adipocytes.

OBJECTIVE It has been suggested that interleukin (IL)-6 is one of the mediators linking obesity-derived chronic inflammation with insulin resistance through activation of STAT3, with subsequent upregulation of suppressor of cytokine signaling 3 (SOCS3). We evaluated whether peroxisome proliferator-activated receptor (PPAR)-β/-δ prevented activation of the IL-6-STAT3-SOCS3 pathway and insulin resistance in adipocytes. RESEARCH DESIGN AND METHODS First, we observed that the PPAR-β/-δ agonist GW501516 prevented both IL-6-dependent reduction in insulin-stimulated Akt phosphorylation and glucose uptake in adipocytes. In addition, this drug treatment abolished IL-6-induced SOCS3 expression in differentiated 3T3-L1 adipocytes. This effect was associated with the capacity of the drug to prevent IL-6-induced STAT3 phosphorylation on Tyr(705) and Ser(727) residues in vitro and in vivo. Moreover, GW501516 prevented IL-6-dependent induction of extracellular signal-related kinase (ERK)1/2, a serine-threonine-protein kinase involved in serine STAT3 phosphorylation. Furthermore, in white adipose tissue from PPAR-β/-δ-null mice, STAT3 phosphorylation (Tyr(705) and Ser(727)), STAT3 DNA-binding activity, and SOCS3 protein levels were higher than in wild-type mice. Several steps in STAT3 activation require its association with heat shock protein 90 (Hsp90), which was prevented by GW501516 as revealed in immunoprecipitation studies. Consistent with this finding, the STAT3-Hsp90 association was enhanced in white adipose tissue from PPAR-β/-δ-null mice compared with wild-type mice. CONCLUSIONS Collectively, our findings indicate that PPAR-β/-δ activation prevents IL-6-induced STAT3 activation by inhibiting ERK1/2 and preventing the STAT3-Hsp90 association, an effect that may contribute to the prevention of cytokine-induced insulin resistance in adipocytes.

Gene transfer of interleukin-18-binding protein attenuates cardiac allograft rejection.

Interleukin (IL) 18 is a potent pro-inflammatory Th1 cytokine that exerts pleiotropic effector functions in both innate and acquired immune responses. Increased IL-18 production during acute rejection has been reported in experimental heart transplantation models and in kidney transplant recipients. IL-18-binding protein (IL-18BP) binds IL-18 with high affinity and neutralizes its biologic activity. We have analyzed the efficacy of an adenoviral vector expressing an IL-18BP-Ig fusion protein in a rat model of heart transplantation. IL-18BP-Ig gene transfer into Fisher (F344) rat donor hearts resulted in prolonged graft survival in Lewis recipients (15.8 +/- 1.4 days vs. 10.3 +/- 2.5 and 10.1 +/- 2.1 days with control virus and buffer solution alone, respectively; P < 0.001). Immunohistochemical analysis revealed decreased intra-graft infiltrates of monocytes/macrophages, CD4(+), CD8alpha(+) and T-cell receptor alphabeta(+) cells after IL-18BP-Ig versus mock gene transfer (P < 0.05). Real-time reverse transcriptase polymerase chain reaction analysis showed decreased cytokine transcripts for the RANTES chemokine and transforming growth factor-beta after IL-18BP-Ig gene transfer (P < 0.05). IL-18BP-Ig gene transfer attenuates inflammatory cell infiltrates and prolongs cardiac allograft survival in rats. These results suggest a contributory role for IL-18 in acute rejection. Further studies aiming at defining the therapeutic potential of IL-18BP are warranted.

Occurrence of blaOXA-23 gene in imipenem-susceptible Acinetobacter baumannii

The aim of the current study was to describe the occurrence of the blaOXA-23 gene and the ISAba1 element in imipenem-susceptible Acinetobacter baumannii strains. By performing the polymerase chain reaction mapping using combinations of ISAba1 forward primers and the blaOXA-23-like gene reverse primers, we demonstrated that the ISAba1 element did not occur upstream of the blaOXA-23 gene in five of 31 isolates, which explained the lack of resistance to imipenem despite the presence of the blaOXA-23 gene. All of the blaOXA-23-positive isolates were susceptible to imipenem and meropenem with minimal inhibitory concentration < 4 µg/mL. Pulsed-field gel electrophoresis analysis revealed four genotypes among the five blaOXA-23-positive isolates. The current report of the blaOXA-23 gene in imipenem-susceptible isolates provided evidence that this gene may be silently spread in a hospital environment and highlighted the threat of undetected reservoirs of carbapenemase genes.

Multiple cytokine expression profiles reveal immune-based differences in occult hepatitis B genotype H-infected Mexican Nahua patients

A high prevalence of occult hepatitis B (OHB) genotype H infections has been observed in the native Mexican Nahua population. In addition, a low incidence of hepatitis B virus (HBV)-associated hepatocellular carcinoma has been described in Mexico. The immune response to infection among OHB-infected patients has been poorly evaluated in vivo. Therefore, we assessed the expression profiles of 23 cytokines in OHB genotype H-infected Nahua patients. A total of 41 sera samples from natives of the Nahua community were retrospectively analysed. Based on their HBV antibody profiles, patients were stratified into two groups: OHB patients (n = 21) and patients that had recovered from HBV infection (n = 20). Herein, we report distinctive cytokines profiles in OHB-infected individuals. Compared to healthy controls (n = 20) and patients who resolved HBV infection, OHB-infected patients displayed an increase in interleukin (IL)-2 secretion in addition to a characteristic inflammation profile (decrease in IL-8 and tumour necrosis factor-alpha levels and increased levels of tumour growth factor-beta). IL-15 and interferon-gamma levels were reduced in OHB-infected individuals when compared to those patients who resolved HBV infection. In contrast, OHB patients showed an increase in monocyte chemoattractant protein (MCP)-1 and MCP-2 compared to healthy controls and patients who resolved HBV infection. These findings suggest that cytokine expression can influence the severity of OHB disease and could lead to new investigation into the treatment of liver and other infectious diseases.