Adipose Tissue-Derived Stem Cells Reduce Acute and Chronic Kidney Damage in Mice

Acute and chronic kidney injuries (AKI and CKI) constitute syndromes responsible for a large part of renal failures, and are today still associated with high mortality rates. Given the lack of more effective therapies, there has been intense focus on the use stem cells for organ protective and regenerative effects. Mesenchymal stem cells (MSCs) have shown great potential in the treatment of various diseases of immune character, although there is still debate on its mechanism of action. Thus, for a greater understanding of the role of MSCs, we evaluated the effect of adipose tissue-derived stem cells (AdSCs) in an experimental model of nephrotoxicity induced by folic acid (FA) in FVB mice. AdSC-treated animals displayed kidney functional improvement 24h after therapy, represented by reduced serum urea after FA. These data correlated with cell cycle regulation and immune response modulation via reduced chemokine expression and reduced neutrophil infiltrate. Long-term analyses, 4 weeks after FA, indicated that AdSC treatment reduced kidney fibrosis and chronic inflammation. These were demonstrated by reduced interstitial collagen deposition and tissue chemokine and cytokine expression. Thus, we concluded that AdSC treatment played a protective role in the framework of nephrotoxic injury via modulation of inflammation and cell cycle regulation, resulting in reduced kidney damage and functional improvement, inhibiting organ fibrosis and providing long-term immune regulation.     

The structure of shallow water fish assemblages in sandy beaches of a tropical bay in the southwestern Atlantic

Ichthyological Research - The spatial and seasonal dynamics of shallow water fish assemblages and their relationship with physical-chemical variables were investigated on Guanabara Bay, one of the...     

Central giant cell lesion of the jaws: study of CCND1 gene amplification and p16INK4a protein levels

Central giant cell lesions (CGCLs) are uncommon benign jaw lesions with uncertain etiology and a variable clinical behavior. In neoplasms, alterations in molecules involved in the G1/S checkpoint are frequently found. Loss of p16^INK4a expression or overexpression of cyclin D1 may stimulate cell proliferation. The purpose of this study was to analyze CCND1 gene amplification and the expression of p16^INK4a in CGCLs. Structural analysis of the CCND1 was performed using chromogenic in situ hybridization. Immmunohistochemistry was used to identify p16^INK4a protein levels. Statistical analysis correlated the two biomarkers with clinical behavior and between each other. Twenty-four lesions were included, being 11 aggressive and 13 non-aggressive. Moderate/high-level CCND1 amplification was found in 12 lesions. Also, immunoreactivity for p16^INK4a was present in 12 cases, mainly in mononuclear cells. There was a significantly higher level of p16^INK4a expression in mononuclear cells of non-aggressive lesions and lesions with moderate/high-level CCND1 amplification in mononuclear cells. It could be speculated that some CGCLs may develop as a true benign neoplasm. The higher expression of p16^INK4a in non-aggressive lesions and in cases with moderate/high-level CCND1 amplification may show that these molecules have a role in CGCLs.     

Comparison of Unplanned Intensive Care Unit Readmission Scores: A Prospective Cohort Study

PurposeEarly discharge from the intensive care unit (ICU) may constitute a strategy of resource consumption optimization; however, unplanned readmission of hospitalized patients to an ICU is associated with a worse outcome. We aimed to compare the effectiveness of the Stability and Workload Index for Transfer score (SWIFT), Sequential Organ Failure Assessment score (SOFA) and simplified Therapeutic Intervention Scoring System (TISS-28) in predicting unplanned ICU readmission or unexpected death in the first 48 hours after discharge from the ICU.MethodsWe conducted a prospective cohort study in a single tertiary hospital in southern Brazil. All adult patients admitted to the ICU for more than 24 hours from January 2008 to December 2009 were evaluated. SWIFT, SOFA and TISS-28 scores were calculated on the day of discharge from the ICU. A stepwise logistic regression was conducted to evaluate the effectiveness of these scores in predicting unplanned ICU readmission or unexpected death in the first 48 hours after discharge from the ICU. Moreover, we conducted a direct accuracy comparison among SWIFT, SOFA and TISS-28 scores.ResultsA total of 1,277 patients were discharged from the ICU during the study period. The rate of unplanned ICU readmission or unexpected death in the first 48 hours after discharge from the ICU was 15% (192 patients). In the multivariate analysis, age (P = 0.001), length of ICU stay (P = 0.01), cirrhosis (P = 0.03), SWIFT (P = 0.001), SOFA (P = 0.01) and TISS-28 (P<0.001) constituted predictors of unplanned ICU readmission or unexpected death. The SWIFT, SOFA and TISS-28 scores showed similar predictive accuracy (AUC values were 0.66, 0.65 and 0.74, respectively; P = 0.58).ConclusionsSWIFT, SOFA and TISS-28 on the day of discharge from the ICU have only moderate accuracy in predicting ICU readmission or death. The present study did not find any differences in accuracy among the three scores.     

Characterization of Early Disease Status in Treatment-Naive Male Paediatric Patients with Fabry Disease Enrolled in a Randomized Clinical Trial

Trial Design

This analysis characterizes the degree of early organ involvement in a cohort of oligo-symptomatic untreated young patients with Fabry disease enrolled in an ongoing randomized, open-label, parallel-group, phase 3B clinical trial.

Methods

Males aged 5–18 years with complete α-galactosidase A deficiency, without symptoms of major organ damage, were enrolled in a phase 3B trial evaluating two doses of agalsidase beta. Baseline disease characteristics of 31 eligible patients (median age 12 years) were studied, including cellular globotriaosylceramide (GL-3) accumulation in skin (n = 31) and kidney biopsy (n = 6; median age 15 years; range 13–17 years), renal function, and glycolipid levels (plasma, urine).

Results

Plasma and urinary GL-3 levels were abnormal in 25 of 30 and 31 of 31 patients, respectively. Plasma lyso-GL-3 was elevated in all patients. GL-3 accumulation was documented in superficial skin capillary endothelial cells (23/31 patients) and deep vessel endothelial cells (23/29 patients). The mean glomerular filtration rate (GFR), measured by plasma disappearance of iohexol, was 118.1 mL/min/1.73 m² (range 90.4–161.0 mL/min/1.73 m²) and the median urinary albumin/creatinine ratio was 10 mg/g (range 4.0–27.0 mg/g). On electron microscopy, renal biopsy revealed GL-3 accumulation in all glomerular cell types (podocytes and parietal, endothelial, and mesangial cells), as well as in peritubular capillary and non-capillary endothelial, interstitial, vascular smooth muscle, and distal tubules/collecting duct cells. Lesions indicative of early Fabry arteriopathy and segmental effacement of podocyte foot processes were found in all 6 patients.

Conclusions

These data reveal that in this small cohort of children with Fabry disease, histological evidence of GL-3 accumulation, and cellular and vascular injury are present in renal tissues at very early stages of the disease, and are noted before onset of microalbuminuria and development of clinically significant renal events (e.g. reduced GFR). These data give additional support to the consideration of early initiation of enzyme replacement therapy, potentially improving long-term outcome.

Trial Registration

ClinicalTrials.gov NCT00701415     

Analysis of the marine ornamental fish trade at Ceará State, northeast Brazil

Brazil is one of the leading exporters of ornamental fishes, mostly freshwater; however, monitoring of the trade is nearly non-existent in the country. This paper provides an initial assessment of a new venture, the marine aquarium fish trade at Ceará State, northeast Brazil, aiming to document the species traded, to provide preliminary estimates of numbers of specimens traded, and to identify priorities in data collection and monitoring. A total of 143 species and 199 304 fishes were traded. From the total, 109 species were native and represented 84% of the fishes traded. Thirty-four exotic species figured on the permits and amounted to nearly 16% of the exports; however, most of them consist of misidentified native species. Nearly 90% of the fish trade was directed to the international market. Official figures represent an underestimation of the total number of captured specimens.     

Dasatinib Reduces Lung Inflammation and Fibrosis in Acute Experimental Silicosis

Silicosis is an occupational lung disease with no effective treatment. We hypothesized that dasatinib, a tyrosine kinase inhibitor, might exhibit therapeutic efficacy in silica-induced pulmonary fibrosis. Silicosis was induced in C57BL/6 mice by a single intratracheal administration of silica particles, whereas the control group received saline. After 14 days, when the disease was already established, animals were randomly assigned to receive DMSO or dasatinib (1 mg/kg) by oral gavage, twice daily, for 14 days. On day 28, lung morphofunction, inflammation, and remodeling were investigated. RAW 264.7 cells (a macrophage cell line) were incubated with silica particles, followed by treatment or not with dasatinib, and evaluated for macrophage polarization. On day 28, dasatinib improved lung mechanics, increased M2 macrophage counts in lung parenchyma and granuloma, and was associated with reduction of fraction area of granuloma, fraction area of collapsed alveoli, protein levels of tumor necrosis factor-α, interleukin-1β, transforming growth factor-β, and reduced neutrophils, M1 macrophages, and collagen fiber content in lung tissue and granuloma in silicotic animals. Additionally, dasatinib reduced expression of iNOS and increased expression of arginase and metalloproteinase-9 in silicotic macrophages. Dasatinib was effective at inducing macrophage polarization toward the M2 phenotype and reducing lung inflammation and fibrosis, thus improving lung mechanics in a murine model of acute silicosis.     

Pervasive defaunation of forest remnants in a tropical biodiversity hotspot

Tropical deforestation and forest fragmentation are among the most important biodiversity conservation issues worldwide, yet local extinctions of millions of animal and plant populations stranded in unprotected forest remnants remain poorly explained. Here, we report unprecedented rates of local extinctions of medium to large-bodied mammals in one of the world's most important tropical biodiversity hotspots. We scrutinized 8,846 person-years of local knowledge to derive patch occupancy data for 18 mammal species within 196 forest patches across a 252,669-km(2) study region of the Brazilian Atlantic Forest. We uncovered a staggering rate of local extinctions in the mammal fauna, with only 767 from a possible 3,528 populations still persisting. On average, forest patches retained 3.9 out of 18 potential species occupancies, and geographic ranges had contracted to 0-14.4% of their former distributions, including five large-bodied species that had been extirpated at a regional scale. Forest fragments were highly accessible to hunters and exposed to edge effects and fires, thereby severely diminishing the predictive power of species-area relationships, with the power model explaining only ～9% of the variation in species richness per patch. Hence, conventional species-area curves provided over-optimistic estimates of species persistence in that most forest fragments had lost species at a much faster rate than predicted by habitat loss alone.