University of Louisville

About: University of Louisville is a education organization based out in Louisville, Kentucky, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 24600 authors who have published 49248 publications receiving 1573346 citations. The organization is also known as: UofL.

Best Practice Guide for the Treatment of REM Sleep Behavior Disorder (RBD)

Abstract: Summary of Recommendations: Modifying the sleep environment is recommended for the treatment of patients with RBD who have sleep-related injury. Level A Clonazepam is suggested for the treatment of RBD but should be used with caution in patients with dementia, gait disorders, or concomitant OSA. Its use should be monitored carefully over time as RBD appears to be a precursor to neurodegenerative disorders with dementia in some patients. Level B Clonazepam is suggested to decrease the occurrence of sleep-related injury caused by RBD in patients for whom pharmacologic therapy is deemed necessary. It should be used in caution in patients with dementia, gait disorders, or concomitant OSA, and its use should be monitored carefully over time. Level B Melatonin is suggested for the treatment of RBD with the advantage that there are few side effects. Level B Pramipexole may be considered to treat RBD, but efficacy studies have shown contradictory results. There is little evidence to support the use of paroxetine or L-DOPA to treat RBD, and some studies have suggested that these drugs may actually induce or exacerbate RBD. There are limited data regarding the efficacy of acetylcholinesterase inhibitors, but they may be considered to treat RBD in patients with a concomitant synucleinopathy. Level C The following medications may be considered for treatment of RBD, but evidence is very limited with only a few subjects having been studied for each medication: zopiclone, benzodiazepines other than clonazepam, Yi-Gan San, desipramine, clozapine, carbamazepine, and sodium oxybate. Level C

Melatonin Prevents Death of Neuroblastoma Cells Exposed to the Alzheimer Amyloid Peptide

Abstract: Studies from several laboratories have generated evidence suggesting that oxidative stress is involved in the pathogenesis of Alzheimer’s disease (AD). The finding that the amyloid β protein (Aβ) has neurotoxic properties and that such effects are, in part, mediated by free radicals has provided insights into mechanisms of cell death in AD and an avenue to explore new therapeutic approaches. In this study we demonstrate that melatonin, a pineal hormone with recently established antioxidant properties, is remarkably effective in preventing death of cultured neuroblastoma cells as well as oxidative damage and intracellular Ca2+ increases induced by a cytotoxic fragment of Aβ. The effects of melatonin were extremely reproducible and corroborated by multiple quantitative methods, including cell viability studies by confocal laser microscopy, electron microscopy, and measurements of intracellular calcium levels. The importance of this finding is that, in contrast to conventional antioxidants, melatonin has a proposed physiological role in the aging process. Secretion levels of this hormone are decreased in aging and more severely reduced in AD. The reported phenomenon may be of therapeutic relevance in AD.

Pilocarpine Tablets for the Treatment of Dry Mouth and Dry Eye Symptoms in Patients With Sjögren Syndrome: A Randomized, Placebo-Controlled, Fixed-Dose, Multicenter Trial

Abstract: Background: Patients with Sjogren syndrome (SS) ex- perience slowly progressive infiltration of lacrimal and salivary glands by mononuclear cells. This leads to di- minished secretions, with resultant symptoms of xero- stomia and xerophthalmia. Although pilocarpine hydro- chloride tablets are currently indicated for the treatment of radiation-induced xerostomia, their effects on dry mouth or dry eyes in patients with SS are unclear. Objective: To assess the safety and efficacy of pilocar- pine (Salagen) tablets as symptomatic treatment for dry mouth and dry eyes caused by SS in a multicenter, double- blind, placebo-controlled trial. Methods: After providing written informed consent, 373 patients with primary or secondary SS and clinically sig- nificant dry mouth and dry eyes were randomized to re- ceive 2.5-mg pilocarpine, 5-mg pilocarpine, or placebo tablets 4 times daily for 12 weeks. Symptoms were as- sessed by questionnaires with visual analog scales or cat- egorical checkboxes. Whole-mouth salivary flow rates were measured. Results: A significantly greater proportion of patients in the 5-mg pilocarpine group showed improvement com- pared with the placebo group (P#.01) in global assess- ments of dry mouth, dry eyes, and other symptoms of dryness (P#.05). Salivary flow was significantly in- creased 2- to 3-fold (P,.001) after administration of the first dose and was maintained throughout the 12-week study. The most common adverse effect was sweating, and no serious drug-related adverse experiences were re- ported.

Small-molecule inhibition of 6-phosphofructo-2-kinase activity suppresses glycolytic flux and tumor growth

Abstract: 6-phosphofructo-1-kinase, a rate-limiting enzyme of glycolysis, is activated in neoplastic cells by fructose-2,6-bisphosphate (Fru-2,6-BP), a product of four 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isozymes (PFKFB1-4). The inducible PFKFB3 isozyme is constitutively expressed by neoplastic cells and required for the high glycolytic rate and anchorage-independent growth of ras-transformed cells. We report herein the computational identification of a small-molecule inhibitor of PFKFB3, 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO), which suppresses glycolytic flux and is cytostatic to neoplastic cells. 3PO inhibits recombinant PFKFB3 activity, suppresses glucose uptake, and decreases the intracellular concentration of Fru-2,6-BP, lactate, ATP, NAD+, and NADH. 3PO markedly attenuates the proliferation of several human malignant hematopoietic and adenocarcinoma cell lines (IC50, 1.4-24 micromol/L) and is selectively cytostatic to ras-transformed human bronchial epithelial cells relative to normal human bronchial epithelial cells. The PFKFB3 enzyme is an essential molecular target of 3PO because transformed cells are rendered resistant to 3PO by ectopic expression of PFKFB3 and sensitive to 3PO by heterozygotic genomic deletion of PFKFB3. Importantly, i.p. administration of 3PO (0.07 mg/g) to tumor-bearing mice markedly reduces the intracellular concentration of Fru-2,6-BP, glucose uptake, and growth of established tumors in vivo. Taken together, these data support the clinical development of 3PO and other PFKFB3 inhibitors as chemotherapeutic agents.