Clinical and functional characterisation of rheumatic mitral regurgitation in children and adolescents including the brain natriuretic peptide.

Rheumatic fever is a public health problem of universal distribution, predominantly affecting individuals in developing countries. In individuals less than 20 years of age, pure mitral regurgitation is the most commonly found condition in chronic rheumatic valve disease. In the present study, rheumatic mitral regurgitation was assessed in children and adolescents, addressing its clinical (duration of the disease, symptoms, use of benzathine penicillin, and number of outbreaks of the acute phase of rheumatic fever), electrocardiographic (left atrium abnormality and/or left ventricle hypertrophy) and echocardiographic characteristics (left atrium and ventricle measurements, ejection fraction and pulmonary artery pressure), as well as plasma dose of N-terminal portion of the brain natriuretic peptide through electrochemiluminescence immunoassay. Fifty-three patients were studied. The patients had moderate (41.5%) or severe (58.5%) rheumatic mitral regurgitation; had not undergone surgery; were not in the acute phase of the disease; and were being treated at a paediatric cardiology reference hospital in Northeastern Brazil. Mean patient age was 10.6 years (minimum of 3 and maximum of 19 years). With the exception of the ejection fraction, the echocardiographic variables had a significant correlation to the natriuretic peptide, demonstrating that this hormone reflects the haemodynamic consequences of mitral regurgitation. It was concluded that cardiac remodelling that occurs in rheumatic mitral regurgitation in children and adolescents leads to the production of the brain natriuretic peptide, which could be used as a complementary diagnostic tool in the follow-up of such patients.

Symptomatic polyautoimmunity at diagnosis of 1463 childhood-onset lupus: A Brazilian multicenter study.

OBJECTIVE: To evaluate symptomatic polyautoimmunity (PA) at childhood-onset systemic lupus erythematosus(cSLE) diagnosis, and its association with demographic data, disease activity, clinical manifestations and laboratorial abnormalities in a large Brazilian cSLE population. METHODS: A multicenter retrospective study was performed in 1463 cSLE(ACR criteria) patients from 27 Pediatric Rheumatology services. Symptomatic PA was defined according to the presence of more than one concomitant autoimmune disease(AD) and symptomatic multiple autoimmune syndrome(MAS) was defined as three or more AD. An investigator meeting was held to define the protocol. Demographic data, SLICC classification criteria and SLEDAI-2K were evaluated. RESULTS: At cSLE diagnosis symptomatic PA was observed in 144/1463(9.8%) and symptomatic MAS occurred in solely 10/1463(0.7%). In the former group the more frequently observed associated AD were Hashimoto thyroiditis n = 42/144(29%), antiphospholipid syndrome n = 42/144(29%), autoimmune hepatitis n = 26/144(18%) and type 1 diabetes mellitus n = 23/144(15.9%). Further comparisons between cSLE patients with and without PA showed a higher median age(p = 0.016) and lower mean SLICC criteria (p = 0.039) in those with PA. Additionally, these cSLE patients had less renal involvement(35% vs. 44%, p = 0.038) and red blood cell cast(6% vs. 12%, p = 0.042) and more antiphospholipid antibodies(29% vs. 15%, p < 0.0001). CONCLUSIONS: Approximately 10% of cSLE had symptomatic PA at diagnosis, particularly endocrine autoimmune disorders and antiphospholipid syndrome. Lupus was characterized by a mild disease onset and MAS was infrequently evidenced. Further studies are necessary to determine if this subgroup of cSLE patients have a distinct genetic background with a less severe disease and a better long-term outcome.

Echocardiographic findings in infants with presumed congenital Zika syndrome: Retrospective case series study.

OBJECTIVE: To report the echocardiographic evaluation of 103 infants with presumed congenital Zika syndrome. METHODS: An observational retrospective study was performed at Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Recife, Brazil. 103 infants with presumed congenital Zika syndrome. All infants had microcephaly and head computed tomography findings compatible with congenital Zika syndrome. Zika IgM antibody was detected in cerebrospinal fluid samples of 23 infants. In 80 infants, the test was not performed because it was not available at that time. All infants had negative serology for HIV, syphilis, rubella, cytomegalovirus and toxoplasmosis. A complete transthoracic two-dimensional, M-mode, continuous wave and pulsed wave Doppler and color Doppler echocardiographic (PHILIPS HD11XE or HD15) examination was performed on all infants. RESULTS: 14/103 (13.5%) echocardiograms were compatible with congenital heart disease: 5 with an ostium secundum atrial septal defect, 8 had a hemodynamically insignificant small apical muscular ventricular septal defect and one infant with dyspnea had a large membranous ventricular septal defect. The echocardiograms considered normal included 45 infants with a persistent foramen ovale and 16 with a minimum patent ductus arteriosus. CONCLUSIONS: Preliminarily this study suggests that congenital Zika syndrome may be associated with an increase prevalence of congenital heart disease. However the types of defects noted were septal defects, a proportion of which would not be hemodynamically significant.

Rheological Characterization and Safety Evaluation of Non-Ionic Lamellar Liquid Crystalline Systems Containing Retinyl Palmitate.

Retinyl palmitate (RP) is widely used as a special interest ingredient in dermatological formulations to improve the elasticity of the skin and to reduce wrinkles by stimulating collagen synthesis. Nanotechnology-based drug delivery systems, such as liquid crystalline systems (LCSs), can modulate drug permeation into skin and improve the drug action. The effects of such systems on the skin, however, are not completely known. Possible undesirable effects of these formulations on the skin can be detected and interpreted by histopathology and histomorphometry. The objective of this study was to perform a rheological characterization to evaluate the safety of RP used in a lamellar LCS in vitro and in vivo. LCSs containing polyether functional siloxane as a surfactant, silicon glycol copolymer as an oil phase and water at ratios of 60:10:30 and 40:30:30, with (F1v and F2v, respectively) and without (F1 and F2 respectively) RP, were investigated. The rheological characterization was performed using steady shear rate sweep tests and dynamic frequency sweep tests carried out for up to 30 days for various storage temperature conditions (25 ± 2 °C, 37 ± 2 °C and 5 ± 2 °C). Cytotoxic effects were evaluated using J-774 mouse macrophages as a cellular model system. The in vivo tests were conducted on rabbits that had areas of skin treated as follows for 15 days: C (Control); F1; F1v; F2; and F2v. Histomorphometric and histopathological techniques were used to estimate the thicknesses of the epidermis and stratum corneum and the numbers of fibroblasts and leukocytes in the papillary dermis. Mean values were compared by ANOVA, followed by the Tukey test (p < 0.05). The steady shear rate sweep and dynamic frequency sweep tests confirmed the high viscosity of the LCS and the typical pseudo-plastic characteristic of the lamellar system. The RP-unloaded LCS and the RP-loaded LCS did not produce cytotoxicity, nor did they provoke significant thickening of the epidermis and stratum corneum. The number of leukocytes in the treated areas did not change; however, the number of fibroblasts in the area treated with F1v was higher than in the areas treated with the control and F2. The histological analyses demonstrated that none of the formulations irritated the skin and that formulation F1v significantly increased the number of fibroblasts in the dermis, which could result in an increase in the production of collagen.

Mechanisms of buffer therapy resistance.

Many studies have shown that the acidity of solid tumors contributes to local invasion and metastasis. Oral pH buffers can specifically neutralize the acidic pH of tumors and reduce the incidence of local invasion and metastatic formation in multiple murine models. However, this effect is not universal as we have previously observed that metastasis is not inhibited by buffers in some tumor models, regardless of buffer used. B16-F10 (murine melanoma), LL/2 (murine lung) and HCT116 (human colon) tumors are resistant to treatment with lysine buffer therapy, whereas metastasis is potently inhibited by lysine buffers in MDA-MB-231 (human breast) and PC3M (human prostate) tumors. In the current work, we confirmed that sensitive cells utilized a pH-dependent mechanism for successful metastasis supported by a highly glycolytic phenotype that acidifies the local tumor microenvironment resulting in morphological changes. In contrast, buffer-resistant cell lines exhibited a pH-independent metastatic mechanism involving constitutive secretion of matrix degrading proteases without elevated glycolysis. These results have identified two distinct mechanisms of experimental metastasis, one of which is pH-dependent (buffer therapy sensitive cells) and one which is pH-independent (buffer therapy resistant cells). Further characterization of these models has potential for therapeutic benefit.

Theoretical and experimental analysis of electroporated membrane conductance in cell suspension.

An intense electric field can be applied to increase the membrane conductance G(m) and consequently, the conductivity of cell suspension. This phenomenon is called electroporation. This mechanism is used in a wide range of medical applications, genetic engineering, and therapies. Conductivity measurements of cell suspensions were carried out during application of electric fields from 40 to 165 kV/m. Experimental results were analyzed with two electroporation models: the asymptotic electroporation model was used to estimate G(m) at the beginning and at the end of electric field pulse, and the extended Kinosita electroporation model to increase G(m) linearly in time. The maximum G(m) was 1-7 × 10(4) S/m(2), and the critical angle (when the G(m) is insignificant) was 50°-65°. In addition, the sensitivity of electroporated membrane conductance to extracellular and cytoplasmatic conductivity and cell radius has been studied. This study showed that external conductivity and cell radius are important parameters affecting the pore-opening phenomenon. However, if the cell radius is larger than 7 µm in low conductivity medium, the cell dimensions are not so important.

Biphosphonate-induced radiographic changes in two pediatric patients with rheumatic diseases.

Biphosphonates are now being used experimentally in children to increase bone mass, but their long-term effects remain an issue of concern. We report two cases of biphosphonate-induced radiographic changes in children with rheumatic diseases. Our experience supports the view that clinical improvement and radiographic findings after biphosphonate therapy are related to increased bone mineral density, without effects on the inflammatory process itself. Biphosphonates seem to act in rheumatic diseases by reducing bone turnover instead of improving disease activity.