A 15-year-old primigravida registered late for antenatal care (2.3 weeks). Ultrasound examination revealed massive idiopathic fetal ascites necessitating in utero paracentesis at 27 weeks. The family was socially dislocated, and the patient's alcoholic father doted on her. A live female fetus with ascites and multiple congenital abnormalities was delivered at 34 weeks. Following repeated hospitalization, the infant died of pneumonitis, at 5 months of age autopsy could not determine the cause of the ascites. Young pregnant teenagers from broken homes with doting behavior from an alcoholic father should be suspected of being incest victims.

To determine the frequency, causes, and clinical significance of hyponatremia in hospitalized children, we reviewed the clinical and laboratory data of all hyponatremic children in Texas Children's Hospital over a 12-month period. One hundred sixty-one patients from among 11,702 hospital admissions were found to have hyponatremia, defined as serum sodium value of less than 130 mEq/L, an overall frequency of 1.38%. Sixty-nine patients (43%) had hyponatremia on admission, and 92 patients (57%) had hospital-acquired hyponatremia. Thirty-seven (23%) were previously healthy children, and 124 (77%) had chronic illnesses. Acute gastroenteritis was the leading cause of hyponatremia present on admission, and diuretic therapy was the leading cause of hospital-acquired hyponatremia. Only four patients (2.5%) had a serum sodium concentration of less than 120 mEq/L. Six patients (3.7%) had neurologic impairment on discharge, and 19 patients (12%) ultimately died long after their hyponatremia was corrected. Each patient who had neurologic sequelae and each patient who died had underlying medical conditions which could explain their morbidity and/or mortality. The prognosis appears to be more clearly related to the underlying medical disorder rather than to the hyponatremic state or its correction.

A new spectrophotometric assay for determining the activity of acylglycerol hydrolases (lipases, E.C. 3.1.1.3) was developed and optimized for yeast lipase (Candida cylindracea). Studies with porcine pancreatic lipase were also conducted and the influence of various detergents and divalent cations on the assay was evaluated. The assay uses cis-parinaric acid (PnA), a naturally occurring fatty acid that has unique spectroscopic properties, and takes advantage of the reversible binding of fatty acids to bovine serum albumin (BSA). Free PnA has an ultraviolet absorption peak at 321.2 nm. When PnA is bound to BSA, however, the peak shifts to 324.2 nm. The assay mixture contains 6 μM PnA, 1 μM BSA, 75 μM triolein, and 0.3 mM taurocholate in a 50 mM tris-HCl buffer with 1 μM EDTA. The release of oleic acid from triolein is monitored over time by measuring the ratio of optical densities (OD) at 319.0 and 329.0 nm. Initially, there is maximum binding of PnA to BSA, and the OD ratio is approximately 1.0. Upon addition of lipase, PnA is displaced from the BSA by oleic acid released from triolein, and the OD ratio increases to a maximum of about 1.8. However, when calcium is present in the reaction mixture an insoluble calcium-PnA complex forms, resulting in a progressive decrease in OD at both 319.0 and 329.0 nm. The kinetic assay described here is simple, rapid, sensitive, reproducible, inexpensive, and it can be adapted to measure the activity of a variety of calcium-independent lipases. Under similar assay conditions, activities for Candida cylindracea lipase obtained with this assay are similar to those obtained with14C-labelled triolein.

Colorectal cancer is the second most common cause of cancer deaths in the United States for both sexes. Considerable evidence suggests that the risk of this cancer is increased by the mutagenic actions of free radicals, which are produced during oxidation reactions. Dietary factors, the intestinal flora (bacteria), and endogenously produced metabolites contribute to the production of free radicals in the colon. Dietary antioxidants, such as vitamin E, should reduce the levels of these harmful oxidation products. In the absence of vitamin E, polyunsaturated fats can be oxidized in the colon to produce mutagens, such as lipid hydroperoxides and malondialdehyde. Furthermore, fecal bacteria can generate a high flux of reactive oxygen species (e.g., the superoxide radical [O2*-]) at the surface of the intestinal lumen, and inflammatory cells in close proximity to the colon can produce reactive nitrogen species (e.g., nitrogen dioxide [NO2]). Increasing evidence suggests that the different chemical (e.g., α- and γ-tocopherol) and stereochemical (e.g., RRR- and all-racemic-α-toeopherol) forms of vitamin E have distinct biologic potencies, pharmacokinetics, and different abilities to prevent neoplastic transformation. This review considers and evaluates recent studies relating vitamin E and oxidative stress to colon cancer, emphasizing the distinct roles of α-and γ-tocopherols. In addition, recent findings on the anti-oxidant/pro-oxidant status of the digesta (ingested food) are discussed with respect to the use of antioxidants in chemoprevention trials for colon cancer.

Objective: Evaluate association between fluid balance and intraventricular hemorrhage (IVH). Study design: Retrospective review of infants <30 weeks gestation admitted to Kentucky Children’s Hospital Neonatal Intensive Care Unit. Results: Infants with acute kidney injury (AKI) had a 2.4-fold increased risk of IVH (OR 2.38, 95% CI 1.46–3.87) and a 3.5-fold increased risk of severe IVH (OR 3.45, 95% CI 1.98–6.04). Infants above birthweight on day 4 had a 1.9-fold increased risk of IVH (OR 1.86, 95% CI 1.05–3.27) and a 2.0-fold increased risk of severe IVH (OR 1.96, 95% CI 1.03–3.74). When controlling for confounding factors, infants with AKI or above birthweight on day 4 had a 4.6-fold (aOR 4.60, 95% CI 1.80–11.78) and 3.0-fold (aOR 2.96, 95% CI 1.01–8.65) increased risk of severe IVH, respectively. Conclusion: Infants with AKI during the first week of life had a higher association of severe IVH even after controlling for confounding factors.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Hyperlipidemia is a major risk factor for the development of cardiovascular disease. Considerable evidence suggests that drugs with the ability to lower low density lipoprotein-cholesterol also lower cardiovascular deaths. This review will focus on new developments in the design of pharmacological agents and therapies that can favorably affect hyperlipidemia. A broad range of therapeutic agents will be discussed, including food additives, nutraceuticals, conventional pharmaceuticals as well as gene therapy. The potential adverse effects caused by these agents will also be discussed. Appetite suppressants, intestinal lipase inhibitors, inhibitors of dietary cholesterol absorption, inhibitors of chylomicron assembly, HMG CoA reductase inhibitors (statins) and adenovirus-mediated gene therapy are specifically discussed in detail. Treatments and issues specific to the elderly and to children are also described. The specific application of pharmacogenics to the problem of hyperlipidemia is presented as a likely direction for future research emphasis.

OBJECTIVE: Sulfur mustard (bis-2-(chloroethyl) sulfide) is a chemical warfare agent (military code: HD) causing extensive skin injury. The mechanisms underlying HD-induced skin damage are not fully elucidated. This review will critically evaluate the evidence showing that oxidative stress is an important factor in HD skin toxicity. Oxidative stress results when the production of reactive oxygen (ROS) and/or reactive nitrogen oxide species (RNOS) exceeds the capacity of antioxidant defense mechanisms. METHODS: This review will discuss the role of oxidative stress in the pathophysiology of HD skin toxicity in both in vivo and in vitro model systems with emphasis on the limitations of the various model systems. Evidence supporting the therapeutic potential of antioxidants and antioxidant liposomes will be evaluated. Antioxidant liposomes are effective vehicles for delivering both lipophilic (incorporated into the lipid bilayers) and water-soluble (encapsulated in the aqueous inner-spaces) antioxidants to skin. The molecular mechanisms interconnecting oxidative stress to HD skin toxicity are also detailed. RESULTS: DNA repair and inflammation, in association with oxidative stress, induce intracellular events leading to apoptosis or to a programmable form of necrosis. The free radical, nitric oxide (NO), is of considerable interest with respect to the mechanisms of HD toxicity. NO signaling pathways are important in modulating inflammation, cell death, and wound healing in skin cells. CONCLUSIONS: Potential future directions are summarized with emphasis on a systems biology approach to studying sulfur mustard toxicity to skin as well as the newly emerging area of redox proteomics.

An international team of accomplished researchers has been assembled to define the role that antioxidants and pro-oxidants play in cancer. Increasing scientific evidence points to the importance of antioxidants and pro-oxidants in both the etiology of cancer development and in cancer treatments. This book should prove useful for research scientists wanting a comprehensive review of the latest accomplishment in this area and for health care-providers who advise patients and the general public about dietary antioxidants and the safety and appropriate use of antioxidant supplements. Endogenous antioxidants systems that play key roles in modulating the in vivo effects of reactive oxygen species (ROS) are reviewed in detail. Many exogenous antioxidants such as vitamin E (tocopherols and tocotrienols), vitamin C, green tea polyphenols, beta-carotene and curcumin are individually discussed as well as their potential roles in alternative and complementary medicine approaches to cancer prevention and treatment. For public health professionals the question of whether or not antioxidants have a safe chemopreventive role is central: it is clearly much more effective to prevent cancer than deal with its consequences including the damaging side effects of many chemotherapeutics. A key theme explored throughout this book is the cancer-related events arising from oxidative stress and the over production of ROS. On the one hand, oxidative stress has been linked to DNA damage, mutations and an increased risk of cancer. Quite remarkably, cancer cells often exhibit a high level of intrinsic oxidative stress that is fundamental to the expression of many cancer phenotypes. The molecular mechanism whereby ROS modulate cell signaling pathways related to cancer phenotypes is, therefore, carefully reviewed. One chapter, based on original research, describes a novel methodology for measuring the cellular production of specific reactive oxygen species. A most important question is whether or not antioxidants can reduce the incidence of cancers or block the expression of cancer phenotypes. Oxidative stress in cancer cells is, however, a dual-edged sword and many cancer therapies rely on using an additional oxidative stressor to selectively drive cancer cells into programmed cell death. The high level of intrinsic oxidative stress expressed by many cancer cells has often been called the "Achilles' heal" of cancer. A second question is whether antioxidants could negatively interfere with pro-oxidant based cancer therapies. These two questions and related issues are addressed in this book. Pharmacologists with an interest in the rationale design of drugs and prodrugs for treating cancer by exploiting its high level of intrinsic oxidative stress will also benefit from this book since this issue is specifically addressed in a number of chapters. Issues related to antioxidants and pro-oxidants are also discussed in relationship to specific cancers such colorectal cancer, pancreatic cancer and prostate cancer. / https://dc.etsu.edu/etsu_books/1253/thumbnail.jpg

Thesis (PhD) -- AUT University, 2008. / Includes bibliographical references. Also held in print (vii, 254 leaves ; 30 cm.) in the Archive at the City Campus (T 618.92 WAT)