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Fudin J.,Albany College of Pharmacy and Health Sciences | Fudin J.,Stratton Veterans Administration Medical Center | Fudin J.,The Academy of Management
Drug Topics | Year: 2011

Pain has a high prevalence in medical practice, yet nearly half of all patients do not receive adequate treatment for pain. Although a wide variety of opioids provide effective pain relief, barriers to their use often result in undertreatment, especially for chronic pain. Extended-release products are most useful in treating chronic pain, while rapid-release products are most useful in controlling acute and breakthrough pain. Opioids work as agonists and/or antagonists at endogenous delta, kappa, and mu opioid receptors and mostly belong to one of four chemical categories: phenanthrenes, benzomorphans, phenylpiperidines, or diphenylheptanes. Patients' adverse reactions to the members of one class are often a predictor of how they will react to other members of that class. Opioids such as methadone that block NMDA receptors may be particularly effective in treating neuropathic pain, but the long half-life and polymorphic differences associated with methadone require careful dosing strategies as well as a specifi c method for calculating dosing equivalencies when patients transition to methadone from other opioids. Bone pain, connective tissue pain, and neuropathic pain usually require adjuvant therapies with NSAIDs, anti-infl ammatories, or anticonvulsants, although these medications may increase the risk of undesirable side effects, especially in elderly patients. Risks of opioid therapy include gastrointestinal disorders, hyperalgesia, and addiction/abuse. New "abuse-deterrent" formulations have become available, and FDA's new Risk Evaluation and Mitigation Strategy (REMS) program is currently focused on educating healthcare providers about the risks and appropriate use of extended-release and rapid-onset opioids.


Goyal G.,Creighton University | Mehdi S.A.,Stratton Veterans Administration Medical Center | Ganti A.K.,University of Nebraska Medical Center
ONCOLOGY (United States) | Year: 2015

This article reviews the pathology and current evidence on systemic therapies for the management of advanced salivary gland cancers that are not amenable to local therapy. © 2015, UBM Medica Healthcare Publications. All rights reserved.


Radu F.,Albany College of Pharmacy and Health Sciences | Leggett R.E.,Albany College of Pharmacy and Health Sciences | Leggett R.E.,Stratton Veterans Administration Medical Center | Schuler C.,Stratton Veterans Administration Medical Center | And 3 more authors.
Molecular and Cellular Biochemistry | Year: 2011

To evaluate the protective effects of two naturally occurring antioxidants, α-Lipoic acid and coenzyme Q10 on the response to in vitro ischemia of the rabbit urinary bladder. We measured free fatty acid (FFA) content, phospholipid (PL) content, malondialdehyde (MDA) levels, and phospholipase A 2 activity (PLA) of subcellular compartments. Twenty New Zealand White male rabbits were separated into four groups of five rabbits each. The in vitro whole bladders from Groups 1 and 2 received a 3 h incubation under normal oxygenated physiological conditions. The bladders were stimulated by field stimulation at 1 and 3 h. The bladders from groups 3 and 4 underwent 1 h incubation time under normal oxygenated physiological conditions. After 1 h, the bladders were stimulated with field stimulation. After a maximal pressure response was recorded, the stimulation was turned off and the bath medium changed to one equilibrated with 95% nitrogen, 5% oxygen without glucose (ischemic medium) and incubated for 1 h with field stimulations occurring at 5 min intervals during this time. At the end of this hour of ischemia with repetitive stimulation, the bath was changed to an oxygenated medium with glucose for a 1-h reperfusion period after which the stimulation was repeated. The rabbits from groups 2 and 4 received α-Lipoic acid (10 mg/kg/day) + Coenzyme Q10 (3 mg/kg/day) by gavage for 4 weeks before the experiment. At the end of the experimental period, each bladder was opened longitudinally, and the muscle and mucosa separated by blunt dissection, frozen under liquid nitrogen, and stored at -80°C for biochemical analyses. Each tissue was fractionated by differential centrifugation into nuclear, mitochondrial, synaptosomal, and cytosol (supernatant) components. PL, FFA, MDA, and PLA were analyzed using standard biochemical techniques. Post-ischemic contractility only returned to 30% of control of the untreated group. However, post-ischemic contractility of the treated group returned to approximately 70% of control. PL loss in the muscle mitochondria and synaptosomes was prevented by antioxidant treatment, while the mucosal layer showed a significant drop in PL with antioxidants treatment. Administration of CoQ + LA significantly decreased MDA levels in both control and ischemic tissues in both the muscle and mucosal bladder layers, especially substantial in the microsomal and mitochondrial components. Treatment had variable effects on PLA 2 activity. Treatment of bladder dysfunction with antioxidants daily can be beneficial in man to prevent or delay the onset of progressive loss of bladder function especially that due to ischemic damage to mitochondrial and microsomal lipids. CoQ10 + LA can provide similar protection of the bladder muscle and mucosa against lipid oxidative stress as they have been shown to protect against protein oxidative damage. © 2011 Springer Science+Business Media, LLC.


Radu F.,Albany College of Pharmacy and Health Sciences | Leggett R.E.,Albany College of Pharmacy and Health Sciences | Leggett R.E.,Stratton Veterans Administration Medical Center | Schuler C.,Stratton Veterans Administration Medical Center | And 3 more authors.
Molecular and Cellular Biochemistry | Year: 2011

To evaluate the effects of in vitro ischemia/reperfusion on contractile response to field stimulation (FS), free fatty acid (FFA) content, phospholipid (PL) content, and malondialdehyde (MDA) levels of the rabbit urinary bladder. There is significant evidence that ischemia/reperfusion injury is linked to obstructive bladder dysfunction secondary to men with benign prostatic hyperplasia (BPH). Twelve New Zealand White male rabbits were separated into two groups of six rabbits each. Each rabbit was euthanized, and the bladder was surgically removed intact for whole bladder incubation. The bladders in Group 1 received a 3-h incubation under normal oxygenated physiological conditions. These bladders received electrical field stimulation (32 Hz) after 1 and 3 h. The bladders associated with Group 2 received a 1-h incubation under normal oxygenated physiological conditions. At the end of this 1-h period, the bladders were subjected to FS. After a maximal pressure response was recorded, the stimulation was turned off and the bath medium was changed to one equilibrated with 95% nitrogen, 5% oxygen without glucose (ischemic medium) and incubated for 1 h with field stimulations (32 Hz) occurring at 5-min intervals to represent overactive bladder dysfunction. At the end of this hour of ischemia with repetitive stimulation, the bath was changed to an oxygenated medium with glucose for a 1-h period after which the stimulation was repeated. At the end of the experimental period, each bladder was opened longitudinally and the muscle and mucosa separated by blunt dissection, frozen under liquid nitrogen, and stored at -80°C for biochemical analyses. Each tissue was fractionated by differential centrifugation into nuclear, mitochondrial, synaptosomal, and supernatant (cytosol) components. PL, FFA, and MDA content were analyzed for each fraction using standard biochemical techniques. The bladder contractile responses decreased during the period of in vitro ischemia and returned to only 30% of control after reperfusion. In vitro ischemia/reperfusion showed the following: (1) There was a modest but significant decrease in the FFA content of the microsomes of the muscle and significant increases in the FFA content of the nuclei and mitochondria of the mucosa. (2) There were decreases in the PL content of the homogenate and microsomes of the muscle and decreases in the PL content of the homogenate, microsomes, and supernatant of the mucosa. (3) Significant increases were observed in the MDA levels of the homogenate, mitochondria, and microsomes of both the muscle and mucosa. The significant increases in the lipid peroxidation of the bladder smooth muscle are consistent with the marked decrease in the contractile ability of the bladder following ischemia/reperfusion. The specific increased lipid peroxidation of the mitochondrial and microsomal components is consistent with the specific dysfunctions of the mitochondria and innervations observed following I/R in earlier published studies. The marked increases in lipid peroxidation in the mucosa associated with the loss of PL and FFA from this component are consistent with the significant dysfunction in both the antiadherence and antipermeability properties of the mucosa and may play a major role in the symptomatic nature of I/R-linked diseases of the bladder. © 2010 Springer Science+Business Media, LLC.

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