ABSTRACT
BACKGROUND: Edema represents one of the earliest negative markers of survival and consecutive neurological deficit following stroke. The mixture of cellular and vasogenic edema makes treating this condition complicated, and to date, there is no pathogenically oriented drug treatment for edema, which leaves parenteral administration of a hypertonic solution as the only non-surgical alternative. OBJECTIVE: New insights into water metabolism in the brain have opened the way for molecular targeted treatment, with aquaporin 4 channels (AQP4) taking center stage. We aimed here to assess the effect of inhibiting AQP4 together with the administration of a neurotropic factor (Cerebrolysin) in ischemic stroke. METHODS: Using a permanent medial cerebral artery occlusion rat model, we administrated a single dose of the AQP4 inhibitor TGN-020 (100 mg/kg) at 15 minutes after ischemia followed by daily Cerebrolysin dosing (5ml/kg) for seven days. Rotarod motor testing and neuropathology examinations were next performed. RESULTS: We showed first that the combination treatment animals have a better motor function preservation at seven days after permanent ischemia. We have also identified distinct cellular contributions that represent the bases of behavior testing, such as less astrocyte scarring and a larger neuronalsurvival phenotype rate in animals treated with both compounds than in animals treated with Cerebrolysin alone or untreated animals. CONCLUSION: Our data show that water diffusion inhibition and Cerebrolysin administration after focal ischemic stroke reduces infarct size, leading to a higher neuronal survival in the peri-core glial scar region.
Subject(s)
Amino Acids/antagonists & inhibitors , Aquaporin 4/antagonists & inhibitors , Brain Ischemia/drug therapy , Neuroprotective Agents/pharmacology , Recovery of Function/drug effects , Stroke/drug therapy , Amino Acids/metabolism , Animals , Aquaporin 4/metabolism , Brain Edema/drug therapy , Brain Edema/etiology , Disease Models, Animal , Infarction, Middle Cerebral Artery/complications , Male , Rats, Sprague-Dawley , Stroke/complications , Stroke/metabolismABSTRACT
BACKGROUND: Bladder cancer (BC) currently accounts for 5% of all malignancies and the most common tumor of the urinary tract. Diagnosis of bladder cancer is based on urine cytology and white-light cystoscopy (WLC) performed for patients with suspected bladder mass and÷or hematuria. Recent studies suggest that using the fluorescence photodynamic diagnosis (PDD) significantly improves diagnostic sensitivity with a positive influence upon the recurrence rate of bladder cancer. OBJECTIVE: To evaluate the diagnostic efficiency and long-term influence upon the tumor recurrence rate for patients with non-muscle-invasive bladder cancer (NMIBC) undergoing hexaminolevulinate PDD compared to standard WLC. PATIENTS, MATERIALS AND METHODS: Between 2009 and 2011, 113 primary NMIBC patients were enrolled in our prospective study and randomized in two parallel groups: 57 patients in the study group (PDD) and 56 patients in the control group (WLC). All patients had primary Ta÷T1 NMIBC with good life expectancy and no significant bladder outlet obstruction [postvoid residual urine volume (PVR) <100 mL]. RESULTS: Fluorescence cystoscopy examination identified 26.3% more tumors than the conventional examination (p=0.034) in the PDD group. Tumor recurrence rate analysis proved a significant reduction by up to 20% after five years of follow-up by using PDD [hazard ratio (HR) 0.566, 95% confidence interval (CI) 0.343-0.936; p=0.0267]. CONCLUSIONS: The use of PDD for patients with NMIBC results in a significant 26% diagnostic sensitivity improvement as well as superior patient prognosis and quality of life following conservative treatment by reducing the tumor recurrence rate with up to 20% after five years of follow-up.
