Phase I clinical and pharmacokinetic evaluation of the vascular-disrupting agent OXi4503 in patients with advanced solid tumors

Preclinical studies show that OXi4503 (combretastatin A1 diphosphate, CA1P) is more potent than other clinically evaluated vascular-disrupting agents.

Pain and swelling after periapical surgery related to the hemostatic agent used: anesthetic solution with vasoconstrictor or aluminum chloride

To assess pain and swelling in the first 7 days after periapical surgery and their relationship with the agent used for bleeding control.

Squirrel Monkeys (Saimiri sciureus) Infected with the Agent of Bovine Spongiform Encephalopathy Develop Tau Pathology

Squirrel monkeys (Saimiri sciureus) were infected experimentally with the agent of classical bovine spongiform encephalopathy (BSE). Two to four years later, six of the monkeys developed alterations in interactive behaviour and cognition and other neurological signs typical of transmissible spongiform encephalopathy (TSE). At necropsy examination, the brains from all of the monkeys showed pathological changes similar to those described in variant Creutzfeldt-Jakob disease (vCJD) of man, except that the squirrel monkey brains contained no PrP-amyloid plaques typical of that disease. Constant neuropathological features included spongiform degeneration, gliosis, deposition of abnormal prion protein (PrP(TSE)) and many deposits of abnormally phosphorylated tau protein (p-Tau) in several areas of the cerebrum and cerebellum. Western blots showed large amounts of proteinase K-resistant prion protein in the central nervous system. The striking absence of PrP plaques (prominent in brains of cynomolgus macaques [Macaca fascicularis] with experimentally-induced BSE and vCJD and in human patients with vCJD) reinforces the conclusion that the host plays a major role in determining the neuropathology of TSEs. Results of this study suggest that p-Tau, found in the brains of all BSE-infected monkeys, might play a role in the pathogenesis of TSEs. Whether p-Tau contributes to development of disease or appears as a secondary change late in the course of illness remains to be determined.

The vascular-disrupting agent combretastatin impairs splitting and sprouting forms of physiological angiogenesis

Vascular-disrupting agents like combretastatin (CA-4-P), used to attenuate tumor blood flow in vivo, exert anti-mitotic and anti-migratory effects on endothelial cells in vitro. We tested whether anti-vascular or anti-angiogenic effects of CA-4-P are evident with physiological angiogenesis in skeletal muscle (EDL) due to sustained hyperemia (intraluminal splitting) and chronic muscle overload (abluminal sprouting).

Evaluation of cell death mechanisms induced by the vascular disrupting agent OXi4503 during a phase I clinical trial

OXi4503 is a tubulin-binding vascular disrupting agent that has recently completed a Cancer Research UK-sponsored phase I trial. Preclinical studies demonstrated early drug-induced apoptosis in tumour endothelial cells at 1-3 h and secondary tumour cell necrosis between 6 and 72 h.

DEVELOPMENT OF POROUS CONCRETE GEOPOLYMER USING HYDROGEN PEROXIDE AS BLOWING AGENT.

Metakaolin and volcanic ashes respectively called MK and ZG were used as aluminosilicate raw materials for the synthesis of porous geopolymers. The hydrogen peroxide was used as a blowing agent. The geopolymer prepared were characterized by Spectroscopy Fourier Transform Infrared (SFTI), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM) and the determination of some physical properties such as bulk density, total porosity, volume shrinkage, compressive strength and thermal conductivity was also carried out. The presence of pores in the geopolymer obtained is function of the percentage of hydrogen peroxide added, causing the concomitantly decrease in compressive strength, apparent density and thermal conductivity. The use of hydrogen peroxide as a blowing agent gave some thermal insulation properties to these geopolymers which could be close to the properties of some commercial insulation materials.