Posted by: kelsijo97 | November 28, 2012

December 2012

Nicholson, T. M., Ricke, E. A., Marker, P. C., Timms, Barry G., Vom Saal, F. S., Wood, R. W., et al. (2012). Testosterone and 17 beta-Estradiol Induce Glandular Prostatic Growth, Bladder Outlet Obstruction, and Voiding Dysfunction in Male Mice. Endocrinology, 153(11), 5556-5565.
 
Benign prostatic hyperplasia (BPH) and bladder outlet obstruction (BOO) are common in older men and can contribute to lower urinary tract symptoms that significantly impact quality of life. Few existing models of BOO and BPH use physiological levels of hormones associated with disease progression in humans in a genetically manipulable organism. We present a model of BPH and BOO induced in mice with testosterone (T) and 17 beta-estradiol (E(2)). Male mice were surgically implanted with slow-releasing sc pellets containing 25 mg T and 2.5 mg E(2) (T + E(2)). After 2 and 4 months of hormone treatment, we evaluated voiding patterns and examined the gross morphology and histology of the bladder, urethra, and prostate. Mice treated with T + E(2) developed significantly larger bladders than untreated mice, consistent with BOO. Some mice treated with T + E(2) had complications in the form of bladder hypertrophy, diverticula, calculi, and eventual decompensation with hydronephrosis. Hormone treatment caused a significant decrease in the size of the urethral lumen, increased prostate mass, and increased number of prostatic ducts associated with the prostatic urethra, compared with untreated mice. Voiding dysfunction was observed in mice treated with T + E(2), who exhibited droplet voiding pattern with significantly decreased void mass, shorter void duration, and fewer sustained voids. The constellation of lower urinary tract abnormalities, including BOO, enlarged prostates, and voiding dysfunction seen in male mice treated with T + E(2) is consistent with BPH in men. This model is suitable for better understanding molecular mechanisms and for developing novel strategies to address BPH and BOO. (Endocrinology 153: 5556-5565, 2012)
 
Basic Biomedical Sciences, Vermillion Campus.
 
 
Breinholt, J. W., Porter, Megan L., & Crandall, K. A. (2012). Testing Phylogenetic Hypotheses of the Subgenera of the Freshwater Crayfish Genus Cambarus (Decapoda: Cambaridae). Plos One, 7(9).
 
Background: The genus Cambarus is one of three most species rich crayfish genera in the Northern Hemisphere. The genus has its center of diversity in the Southern Appalachians of the United States and has been divided into 12 subgenera. Using Cambarus we test the correspondence of subgeneric designations based on morphology used in traditional crayfish taxonomy to the underlying evolutionary history for these crayfish. We further test for significant correlation and explanatory power of geographic distance, taxonomic model, and a habitat model to estimated phylogenetic distance with multiple variable regression. Methodology/Principal Findings: We use three mitochondrial and one nuclear gene regions to estimate the phylogenetic relationships for species within the genus Cambarus and test evolutionary hypotheses of relationships and associated morphological and biogeographical hypotheses. Our resulting phylogeny indicates that the genus Cambarus is polyphyletic, however we fail to reject the monophyly of Cambarus with a topology test. The majority of the Cambarus subgenera are rejected as monophyletic, suggesting the morphological characters used to define those taxa are subject to convergent evolution. While we found incongruence between taxonomy and estimated phylogenetic relationships, a multiple model regression analysis indicates that taxonomy had more explanatory power of genetic relationships than either habitat or geographic distance. Conclusions: We find convergent evolution has impacted the morphological features used to delimit Cambarus subgenera. Studies of the crayfish genus Orconectes have shown gonopod morphology used to delimit subgenera is also affected by convergent evolution. This suggests that morphological diagnoses based on traditional crayfish taxonomy might be confounded by convergent evolution across the cambarids and has little utility in diagnosing relationships or defining natural groups. We further suggest that convergent morphological evolution appears to be a common occurrence in invertebrates suggesting the need for careful phylogenetically based interpretations of morphological evolution in invertebrate systematics.
 
Biology Department.
 
 
Jarchow, Meghann E., Liebman, M., Rawat, V., & Anex, R. P. (2012). Functional group and fertilization affect the composition and bioenergy yields of prairie plants. Global Change Biology Bioenergy, 4(6), 671-679.
 
Prairies used for bioenergy production have potential to generate marketable products while enhancing environmental quality, but little is known about how prairie species composition and nutrient management affect the suitability of prairie biomass for bioenergy production. We determined how functional-group identity and nitrogen fertilization affected feedstock characteristics and estimated bioenergy yields of prairie plants, and compared those prairie characteristics to that of corn stover. We tested our objectives with a field experiment that was set up as a 5 x 2 incomplete factorial design with C3 grasses, C4 grasses, legumes, and multi-functional-group mixtures grown with and without nitrogen fertilizer; a fertilized corn treatment was also included. We determined cell wall, hemicellulose, cellulose, and ash concentrations; ethanol conversion ratios; gross caloric ratios; aboveground biomass production; ethanol yields; and energy yields for all treatments. Prairie functional-group identity affected the biomass feedstock characteristics, whereas nitrogen fertilization did not. Functional group and fertilization had a strong effect on aboveground biomass production, which was the major predictor of ethanol and energy yields. C4 grasses, especially when fertilized, had among the most favorable bioenergy characteristics with high estimated ethanol conversion ratios and nongrain biomass production, relatively high gross caloric ratios, and low ash concentrations. The bioenergy characteristics of corn stover, from an annual C4 grass, were similar to those of the biomass of perennial C4 grasses. Both functional-group composition and nitrogen fertility management were found to be important in optimizing bioenergy production from prairies.
 
Biology Department.
 
 
Sereda, Grigoriy, Moorthy, Ramkumar, Gamarra-Luques, Carlos, & Telleria, Carlos. (2013). Facile Synthesis of a Phototoxic Monofunctionalized Tetraarylporphyrin as Scaffold for Porphyrin-Quinone Conjugates. Synthetic Communications, 43(2), 182-190.
 
A new carboxy-monofunctionalized tertraarylporphyrin has been tested for cytotoxicity toward OV2008 human ovarian cancer cells. This compound acutely inhibits growth of ovarian cancer cells upon exposure to ambient light while suppresses long-term clonogenic survival of cells under both dark and light stimulated conditions. Because of the variable length of the linkage between the anthraquinone and porphyrin moieties, the synthesized monocarboxylated porphyrin presents a versatile scaffold for fine-tuning of the photoelectron transfer in the quinone-porphyrin conjugate. To demonstrate its synthetic value, we converted the carboxy derivative to its amino counterpart.
 
Chemistry Department and Basic Biomedical Sciences [Vermillion Campus]
 
 
Peng, Rui, Banerjee, Subhash, Sereda, Grigoriy, & Koodali, Ranjit T. (2012). TiO2–SiO2 mixed oxides: Organic ligand templated controlled deposition of titania and their photocatalytic activities for hydrogen production. International Journal of Hydrogen Energy, 37(22), 17009-17018.
 
Abstract: A simple approach to the controlled deposition of titania with different particle sizes on silica surface has been developed by impregnation of an organic titania precursor followed by calcination. Among the several Ti-complexes tested, the templating effect of titanium phthalocyanine dichloride resulted in silica-supported titania with enhanced photocatalytic activity for photosplitting of water under UV light irradiation. The titania–silica materials were characterized by Powder X-ray diffraction (XRD), UV–Vis diffuse reflectance spectra (DRS), nitrogen adsorption studies, and Raman spectroscopic studies. The photocatalytic activity for hydrogen production is maximum at an optimal particle size wherein surface and volume recombination is minimized.
 
Chemistry Department.
 
 
Zhang, L. F., Gong, Xiao, Bao, Ying, Zhao, Y., Xu, M., Jiang, Chayong, et al. (2012). Electrospun Nanofibrous Membranes Surface-Decorated with Silver Nanoparticles as Flexible and Active/Sensitive Substrates for Surface-Enhanced Raman Scattering. Langmuir, 28(40), 14433-14440.
 
The development of novel nanomaterials with well-controlled morphologies/structures to achieve excellent activities/sensitivities in surface-enhanced Raman scattering (SERS) is crucial in advancing the high-performance SERS detections of chemical and biological species. In this study, amidoxime surface-functionalized polyacrylonitrile (ASFPAN) nanofibrous membranes surface-decorated with silver nanoparticles (Ag NPs) were prepared via the technique of electrospinning followed by the method of seed-mediated electroless plating. High SERS activities/sensitivities were observed from the ASFPAN-Ag NPs nanofibrous membranes, while the density and size of Ag NPs had an important impact on the SEAS activity/sensitivity. The results confirmed that the enhancement of Raman signals is due to the presence of hot spots between/among Ag NPs on the nanofiber surfaces. Electrospun nanofibrous membranes surface-decorated with Ag NPs were mechanical flexible/resilient and could be used as highly active/sensitive SERS substrates for a broad range of applications.
 
Chemistry Department.
 
 
Wray, Tyler B., Dvorak, Rob D., Hsia, Jennifer F., Arens, Ashley M., & Schweinle, William E. (2013). Optimism and Pessimism as Predictors of Alcohol Use Trajectories in Adolescence. Journal of Child & Adolescent Substance Abuse, 22(1), 58-68.
 
A range of research has recognized the benefits of optimism in a variety of health-related outcomes. Pessimism has received less attention but may be a distinct concept that is uniquely related to certain health behaviors, including drug use. The present study examined relationships between optimism and pessimism and alcohol use trajectories of adolescents using latent growth modeling. Results suggest that optimism was negatively associated with alcohol use at age 14, but pessimism was negatively associated with alcohol use at that age for boys. Findings illustrate the importance of perceptions about the future to patterns of alcohol use at younger ages.
 
Psychology Department.
 
 
Chen, Jinghai, Ortmeier, Steven B., Savinova, Olga V., Nareddy, Vijaya B., Beyer, April J., Wang, Dajun, et al. (2012). Thyroid hormone induces sprouting angiogenesis in adult heart of hypothyroid mice through the PDGF-Akt pathway. Journal of cellular and molecular medicine, 16(11), 2726-2735.
 
Study of physiological angiogenesis and associated signalling mechanisms in adult heart has been limited by the lack of a robust animal model. We investigated thyroid hormone-induced sprouting angiogenesis and the underlying mechanism. Hypothyroidism was induced in C57BL/6J mice by feeding with propylthiouracil (PTU). One year of PTU treatment induced heart failure. Both 12weeks- (young) and 1year-PTU (middle age) treatment caused a remarkable capillary rarefaction observed in capillary density. Three-day Triiodothyronine (T3) treatment significantly induced cardiac capillary growth in hypothyroid mice. In cultured left ventricle (LV) tissues from PTU-treated mice, T3 also induced robust sprouting angiogenesis where pericyte-wrapped endothelial cells formed tubes. The in vitro T3 angiogenic response was similar in mice pre-treated with PTU for periods ranging from 1.5 to 12months. Besides bFGF and VEGF(164) , PDGF-BB was the most robust angiogenic growth factor, which stimulated notable sprouting angiogenesis in cultured hypothyroid LV tissues with increasing potency, but had little effect on tissues from euthyroid mice. T3 treatment significantly increased PDGF receptor beta (PDGFR-beta) protein levels in hypothyroid heart. PDGFR inhibitors blocked the action of T3 both on sprouting angiogenesis in cultured LV tissue and on capillary growth in vivo. In addition, activation of Akt signalling mediated in T3-induced angiogenesis was blocked by PDGFR inhibitor and neutralizing antibody. Our results suggest that hypothyroidism leads to cardiac microvascular impairment and rarefaction with increased sensitivity to angiogenic growth factors. T3-induced cardiac sprouting angiogenesis in adult hypothyroid mice was associated with PDGF-BB, PDGFR-beta and downstream activation of Akt. 2012 The Authors Journal of Cellular and Molecular Medicine 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
Fox, J. P., Gustafson, J., Desai, M. M., Hellan, M., Thambi-Pillai, Thav, & Ouellette, J. (2012). Short-Term Outcomes of Ablation Therapy for Hepatic Tumors: Evidence from the 2006-2009 Nationwide Inpatient Sample. Annals of Surgical Oncology, 19(12), 3677-3686.
 
Radiofrequency ablation (RFA) for the treatment of hepatic tumors has been increasingly used across the United States. Whether treatment-related morbidity has remained low with broader adoption is unclear. We conducted this study to describe in-hospital morbidity associated with RFA for hepatic tumors and to identify predictors of adverse events in a nationally representative database. Using the 2006-2009 Nationwide Inpatient Sample, we evaluated all patients aged a parts per thousand yen40 years who underwent an elective RFA for primary or metastatic liver tumors (N = 1298). Outcomes included in-hospital procedure-specific and postoperative complications. Multivariable logistic regression analyses were performed to identify patient and facility predictors of complications. Most patients underwent a percutaneous (39.9 %) or laparoscopic (22.0 %) procedure for metastatic liver tumors (57.5 %). Procedure-specific complications were frequent (18.2 %), with transfusion requirements (10.7 %), intraoperative bleeding (4.3 %), and hepatic failure (2.8 %) being the most common. Arrhythmias [adjusted odds ratio (AOR) = 1.93 (1.23-3.04)], coagulopathy [AOR = 4.65 (2.95-7.34)], and an open surgical approach [AOR = 2.77 (1.75-4.36)] were associated with an increased likelihood of procedure-specific complications, whereas hospital RFA volume a parts per thousand yen16/year was associated with a reduced likelihood [AOR = 0.59 (0.38-0.91)]. Postoperative complications were also common (12.0 %), with arrhythmias, heart failure, coagulopathy, and open surgical approach acting as significant predictors. In-hospital morbidity is common after RFA for hepatic tumors. While several patient factors are associated with more frequent procedure-specific complications, treatment at hospitals with an annual volume a parts per thousand yen16 cases/year was associated with a 41 % reduction in the odds of procedure-specific complications.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
Gupta, Brij K., Maher, Diane M., Ebeling, Mara C., Sundram, Vasunda, Koch, Michael D., Lynch, Douglas W., et al. (2012). Increased Expression and Aberrant Localization of Mucin 13 in Metastatic Colon Cancer. Journal of Histochemistry & Cytochemistry, 60(11), 822-831.
 
MUC13 is a newly identified transmembrane mucin. Although MUC13 is known to be overexpressed in ovarian and gastric cancers, limited information is available regarding the expression of MUC13 in metastatic colon cancer. Herein, we investigated the expression profile of MUC13 in colon cancer using a novel anti-MUC13 monoclonal antibody (MAb, clone ppz0020) by immunohistochemical (IHC) analysis. A cohort of colon cancer samples and tissue microarrays containing adjacent normal, non-metastatic colon cancer, metastatic colon cancer, and liver metastasis tissues was used in this study to investigate the expression pattern of MUC13. IHC analysis revealed significantly higher (p < 0.001) MUC13 expression in non-metastatic colon cancer samples compared with faint or very low expression in adjacent normal tissues. Interestingly, metastatic colon cancer and liver metastasis tissue samples demonstrated significantly (p < 0.05) higher cytoplasmic and nuclear MUC13 expression compared with non-metastatic colon cancer and adjacent normal colon samples. Moreover, cytoplasmic and nuclear MUC13 expression correlated with larger and poorly differentiated tumors. Four of six tested colon cancer cell lines also expressed MUC13 at RNA and protein levels. These studies demonstrate a significant increase in MUC13 expression in metastatic colon cancer and suggest a correlation between aberrant MUC13 localization (cytoplasmic and nuclear expression) and metastatic colon cancer. (J Histochem Cytochem 60:822-831, 2012)
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
Hanson, Jessica D., Winberg, Austin, & Elliott, Amy. (2012). Development of a media campaign on fetal alcohol spectrum disorders for northern plains american Indian communities. Health promotion practice, 13(6), 842-847.
 
Alcohol-exposed pregnancies are especially of concern for American Indians. The Indian Health Service reported that 47% to 56% of pregnant patients admitted to drinking alcohol during their pregnancy. In addition, rates of Fetal Alcohol Syndrome are estimated to be as high as 3.9 to 9.0 per 1,000 live births among American Indians in the Northern Plains, making prevention of alcohol-exposed pregnancies an important public health effort for this population. The goal of this article is to add to the literature on universal prevention of Fetal Alcohol Spectrum disorders by describing the development, dissemination, and evaluation of a media campaign on Fetal Alcohol Spectrum Disorders that was created by and for American Indian communities in the Northern Plains.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
Harrison, Blair, Finkelstein, Marsha, Puumala, Susan, & Payne, Nathaniel R. (2012). The complex association of race and leaving the pediatric emergency department without being seen by a physician. Pediatric emergency care, 28(11), 1136-1145.
 
OBJECTIVES: This study examined the influence of race and language on leaving the emergency department (ED) without complete evaluation and treatment (LWCET).; METHODS: This retrospective, case-cohort study examined LWCET among patients discharged home from 2 EDs between March 2, 2009, and March 31, 2010. Race and language were obtained by family self-report. We also explored wait time to see a physician as an explanation of racial disparities.; RESULTS: One thousand two hundred eighty-five (1.7%) of 76,931 ED encounters ended in LWCET. Factors increasing LWCET were high ED activity, low acuity, and medical assistance (MA) insurance. American Indian, biracial, African American, and Hispanic races were also associated with higher odds of LWCET among visits by MA insurance patients compared with those of white patients on private insurance. Restricting the analysis to visits by MA insurance patients, only American Indian race was associated with LWCET compared with white race. Visits by patients using an interpreter or speaking a language other than English at home had lower odds of ending in LWCET. Sensitivity analyses in subgroups confirmed these findings. We developed a measure of ED activity that correlated well with wait time to see a physician (correlation coefficient = 0.993; P < 0.001). Among non-LWCET visits, wait time to see a practitioner did not correlate with racial disparities in LWCET.; CONCLUSIONS: Race, language, and insurance status interact to form a complex relationship with LWCET. Medical assistance insurance status appears to account for much of the excessive instances of LWCET seen in nonwhites. After restricting the analysis to MA insurance patients, only visits by American Indian patients had higher odds of LWCET compared with whites on MA insurance. Wait time to see a physician did not explain racial differences in LWCET.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
Hu, Y. S., Ehli, Erik A., Kittelsrud, J., Ronan, Patrick J., Munger, K., Downey, T., et al. (2012). Lipid-lowering effect of berberine in human subjects and rats. Phytomedicine, 19(10), 861-867.
 
Due to serious adverse effects and the limited effectiveness of currently available pharmacological therapies for obesity, many research efforts have focused on the development of drugs from natural products. Our previous studies demonstrated that berberine, an alkaloid originally isolated from traditional Chinese herbs, prevented fat accumulation in vitro and in vivo. In this pilot study, obese human subjects (Caucasian) were given 500 mg berberine orally three times a day for twelve weeks. The efficacy and safety of berberine treatment was determined by measurements of body weight, comprehensive metabolic panel, blood lipid and hormone levels, expression levels of inflammatory factors, complete blood count, and electrocardiograph. A Sprague-Dawley rat experiment was also performed to identify the anti-obesity effects of berberine treatment. The results demonstrate that berberine treatment produced a mild weight loss (average 5 lb/subject) in obese human subjects. But more interestingly, the treatment significantly reduced blood lipid levels (23% decrease of triglyceride and 12.2% decrease of cholesterol levels) in human subjects. The lipid-lowering effect of berberine treatment has also been replicated in the rat experiment (34.7% decrease of triglyceride and 9% decrease of cholesterol level). Cortisol, calcitriol, ACTH, TSH, FT4, and SHBG levels were not significantly changed following 12 weeks of berberine treatment. However, there was interestingly, an increase in calcitriol levels seen in all human subjects following berberine treatment (mean 59.5% increase, p=0.11). Blood inflammatory factors (CRP, IL-6, TNF alpha, COX-2) and erythrocyte sedimentation rate (ESR) were not significantly affected by treatment with berberine. Tests of hematological, cardiovascular, liver, and kidney function following berberine treatment showed no detrimental side effects to this natural compound. Collectively, this study demonstrates that berberine is a potent lipid-lowering compound with a moderate weight loss effect, and may have a possible potential role in osteoporosis treatment/prevention. (C) 2012 Elsevier GmbH. All rights reserved.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
Kobayashi, Satoru, Xu, Xianmin, Chen, Kai, & Liang, Qiangrong. (2012). Suppression of autophagy is protective in high glucose-induced cardiomyocyte injury. Autophagy, 8(4), 577-592.
 
Hyperglycemia is linked to increased heart failure among diabetic patients. However, the mechanisms that mediate hyperglycemia-induced cardiac damage remain poorly understood. Autophagy is a cellular degradation pathway that plays important roles in cellular homeostasis. Autophagic activity is altered in the diabetic heart, but its functional role has been unclear. In this study, we determined if mimicking hyperglycemia in cultured cardiomyocytes from neonatal rats and adult mice could affect autophagic activity and myocyte viability. High glucose (17 or 30 mM) reduced autophagic flux compared with normal glucose (5.5 mM) as indicated by the difference in protein levels of LC3-II (microtubule-associated protein 1 light chain 3 form II) or the changes of punctate fluorescence patterns of GFP-LC3 and mRFP-LC3 in the absence and presence of the lysosomal inhibitor bafilomycin A1. Unexpectedly, the inhibited autophagy turned out to be an adaptive response that functioned to limit high glucose cardiotoxicity. Indeed, suppression of autophagy by 3-methyladenine or short hairpin RNA-mediated silencing of the Becn1 or Atg7 gene attenuated high glucose-induced cardiomyocyte death. Conversely, upregulation of autophagy with rapamycin or overexpression of Becn1 or Atg7 predisposed cardiomyocytes to high glucose toxicity. Mechanistically, the high glucose-induced inhibition of autophagy was mediated at least partly by increased mTOR signaling that likely inactivated ULK1 through phosphorylation at serine 467. Together, these findings demonstrate that high glucose inhibits autophagy, which is a beneficial adaptive response that protects cardiomyocytes against high glucose toxicity. Future studies are warranted to determine if autophagy plays a similar role in diabetic heart in vivo.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
Reindl, Bailey A., Lynch, Douglas W., Ramirez, Michael, Valbracht, Marcia, Davis-Keppen, Laura, Tams, Kimberlee C., et al. (2012). Sani-cloth wipe mimics rare enzyme deficiency malonic aciduria on newborn screen. Pediatrics, 130(5), e1363-1368.
 
Within a 7-month period at our institution, newborn screening by tandem mass spectrometry revealed 10 cases with elevated levels of malonylcarnitine, which suggested malonic aciduria. Malonic aciduria is a rare autosomal recessive inborn error of metabolism. Confirmatory testing yielded normal results in all the newborns involved. The application of quality improvement practices dictated investigating the dried blood spot collection process, which revealed the use of multiple blood-collection techniques by newborn nursery staff, improper handling of the dried blood spot specimens, and sanitary wipe contamination as the causes of the aberrant false-positive results at our institution. This systematic evaluation identified the cause of the aberrant false-positive results and a strategy was implemented to avoid aberrant results in the future. Thus far, no false-positive results have occurred since the investigative process. False-positive results on a newborn screen can cause unnecessary emotional and economic stress on families, a finding that was identified at our institution. Historically, false-positive newborn screening results have been identified in infants born by cesarean delivery in which iodine antiseptic was used and in newborns who receive total parenteral nutrition, such as premature infants in the NICU. Therefore, if an unusually high number of false-positive results are found during the newborn screening process, contamination should be considered as a contributing factor.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
Weltman, Nathan Y., Wang, Dajun, Redetzke, Rebecca A., & Gerdes, A. Martin. (2012). Longstanding Hyperthyroidism Is Associated with Normal or Enhanced Intrinsic Cardiomyocyte Function despite Decline in Global Cardiac Function. Plos One, 7(10).
 
Thyroid hormones (THs) play a pivotal role in cardiac homeostasis. TH imbalances alter cardiac performance and ultimately cause cardiac dysfunction. Although short-term hyperthyroidism typically leads to heightened left ventricular (LV) contractility and improved hemodynamic parameters, chronic hyperthyroidism is associated with deleterious cardiac consequences including increased risk of arrhythmia, impaired cardiac reserve and exercise capacity, myocardial remodeling, and occasionally heart failure. To evaluate the long-term consequences of chronic hyperthyroidism on LV remodeling and function, we examined LV isolated myocyte function, chamber function, and whole tissue remodeling in a hamster model. Three-month-old F1b hamsters were randomized to control or 10 months TH treatment (0.1% grade I desiccated TH). LV chamber remodeling and function was assessed by echocardiography at 1, 2, 4, 6, 8, and 10 months of treatment. After 10 months, terminal cardiac function was assessed by echocardiography and LV hemodynamics. Hyperthyroid hamsters exhibited significant cardiac hypertrophy and deleterious cardiac remodeling characterized by myocyte lengthening, chamber dilatation, decreased relative wall thickness, increased wall stress, and increased LV interstitial fibrotic deposition. Importantly, hyperthyroid hamsters demonstrated significant LV systolic and diastolic dysfunction. Despite the aforementioned remodeling and global cardiac decline, individual isolated cardiac myocytes from chronically hyperthyroid hamsters had enhanced function when compared with myocytes from untreated age-matched controls. Thus, it appears that long-term hyperthyroidism may impair global LV function, at least in part by increasing interstitial ventricular fibrosis, in spite of normal or enhanced intrinsic cardiomyocyte function.
 
Sanford School of Medicine, Sioux Falls Campus.
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