Induction of cancer cell death by apoptosis and slow release of 5-fluoracil from metal-organic frameworks Cu-BTC

This study aimed to evaluate the mechanism associated with cytotoxic activity displayed by the drug 5-fluorouracil incorporated in Cu-BTC MOF and its slow delivery from the Cu-BTC MOF. Structural characterization encompasses elemental analysis (CHNS), differential scanning calorimetry (DSC), thermogravimetric analysis (TG/DTG), Fournier transform infrared (FIT-IR) and X-ray diffraction (XRD) was performed to verify the process of association between the drug 5-FU and Cu-BTC MOF. Flow cytometry was done to indicate that apoptosis is the mechanism responsible for the cell death. The release profile of the drug 5-FU from Cu-BTC MOF for 48 hours was obeisant. Also, the anti-inflammatory activity was evaluated by the peritonitis testing and the production of nitric oxide and pro-inflammatory cytokines were measured. The chemical characterization of the material indicated the presence of drug associated with the coordination network in a proportion of 0.82 g 5-FU per 1.0 g of Cu-BTC MOF. The cytotoxic tests were carried out against four cell lines: NCI-H292, MCF-7, HT29 and HL60. The Cu-BTC MOF associated drug was extremely cytotoxic against the human breast cancer adenocarcinoma (MCF-7) cell line and against human acute promyelocytic leukemia cells (HL60), cancer cells were killed by apoptosis mechanisms. The drug demonstrated a slow release profile where 82% of the drug was released in 48 hours. The results indicated that the drug incorporated in Cu-BTC MOF decreased significantly the number of leukocytes in the peritoneal cavity of rodents as well as reduced levels of cytokines and nitric oxide production.     

MR susceptometry: an external-phantom method for measuring bulk susceptibility from field-echo phase reconstruction maps

A novel method for estimating the susceptibility of an object by using the magnetic resonance (MR) imaging field distortions in an external-reference water bath next to the object is described. The field measurement was obtained with a phase reconstruction from a gradient-echo acquisition. A field model of an arbitrary object in a static magnetic field was discretely calculated from geometry determined from the magnitude reconstruction. Least-squares estimation yields the susceptibility of the object. Required (and proven) assumptions include validity of superposition, object homogeneity, negligible higher-order field terms, field-model accuracy, geometric-model accuracy, and correlation of gradient-echo phase to field distortion. MR susceptometry estimation of phantoms yielded susceptibility estimates that correlated well with known values (r >.9975). This MR susceptometry method is a first step toward quantitation of iron levels through MR imaging phase information in patients with iron overload.     

Assessing the evolution of publications by Brazilian spine surgeons in the last decade

Purpose

To evaluate the scientific contribution of Brazilian Spine Surgeons not only in number of publications but also in their quality between January 2000 to December 2011.

Methods

A literature search of publications by Brazilian spinal surgeons on topics concerning the spine or spinal cord was performed using an online database; Pubmed.gov. The results were limited to articles published from January 2000 to December 2011. A total of 1,778 articles were identified after a Medline search. After exclusion criteria, the study comprised 206 articles. The quality of the Journals was assessed with IF and the article quality using the Oxford classification.

Results

An increasing number of publications by Brazilian spine surgeons was observed in recent years: 45.1 % of those papers were published during the last 4 years (2008–2011). Clinical studies and case reports were the most frequent types of article published (37.5 vs 31.1 %). An increasing number of Brazilian publications in non-Brazilian journals has been observed in recent years (linear-by-linear association: 5.449, P = 0.020). The Arquivos de Neuro-Psiquiatria was the most frequent journal in which the papers were published (N = 67, 32 %). The IF of the publications varied from 0.021 to 8.017. The analysis of quality of the articles using the Oxford classification demonstrated that most of them provided LOE 4 (N = 113, 54.9 %) or 5 (N = 45, 21.8 %).

Conclusions

There have been an increasing number of publications by Brazilian spine surgeons in recent years and the quality of the articles published has improved. Also the number of publications by Brazilians in non-Brazilian journals has increased in recent years.     

D1 dopamine receptor signaling involves caveolin-2 in HEK-293 cells

BACKGROUND: Dopamine receptors in the kidney, especially those belonging to the D1-like receptor family, are important in the regulation of renal function and blood pressure. Because of increasing evidence that G protein-coupled receptors (GPCRs) are associated with caveolae and lipid rafts, we tested the hypothesis that the D1 dopamine receptor (D1R) and signaling molecules are regulated by caveolin in caveolae or lipid rafts. METHODS: Six experimental approaches were used: (1) construction of tagged human D1Rs (hD1Rs) and transfectants; (2) cell culture [human embryonic kidney (HEK)-293 and immortalized rat renal proximal tubule cells] and biotinylation; (3) cell fractionation by sucrose gradient centrifugation; (4) immunoprecipitation and immunoblotting; (5) immunofluorescence and confocal microscopy; and (6) adenylyl cyclase assays. RESULTS: hD1Rs, heterologously expressed in HEK-293 cells, formed protein species with molecular mass ranging from 50 to 250 kD, and were localized in lipid rafts and nonraft plasma membranes. The hD1Rs cofractionated with caveolin-2, G protein subunits, and several signaling molecules. Both exogenously expressed hD1Rs and endogenously expressed rat D1Rs colocalized and coimmunoprecipitated with caveolin-2. A D1R agonist (fenoldopam) increased the amount of caveolin-2beta associated with hD1Rs and activated adenylyl cyclase to a greater extent in lipid rafts than in nonraft plasma membranes. Reduction in the expression of caveolin-2 with antisense oligonucleotides attenuated the stimulatory effect of fenoldopam on cyclic adenosine monophosphate (cAMP) accumulation. CONCLUSION: The majority of hD1Rs are distributed in lipid rafts. Heterologously and endogenously expressed D1Rs in renal cells are associated with and regulated by caveolin-2.     

Minimum 10 Year Survivorship Analysis of a Partially Coated Hydroxyapatite Tapered Femoral Stem in Elderly Patients With an Average Age Over 75

This is a retrospective, non-comparative study of 212 consecutive patients who underwent Total Hip Arthroplasty with an uncemented hydroxyapatite (HA) coated stem system from November 1997 to March 2000. The objective of the study was to analyze the performance of the implant at a minimum of 10 years in older patients (mean age 79.6 years). The Kaplan-Meier survivorship of the femoral stem at 10 years was 100%, and 97.5% for the whole prosthesis. The mean Merle d'Aubigné clinical score improved from 4.4 ± 2.1 points pre-operatively to 13.39 ± 3.77 points at final follow-up (p < 0.05), and the mean VAS score for thigh pain was 1.25. The radiographic analysis showed that there were no significant radiolucent lines or osteolysis compromising the fixation of the implant.