Ocular surface evaluation in patients treated with a fixed combination of prostaglandin analogues with 0.5% timolol maleate topical monotherapy: a randomized clinical trial

OBJECTIVES:

To compare ocular surface changes induced via glaucoma treatment in patients using fixed combinations of prostaglandin analogues (travoprost, latanoprost and bimatoprost) with 0.5% timolol maleate

METHODS:

A prospective, multicenter, randomized, parallel group, single-blind clinical trial was performed in 33 patients with ocular hypertension or open angle glaucoma who had not been previously treated. The ocular surface was evaluated prior to and three months after treatment, with a daily drop instillation of one of the three medications. The main outcome measurements included the tear film break-up time, Schirmer''s test, Lissamine green staining, the Ocular Surface Disease Index questionnaire, impression cytology using HE and PAS and immunocytochemistry for interleukin-6 and HLA-DR. Ensaiosclinicos.gov.br: UTN - U1111-1129-2872

RESULTS:

All of the drugs induced a significant reduction in intraocular pressure. Decreases in the Schirmer''s test results were observed with all of the drugs. Decreases in tear-film break-up time were noted with travoprost/timolol and latanoprost/timolol. An increase in the Lissamine green score was noted with travoprost/timolol and bimatoprost/timolol. The Ocular Surface Disease Index score increased after treatment in the travoprost/timolol group. Impression cytology revealed a significant difference in cell-to-cell contact in the same group, an increase in cellularity in all of the groups and an increase in the number of goblet cells in all of the groups. The fixed combinations induced an increase in IL-6 expression in the travoprost/timolol group, in which there was also an increase in HLA-DR expression.

CONCLUSIONS:

All of the fixed combinations induced a significant reduction in intraocular pressure, and the travoprost/timolol group showed increased expression of the inflammatory markers HLA-DR and interleukin-6. All three tested medications resulted in some degree of deterioration in the ocular surface after three months of glaucoma treatment.     

Acquired brain injury, visual attention, and the useful field of view test: A pilot study

OBJECTIVE: To compare the findings of the Useful Field of View (UFOV) test with those of conventional neuropsychologic tests to determine the utility of the UFOV test as a measure of attention in a population with brain injury. DESIGN: Cohort study. SETTING: Freestanding rehabilitation hospital. PARTICIPANTS: Fifteen inpatients with severe brain injury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: UFOV test, FIM\T instrument, length of stay (LOS), and standard neuropsychologic testing. RESULTS: The UFOV subtest UF2 correlated strongly with the other 2 subtests, UF1 and UF3. The UF2 subtest correlated most strongly with paper and pencil tests of visual attention. The UF2 predicted 52% of the FIM change and 60% of the LOS variance, second only to admission FIM score, which predicted 75% and 80% of FIM change and LOS variance, respectively. CONCLUSIONS: Among the patients in our study, the UFOV test can be used to determine the visual divided attention of patients with acquired brain injury. The results also showed that the UFOV test correlated with LOS and FIM change in patients with acquired brain injury recovering in a rehabilitation facility. Because the UFOV test is much more quickly administered and scored than other measures of attention and divided attention, these results suggest that the UFOV test may provide an easy means to measure a critical variable in the population with head injury.     

Comparison of C(18)-carboxypropylbetaine and standard N-acetyl-L-cysteine-NaOH processing of respiratory specimens for increasing tuberculosis smear sensitivity in Brazil

Techniques to improve the sensitivity of smear microscopy would facilitate early tuberculosis (TB) diagnosis and disease control, especially in low-income countries where the positive predictive value is high. C(18)-carboxypropylbetaine (CB-18) is a zwitterionic detergent that helps to compensate for the innate buoyancy of mycobacteria, potentially enhancing recovery by centrifugation. Previous data suggest that CB-18 may increase the sensitivity of smear, culture, and molecular amplification diagnostic testing. The goal of the present study was to evaluate if the sensitivity of the smear technique using light microscopy could be improved by treating respiratory samples with CB-18. In the first phase, respiratory specimens were collected consecutively from patients with suspected pulmonary tuberculosis in a tertiary-care hospital in Rio de Janeiro, Brazil (236 specimens were analyzed). After protocol modifications, another 120 respiratory specimens were evaluated. The standard technique was N-acetyl-L-cysteine with sodium hydroxide (NALC-NaOH) treatment, smear concentration with centrifugation, and Ziehl-Neelsen staining. Culture on L?wenstein-Jensen slants was performed on all specimens for use as the "gold standard." No specimens from patients undergoing active TB treatment were included. The initial protocol for CB-18 processing resulted in a sensitivity of 59.6% and specificity of 96.8% compared to standard processing with a sensitivity of 66.0% and specificity of 96.8%. Using the modified protocol, the sensitivity of CB-18 increased to 71.4% with a specificity of 97.0% versus standard processing with a sensitivity of 61.9% and a specificity of 99.0%. The diagnostic yield of acid-fast bacillus smear with CB-18 in the absence of fluorescence microscopy and PCR compared to standard processing with NALC-NaOH was not significantly different, although the power to detect a difference by the modified assay was low.     

Hybridization signatures of gamma-irradiated murine fetal thymus organ culture (FTOC) reveal modulation of genes associated with T-cell receptor V(D)J recombination and DNA repair

In this study, we observed the occurrence of TRBV8.1-DB2.1 V(D)J recombination in murine fetal thymus organ culture (FTOC), in which the thymic microenvironment is mimicked. Since ionizing radiation affects T-cell development, we irradiated FTOCs with gamma rays to evaluate the modulation of genes implicated in TRBV8.1-BD2.1 rearrangements. The nylon cDNA microarray method was employed to monitor the expression of 9216 genes, which were organized in coexpression clusters. Clustering analysis showed similar expression profiling of genes implicated in the V(D)J recombination and DNA double strand break (DSB) repair processes such as XRCC4, RAG-2, Artemis and DNA-PK-cs, thus suggesting overlap between the two processes. The RUNX3 gene, whose coded protein binds to the enhancers of TR genes, was also modulated and the DNA cross-linking LR1 gene, which plays a role in the opening of hairpin DNA structures and whose expression pattern is similar to Artemis, may play a role in the control of V(D)J recombination. Furthermore, our data demonstrate that the FTOC model system and cDNA microarray method are useful tools to evidentiate genes that may play a role in both processes V(D)J recombination and DNA repair.     

Functional characterization of five NR5A1 gene mutations found in patients with 46,XY disorders of sex development

Steroidogenic factor‐1 (SF1), encoded by the NR5A1 gene, is a key regulator of steroidogenesis and reproductive development. NR5A1 mutations described in 46,XY patients with disorders of sex development (DSD) can be associated with a range of conditions of phenotypes; however, the genotype–phenotype correlation remains elusive in many cases. In the present study, we describe the impact of five NR5A1 variants (three novel: p.Arg39Cys, p.Ser32Asn, and p.Lys396Argfs*34; and two previously described: p.Cys65Tyr and p.Cys247*) on protein function, identified in seven patients with 46,XY DSD. In vitro functional analyses demonstrate that NR5A1 mutations impair protein functions and result in the DSD phenotype observed in our patients. Missense mutations in the DNA binding domain and the frameshift mutation p.Lys396Argfs*34 lead to both, markedly affected transactivation assays, and loss of DNA binding, whereas the mutation p.Cys247* retained partial transactivation capacity and the ability to bind a consensus SF1 responsive element. SF1 acts in a dose‐dependent manner and regulates a cascade of genes involved in the sex determination and steroidogenesis, but in most cases reported so far, still lead to a sufficient adrenal steroidogenesis and function, just like in our cases, in which heterozygous mutations are associated to 46,XY DSD with intact adrenal steroid biosynthesis.     

Alpha‐melanocyte stimulating hormone ameliorates disease activity in an induced murine lupus‐like model

Alpha‐melanocyte stimulating hormone (α‐MSH) is a neuropeptide exhibiting anti‐inflammatory activity in experimental models of autoimmune diseases. However, no studies thus far have examined the effects of α‐MSH on systemic lupus erythematosus (SLE). This study aimed to determine the effects of an α‐MSH agonist in induced murine lupus. Here we employed female Balb/cAn mice in which lupus was induced by pristane. Groups of lupus animals were treated daily with the α‐MSH analogue [Nle4, DPhe7]‐α‐MSH (NDP–MSH) (1·25 mg/kg) injected intraperitoneally or saline for 180 days. Normal animals comprised the control group. Arthritis incidence, plasma immunoglobulin (Ig)G isotypes, anti‐nuclear antibodies (ANA) and plasma cytokines were evaluated. Renal function was assessed by proteinuria and histopathological lesion. Glomerular levels of IgG, α‐smooth muscle actin (α‐SMA), inducible nitric oxide synthase (iNOS), C3, CD3, melanocortin receptors (MCR)1, corticotrophin‐releasing factor (CRF) and α‐MSH was estimated by immunohistochemistry. When compared with normal controls, lupus animals exhibited increased arthritis, IgG levels, ANA, interleukin (IL)‐6, IL‐10, proteinuria and mesangial cell proliferation together with glomerular expression of α‐SMA and iNOS. Glomerular expression of MCR1 was reduced in lupus animals. NDP‐MSH treatment reduced arthritis scores by 70% and also diminished IgG1 and IgG2a levels and ANA incidence. In the glomerulus, NDP–MSH treatment reduced cellularity by 50% together with reducing IgG deposits, and expression levels of α‐SMA, iNOS and CRF were also all decreased. Taken together, our results suggest for the first time that α‐MSH treatment improves several parameters of SLE disease activity in mice, and indicate that this hormone is an interesting potential future treatment option.     

Acaricidal properties of the formulations based on essential oils from Cymbopogon winterianus and Syzygium aromaticum plants

The cattle tick, Rhipicephalus (Boophilus) microplus, has caused serious harm to livestock raising in Brazil, considering the costs of controlling it, loss of revenue due to smaller production of milk and meat, and damage to leather, in addition to transmitting diseases. The use of medicinal plants is considered an alternative to the recurring resistance to chemicals. Due to the need for efficient alternatives with less environmental impact, this study aimed to develop contact formulations with essential oils from the Java citronella (Cymbopogon winterianus) and clove (Syzygium aromaticum) plants and to assess in vitro the effects in different stages of the tick cycle. In the present study, concentrations from 0.5–15.0 % of the essential oils incorporated in the formulations were used. The ticks from different geographical areas were treated with those formulations, and their effects on the production levels of eggs, on the larvae hatching, and their efficiency on ticks were assessed. The obtained results were compared with other commercial acaricidal products. After the 20th day of treatment, the formulations with citronella essential oil had 2.09–55.51 % efficiency, depending on the concentration of the oil incorporated. The efficiency of the treatment with formulations containing clove essential oil was higher, from 92.47–100 %. The results showed the acaricidal effects of the formulations tested when compared to commercial chemical products. In vivo studies should be performed in order to assess the efficiency of those formulations in the fields, aiming to use these products as an alternative for controlling cattle ticks.     

Reproducibility of three-dimensional power Doppler placental vascular indices in pregnancies between 26 and 35 weeks

Purpose  

Assess intra and interobserver reproducibility of three-dimensional power Doppler (3DPD) placental vascular indices in normal pregnancies between 26 and 35 weeks.     

Factors associated with survival of very-low-birth-weight infants in a Brazilian fee-paying maternity in the 1990s

This study describes intra-hospital survival rates of very-low-birth-weight infants, as well as factors present at birth associated with survival, during a period of 10 years. This is a Retrospective cohort study performed in a 3rd level nursery at Santa Joana Maternity Hospital, a fee-paying institution in Sao Paulo, Brazil. From January 1991 to December 2000, 963 live-born infants with a birth weight of 500-1499 g, without congenital anomalies, were followed until discharge. Survival was studied according with year of birth, and stratified by birth weight and gestational age. Factors present at birth associated with survival were analyzed by logistic regression. Patient characteristics were: birth weight 500-999 g (38%), gestational ages or=750 g, and gestational age >or=26 weeks.