Toxicant-associated steatohepatitis.

Hepatotoxicity is the most common organ injury due to occupational and environmental exposures to industrial chemicals. A wide range of liver pathologies ranging from necrosis to cancer have been observed following chemical exposures both in humans and in animal models. Toxicant-associated fatty liver disease (TAFLD) is a recently named form of liver injury pathologically similar to alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD). Toxicant-associated steatohepatitis (TASH) is a more severe form of TAFLD characterized by hepatic steatosis, inflammatory infiltrate, and in some cases, fibrosis. While subjects with TASH have exposures to industrial chemicals, such as vinyl chloride, they do not have traditional risk factors for fatty liver such as significant alcohol consumption or obesity. Conventional biomarkers of hepatotoxicity including serum alanine aminotransferase activity may be normal in TASH, making screening problematic. This article examines selected chemical exposures associated with TAFLD in human subjects or animal models and concisely reviews the closely related NAFLD and ALD.

Obesity, inflammation, and the potential application of pharmaconutrition.

Obesity is an emerging problem worldwide. Hospitalized obese patients often have a worse outcome than patients of normal weight, particularly in the setting of trauma and critical care. Obesity creates a low-grade systemic inflammatory response syndrome (SIRS) that is similar (but on a much smaller scale) to gram-negative sepsis. This process involves up-regulation of systemic immunity, is characterized clinically by insulin resistance and the metabolic syndrome, and puts the patient at increased risk for organ failure, infectious morbidity, and mortality. Through lipotoxicity and cytokine dysregulation, obesity may act to prime the immune system, predisposing to an exaggerated subsequent immune response when a second clinical insult occurs (such as trauma, burns, or myocardial infarction). Specialized nutrition therapy for such patients currently consists of a hypocaloric, high-protein diet. However, this approach does not address the putative pathophysiologic mechanisms of inflammation and altered metabolism associated with obesity. A number of dietary agents such as arginine, fish oil, and carnitine may correct these problems at the molecular level. Pharmaconutrition formulas may provide exciting innovations for the nutrition therapy of the obese patient.

Differences in Referral Access to Care Between Gastrointestinal Subspecialty Patients: Barriers and Opportunities.

Purpose: Referral access to subspecialty care for patients with gastrointestinal (GI) diseases is not well defined, but has significant importance to patients. We hypothesized that patients experience barriers to care in two common gastroenterology subspecialties, Hepatology and Motility, in a university medical center. Methods: Two hundred thirteen clinic patients (mean age 46.5 years; 66.5% female; 85.6% Caucasians) completed a formatted questionnaire on access to care. Hepatology patients were older (49.7 years, p=0.008); motility patients predominantly female (76.8%, p<0.001). Gender distribution was even for hepatology (51.2% female). Both groups were overweight (mean body mass index 28.4). Results: Patients waited a mean 89.5 days to be seen by a subspecialist. There were differences by subspecialty (107.6 days for motility vs. 64.3 days for hepatology, p=0.022). A larger percentage of motility patients were told nothing was wrong with them (16.8%, p<0.01) and could not be helped (42.1%, p=0.000). Conclusions: Access to care for subspecialty gastroenterology patients in a university center appears to be impacted by a number of variables. While there are similarities, differences exist between these two subspecialties. Motility patients were more likely to have been told they have nothing wrong with them, suffer setbacks financially, and suffer mood problems. Their wait time for appointments was also greater than hepatology patients. Further investigations of referral access for gastroenterology patients may yield additional insights into disease-specific barriers to accessing subspecialty care.

Role of Cytochrome P450 Monooxygenase in Carcinogen and Chemotherapeutic Drug Metabolism.

The purpose of this chapter is to provide insight into which human cytochromes P450 (CYPs) may be involved in metabolism of chemical carcinogens and anticancer drugs. A historical overview of this field and the development of literature using relevant animal models and expressed human CYPs have provided information about which specific CYPs may be involved in carcinogen metabolism. Definition of the biochemical properties of CYP activity came from several groups who studied the reaction stoichiometry of butter yellow and benzo[α]pyrene, including their role in induction of these enzyme systems. This chapter will list as much as is known about the human CYPs involved in carcinogen and anticancer drug metabolism, as well as summarize studies with rodent CYPs. A review of three major classes of anticancer drugs and their metabolism in humans is covered for cyclophosphamide, procarbazine, and anthracycline antibiotics, cancer chemotherapeutic compounds extensively metabolized by CYPs. The emerging information about human CYP gene polymorphisms as well as other enzymes involved in foreign compound metabolism provides considerable information about how these genetic variants affect carcinogen and anticancer drug metabolism. With information available from individual's genomic sequences, consideration of populations who may be at risk due to environmental exposure to carcinogens or how to optimize their cancer therapy regimens to enhance efficacy of the anticancer drugs appears to be an important field of study to benefit individuals in the future.

Pharmaconutrition for the obese, critically ill patient.

Obesity is an epidemic that affects approximately 30% of the adult population in the United States. The prevalence of obesity in the critically ill seems to correlate with the rise in obesity in the general population. Delivery of standard enteral nutrition (EN) to patients in the intensive care unit (ICU) has been shown to decrease infectious complications. Obese ICU patients may be at increased risk for infections, ICU length of stay, and ventilation requirements compared to the nonobese. Pharmaconutrition has been shown to decrease many of these negative ICU outcomes. Because of obesity-associated increased ICU risk, provision of certain pharmaconutrients should be considered in obese patients requiring EN therapy. This review examines the evidence for specific nutrients such as green tea, curcumin, sulforaphane, poly-unsaturated fatty acids, L-arginine, L-citrulline, L-leucine, protein, probiotics, magnesium, medium-chain triglycerides, and zinc for the treatment of obesity. These nutrients could potentially be added to current EN formulas or provided as supplements.