University of Tennessee Health Science Center

About: University of Tennessee Health Science Center is a education organization based out in Memphis, Tennessee, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 15716 authors who have published 26884 publications receiving 1176697 citations.

Emerging Trends in Oral Delivery of Peptide and Protein Drugs

Abstract: Most peptide and protein drugs are currently used as parenteral formulations because of their poor oral bioavailability. Development of an effective oral delivery system for these macromolecular drugs requires a thorough understanding of their physicochemical properties, such as molecular weight, hydrophobicity, ionization constants, and pH stability, as well as biological barriers that restrict protein and peptide absorption from the gastrointestinal (GI) tract, including pH variability, enzymatic degradation, and membrane efflux. Various strategies currently under investigation include amino acid backbone modifications, formulation approaches, chemical conjugation of hydrophobic or targeting ligand, and use of enzyme inhibitors, mucoadhesive polymers, and absorption enhancers. However, there is only limited success because of the hostile environment of the GI tract--e.g., strong pH extremes and abundant presence of potent luminal enzymes. This review focuses on the challenges posed by the GI system and how different pharmaceutical approaches can be used to make oral delivery of protein and peptide drugs more feasible. The roles of P-glycoprotein and CYP3A4 in controlling the extent of intestinal absorption and metabolism will also be discussed.

Successful intermittent chemoprophylaxis for Pneumocystis carinii pneumonitis.

Abstract: We conducted a prospective, randomized clinical trial over a two-year period in patients with acute lymphocytic leukemia to assess the effectiveness of trimethoprim–sulfamethoxazole given on three consecutive days each week as compared with daily in the prevention of Pneumocystis carinii pneumonitis. P. carinii pneumonitis did not develop in any of 92 patients receiving the drug daily (30,602 patient-days) or in any of 74 who received it three consecutive days a week (27,329 patient-days), whereas the incidence of the infection expected without prophylaxis is 21 percent. One patient, excluded from both groups because of an adverse reaction to sulfonamides in the past, acquired P. carinii pneumonitis. Especially noteworthy was a difference in the occurrence of systemic mycoses, with 10 cases in the daily-treatment group and only 1 case in the three-days-a-week group (P = 0.024). No differences were observed in the rates of other infections or adverse effects associated with the drug. We conclude t...

Contribution of organic cation transporter 2 (OCT2) to cisplatin-induced nephrotoxicity.

Abstract: Cisplatin is one of the most widely used anticancer agents for the treatment of solid tumors. The clinical use of cisplatin is associated with dose-limiting nephrotoxicity, which occurs in one-third of patients despite intensive prophylactic measures. Organic cation transporter 2 (OCT2) has been implicated in the cellular uptake of cisplatin, but its role in cisplatin-induced nephrotoxicity remains unknown. In mice, deletion of Oct1 and Oct2 resulted in significantly impaired urinary excretion of cisplatin without an apparent influence on plasma levels. Furthermore, the Oct1/Oct2-deficient mice were protected from severe cisplatin-induced renal tubular damage. Subsequently, we found that a nonsynonymous single-nucleotide polymorphism (SNP) in the OCT2 gene SLC22A2 (rs316019) was associated with reduced cisplatin-induced nephrotoxicity in patients. Collectively, these results indicate the critical importance of OCT2 in the renal handling and related renal toxicity of cisplatin and provide a rationale for the development of new targeted approaches to mitigate this debilitating side effect.

NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 1.2020.

Abstract: The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic provide recommendations for genetic testing and counseling for hereditary cancer syndromes, and risk management recommendations for patients who are diagnosed with syndromes associated with an increased risk of these cancers. The NCCN panel meets at least annually to review comments, examine relevant new data, and reevaluate and update recommendations. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding criteria for high-penetrance genes associated with breast and ovarian cancer beyond BRCA1/2, pancreas screening and genes associated with pancreatic cancer, genetic testing for the purpose of systemic therapy decision-making, and testing for people with Ashkenazi Jewish ancestry.