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Item Effects of electrical stimulation and testosterone on regeneration-associated gene expression and functional recovery in a rat model of sciatic nerve crush injury(2014) Meadows, Rena Marie; Xu, Xiao-Ming; Chen, Jinhui; Jones, Kathryn J.; White, Fletcher A.Although peripheral motoneurons are phenotypically endowed with robust regenerative capacity, functional recovery is often suboptimal following peripheral nerve injury (PNI). Research to date indicates that the greatest success in achieving full functional recovery will require the use of a combinatorial approach that can simultaneously target different aspects of the post-injury response. In general, the concept of a combinatorial approach to neural repair has been established in the scientific literature but has yet to be successfully applied in the clinical situation. Emerging evidence from animal studies supports the use of electrical stimulation (ES) and testosterone as one type of combinatorial treatment after crush injury to the facial nerve (CN VII). With the facial nerve injury model, we have previously demonstrated that ES and testosterone target different stages of the regeneration process and enhance functional recovery after facial nerve crush injury. What is currently unknown, but critical to determine, is the impact of a combinatorial treatment strategy of ES and testosterone on functional recovery after crush injury to the sciatic nerve, a mixed sensory and motor spinal nerve which is one of the most serious PNI clinical problems. The results of the present study indicate that either treatment alone or in combination positively impact motor recovery. With regard to molecular effects,single and combinatorial treatments differentially alter the expression of regeneration-associated genes following sciatic nerve crush injury relative to facial nerve injury. Thus, our data indicate that not all injuries equally respond to treatment. Furthermore, the results support the importance of treatment strategy development in an injury-dependent manner and based upon the functional characteristics of spinal vs. cranial nerves.Item Effects of Sex Hormones on Ocular Blood Flow and Intraocular Pressure in Primary Open Angle Glaucoma: A Review(Wolters Kluwer, 2018-10) Patel, Pooja; Harris, Alon; Toris, Carol; Lang, Matthew; Tobe, Leslie; Belamkar, Aditya; Ng, Adrienne; Verticchio Vercellin, Alice C.; Matthew, Sunu; Siesky, Brent; Ophthalmology, School of MedicinePrimary open-angle glaucoma (POAG) is a multifactorial optic neuropathy characterized by progressive retinal ganglion cell death and visual field loss. Some speculate that gender plays a role in the risk of developing POAG and that the physiologic differences between men and women may be attributed to the variable effects of sex hormones on intraocular pressure (IOP), ocular blood flow, and/or neuroprotection. Estrogen, in the form of premenopausal status, pregnancy, and post-menopausal hormone therapy is associated with increase in ocular blood flow, decrease in IOP and neuroprotective properties. The vasodilation caused by estrogen and its effects on aqueous humor outflow may contribute. On the other hand, although testosterone may have known effects in the cardiovascular and cerebrovascular systems, there is no consensus as to its effects in ocular health or POAG. With better understanding of sex hormones in POAG, sex hormone-derived preventative and therapeutic considerations in disease management may provide for improved gender-specific patient care.Item Relations of Sex Hormone Levels to Leukocyte Telomere Length in Black, Hispanic, and Asian/Pacific Islander Postmenopausal Women(Wiley, 2017) Song, Yan; Cho, Michele; Brennan, Kathleen; Chen, Brian H.; Song, Yiqing; Manson, JoAnn E.; Hevener, Andrea L.; You, Nai-Chieh Y.; Butch, Anthony W.; Liu, Simin; Department of Epidemiology, Richard M. Fairbanks School of Public HealthBackground Sex hormones may play important roles in sex-specific biological aging. We specifically examined the associations between circulating concentrations of sex hormones and leukocyte telomere length (TL). Methods We conducted a cross-sectional study of 1124 black, 444 Hispanic, and 289 Asian/Pacific Islander women in the Women's Health Initiative Observational Cohort. Concentrations of estradiol and testosterone were measured using electrochemiluminescence immunoassays. TL was measured using quantitative PCR. Results Women included in the study were 50 to 79 years of age. Levels of estradiol were not significantly associated with TL in this sample of women. The associations between total and free testosterone and TL differed by race/ethnicity (P for interaction = 0.03 for total testosterone and 0.05 for free testosterone). Total and free testosterone concentrations were not associated with TL in black and Hispanic women, whereas in Asian/Pacific Islanders, their concentrations were inversely associated with TL (P-trend = 0.003 for both). These associations appeared robust in multiple subgroup analysis and multivariable models adjusted for potential confounding factors. In Asian/Pacific Islanders, doubling of serum free testosterone concentration was associated with 202 bp shorter TL (95% CI, 51 to 353 bp), and doubling of total testosterone concentration was associated with 203 bp shorter TL (95% CI, 50 to 355 bp). Conclusions Serum concentration of estradiol was not associated with leukocyte TL in this large sample of postmenopausal women. Total and free testosterone levels were inversely associated with TL in Asian/Pacific Islander women but not in black and Hispanic women, although future studies to replicate our observations are warranted particularly to address potential ethnicity-specific relations. The significant findings of the study This study elucidates the potential roles of sex hormones in biological aging, and identified that total and free testosterone levels were inversely associated with telomere length in Asian/Pacific Islander women but not in black and Hispanic women. The study adds The findings of this study suggest that Asian/Pacific Islander women may be susceptible to the potential detrimental effects of high testosterone level on biologic aging.Item Testosterone Therapy and Cardiovascular Risk(Elsevier, 2015-04) Walsh, James P.; Kitchens, Anne C.; Department of Medicine, IU School of MedicineEndogenous testosterone levels are inversely associated with cardiovascular risk in older men and men with cardiovascular disease. Current data on cardiovascular outcomes of testosterone therapy include only observational studies and adverse event monitoring in short-term trials that were not designed to measure cardiovascular outcomes. These studies have yielded conflicting results, and some have raised concerns that testosterone therapy may increase cardiovascular risk. A well-designed, adequately powered, prospective trial will ultimately be required to clarify whether testosterone therapy impacts cardiovascular outcomes. This review describes the findings and limitations of recent studies of cardiovascular risk in older men on testosterone therapy and discusses some of the mechanisms through which testosterone may modify cardiovascular risk.