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Jang D.H.,Clinical Translational Science Institute | Weaver M.D.,University of Pittsburgh | Pizon A.F.,University of Pittsburgh | Pizon A.F.,Robert rd Health Science Center
Journal of Medical Toxicology

Introduction: In the treatment of acetaminophen toxicity, clinicians believe that N-acetylcysteine (NAC) artificially elevates prothrombin time (PT). However, the effect of NAC on human blood coagulation remains unverified. In a previous study, we show that NAC had a dose-dependent effect on PT. To our knowledge, there are no studies that specifically examine the mechanism by which NAC affects PT. This study evaluates the effect from a therapeutic NAC dose on the activity of coagulation factors II, VII, IX, and X in human plasma. Method: We obtained blood samples from ten volunteer subjects. After centrifugation of each volunteer's blood sample, the plasma was pipetted and divided into two 1-mL aliquots. We used the first-1 mL sample as a control. The second 1-mL plasma sample had 5 μL of 20 % NAC, added to make a final concentration of 1,000 mg of NAC per L of plasma. This concentration of NAC approximates the plasma levels achieved after a 150-mg/kg dose. We incubated the two samples for each subject (control and 1,000 mg/L) at 37°C for 1 h and measured the activity of coagulation factors II, VII, IX, and X. We compared factor activity using the paired student t test. Results: Participants included ten healthy subjects; six males, four females, median age 31 years. Mean values of the control samples for factors II, VII, IX, and X were 134 (CI 119-149), 126 (CI 90-163), 137 (CI 117-157), and 170 (CI 144-196) %, respectively. Mean values of the NAC-containing samples for factors II, VII, IX, and X were 90 (CI 79-100), 66 (CI 51-80), 74 (CI 63-85), and 81 (CI 71-90) %, respectively. All samples containing NAC had significantly lower coagulation factor activity level than their controls with a p < 0. 001. Discussion: In a previous study, we were able to demonstrate that NAC had a dose-dependent effect on PT. In this study, we compared activity of factors II, VII, IX, and X at baseline and for samples that received NAC. All factor activity had a significant decrease with the addition of NAC. This fall in factor activity is not explained by the dilution of adding NAC to the test samples. Conclusion: We are able to demonstrate a significant decrease in the activity of coagulation factors II, VII, IX, and X with the addition of NAC. This may be the mechanism by which PT increased in our previous study. © 2012 American College of Medical Toxicology. Source

Murray G.F.,Robert rd Health Science Center
The Annals of thoracic surgery

The 29th President of the Society of Thoracic Surgeons, Benson R. Wilcox, MD, died at his home in Fearington Village Center, NC, on May 11, 2010. In 2 weeks, he would have been 78 years old, and the focus of a birthday celebration for his wife, Patsy Davis, his 4 children, Adelaide, Sandra, Melissa, and Reid, 11 grandchildren, and many loved ones. With his death, caused by brain cancer, the University of North Carolina lost one of its most prolific and loyal sons, and the profession of thoracic surgery, one of its wisest leaders. Two facts are certain: Ben will be remembered forever by his students, residents, and colleagues, and our sky is, indeed, Carolina blue. 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved. Source

Higa G.M.,West Virginia University | Higa G.M.,Robert rd Health Science Center
Breast Cancer

Manifestations of non-equilibrium polarity, random transgressions, and catastrophes are not conditions usually associated with a sense of normalcy. Yet these disquieting features distinguish a utilitarian behavior known as dynamic instability, the signature characteristic of the microtubule. Long known to be a tumor target, disruption of this fragile attribute is associated with some of the most effective agents used to treat breast cancer today. Although the biology of the microtubule is under intense investigation much still remains unknown. As such, our understanding of regulatory molecules and resistance mechanisms are still rudimentary, further compromising our ability to develop novel therapeutic strategies to improve microtubule inhibitors. This review focuses on several classes of anti-microtubule agents and their effects on the functional dynamics of the targeted polymer. The primary objective is to critically examine the molecular mechanisms that contribute to tumor cell death, tumor-resistance, and incident neurotoxicity. © 2010 The Japanese Breast Cancer Society. Source

Goins R.T.,Oregon State University | Innes K.,Robert rd Health Science Center | Dong L.,West Virginia University
Journal of the American Geriatrics Society

The objective of this study was to use performance-based measurements to identify, in a population of community-dwelling American Indians aged 55 and older, the prevalence and correlates of lower body functioning. Data were collected as part of a cross-sectional study of disability from members of a tribe in the southeast. Lower body functioning was measured using the Short Physical Performance Battery (SPPB), where higher scores reflect better functioning. Independent variables included age, sex, marital status, educational attainment, current cigarette smoking, physical activity, body mass index (BMI), hearing loss, vision loss, bone or joint trauma, chronic pain syndrome, osteoporosis, medical comorbidity, and depressive symptomatology. The total composite SPPB score (8.8 ± 3.4) declined significantly with increasing age and was negatively associated with unmarried status, physical inactivity, vision loss, bone or joint trauma, and medical comorbidity after adjustment for all other factors in the model. Likewise, all individual SPPB component scores declined significantly with increasing age and were negatively associated with physical inactivity and comorbidity. The balance test score was significantly and negatively associated with unmarried status and vision loss; gait speed was negatively related to unmarried status; and chair stand test score was negatively related to BMI, vision loss, bone or joint trauma, and chronic pain syndrome. In the clinical setting, the SPPB can be an important screening tool for adverse health-related events. Further studies are needed to investigate the determinants and sequelae of physical dysfunction in this population. © 2012, The American Geriatrics Society. Source

Billings H.J.,West Virginia University | Connors J.M.,Robert rd Health Science Center | Altman S.N.,Robert rd Health Science Center | Hileman S.M.,Robert rd Health Science Center | And 6 more authors.

Recent data have demonstrated that mutations in the receptor for neurokinin B (NKB), the NK-3 receptor (NK3R), produce hypogonadotropic hypogonadism in humans. These data, together with reports that NKB expression increases after ovariectomy and in postmenopausal women, have led to the hypothesis that this tachykinin is an important stimulator of GnRH secretion. However, the NK3R agonist, senktide, inhibited LH secretion in rats and mice. In this study, we report that senktide stimulates LH secretion in ewes. A dramatic increase in LH concentrations to levels close to those observed during the preovulatory LH surge was observed after injection of 1 nmol senktide into the third ventricle during the follicular, but not in the luteal, phase. Similar increases in LH secretion occurred after insertion of microimplants containing this agonist into the retrochiasmatic area (RCh) in anestrous or follicular phase ewes. A low-dose microinjection (3 pmol) of senktide into the RCh produced a smaller but significant increase in LH concentrations in anestrous ewes. Moreover, NK3R immunoreactivity was clearly evident in the RCh, although it was not found in A15 dopaminergic cell bodies in this region. These data provide evidence that NKB stimulates LH (and presumably GnRH) secretion in ewes and point to the RCh as one important site of action. Based on these data, and the effects of NK3R mutations in humans, we hypothesize that NKB plays an important stimulatory role in the control of GnRH and LH secretion in nonrodent species. Copyright © 2010 by The Endocrine Society. Source

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