Lio Gonçalves

Abstract
Background/Aim: This study aimed to evaluate the in vitro efficacy of carboplatin and piroxicam, both in isolation and combined, against T24 and 5637 human urinary bladder cancer cell lines. Materials and Methods: Cell viability, drug interaction, cell morphology, cell proliferation, apoptosis and autophagy were analyzed after 72 h of drug exposure. Statistical analysis was performed and values of p<0.05 were considered statistically significant. Results: Drug exposure in combination led to a significant reduction of cell viability comparatively to single-drug exposure. These combinations resulted in a synergistic interaction in the T24 (combination index for 50% effect (CI50)=0.65) and 5637 (CI50=0.17) cell lines. Notable increase of morphological alterations, a marked decrease of Ki-67 expression, a considerable enhancement of autophagic vacuoles and a minimal effect on apoptosis was observed in both cell lines treated with combined drugs. Conclusion: Data showed that in vitro combination of carboplatin and piroxicam produced a more potent antiproliferative effect when compared to single drugs.

Abstract
Elbow joint incongruity is recognized as an important factor in the development, treatment, and prognosis of canine elbow dysplasia. Elbow incongruity has been measured based on radiographic joint space widths, however these values can be affected by the degree of elbow joint flexion. Recent studies have reported radiographic curvature radii asmore precise measures of humeroulnar congruity in dogs. The aim of this prospective observational study was to describe radiographic curvature radii measured from flexed and extended elbow radiographs for a sample of dogs representing a medium breed (Portuguese Pointing Dog) and a large breed (Estrela Mountain Dog). The curvature radii from the ulnar trochlear notch and humeral trochlea were measured in 114 mediolateral elbow extended radiographic views (30 Portuguese Pointing Dog and 27 Estrela Mountain Dog), and 84 mediolateral flexed views (22 Portuguese Pointing Dog and 20 Estrela Mountain Dog). The sampled animals' ages ranged from 12 to 84 months (34.6 +/- 17.8 months). Good agreement was observed between curvature radii measurements for flexed vs. extended views in both breed groups. Ulnar trochlear notch curvature radii measurements were greater than humeral trochlea curvature radii measurements in both breed groups. Both curvature radii were greater in the large-breed dog group vs. the medium-breed dog group. Both breed groups had ulnar and humeral curves with similar typology. However, the large breed group had greater intermediate differences between the humeroulnar surface curvature radii. Results from this study supported the use of curvature radii as measures of humeroulnar congruity in mediolateral flexed elbow radiographs of medium and large breed dogs.

Abstract
The present work proposed to study the oxygen uptake slow component (VO2 SC) of breaststroke swimmers at four different intensities of submaximal exercise, via mathematical modeling of a multi-exponential function. The slow component (SC) was also assessed with two different fixed interval methods and the three methods were compared. Twelve male swimmers performed a test comprising four submaximal 300 m bouts at different intensities where all expired gases were collected breath by breath. Multi-exponential modeling showed values above 450 ml.min-1 of the SC in the two last bouts of exercise (those with intensities above the lactate threshold). A significant effect of the method that was used to calculate the VO2 SC was revealed. Higher mean values were observed when using mathematical modeling compared with the fixed interval 3rd min method (F=7.111; p=0.012; eta 2=0.587); furthermore, differences were detected among the two fixed interval methods. No significant relationship was found between the SC determined by any method and the blood lactate measured at each of the four exercise intensities. In addition, no significant association between the SC and peak oxygen uptake was found. It was concluded that in trained breaststroke swimmers, the presence of the VO2 SC may be observed at intensities above that corresponding to the 3.5 mM-1 threshold. Moreover, mathematical modeling of the oxygen uptake on-kinetics tended to show a higher slow component as compared to fixed interval methods.

Abstract
Background/Aim: In this study, we evaluated the dimensions and volume of rat mammary tumors and the association of these variables with tumor invasiveness. Materials and Methods: Tumors were measured by caliper and ultrasonography. Volume was determined by water displacement and by application of four formulas using tumor length (L), width (W) and depth (D) or tumor weight. Results: Results confirmed the data obtained in our previous work, where we verified that mammary tumors grow as oblate spheroids. Conclusion: The determination of mammary tumor volume by applying the formula V=(4/3) x pi x(L/2) x(L/2) x(D/2) is the best way to evaluate tumor volume in vivo. Beyond volume evaluation by water displacement, the determination on the basis of tumor weight is the most accurate way to evaluate tumor volume after animal sacrifice or tumor excision. According to our results, it is not possible to predict if a tumor is invasive or non-invasive by its dimensions, volume or weight. Future work in chemically-induced mammary cancer should use ultrasonography and water displacement or tumor weight to determine tumor volume in vivo and after animal sacrifice or tumor excision, respectively.

Abstract
To evaluate the in vitro effects of sunitinib malate and meloxicam in isolation, and to analyse the ability of meloxicam to enhance the cytotoxicity of sunitinib malate in three human bladder-cancer call lines. Cell lines were treated with sunitinib malate and meloxicam, either in isolation or combined. Leishman staining, MTT method, comet assay, MDC staining and M30 CytoDEATH antibody were performed. The Chou and Talalay method was applied. Sunitinib malate and meloxicam supressed cell proliferation in bladder-cancer cells in isolation, in a concentration-dependent manner. Treatment of bladder-cancer cells with a combination of sunitinib malate and meloxicam showed a synergistic effect. When exploring the mechanism of this combination by means of comet assay, there is the suggestion that meloxicam increases sunitinib malate cytotoxicity through DNA damage. Autophagic and apoptotic studies show a greater incidence of autophagic vacuoles and early apoptotic cells when the combined treatment was put into use. In isolation, sunitinib malate and meloxicam demonstrated anti-tumor effects in our study. Furthermore, simultaneous exposure of cells to sunitinib malate and meloxicam provided a combinatorial beneficial effect. This hints at the possibility of a new combined therapeutic regimen, which could lead to improvements in the treatment of patients with bladder cancer.