Targeting Colorectal Cancer Cells with a Functionalised Calix[4]arene Receptor: Biophysical Studies.

Colorectal cancer (CRC) is a disease which is causing a high degree of mortality around the world. The present study reports the antiproliferative impact of the thioacetamide calix[4]arene, CAII receptor on a highly differentiated Caco-2 cell line. This statement is corroborated by the MTT assay results which revealed a reduction in the cell viability with an IC50 value of 19.02 ± 0.04 µM. Microscopic results indicated that at the starting amount of 10 µM of CAII, a decrease in cells confluency can already be observed in addition to changes in cells morphology. Cell metabolic pathway changes were also investigated. 1H NMR findings showed downregulation in lactate, pyruvate, phosphocholine, lipids, and hydroxybutyrate with the upregulation of succinate, indicating a decline in the cells proliferation. Some biochemical alterations in the cells as a result of the CAII treatment were found by Raman spectroscopy.

Role of carbonic anhydrase II in ectopic calcification.

INTRODUCTION: Osteopontin (OPN) is a potent inhibitor of ectopic calcification. Previous studies suggested that, in addition to blocking apatite crystal growth, OPN promoted regression of ectopic calcification by inducing the expression of acid-generating carbonic anhydrase II (CAR2) in monocyte-derived cells. METHODS: To test this hypothesis, OPN and CAR2 expression and calcification of subcutaneously implanted glutaraldehyde-fixed bovine pericardium (GFBP) were studied in CAR2 mutant mice. RESULTS: Consistent with previous studies in Black Swiss mice, GFBP calcified to a greater extent in OPN-deficient mice compared to wild types on the C57Bl/6 background. GFBP implanted in CAR2-deficient mice (CAR2(-/-)) were significantly more calcified than those implanted into wild-type mice (CAR2(+/+)) [37+/-5 vs. 20+/-6.5 microg Ca/mg tissue, respectively, at 30 days (P<.001), and 42+/-5 versus 20+/-4 microg Ca/mg tissue at 60 days, respectively (P<.001)]. On the other hand, OPN levels within and surrounding the implants were similar in CAR2(+/+) and CAR2(-/-) mice, suggesting that OPN expression in the absence of CAR2 was not sufficient to mitigate ectopic calcification. CONCLUSIONS: These results indicate that CAR2 expression is an important regulator of ectopic calcification, potentially by facilitating OPN mediated mineral regression.

Renal tubular acidosis: developments in our understanding of the molecular basis.

Renal tubular acidosis is a metabolic acidosis due to impaired acid excretion by the kidney. Hyperchloraemic acidosis with a normal anion gap and normal (or near normal) glomerular filtration rate, and in the absence of diarrhoea, defines this disorder. However, systemic acidosis is not always evident and renal tubular acidosis can present with hypokalaemia, medullary nephrocalcinosis and recurrent calcium phosphate stone disease, as well as growth retardation and rickets in children, or short stature and osteomalacia in adults. Renal dysfunction in renal tubular acidosis is not always confined to acid excretion and can be part of a more generalised renal tubule defect, as in the renal Fanconi syndrome. Isolated renal tubular acidosis is more usually acquired, due to drugs, autoimmune disease, post-obstructive uropathy or any cause of medullary nephrocalcinosis. Less commonly, it is inherited and may be associated with deafness, osteopetrosis or ocular abnormalities. The clinical classification of renal tubular acidosis has been correlated with our current physiological model of how the nephron excretes acid, and this has facilitated genetic studies that have identified mutations in several genes encoding acid and base ion transporters. In vitro functional studies of these mutant proteins in cell expression systems have helped to elucidate the molecular mechanisms underlying renal tubular acidosis, which ultimately may lead to new therapeutic options in what is still treatment only by giving an oral alkali.