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Tampa, FL, United States

Benbadis S.R.,University of South Florida | Sanchez-Ramos J.,University of South Florida | Bozorg A.,University of South Florida | Giarratano M.,University of South Florida | And 6 more authors.
Expert Review of Neurotherapeutics | Year: 2014

Constituents of the Cannabis plant, cannabinoids, may be of therapeutic value in neurologic diseases. The most abundant cannabinoids are Δ9-tetrahydrocannabinol, which possesses psychoactive properties, and cannabidiol, which has no intrinsic psychoactive effects, but exhibits neuroprotective properties in preclinical studies. A small number of high-quality clinical trials support the safety and efficacy of cannabinoids for treatment of spasticity of multiple sclerosis, pain refractory to opioids, glaucoma, nausea and vomiting. Lower level clinical evidence indicates that cannabinoids may be useful for dystonia, tics, tremors, epilepsy, migraine and weight loss. Data are also limited in regards to adverse events and safety. Common nonspecific adverse events are similar to those of other CNS 'depressants' and include weakness, mood changes and dizziness. Cannabinoids can have cardiovascular adverse events and, when smoked chronically, may affect pulmonary function. Fatalities are rare even with recreational use. There is a concern about psychological dependence, but physical dependence is less well documented. Cannabis preparations may presently offer an option for compassionate use in severe neurologic diseases, but at this point, only when standard-of-care therapy is ineffective. As more high-quality clinical data are gathered, the therapeutic application of cannabinoids will likely expand. © Informa UK, Ltd.

Niu Y.,University of South Florida | Padhee S.,University of South Florida | Wu H.,University of South Florida | Bai G.,University of South Florida | And 5 more authors.
Chemical Communications | Year: 2011

We report the identification of a new class of antimicrobial peptidomimetics-γ-AApeptides with potent and broad-spectrum activity, including clinically-relevant strains that are unresponsive to most antibiotics. They are also not prone to select for drug-resistance. © The Royal Society of Chemistry 2011.

Padhee S.,University of South Florida | Hu Y.,University of South Florida | Niu Y.,University of South Florida | Bai G.,University of South Florida | And 7 more authors.
Chemical Communications | Year: 2011

We report a new class of peptide mimetics, α-AApeptides, that display broad-spectrum activity against both Gram-negative and Gram-positive bacteria and fungi. With non-hemolytic activity, resistance to protease hydrolysis, and easy sequence programmability, α-AApeptides may emerge as a novel class of antibiotics. © The Royal Society of Chemistry 2011.

Palavicini J.P.,Torrey Pines Institute for Molecular Studies | Wang H.,Torrey Pines Institute for Molecular Studies | Bianchi E.,Institute Pasteur Paris | Xu S.,Florida Institute of Technology | And 3 more authors.
Cell Death and Disease | Year: 2013

We previously demonstrated that overexpression of RanBP9 led to enhanced Aβ generation in a variety of cell lines and primary neuronal cultures, and subsequently, we confirmed increased amyloid plaque burden in a mouse model of Alzheimer's disease (AD). In the present study, we found striking reduction of spinophilin protein levels when RanBP9 is overexpressed. At 12 months of age, we found spinophilin levels reduced by 70% (P<0.001) in the cortex of APΔE9/RanBP9 mice compared with that in wild-type (WT) controls. In the hippocampus, the spinophilin levels were reduced by 45% (P<0.01) in the APΔE9/RanBP9 mice. Spinophilin immunoreactivity was also reduced by 22% (P<0.01) and 12% (P<0.05) in the cortex of APΔE9/RanBP9 and APΔE9 mice, respectively. In the hippocampus, the reductions were 27% (P<0.001) and 14% (P<0.001) in the APΔE9/RanBP9 and APΔE9 mice, respectively. However, in the cerebellum, spinophilin levels were not altered in either APΔE9 or APΔE9/RanBP9 mice. Additionally, synaptosomal functional integrity was reduced under basal conditions by 39% (P<0.001) in the APΔE9/RanBP9 mice and ∼23% (P<0.001) in the APΔE9 mice compared with that in WT controls. Under ATP-and KCl-stimulated conditions, we observed higher mitochondrial activity in the WT and APΔE9 mice, but lower in the APΔE9/RanBP9 mice. Significantly, we confirmed the inverse relationship between RanBP9-N60 and spinophilin in the synaptosomes of Alzheimer's brains. More importantly, both APΔE9 and APΔE9/RanBP9 mice showed impaired learning and memory skills compared to WT controls. These data suggest that RanBP9 might play a crucial role in the loss of spines and synapses in AD. © 2013 Macmillan Publishers Limited All rights reserved. © 2013 Macmillan Publishers Limited All rights reserved.

Woods N.K.,USF Health Byrd Alzheimers Institute | Woods N.K.,University of South Florida | Padmanabhan J.,USF Health Byrd Alzheimers Institute | Padmanabhan J.,University of South Florida
Journal of Biological Chemistry | Year: 2013

Background: Amyloid precursor protein (APP) and ADAM10, main α-secretase involved in generation of secreted APP (sAPPα), are overexpressed in pancreatic cancer. Results: Inhibition of APP processing by ADAM10 prevents anchorage independent growth and survival of cancer cells. Conclusion: Inhibition of sAPPα generation enhances chemotherapeutic potential of gemcitabine. Significance: Supplementing established pancreatic cancer therapy regimen with sAPPα inhibition will significantly improve the efficacy of treatment. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.

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