Factors associated with non-treatment of hypertension and gender differences at baseline in the ELSA-Brasil cohort.

The treatment of arterial hypertension (AH) contributes to the reduction of morbidity and mortality. Gender differences are likely to play a role, as non-treatment is associated with clinical and sociodemographic aspects. The aim of this study was to investigate the factors associated with non-treatment of AH and gender differences in hypertensive individuals from the ELSA-Brasil cohort. The study was conducted with 5,743 baseline hypertensive cohort participants. AH was considered if there was a previous diagnosis or if systolic blood pressure (SBP) was ≥140 and/or diastolic BP (DBP) was ≥90 mmHg. Sociodemographic and anthropometric data, lifestyle, comorbidities, and use of antihypertensive medications were evaluated through interviews and in-person measurements. Treatment with renin-angiotensin-aldosterone system inhibitors (RAASi) or other antihypertensive medications and non-treatment were evaluated with multivariate logistic regression. Non-treatment was observed in 32.8% of hypertensive individuals. Of the 67.7% treated individuals, 41.1% received RAASi. Non-treatment was associated with alcohol consumption in women (OR=1.41; 95%CI: 1.15-1.73; P=0.001), lowest schooling level in men (OR=1.70; 95%CI: 1.32-2.19; P<0.001), and younger age groups in men and women (strongest association in males aged 35-44 years: OR=4.58, 95%CI: 3.17-6.6, P<0.001). Among those using RAASi, a higher proportion of white, older individuals, and with more comorbidities was observed. The high percentage of non-treatment, even in this civil servant population, indicated the need to improve the treatment cascade for AH. Public health policies should consider giving special attention to gender roles in groups at higher risk of non-treatment to reduce inequities related to AH in Brazil.

Factors associated with non-treatment of hypertension and gender differences at baseline in the ELSA-Brasil cohort

The treatment of arterial hypertension (AH) contributes to the reduction of morbidity and mortality. Gender differences are likely to play a role, as non-treatment is associated with clinical and sociodemographic aspects. The aim of this study was to investigate the factors associated with non-treatment of AH and gender differences in hypertensive individuals from the ELSA-Brasil cohort. The study was conducted with 5,743 baseline hypertensive cohort participants. AH was considered if there was a previous diagnosis or if systolic blood pressure (SBP) was ≥140 and/or diastolic BP (DBP) was ≥90 mmHg. Sociodemographic and anthropometric data, lifestyle, comorbidities, and use of antihypertensive medications were evaluated through interviews and in-person measurements. Treatment with renin-angiotensin-aldosterone system inhibitors (RAASi) or other antihypertensive medications and non-treatment were evaluated with multivariate logistic regression. Non-treatment was observed in 32.8% of hypertensive individuals. Of the 67.7% treated individuals, 41.1% received RAASi. Non-treatment was associated with alcohol consumption in women (OR=1.41; 95%CI: 1.15-1.73; P=0.001), lowest schooling level in men (OR=1.70; 95%CI: 1.32-2.19; P<0.001), and younger age groups in men and women (strongest association in males aged 35-44 years: OR=4.58, 95%CI: 3.17-6.6, P<0.001). Among those using RAASi, a higher proportion of white, older individuals, and with more comorbidities was observed. The high percentage of non-treatment, even in this civil servant population, indicated the need to improve the treatment cascade for AH. Public health policies should consider giving special attention to gender roles in groups at higher risk of non-treatment to reduce inequities related to AH in Brazil.

Association between dietary patterns and renal function in a cross-sectional study using baseline data from the ELSA-Brasil cohort.

Previous analyses of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) identified four main dietary patterns (DP). The aim of this study was to explore the association between the previously defined DP and renal function (RF). A cross-sectional study using the ELSA-Brasil baseline data was carried out. DP ("traditional", "fruits and vegetables", "bakery", and "low sugar/low fat), metabolic syndrome (MS) using the Joint Interim Statement criteria, microalbuminuria (MA), and glomerular filtration rate (eGFR) through the CKD-EPI equation were evaluated. Abnormal RF was defined as eGFR<60 mL·min-1·(1.73 m2)-1 and MA≥3.0 mg/dL. Factors associated with RF were determined and mediation analysis was performed to investigate the association between DP, MS, and RF. A total of 15,105 participants were recruited, with a mean age of 52±9 years; 8,134 participants (54%) were females. The mediation analysis identified indirect associations between "bakery" and "fruits and vegetables", and both were associated with decreased eGFR and albuminuria in both genders, compared with "traditional" and "low sugar/low fat" patterns in the general population. There was a direct association of the "bakery" pattern with MA in men (OR: 1.17, 95%CI: 1.92-1.48). The "fruits and vegetables" pattern also showed a direct association with reduced eGFR in women (OR: 1.65, 95%CI: 1.28-2.12), although there was no significance after adjustment. The "fruits and vegetables" and "bakery" DPs were associated with renal dysfunction. The only independent, direct association was between "bakery" DP and MA in men, raising concerns about DP and renal damage in men.

Association between dietary patterns and renal function in a cross-sectional study using baseline data from the ELSA-Brasil cohort

Previous analyses of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) identified four main dietary patterns (DP). The aim of this study was to explore the association between the previously defined DP and renal function (RF). A cross-sectional study using the ELSA-Brasil baseline data was carried out. DP ("traditional", "fruits and vegetables", "bakery", and "low sugar/low fat), metabolic syndrome (MS) using the Joint Interim Statement criteria, microalbuminuria (MA), and glomerular filtration rate (eGFR) through the CKD-EPI equation were evaluated. Abnormal RF was defined as eGFR<60 mL·min-1·(1.73 m2)-1 and MA≥3.0 mg/dL. Factors associated with RF were determined and mediation analysis was performed to investigate the association between DP, MS, and RF. A total of 15,105 participants were recruited, with a mean age of 52±9 years; 8,134 participants (54%) were females. The mediation analysis identified indirect associations between "bakery" and "fruits and vegetables", and both were associated with decreased eGFR and albuminuria in both genders, compared with "traditional" and "low sugar/low fat" patterns in the general population. There was a direct association of the "bakery" pattern with MA in men (OR: 1.17, 95%CI: 1.92-1.48). The "fruits and vegetables" pattern also showed a direct association with reduced eGFR in women (OR: 1.65, 95%CI: 1.28-2.12), although there was no significance after adjustment. The "fruits and vegetables" and "bakery" DPs were associated with renal dysfunction. The only independent, direct association was between "bakery" DP and MA in men, raising concerns about DP and renal damage in men.

Correction to: PANLAR consensus statement on biosimilars.

The two co-authors of the mentioned above article were incorrect. The correct are authors should have been "P. A. Beltrán" instead of "P. A. B. Roa" and "J. F. Diaz-Coto" instead of "L. Diaz Soto".

PANLAR consensus statement on biosimilars.

INTRODUCTION: Biologics have improved the treatment of rheumatic diseases, resulting in better outcomes. However, their high cost limits access for many patients in both North America and Latin America. Following patent expiration for biologicals, the availability of biosimilars, which typically are less expensive due to lower development costs, provides additional treatment options for patients with rheumatic diseases. The availability of biosimilars in North American and Latin American countries is evolving, with differing regulations and clinical indications. OBJECTIVE: The objective of the study was to present the consensus statement on biosimilars in rheumatology developed by Pan American League of Associations for Rheumatology (PANLAR). METHODS: Using a modified Delphi process approach, the following topics were addressed: regulation, efficacy and safety, extrapolation of indications, interchangeability, automatic substitution, pharmacovigilance, risk management, naming, traceability, registries, economic aspects, and biomimics. Consensus was achieved when there was agreement among 80% or more of the panel members. Three Delphi rounds were conducted to reach consensus. Questionnaires were sent electronically to panel members and comments about each question were solicited. RESULTS: Eight recommendations were formulated regarding regulation, pharmacovigilance, risk management, naming, traceability, registries, economic aspects, and biomimics. CONCLUSION: The recommendations highlighted that, after receiving regulatory approval, pharmacovigilance is a fundamental strategy to ensure safety of all medications. Registries should be employed to monitor use of biosimilars and to identify potential adverse effects. The price of biosimilars should be significantly lower than that of reference products to enhance patient access. Biomimics are not biosimilars and, if they are to be marketed, they must first be evaluated and approved according to established regulatory pathways for novel biopharmaceuticals. KEY POINTS: • Biologics have improved the treatment of rheumatic diseases. • Their high cost limits access for many patients in both North America and Latin America. • Biosimilars typically are less expensive, providing additional treatment options for patients with rheumatic diseases. • PANLAR presents its consensus on biosimilars in rheumatology.

Evaluation of polymorphic variants in apoptotic genes and their role in susceptibility and clinical progression to systemic lupus erythematosus.

Background Systemic lupus erythematosus (SLE) is an autoimmune disease marked by the disruption of the immune homeostasis. Patients exhibit a wide range of clinical manifestations, and environmental and genetic factors are involved in SLE pathogenesis. Evidence suggests that abnormalities in the cellular and molecular events that coordinate apoptosis may favour the generation of autoantigens involved in autoimmunity. In this way, the apoptotic deregulation may be affected by polymorphic variants in apoptotic-related genes. Methods We analyzed FAS, FASL, BCL-2 and BAX polymorphisms in order to correlate to SLE susceptibility and clinical features. A total of 427 SLE patients from the Hospital de Clínicas de Porto Alegre and 543 controls from southern Brazil were evaluated. Results We observed higher frequencies of the FASL -844CC genotype and -844C allele, as well as of the FASL-844C/IVS2nt-124A haplotype in African-derived SLE patients when compared to controls ( P < 0.001). FASL -844C, which is related to high FasL expression, could contribute to increased apoptosis and to the breakdown of immunological tolerance, favouring autoantibody production and inflammation. On the other hand, the BAX -248GA genotype and the -248A allele , related to low protein expression, were observed as a protective factor against SLE in this same population. The rate of apoptosis and cell death was evaluated in peripheral lymphocytes, and SLE patients presented a higher percentage of dead lymphocytes (CD3+Annexin V+ 7-AAD+) compared to the control group. Conclusion Our data support a role for apoptosis in SLE susceptibility.

Matrix metalloproteinase gene polymorphisms and susceptibility to systemic sclerosis.

The major pathological hallmark of the systemic sclerosis (SSc) is skin and internal organ fibrosis, which results from normal tissue architecture alterations and extracellular matrix (ECM) protein deposition. ECM components are degraded by matrix metalloproteinases (MMP). Promoter region polymorphisms in MMP genes may influence gene expression, resulting in an imbalance between ECM protein production and degradation. Here, we analyzed MMP1 -1607 1G/2G (rs1799750), MMP3 -1171 5A/6A (rs3025058), and MMP9 -1562 C/T (rs3918242) polymorphisms in relation to susceptibility to SSc and its clinical features. The patient group included 98 individuals with longstanding or recently diagnosed disease, meeting the American College of Rheumatology or LeRoy and Medsger criteria for SSc; the control group included 100 healthy blood donors. All participants were of European descent. Genotyping was performed by polymerase chain reaction followed by restriction digestion. Genotype and allele frequencies of MMP polymorphisms were similar between the two groups. In secondary analyses, significantly higher frequency of 1G/2G genotype from MMP1 polymorphism was observed for patients testing positive for antinuclear autoantibodies (P = 0.007), while 1G/1G genotype was associated with interstitial lung disease development (P = 0.018). The 6A/6A genotype from MMP3 polymorphism was absent in patients with calcinosis (P = 0.011), while the MMP3 5A/5A genotype correlated with the presence of anti-topoisomerase I antibodies (P = 0.009) and reduced diffusing capacity for carbon monoxide (P = 0.024). These results suggest that MMP polymorphisms are not associated with SSc susceptibility, although MMP1 and MMP3 variants are associated with specific SSc clinical and laboratory features.

Assessment of anti-Müllerian hormone levels in premenopausal patients with systemic lupus erythematosus.

OBJECTIVE: The ovarian reserve of patients with systemic lupus erythematosus (SLE) may be affected by disease activity and medication use. Studies have found that patients with SLE have similar fertility rates as healthy women of the same age. The goal of the present study was to investigate the ovarian reserve of patients with SLE by measuring anti-Müllerian hormone (AMH) levels, and compare it to that of healthy controls. METHOD: This was a case-control study performed on 80 premenopausal women, of whom 40 fulfilled the 1997 American College of Rheumatology (ACR) criteria for SLE and 40 healthy controls paired by oral contraceptive use. Serum concentrations of AMH in peripheral venous blood were measured using a human AMH ELISA kit (CUSABIO, Wuhan, China). RESULTS: AMH serum levels did not differ between patients with SLE and controls (22.79 ± 17.32 ng/ml versus 21.41 ± 16.22 ng/ml, respectively, p = 0.7), even after adjusting for age (21.03 ± 2.074 ng/ml versus 23.97 ± 2.71 ng/ml; p = 0.5). AHM levels were not significantly correlated with disease duration (r = 0.2; p = 0.3), body mass index (r = 0.2; p = 0.2) and disease activity (SLEDAI (r = 0.1; p = 0.7)) and damage indices (SLICC (r = 0.1; p = 0.7)). No associations were found between AMH and ethnicity, current smoking, as well as current or prior use of cyclophosphamide and other immunosuppressants. CONCLUSION: In this cross-sectional study, women with SLE demonstrated similar AMH levels as healthy controls, suggesting preserved ovarian reserve in this population.

Electroconvulsive therapy as a treatment for refractory neuropsychiatric lupus with catatonia: three case studies and literature review.

Neuropsychiatric disorders associated with systemic lupus erythematosus are very common. Treatment generally consists of glucocorticoids and immunosuppressive therapy; however, some cases are unresponsive. Electroconvulsive therapy (ECT) is a recognized treatment modality in psychiatry and is an option for refractory cases of neuropsychiatric lupus. This report describes three cases of neuropsychiatric lupus that improved with ECT after failure of antipsychotics and immunosuppressive therapy. All cases met DSM-5 criteria for catatonia (case 1: agitation, stereotypies, and grimacing; case 2: stupor, mutism, and grimacing; case 3: agitation, mutism, and stereotypies); therefore, ECT was indicated. This case series shows that ECT can be a therapeutic option in patients with neuropsychiatric lupus, especially when associated with catatonia and unresponsive to conventional treatment.

HLA-G +3142 polymorphism as a susceptibility marker in two rheumatoid arthritis populations in Brazil.

In this study, we sought to investigate the genetic influence of two HLA-G 3'-untranslated region (3'-UTR) polymorphisms - 14 bp (rs66554220) and +3142C>G (rs1063320) and their compounding haplotypes in susceptibility to rheumatoid arthritis (RA) in a two-region Brazilian study comprising of 539 patients and 489 controls. All subjects were polymerase chain reaction (PCR) genotyped for the referred polymorphisms and logistic regression models controlling for sex, city and age were performed. Homozygozity for the +3142G allele was associated with an increased risk of RA [odds ratio (OR) = 1.45, 95% confidence interval (CI) = 1.075-1.959, P(Bonf) = 0.030], whereas no association was observed for the 14 bp polymorphism. Haplotype comparisons between patients and controls showed a decreased frequency of the delC haplotype in patients (OR = 0.70, 95% CI = 0.521-0.946, P(Bonf) = 0.040), which remained significant in the rheumatoid factor (RF)-positive group (OR = 0.66, 95% CI = 0.482-0.900, P(Bonf) = 0.018), but not in the RF-negative group. These results corroborate the hypothesis of an involvement of HLA-G in the susceptibility of RA. The +3142G allele is associated with haplotype lineages that share high identity and are regarded as low producers. The presence of the G allele in homozygosis could be responsible for a low HLA-G expression profile that could favor the triggering of RA.

Assessment of nailfold capillaroscopy in systemic sclerosis by different optical magnification methods.

BACKGROUND: Systemic sclerosis (SSc) is characterized by target-organ fibrosis and microvascular dysfunction, which can be assessed using nailfold capillaroscopy. Dermoscopy is a useful and easily performed method for diagnosing skin lesions. AIM: To compare conventional capillaroscopy, using the gold-standard method (conventional stereomicroscope nailfold capillaroscopy; SNFC), with polarized light noncontact dermoscopy (PNCD) and nonpolarized light contact dermoscopy (NPCD), and to evaluate their accuracy in diagnosing characteristic SSc-related alterations. METHODS: The study enrolled 45 patients with SSc. Capillaroscopy images and photographs were taken with three devices, SNFC, NPCD and PNCD, and these images were randomly analysed by a blinded observer. RESULTS: The scleroderma pattern was found in 83% of patients. PNCD and NPCD were highly sensitive in identifying the presence of focal capillary loss (96.4% and 100%, respectively), haemorrhage (96.2% and 92%, respectively), and scleroderma (91.9%, 94.6%), and showed high specificity for haemorrhage and enlarged loops. The intra-observer kappa values for detection of the scleroderma pattern by SNFC images, NPCD and PNCD were moderate to good: (κ = 0.71 (95% CI 0.44-0.95), κ = 0.60 (95% CI 0.35-0.83) and κ = 0.60 (95% CI 0.32-0.86), respectively. Evaluation of haemorrhage presence gave high kappa values for all methods: κ = 0.77 (95% CI 0.57-0.95), κ = 0.90 (95% CI 0.76-1.00) and κ = 0.95 (95% CI 0.85-1.00), respectively. CONCLUSIONS: Both polarized and nonpolarized dermoscopy are reliable methods for valuation of nailfold capillaroscopy in patients with SSc. They are easy to perform, with good rates of accuracy and results that are comparable with traditional capillaroscopy.

CCR5delta32 in systemic lupus erythematosus: implications for disease susceptibility and outcome in a Brazilian population.

The aim of this study was to analyze the allelic and genotypic frequencies of the CCR5delta32 polymorphism in systemic lupus erythematosus (SLE) patients and to investigate a possible association of this allele with SLE susceptibility and clinical outcome. A total of 367 SLE patients and 435 healthy controls were genotyped for the CCR5delta32 polymorphism. We observed that, in European-derived individuals, the frequency of the CCR5delta32 allele was smaller in patients than in controls (2.7% vs. 7.5%, OR 0.34, 95% CI 0.17-0.65, p Bonf=0.002), suggesting that this allele could be considered a protective factor for the disease. Regarding clinical manifestations, we observed that CCR5delta32 female African-derived carrier patients presented a higher predisposition to class IV nephritis when compared with absent nephritis/other class group (13.8% vs. 3.8%, OR 37.1, 95% CI 2.8-1854.7, p Bonf=0.030). A multivariate analysis including all female patients and controlling for the presence or absence of anti-dsDNA antibodies, ethnicity and age at diagnosis showed an increased relative risk of 3.9 times for patients carrying the CCR5delta32 allele to develop class IV nephritis as compared with noncarriers. Our data suggest that the CCR5delta32 allele is a protective factor for the disease in European-derived patients and a susceptibility factor to class IV nephritis in African-derived female patients.

Interleukin-10 gene promoter and NFKB1 promoter insertion/deletion polymorphisms in systemic sclerosis.

Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrotic, immunological and vascular abnormalities. Nuclear factor-kB (NFKB), as a key transcription factor involved in the regulation of immune responses, appears to be a good candidate for studies on the pathogenesis of autoimmune diseases, as well as the interleukin-10 (IL-10) polymorphism, which other studies have suggested an association with SSc. Our objective was to study the association of NFKB and IL-10 gene polymorphisms with SSc. One hundred and fifty-one SSc patients and 147 healthy bone marrow donors were enrolled in a case-control study. Blood was collected for DNA extraction; typing of IL-10 genes was made by polymerase chain reaction with sequence-specific primers (PCR-SSP), and NFKB gene typing was made by restriction fragment length polymorphism (RFLP). Patients underwent clinical evaluation, serology, Doppler echocardiography and chest high-resolution computed tomography. The frequency of IL-10 (-1082) GG genotype was found to be significantly higher in SSc patients (36.4%) as compared to healthy controls (22.4%) (P = 0.012). The frequency of heterozygous genotype GA was significantly lower (P = 0.004) in patients (38.4%) in comparison with control subjects (55.8%). A predominance of the high-producing IL-10 phenotype (GCC(+) /GCC(+) ) was observed in SSc patients compared with healthy controls (37.7% versus 24.5%, respectively; OR: 1.87, 95% CI: 1.10-3.19, P = 0.019). No significant difference was found in the allelic and genotype distribution of the NFKB promoter polymorphism between patients and controls. No statistically significant associations were found between IL-10 or NFKB polymorphisms clinical and laboratory features of SSc. Our results confirmed the association of the high-producing phenotype (GCC(+) /GCC(+) ) with increased risk for SSc, but found no correlation with NFKB polymorphisms.

Metabolic syndrome prevalence is increased in rheumatoid arthritis patients and is associated with disease activity.

OBJECTIVES: To evaluate the prevalence of metabolic syndrome (MetS) in patients with rheumatoid arthritis (RA) vs. controls, and to verify possible associations of MetS with specific disease-related factors. METHODS: The subjects were 283 RA patients and 226 healthy controls, frequency matched by age and sex. MetS was defined according to National Cholesterol Education Program (NCEP) criteria. Disease activity was evaluated with the Disease Activity Score using 28 joints (DAS28). A standardized clinical evaluation was performed and cardiovascular risk factors were assessed. RESULTS: The criteria for MetS were met by 39.2% RA patients vs. 19.5% in the control group (p < 0.001). Increased waist circumference, elevated blood pressure (BP), and fasting glucose were more frequent in RA patients than controls (p < 0.001 for all associations). By multiple logistic regression analysis (adjusted for age, sex, and years at school), the risk of having MetS was significantly higher for RA patients than for controls [odds ratio (OR) 1.87, 95% confidence interval (CI) 1.17-3.00, p = 0.009]. The DAS28 was significantly higher in RA patients with MetS than in those without MetS (3.59 ± 1.27 vs. 3.14 ± 1.53; p = 0.01). Disease duration, the presence of rheumatoid factor, and extra-articular manifestations were similar for patients with and without MetS. CONCLUSIONS: MetS frequency was higher in RA patients than in controls. Among RA patients, MetS was associated with disease activity. The higher prevalence of cardiovascular risk factors in RA suggests that inflammatory processes play a notable role in the development of cardiovascular disease (CVD), and indicates that tight control of systemic inflammatory activity and CVD modifiable risk factors should be recommended.

A combined enrichment/polymerase chain reaction based method for the routine screening of Streptococcus agalactiae in pregnant women

Group B Streptococcus (GBS) is the most common cause of life-threatening infection in neonates. Guidelines from CDC recommend universal screening of pregnant women for rectovaginal GBS colonization. The objective of this study was to compare the performance of a combined enrichment/PCR based method targeting the atr gene in relation to culture using enrichment with selective broth medium (standard method) to identify the presence of GBS in pregnant women. Rectovaginal GBS samples from women at ¡Ý36 weeks of pregnancy were obtained with a swab and analyzed by the two methods. A total of 89 samples were evaluated. The prevalence of positive results for GBS detection was considerable higher when assessed by the combined enrichment/PCR method than with the standard method (35.9% versus 22.5%, respectively). The results demonstrated that the use of selective enrichment broth followed by PCR targeting the atr gene is a highly sensitive, specific and accurate test for GBS screening in pregnant women, allowing the detection of the bacteria even in lightly colonized patients. This PCR methodology may provide a useful diagnostic tool for GBS detection and contributes for a more accurate and effective intrapartum antibiotic and lower newborn mortality and morbidity.

TLR7/8/9 polymorphisms and their associations in systemic lupus erythematosus patients from southern Brazil.

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease and can affect several organs and systems. It is characterized by high production of autoantibodies against nuclear compounds. TLR7/8/9 are responsible for nucleic acid recognition and they trigger proinflammatory responses through activation of NK-kappaB and Type I IFN production, making a bridge between the innate and the adaptative immune systems. We analyzed the frequency of TLR7 rs179008, TLR8 rs3764880, TLR9 rs5743836 and rs352140 in 370 patients with SLE and 415 healthy controls from southern Brazil. All analyses were conducted with regard to gender and ethnicity. Genotypic and allelic frequencies were different for TLR7 rs179008 (0.253 vs. 0.163, p = 0.020 and p = 0.003, OR for T allele: 1.74 CI 95% 1.12-2.70) and TLR9 rs5743836 (0.174 vs. 0.112, p = 0.045 and p = 0.017, OR for C allele: 1.59, CI 95% 0.99-2.57) between European-derived female groups. A higher frequency was observed for the presence of Anti-SSa/Ro for TRL9 rs5743836 C allele carriers (0.228 vs 0.126, Bonferroni corrected p = 0.06). No statistical differences were found for TLR9 haplotypic analyses. We suggest that TLR7 rs179008 and TLR9 rs5743836 can be considered SLE susceptibility factors for women of European descent in our population.

The role of BsmI and FokI vitamin D receptor gene polymorphisms and serum 25-hydroxyvitamin D in Brazilian patients with systemic lupus erythematosus.

Vitamin D deficiency has been described in systemic lupus erythematosus (SLE). BsmI VDR (vitamin D receptor) gene polymorphism was associated with SLE in Asian patients. Studies in Brazilian populations have not been realized. A case-control study with 195 SLE patients and 201 healthy controls was conducted to investigate the influence of BsmI and FokI VDR gene polymorphisms on susceptibility to SLE. In addition, 25-hydroxyvitamin D [25(OH)D] was measured in SLE patients to evaluate possible associations with VDR polymorphic variants and clinical and laboratory expressions of disease. Genotyping was performed by RFLP-PCR. The measurement of 25(OH)D was performed by chemiluminescence. There was no statistically significant difference in genotype and allelic frequencies of BsmI and FokI polymorphisms between European-derived cases and controls. The mean serum levels of 25(OH)D were 25.51 ± 11.43 ng/ml in SLE patients. According to genotype distribution, 25(OH)D concentrations were significantly higher in patients carrying the FokI f/f genotype compared with patients carrying the F/F genotype (31.6 ± 14.1 ng/ml versus 23.0 ± 9.2 ng/ml, p = 0.004), reinforcing its role in the functional activity of VDR. This feature may be considered in future clinical and experimental studies involving vitamin D measurements. Therefore, genetic-specific definitions of ideal levels of vitamin D in SLE need to be established in future studies.

A combined enrichment/polymerase chain reaction based method for the routine screening of Streptococcus agalactiae in pregnant women.

Group B Streptococcus (GBS) is the most common cause of life-threatening infection in neonates. Guidelines from CDC recommend universal screening of pregnant women for rectovaginal GBS colonization. The objective of this study was to compare the performance of a combined enrichment/PCR based method targeting the atr gene in relation to culture using enrichment with selective broth medium (standard method) to identify the presence of GBS in pregnant women. Rectovaginal GBS samples from women at ≥36 weeks of pregnancy were obtained with a swab and analyzed by the two methods. A total of 89 samples were evaluated. The prevalence of positive results for GBS detection was considerable higher when assessed by the combined enrichment/PCR method than with the standard method (35.9% versus 22.5%, respectively). The results demonstrated that the use of selective enrichment broth followed by PCR targeting the atr gene is a highly sensitive, specific and accurate test for GBS screening in pregnant women, allowing the detection of the bacteria even in lightly colonized patients. This PCR methodology may provide a useful diagnostic tool for GBS detection and contributes for a more accurate and effective intrapartum antibiotic and lower newborn mortality and morbidity.

Protective effect of RC-3095, an antagonist of the gastrin-releasing peptide receptor, in experimental arthritis.

OBJECTIVE: To evaluate the antiinflammatory effects of RC-3095 in 2 experimental models of arthritis, collagen-induced arthritis (CIA) and antigen-induced arthritis (AIA), and to determine the mechanisms of action involved. METHODS: RC-3095 was administered daily to mice with CIA and mice with AIA, after induction of disease with methylated bovine serum albumin. Disease incidence and severity were assessed using a clinical index and evaluation of histologic features, respectively. In mice with CIA, gastrin-releasing peptide receptor (GRPR) was detected by immunohistochemical analysis, while in mice with AIA, migration of neutrophils, presence of glycosaminoglycans, and lymphocyte proliferation, determined using the MTT assay, were assessed. Expression of cytokines interleukin-17 (IL-17), IL-1ß, and tumor necrosis factor α (TNFα) was evaluated in all mouse knees using enzyme-linked immunosorbent assay. Treg cell production was assessed by flow cytometry in the joints of mice with AIA. RESULTS: In mice with AIA, administration of RC-3095 reduced neutrophil migration, mechanical hypernociception, and proteoglycan loss. These findings were associated with inhibition of the levels of all 3 proinflammatory cytokines, decreased lymphocyte proliferation, and increased Treg cell numbers. In the CIA model, treatment with RC-3095 led to a significant reduction in arthritis clinical scores and the severity of disease determined histologically. Synovial inflammation, synovial hyperplasia, pannus formation, and extensive erosive changes were all dramatically reduced in the arthritic mice treated with RC-3095. Furthermore, arthritic mice treated with RC-3095 showed a significant reduction in the concentrations of IL-17, IL-1ß, and TNFα, and showed a diminished expression of GRPR. CONCLUSION: These findings suggest that the GRP pathway has a significant role in chronic arthritis, and its inhibition can be explored as a possible therapeutic strategy in rheumatoid arthritis.