Haematological and biochemical parameters in Churra-da-Terra-Quente ewes from the northeast of Portugal

Hematological and biochemical parameters, including plasma electrolytes and thyroid hormones, were determined in 73 clinically healthy Churra-da-Terra-Quente ewes, a typical breed from the northeast of Portugal. The hemogram values were: erythrocytes 9.8±1.51012/L; haemoglobin 118.1±19.1g/L; haematocrit 40.8±5.9%; leukocytes 5.7±1.8109/L; and platelets 544.3±177.2109/L. The thrombin time was 17.3±1.7 seconds. The values of biochemical parameters were: total protein 76.4±6.1g/L; glucose 2.87±0.60mmol/L; total cholesterol 1.65±0.33mmol/L; aspartate aminotransferase 155.9±49.2U/L; alanine aminotransferase 23.2±9.6U/L; γ-glutamyl transferase 48.0±18.7U/L; total alkaline phosphatase 121.6±76.1U/L; glutamate dehydrogenase 6.4±3.7U/L; urea 7.32±2.22mmol/L; creatinine 123.0±54.1μmol/L; total calcium 2.53±0.25mmol/L; phosphorus 2.10±0.46mmol/L; magnesium 1.01±0.09mmol/L; sodium 152.04±3.65mmol/L; potassium 4.7±0.4mmol/L; ionized calcium 1.32±0.07mmol/L; total thyroxine 111.75±42.29nmol/L; total triiodothyronine 1.01±0.28nmol/L; free T4 11.93±1.78pmol/L; free T3 4.22±1.33pmol/L; and thyroid-stimulating hormone 0.18±0.19μIU/mL. Although differences among the Churra-da-Terra-Quente breed and other breeds may occur, the hematological and biochemical parameters, plasma electrolytes, and thyroid hormones, for this indigenous breed, were generally situated within the reference intervals previously reported for sheep

Estrogen related receptor alpha in castration-resistant prostate cancer cells promotes tumor progression in bone

Bone metastases are one of the main complications of prostate cancer and they are incurable. We investigated whether and how estrogen receptor-related receptor alpha (ERRα) is involved in bone tumor progression associated with advanced prostate cancer. By meta-analysis, we first found that ERRα expression is correlated with castration-resistant prostate cancer (CRPC), the hallmark of progressive disease. We then analyzed tumor cell progression and the associated signaling pathways in gain-of-function/loss-of-function CRPC models in vivo and in vitro. Increased levels of ERRα in tumor cells led to rapid tumor progression, with both bone destruction and formation, and direct impacts on osteoclasts and osteoblasts. VEGF-A, WNT5A and TGFβ1 were upregulated by ERRα in tumor cells and all of these factors also significantly and positively correlated with ERRα expression in CRPC patient specimens. Finally, high levels of ERRα in tumor cells stimulated the pro-metastatic factor periostin expression in the stroma, suggesting that ERRα regulates the tumor stromal cell microenvironment to enhance tumor progression. Taken together, our data demonstrate that ERRα is a regulator of CRPC cell progression in bone. Therefore, inhibiting ERRα may constitute a new therapeutic strategy for prostate cancer skeletal-related events

Serum intact parathyroid hormone levels in cats with chronic kidney disease

Chronic kidney disease (CKD) is frequently observed in cats and it is characterized as a multisystemic illness, caused by several underlying metabolic changes, and secondary renal hyperparathyroidism (SRHPT) is relatively common; usually it is associated with the progression of renal disease and poor prognosis. This study aimed at determining the frequency of SRHPT, and discussing possible mechanisms that could contribute to the development of SRHPT in cats at different stages of CKD through the evaluation of calcium and phosphorus metabolism, as well as acid-base status. Forty owned cats with CKD were included and divided into three groups, according to the stages of the disease, classified according to the International Renal Interest Society (IRIS) as Stage II (n=12), Stage III (n=22) and Stage IV (n=6). Control group was composed of 21 clinically healthy cats. Increased serum intact parathyroid hormone (iPTH) concentrations were observed in most CKD cats in all stages, and mainly in Stage IV, which hyperphosphatemia and ionized hypocalcemia were detected and associated to the cause for the development of SRHPT. In Stages II and III, however, ionized hypercalcemia was noticed suggesting that the development of SRHPT might be associated with other factors, and metabolic acidosis could be involved to the increase of serum ionized calcium. Therefore, causes for the development of SRHPT seem to be multifactorial and they must be further investigated, mainly in the early stages of CKD in cats, as hyperphosphatemia and ionized hypocalcemia could not be the only factors involved

Direct evidence for Epithelial-Mesenchymal transitions in breast cancer

We developed stromal- and epithelial-specific cre-transgenic mice to directly visualize epithelial-mesenchymal transition (EMT) during cancer progression in vivo. Using three different oncogene-driven mouse mammary tumor models and cell-fate mapping strategies, we show in vivo evidence for the existence of EMT in breast cancer and show that myc can specifically elicit this process. Hierarchical cluster analysis of genome-wide loss of heterozygosity reveals that the incidence of EMT in invasive human breast carcinomas is rare, but when it occurs it is associated with the amplification of MYC. These data provide the first direct evidence for EMT in breast cancer and suggest that its development is favored by myc-initiated events