Comparative analysis between extra-short implants (≤6 mm) and 6 mm-longer implants: a meta-analysis of randomized controlled trial.

The goal of this systematic study was to compare the survival rate (SR), marginal bone loss (MBL) and clinical complications between extra-short implants (≤6 mm) and 6-mm-longer implants in randomized clinical trials. A systematic electronic and manual search was performed using the PubMed, Web of Science, Scopus and DOAJ databases. A meta-analysis was conducted to compare the SR and MBL between both groups. We have selected 17 studies out of 1016 articles for qualitative and quantitative analysis. The data from 956 patients and 1779 implants were used with an overall mean clinical follow-up of 3.88 years ranging from 1 to 8 years. Overall, the SR of extra-short implants (93.12%) was lower than the observed in 6-mm-longer implants (95.98%); however, there was no statistical significance on these findings (P > 0.10). MBL analysis showed that extra-short implants and the 6-mm-longer group presented an average of -0.71 and -0.92 mm after 1-year respectively. Three years follow-up showed MBL of -0.42 mm (≤6 mm) and -0.43 mm (>6 mm); 5 years follow-up showed an MBL of -0.69 mm (≤6 mm) and -0.46 mm (>6 mm); and after 8 years of follow-up, it was found an MBL of -1.58 mm (≤6 mm) and -2.46 mm (>6 mm). Within the limitation of this study, the results indicated that SR of extra-short implants was similar to 6-mm-longer implants. In contrast, MBL and the presence of clinical complications were observed at a lessened rate on extra-short implants.

Continuous erector spinae plane block for analgesia in pediatric thoracic surgery: A case report. / Bloqueo continuo en el plano del músculo erector del espinal para analgesia en cirugía torácica pediátrica: informe de un caso.

Erector spinae plane block has been recently described and it appears as a very promising regional analgesia technique. We report the first continuous erector spinae plane block performed in a pediatric patient for thoracic surgery. A 15-month-old boy, diagnosed with a paracardiac teratoma was scheduled for a tumor resection with a thoracotomy approach. After general anesthesia induction, a continuous erector spinae plane block at T5 level was performed with ropivacaine 0.2%. After surgery, a continuous thoracic interfascial infusion of ropivacaine 0.1% along with multimodal rescue analgesia was initiated. The patient tolerated the procedure well with no complications. It appears that this is a good alternative to thoracic epidural and paravertebral block, given the simple reproducibility and potential greater safety of this technique.

The airway approach to a neonate with Treacher Collins syndrome. Case report / Manejo de la vía aérea en un recién nacido con síndrome de Treacher Collins. Caso clínico

Neonates and small infants with syndromes characterized by the presence of craniofacial abnormalities may represent great challenges regarding the management of the airway. We describe the case of a 9-day-old neonate with Treacher Collins syndrome, in which a laryngeal mask was essential to improve the airway obstruction, ventilate the patient and serve as an airway conduit for a fiberoptic intubation. By presenting this case, we intend to show that in neonates with Treacher Collins syndrome, in whom difficulties ventilation and intubation are expected, a thoughtful airway management planning is mandatory (AU)

Los recién nacidos y los lactantes pequeños con síndromes caracterizados por la presencia de anomalías craneofaciales pueden representar grandes desafíos en el manejo de la vía aérea. Describimos el caso de un recién nacido de 9 días de edad con síndrome de Treacher Collins, en el que una mascarilla laríngea fue esencial para mejorar la obstrucción de la vía aérea, ventilar al paciente y servir como guía para una intubación con fibrobroncoscopio. Con la presentación de este caso se muestra cómo en los recién nacidos con síndrome de Treacher Collins, donde se prevé una ventilación y una intubación difíciles, es obligatoria una planificación cuidadosa del manejo de las vías aéreas (AU)

The airway approach to a neonate with Treacher Collins syndrome - Case report.

Neonates and small infants with syndromes characterized by the presence of craniofacial abnormalities may represent great challenges regarding the management of the airway. We describe the case of a 9-day-old neonate with Treacher Collins syndrome, in which a laryngeal mask was essential to improve the airway obstruction, ventilate the patient and serve as an airway conduit for a fiberoptic intubation. By presenting this case, we intend to show that in neonates with Treacher Collins syndrome, in whom difficulties ventilation and intubation are expected, a thoughtful airway management planning is mandatory.

Acute exercise amplifies inflammation in obese patients with COPD.

Systemic inflammation has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD) systemic effects. However, most COPD patients do not suffer from persistent systemic inflammation even after exacerbations and exercise and scientific evidence has provided conflicting results. Our aim is to evaluate inflammatory gene expression at rest and at 1 and 24h after strenuous exercise in COPD patients and study the patient variables associated with inflammatory expression. A cross-sectional study was conducted in COPD patients who were recruited on entry to a pulmonary rehabilitation (PR) program. Demographic, clinical and functional data were collected. Blood samples were collected and gene expression was analyzed by reverse transcriptase polymerase chain reaction for IFNg, IL1b, IL6, IL8, TNFa, TGFb1 and iNOS. The study included 21 patients (15 men, 71.4%), mean age 66.1 years old (SD=8.27), mean FEV1 46.76% (SD 20.90%), 67% belonging to GOLD grade D, mean BODE index of 3.9, 90.5% with smoking history, mean BMI 25.81 (SD=4.87), median of 1.29 exacerbations in the previous year. There was no statistical significant difference between inflammatory expression at rest and at 1h and 24h after the maximal exercise test for all tested genes. We found an association between BMI and inflammatory expression at all the points of time checked, a slight inverse association occurs with low BMI for mRNA IL1b, IL6, TNFa, TGFb1 and iNOS, and there was a more pronounced positive association for obese patients for all tested genes. This preliminary study did not show an enhanced inflammatory gene expression from rest to 1h and 24h after short-term exercise, but did show an increased inflammatory gene expression in both BMI extremes, both at rest and after exercise, suggesting not only malnourishment, but also obesity as potential links between COPD and systemic inflammation. Studies with larger samples and designed to definitely exclude OSA or OHS as confounding factors in obese patients are required.

KIR genotypic diversity in Portuguese and analysis of KIR gene allocation after allogeneic hematopoietic stem cell transplantation.

The diversity of killer-cell immunoglobulin-like receptors (KIR) genes was evaluated in Portuguese and the observed genotypic profiles were found related to the ones reported in European populations. The KIR repertoire after hematopoietic stem cell transplantation is determined by these gene frequencies and the KIR group B motifs are the less common. We estimated donor-KIR/recipient-ligand interactions in transplants with related donors and unrelated donors found in a local registry or from abroad. A large fraction of transplants had all three ligands of inhibitory receptors, and therefore, in theory were not prone to natural killer cell (NK) mediated alloreactivity. Furthermore, the distribution of KIR alloreactive interactions was found independent of the donor-recipient genetic proximity, probably because of different gene segregation and comparable KIR frequencies in the donor pools.

Atividades antinociceptiva e antiinflamatória do extrato etanólico de Luehea divaricata / Antinociceptive and anti-inflammatory activities of Luehea divaricate ethanol extract

RESUMO Considerando os diferentes usos etnofarmacológicos apresentados pela planta Luehea divaricata, realizou-se este estudo com o objetivo de avaliar as atividades antinociceptiva e antinflamatória do extrato etanólico de suas folhas, em modelo animal, nas dosagens de 20, 40, 80 e 160 mg/Kg, por via oral. Foram realizados os seguintes testes: contorções abdominais induzidas pelo acido acético, placa quente, formalina e edema de pata induzido por carragenina. Foram utilizados camundongos Swiss (20-25 g) para os três primeiros testes e ratos Wistar (180-250 g), para o último, divididos em seis grupos de oito animais, totalizando 48 animais em cada parâmetro de avaliação. Os resultados foram analisados estatisticamente pela análise de variância a 5% de probabilidade, para verificar quais os tratamentos que diferiram entre si, e estes foram submetidos aos testes de Kruskall-Wallis e Student-Newman-Keuls. O extrato etanólico das folhas de L. divaricata (EEtOH-Ld), nas diferentes doses estudadas, apresentou significativa atividade antinociceptiva sobre a dor induzida quimicamente por injeções intraperitoneal de acido acético e intraplantar de formalina. Na dosagem de 160 mg/Kg, esse extrato apresentou ação analgésica central, aos 120 minutos de observação, no teste de placa quente e reduziu o edema de pata induzido pela administração de carragenina, uma hora após a administração do agente inflamatório, semelhante ao efeito produzido pelo fármaco padrão.

ABSTRACT Considering the different ethnopharmacological uses submitted by the plant Luehea divaricata, this study took place in order to evaluate the antinociceptive and anti-inflammatory activities of the ethanol extract of the leaves in an animal model, the dosages of 20, 40, 80 and 160 mg/kg by oral intake. The following tests were performed: writhing induced by acetic acid, hot plate, formalin, and paw edema induced by carrageenan. Swiss mice (20-25 g) were used for the first three tests and Wistar rats (180-250 g) for the last, divided into six groups, each of eight animals, totaling 48 animals for each assessment parameter. The results were statistically analyzed by analysis of variance at 5% probability to verify which treatments differ, and these were tested by Kruskal-Wallis and Student-Newman-Keuls. The ethanol extract of L. divaricataleaves (EEtOH-Ld) at the different studied doses showed significant antinociceptive activity on chemically induced pain by intraperitoneal injections of acetic acid and intraplantar formalin. At a dosage of 160 mg/kg, this extract showed a central analgesic action after 120 minutes of observation in the hot plate test and reduced action in the paw edema induced by carrageenan one hour after the administration of the inflammatory agent, similar to the effect produced by the standard drug.

Clinical outcomes and genetic expression profile in human liver graft dysfunction during ischemia/reperfusion injury.

INTRODUCTION: This study aims to compare the molecular gene expression during ischemia reperfusion injury. Several surgical times were considered: in the beginning of the harvesting (T0), at the end of the cold ischemia period (T1), and after reperfusion (T2) and compared with graft dysfunction after liver transplant (OLT). METHODS: We studied 54 patients undergoing OLT. Clinical, laboratory data, and histologic data (Suzuki classification) as well as the Survival Outcomes Following Liver Transplantation (SOFT) score were used and compared with the molecular gene expression of the following genes: Interleukin (IL)-1b, IL-6, tumor necrosis factor-α, perforin, E-selectin (SELE), Fas-ligand, granzyme B, heme oxygenase-1, and nitric oxide synthetase. RESULTS: Fifteen patients presented with graft dysfunction according to SOFT criteria. No relevant data were obtained by comparing the variables graft dysfunction and histologic variables. We observed a statistically significant relation between SELE at T0 (P = .013) and IL-1ß at T0 (P = .028) and early graft dysfunction. CONCLUSIONS: We conclude that several genetically determined proinflammatory expressions may play a critical role in the development of graft dysfunction after OLT.

Influência da própolis sobre os perfis leucocitário e proteico de camundongos e tempo de fechamento de feridas excisionais limpas e infectadas por Staphylococcus aureus / Influence of Propolis on leukocyte and protein profiles of mice and closing time of excisional wounds clean and infected by Staphylococcus aureus

RESUMO Este estudo teve como objetivo avaliar os efeitos da própolis sobre os perfis leucocitário e protéico de camundongos e sobre o tempo de fechamento de lesões de pele confeccionadas experimentalmente, limpas e infectadas com Staphylococcus aureus. No primeiro, foram utilizados 48 animais divididos em quatro grupos, sendo um tratado com solução hidroalcóolica pura e três tratados com própolis a 10%, nas dosagens de 20 mg, 40 mg e 80 mg por animal de 25 gramas de peso, em única aplicação intraperitoneal. Foram coletadas amostras de sangue no segundo, 10º, 18º e 26º dias após o tratamento para realização de leucograma, proteinograma e fracionamento eletroforético das proteínas. Na avaliação da atividade cicatrizante, também foram utilizados 48 camundongos divididos em seis grupos, nos quais realizou-se a confecção cirúrgica de feridas na dimensão de 1cm2, após anestesia dissociativa. Dois grupos serviram como controle para feridas limpas e infectadas. Dois grupos de feridas infectadas por S. aureuse dois grupos de feridas limpas foram tratados com própolis a 5% e 10%, sendo a escolha destas concentrações baseada em um estudo piloto realizado. Os resultados mostraram que o tratamento com própolis influencia o leucograma e o proteinograma, de forma dose-dependente, sendo que a maior dose utilizada desencadeou leucocitose com linfocitose e aumento de proteínas da fração gamaglobulínica, no 10º dia após o início do tratamento. Também mostraram que a concentração da solução influenciou o tempo de cicatrização das feridas infectadas, ocorrendo em menor tempo no grupo tratado com a solução a 5%.

ABSTRACT This study aimed to evaluate the propolis effects on both the leukocyte and protein profiles of mice and on the closing time of skin lesions made experimentally, clean and infected with Staphylococcus aureus. The first 48 animals were divided into four groups, one treated with pure alcohol solution and three treated with propolis 10% at dosages of 20 mg, 40 mg and 80 mg per 25 g of animal weight in an intraperitoneal single application . Blood samples in the second, and then 10º, 18º and 26º days after treatment were collected in order to perform WBC, proteins and electrophoretic fractionation of proteins. Regarding the healing activity, also 48 mice divided into six groups were used, in whom surgical wounds in the size of 1cm2 were purposely inflicted , after the dissociative anesthesia were applied . Two groups served as control ones, for clean and infected wounds. Two groups of S. aureus with infected wounds and two groups with clean sores were treated with 5% and 10 % propolis, being this concentration choice based on a pilot study previously performed. The results showed that treatment with propolis influences leukocyte and protein concentrations in a dose- dependent manner, with the highest dose triggering leukocytosis with lymphocytosis and increasing the protein fraction of gamaglobulínica, on the 10th day after the start of treatment. It also indicated that the concentration of the solution influence the time of healing of infected wounds, since the process on the group treated with 5% solution happened faster.

Genetic expression profile of human liver grafts in ischemia-reperfusion injury: comparison of familial amyloidotic polyneuropathy and deceased-donor liver grafts.

This study aimed to compare the histologic and molecular gene expression at several surgical times (beginning of harvesting, T0; end of cold ischemia period, T1; and after reperfusion, T2) to characterize the ischemia-reperfusion injury (IRI) in deceased-donor liver grafts harvested from patients with familial amyloidotic polyneuropathy (FAP). For this purpose, 54 patients undergoing liver transplantation were studied and divided into 3 groups: deceased donor to cirrhotic recipient (group 1; n = 27), deceased donor to FAP recipient (group 2; n = 15), and FAP donor to cirrhotic recipient (group 3; n = 12). The main comparison was performed between a histologic score (Suzuki score, adding steatosis and neutrophil infiltration), and molecular gene expression of the following genes: interleukin (IL) 1ß, IL-6, E-selectin, Fas-ligand, granzyme B, heme oxygenase 1 (HO1), and nitric oxide synthetase (iNOS2A). We observed less neutrophil infiltration levels in group 3 in sample T0 (P = .0082), which was associated with gene expression of HO1 in the biopsies at T2 (P = .022). In group 3, the molecular expression of genes related to attenuated proinflammatory reaction during IRI, iNOS2A at T0 and HO1 at T2, was detected. We conclude that FAP liver grafts express differently the genes associated with an attenuated proinflammatory reaction, presenting less neutrophil infiltration at harvesting. These findings add more knowledge about the better short-term outcomes in patients receiving this type of liver graft.

HLA alleles and HLA-B27 haplotypes associated with susceptibility and severity of ankylosing spondylitis in a Portuguese population.

Human leukocyte antigen (HLA)-B27 is the mostly known major histocompatibility complex (MHC) gene associated with ankylosing spondylitis (AS). Nonetheless, there is substantial evidence that other MHC genes appear to be associated with the disease, although it has not yet been established whether these associations are driven by direct associations or by linkage disequilibrium (LD) mechanisms. We aimed to investigate the contributions of HLA class I and II alleles and B27-haplotypes for AS in a case-control study. A total of 188 HLA-B27 AS cases and 189 HLA-B27 healthy controls were selected and typed for HLA class I and II by the Luminex polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method. Allelic and haplotypic distributions were estimated by maximum likelihood method using Arlequin v3.11 and statistical analysis were performed by Stata10.1. No associations were found between non-HLA-B27 loci and AS susceptibility, but several associations were observed for phenotypic features of the disease. DRB1*08 was identified as a risk factor for uveitis and DQB1*04 seems to provide protection for AS severity (functional, metrological and radiological indexes). A*02/B27/C*02/DRB1*01/DQB1*05 [P<0.0001; odds ratio (OR) = 39.06; 95% confidence interval (CI) (2.34-651)] is the only haplotype that seems to confer susceptibility to AS. Moreover, the haplotype A*02/B27/C*01/DRB1*08/DQB1*04 seems to provide protection for disease functional and radiological repercussions. Our findings are compatible with the hypothesis that other genes within the HLA region besides HLA-B27 might play some role in AS susceptibility and severity.

Targeted association analysis identified japonica rice varieties achieving Na(+)/K (+) homeostasis without the allelic make-up of the salt tolerant indica variety Nona Bokra.

During the last decade, a large number of QTLs and candidate genes for rice tolerance to salinity have been reported. Using 124 SNP and 52 SSR markers, we targeted 14 QTLs and 65 candidate genes for association mapping within the European Rice Core collection (ERCC) comprising 180 japonica accessions. Significant differences in phenotypic response to salinity were observed. Nineteen distinct loci significantly associated with one or more phenotypic response traits were detected. Linkage disequilibrium between these loci was extremely low, indicating a random distribution of favourable alleles in the ERCC. Analysis of the function of these loci indicated that all major tolerance mechanisms were present in the ERCC although the useful level of expression of the different mechanisms was scattered among different accessions. Under moderate salinity stress some accessions achieved the same level of control of Na(+) concentration and Na(+)/K(+) equilibrium as the indica reference variety for salinity tolerance Nona Bokra, although without sharing the same alleles at several loci associated with Na(+) concentration. This suggests (a) differences between indica and japonica subspecies in the effect of QTLs and genes involved in salinity tolerance and (b) further potential for the improvement of tolerance to salinity above the tolerance level of Nona Bokra, provided the underlying mechanisms are complementary at the whole plant level. No accession carried all favourable alleles, or showed the best phenotypic responses for all traits measured. At least nine accessions were needed to assemble the favourable alleles and all the best phenotypic responses. An effective strategy for the accumulation of the favourable alleles would be marker-assisted population improvement.

Association of IL23R and ERAP1 genes with ankylosing spondylitis in a Portuguese population.

OBJECTIVE: Association between ankylosing spondylitis (AS) and two genes, ERAP1 and IL23R, has recently been reported in North American and British populations. The population attributable risk fraction for ERAP1 in this study was 25%, and for IL23R, 9%. Confirmation of these findings to ERAP1 in other ethnic groups has not yet been demonstrated. We sought to test the association between single nucleotide polymorphisms (SNPs) in these genes and susceptibility to AS among a Portuguese population. We also investigated the role of these genes in clinical manifestations of AS, including age of symptom onset, the Bath Ankylosing Spondylitis Disease Activity, Metrology and Functional Indices, and the modified Stoke Ankylosing Spondylitis Spinal Score. METHODS: The study was conducted on 358 AS cases and 285 ethnically matched Portuguese healthy controls. AS was defined according to the modified New York Criteria. Genotyping of IL23R and ERAP1 allelic variants was carried out with TaqMan allelic discrimination assays. Association analysis was performed using the Cochrane-Armitage and linear regression tests of genotypes as implemented in PLINK for dichotomous and quantitative variables respectively. A meta-analysis for Portuguese and previously published Spanish IL23R data was performed using the StatsDirect Statistical tools, by fixed and random effects models. RESULTS: A total of 14 nsSNPs markers (8 for IL23R, 5 for ERAP1, 1 for LN-PEP) were analysed. Three markers (2 for IL23R and 1 for ERAP1) showed significant single-locus disease associations, confirming that the association of these genes with AS in the Portuguese population. The strongest associated SNP in IL23R was rs1004819 (OR=1.4, p=0.0049), and in ERAP1 was rs30187 (OR=1.26, p=0.035). The population attributable risk fractions in the Portuguese population for these SNPs are 11% and 9.7% respectively. No association was seen with any SNP in LN-PEP, which flanks ERAP1 and was associated with AS in the British population. No association was seen with clinical manifestations of AS. CONCLUSION: These results show that IL23R and ERAP1 genes are also associated with susceptibility to AS in the Portuguese population, and that they contribute a significant proportion of the population risk for this disease.

Regulatory cells, cytokine pattern and clinical risk factors for asthma in infants and young children with recurrent wheeze.

BACKGROUND: Several risk factors for asthma have been identified in infants and young children with recurrent wheeze. However, published literature has reported contradictory findings regarding the underlying immunological mechanisms. OBJECTIVES: This study was designed to assess and compare the immunological status during the first 2 years in steroid-naive young children with >or= three episodes of physician-confirmed wheeze (n=50), with and without clinical risk factors for developing subsequent asthma (i.e. parental asthma or a personal history of eczema and/or two of the following: wheezing without colds, a personal history of allergic rhinitis and peripheral blood eosinophilia >4%), with age-matched healthy controls (n=30). METHODS: Peripheral blood CD4(+)CD25(+) and CD4(+)CD25(high) T cells and their cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), GITR and Foxp3 expression were analysed by flow cytometry. Cytokine (IFN-gamma, TGF-beta and IL-10), CTLA-4 and Foxp3 mRNA expression were evaluated (real-time PCR) after peripheral blood mononuclear cell stimulation with phorbol 12-myristate 13-acetate (PMA) (24 h) and house dust mite (HDM) extracts (7th day). RESULTS: Flow cytometry results showed a significant reduction in the absolute number of CD4(+)CD25(high) and the absolute and percentage numbers of CD4(+)CD25(+)CTLA-4(+) in wheezy children compared with healthy controls. Wheezy children at a high risk of developing asthma had a significantly lower absolute number of CD4(+)CD25(+) (P=0.01) and CD4(+)CD25(high) (P=0.04), compared with those at a low risk. After PMA stimulation, CTLA-4 (P=0.03) and Foxp3 (P=0.02) expression was diminished in wheezy children compared with the healthy children. After HDM stimulation, CTLA-4 (P=0.03) and IFN-gamma (P=0.04) expression was diminished in wheezy children compared with healthy children. High-risk children had lower expression of IFN-gamma (P=0.03) compared with low-risk and healthy children and lower expression of CTLA-4 (P=0.01) compared with healthy children. CONCLUSIONS: Although our findings suggest that some immunological parameters are impaired in children with recurrent wheeze, particularly with a high risk for asthma, further studies are needed in order to assess their potential as surrogate predictor factors for asthma in early life.

Immunophenotyping of lymphocyte subsets in the third eyelid tissue in dogs (Canis familiaris): morphological, microvascular, and secretory aspects of this ocular adnexa.

The third eyelid is an important adnexa of the eye. The objective of this study was to evaluate (i) morphological aspects (ii) vascularization, and (iii) the immunophenotype of lymphocyte subsets in the third eyelid of dogs. Flow cytometric analysis revealed the presence of three patterns concerning the immunophenotype of the third eyelid tissue. Dogs without ocular insult or deficient tear production might belong to one of the following immunophenotype patterns: I--the number of T-cells that expressed CD3(+) CD8(+) was higher than the number of cells that expressed CD3(+)CD4(+). II--the number of cells CD3(+)C4(+) was higher than the number of cells CD3(+)CD8(+) and in this case a higher number of cells that expressed CD19 were identified. III--Proximity of values of the cells that expressed CD3(+)CD4(+) and CD3(+)CD8(+). These data might suggest that the number of lymphocyte T cells alone should not be considered a direct indicator of the presence of an immune-based inflammation. Besides, a particular population of T-cells does not indicate a particular inflammatory state. The morphological study of the third eyelid revealed a rather uncommon angioarchitecture. The artery that irrigates the eyelid crosses almost the entire length of this structure to achieve its free border, and only then, ramificates deeply towards an inner segmental level. This spatial microvascular arrangement probably results from an adaptation to the fact that the third eyelid, in the medial cantus of the eye, is inwardly compressed into a tiny space. Efficient vascularization is achieved by allowing the first ramifications of the third eyelid artery to run straight to the top. Accini secretor cells of the third eyelid show a mucin content while tubuloacinar cells are mainly serous.

[Genetic basis of ankylosing spondylitis]. / Espondilite Anquilosante e sua base genética.

Ankylosing spondylitis (AS) is a common rheumatic condition, highly heritable. Much of the genetic contribution to the disease lies in the major histocompatibility complex (MHC). The association with the allele group HLA-B*27 has been described worldwide for 30 years. On the other hand, genome wide scans have provided some interesting results showing that other MHC and non-MHC genes could be implicated either in disease susceptibility and phenotypic manifestations. Different hypothesis for disease pathophysiology have been investigated which contribute for a better understanding of the genetic basis of AS. This review aims to summarize the status of the knowledge in this exciting area. New data may, in a near future, change the screening of patients and generate new insights for the emergence of novel therapies.

Influence of human leucocyte antigen-DRB1 on the susceptibility to rheumatoid arthritis and on the production of anti-cyclic citrullinated peptide antibodies in a Portuguese population.

OBJECTIVE: To clarify the influence of the HLA-DRB1 locus on the susceptibility to rheumatoid arthritis and the production of anti-cyclic citrullinated peptide antibodies (anti-CCP) in a Portuguese population. METHODS: 141 patients with rheumatoid arthritis fulfilling the American College of Rheumatology 1987 revised criteria for rheumatoid arthritis were compared with 150 healthy controls. Human leucocyte antigen (HLA)-DRB1 locus genotyping was assessed by polymerase chain reaction reverse probing assays and sequence-specific primers. Anti-CCP antibodies were quantified by ELISA in patients with rheumatoid arthritis. Frequencies between groups were compared by the two-sided Fisher's exact test and considered significant if p<0.05. RESULTS: The HLA-DRB1*04 and HLA-DRB1*10 groups were highly associated with rheumatoid arthritis (p<0.001 and p = 0.031, respectively). High titres of anti-CCP antibodies were largely associated with the presence of HLA-DRB1*04/10. CONCLUSION: The well-recognised susceptibility alleles to rheumatoid arthritis, HLA-DRB1*04, were associated with rheumatoid arthritis in Portuguese patients. The relatively rare DRB1*10 was also associated with rheumatoid arthritis, as was described previously in other southern European countries. Both groups were associated with high anti-CCP titres, reinforcing its relevance to disease onset.

Impact of donor and recipient cytokine genotypes on renal allograft outcome.

Allelic differences in gene promoter or codifying regions have been described to affect regulation of gene expression, consequently increasing or decreasing cytokine production and signal transduction responses to a given stimulus. This observation has been reported for interleukin (IL)-10 (-1082 A/G; -819/-592 CT/CA), transforming growth factor (TGF)-beta (codon 10 C/T, codon 25 G/C), tumor necrosis factor (TNF)-alpha (-308 G/A), TNF-beta (+252 A/G), interferon (IFN)-gamma (+874 T/A), IL-6 (-174 G/C), and IL-4R alpha (+1902 G/A). To evaluate the influence of these cytokine genotypes on the development of acute or chronic rejection, we correlated the genotypes of both kidney graft recipients and cadaver donors with the clinical outcome. Kidney recipients had 5 years follow-up, at least 2 HLA-DRB compatibilities, and a maximum of 25% anti-HLA pretransplantation sensitization. The clinical outcomes were grouped as follows: stable functioning graft (NR, n = 35); acute rejection episodes (AR, n = 31); and chronic rejection (CR, n = 31). The cytokine genotype polymorphisms were defined using PCR-SSP typing. A statistical analysis showed a significant prevalence of recipient IL-10 -819/-592 genotype among CR individuals; whereas among donors, the TGF-beta codon 10 CT genotype was significantly associated with the AR cohort and the IL-6 -174 CC genotype with CR. Other albeit not significant observations included a strong predisposition of recipient TGF-beta codon 10 CT genotype with CR, and TNF-beta 252 AA with AR. A low frequency of TNF-alpha -308 AA genotype also was observed among recipients and donors who showed poor allograft outcomes.

Human herpes virus-8 serology and DNA analysis in recipients of renal allografts showing Kaposi's sarcoma and their respective donors.

Kaposi's sarcoma (KS) developed among 11 of 416 renal allograft recipients transplanted between 1985 and 2000. Only 3 among 364 Caucasian recipients developed KS, while it affected 8 of 52 Black patients, all of whom had been born in African countries (P <.001). All patients had their immunosuppression reduced; two also received daunorubicin and one received electrotherapy. Three patients developed accelerated renal allograft dysfunction, probably due to the reduced immunosuppression. Remission of KS was observed in seven patients, while lesions stabilized or improved partially in the other four. After resuming dialysis 2 of 11 patients died; both were in KS remission. Human herpes virus-8 (HHV-8) serology and DNA analysis was evaluated in sera obtained from seven donors: all were negative. Conversely, among eight sera collected pretransplant from the nine living recipients, HHV-8 IgG was detected in six and DNA was present in one. HHV-8 IgG was expressed in all patients (9/9) at some point posttransplant; DNA was detected in three patients. Therefore, the robust ethnic predisposition to KS was associated with a high pretransplant prevalence of HHV-8 among African recipients. Although some seroconversions were detected posttransplant, there was no evidence for donor-to-recipient transmission.

Filtration induces changes in activity states and leucocyte populations.

The distribution of leucocyte subpopulations in platelet concentrates (PC) derived from pre-storage filtered platelet-rich plasma (PRP), the cell suspension obtained by reverse filter washing and the post-filtered PC, were monitored by immunophenotyping analysis using CD3, CD20 and CD33. Leucocyte activation analysis with the CD11b marker revealed that this molecule is up regulated in neutrophils taken from the filter. This, together with the loss of cell viability during the enrichment process, suggests that contact with the filter matrix and processing and storage of samples containing leucocytes may lead to activation and loss of leucocyte viability. These changes were found to be more pronounced in less stable myeloid cells and account for the differences reported among various authors which in some cases related to operational conditions such as the enrichment process used and the length of time between filtration and analysis of samples. Finally, statistical analysis of the results obtained by immunophenotypic studies indicate that post-filter samples (S) contain significantly higher numbers of CD33+ myeloid cells when compared to (PF) the pre-filter samples (65.03%+/-12.6 and 24.56%+/-14.73, p<0.0000), with a decrease in T cells (50.72%+/-14.80 in PF and 24.05+/-9.48 in the cell suspension (S), p<0.0007) and B cells (14.96+/-9.31 in PF and 9.9+/-5.22 in S, p<0.201). A new strategy for assessing the influence of the filtration process on residual leucocyte activation and viability is described. This has direct relevance to collection, processing, storage and quality monitoring of PC.