This article reviews our understanding of effects of thyroid hormone excess and deficiency on hepatic metabolism of FFA, and consequent effects on production, secretion, and metabolism of plasma lipoproteins. In the hyperthyroid state the following alterations are observed. Fatty acid oxidation and ketogenesis are stimulated simultaneously with a paradoxical stimulation of fatty acid synthesis, which may be linked by virtue of a blunted response of mitochondrial carnitine palmitoyltransferase I (CPT-I) to malonyl coenzyme A (CoA). Esterification of fatty acid to triglyceride (TG) is reduced, as is the secretion of the very low density lipoprotein (VLDL) (including VLDL TG, cholesterol, and apoprotein); this may be due, in part, to decreased concentrations of glycerol-3-phosphate (G3P) in the hepatic cell. In the intact animal or patient, however, serum TG concentration is variable, which may reflect increased adipose tissue lipolysis and elevated concentrations of plasma FFA, which would tend to drive VLDL secretion by the liver. Clearance of the VLDL and its metabolic product, the low density lipoprotein (LDL), is increased, resulting in decreased plasma total and LDL cholesterol. Although high density lipoprotein (HDL) cholesterol may also be reduced, the ratio of LDL/HDL cholesterol is further decreased. The regulatory role of the lipoprotein apoproteins is less clear, but hepatic apolipoprotein (apo) B secretion (required for VLDL) is diminished, while apo-AI secretion (required for HDL) is stimulated, perhaps both reflecting rates of synthesis. Plasma concentrations of apo-AI are variable, dependent on relative rates of secretion and clearance. In the hypothyroid, many of these effects are reversed, which results in hyperlipoproteinemias and greater risk for the development of atherosclerotic cardiovascular disease.

The incidence of traumatic injury, frequently associated with hemorrhagic shock, is higher in the alcohol-intoxicated individual. The outcome, as it pertains to both morbidity and mortality of this population, is partly dependent on duration of alcohol exposure and levels of blood alcohol at time of injury. In previous studies, we demonstrated that prolonged alcohol intoxication (15-h duration) produces marked hemodynamic instability and exacerbated early lung proinflammatory cytokine expression after hemorrhagic shock. The present study examines whether a shorter and more modest period of alcohol intoxication is sufficient to alter hemodynamic and proinflammatory responses to hemorrhagic shock. Chronically instrumented, conscious male Sprague-Dawley rats (250-300 g) received a single intragastric bolus of alcohol (1.75 g/kg) 30 min before the administration of fixed-volume (50%) hemorrhagic shock, followed by fluid resuscitation with Ringer lactate. Time-matched controls were administered on isocaloric dextrose bolus (3 g/kg). Alcohol (blood alcohol concentration, 152 +/- 10 mg/dL) produced a 14% decrease in basal mean arterial blood pressure and a more profound hypotensive response to equal blood loss. The 2-fold rise in circulating norepinephrine levels was similar in alcohol- and dextrose-treated hemorrhaged animals despite greater hypotension in alcohol-treated animals. Significant upregulation in lung and spleen interleukin (IL) 1, IL-6, IL-10, and tumor necrosis factor alpha expression was observed immediately after hemorrhage and fluid resuscitation, as previously reported. Only the hemorrhage-induced rise in lung IL-6 and tumor necrosis factor alpha was prevented by alcohol administration. In contrast, spleen cytokine responses to hemorrhage were not altered by alcohol administration. These results indicate that moderate acute alcohol intoxication results in significant modulation of hemodynamic and neuroendocrine responses to hemorrhagic shock.

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The role of the actin cytoskeleton in endothelial barrier function has been debated for nearly four decades. Our previous investigation revealed spontaneous local lamellipodia in confluent endothelial monolayers that appear to increase overlap at intercellular junctions. We tested the hypothesis that the barrier-disrupting agent histamine would reduce local lamellipodia protrusions and investigated the potential involvement of p38 mitogen-activated protein (MAP) kinase activation and actin stress fiber formation. Confluent monolayers of human umbilical vein endothelial cells (HUVEC) expressing green fluorescent protein-actin were studied using time-lapse fluorescence microscopy. The protrusion and withdrawal characteristics of local lamellipodia were assessed before and after addition of histamine. Changes in barrier function were determined using electrical cell-substrate impedance sensing. Histamine initially decreased barrier function, lamellipodia protrusion frequency, and lamellipodia protrusion distance. A longer time for lamellipodia withdrawal and reduced withdrawal distance and velocity accompanied barrier recovery. After barrier recovery, a significant number of cortical fibers migrated centrally, eventually resembling actin stress fibers. The p38 MAP kinase inhibitor SB203580 attenuated the histamine-induced decreases in barrier function and lamellipodia protrusion frequency. SB203580 also inhibited the histamine-induced decreases in withdrawal distance and velocity, and the subsequent actin fiber migration. These data suggest that histamine can reduce local lamellipodia protrusion activity through activation of p38 MAP kinase. The findings also suggest that local lamellipodia have a role in maintaining endothelial barrier integrity. Furthermore, we provide evidence that actin stress fiber formation may be a reaction to, rather than a cause of, reduced endothelial barrier integrity.

This retrospective study describes the prescription medication profile in an outpatient pediatric population (n =510) retrieved from a hospital pharmacy computer file. The survey covers a three-month period. The study population included 281 male and 229 female patients divided according to age into three groups: infant (age 0-12 months); children (age 1-12 years); and adolescents (age 13-18 years). Medications prescribed were classified according to their pharmacotherapeutic properties as described in the American Hospital Formulary Service Drug Information 87. The findings pointed out that three pharmacotherapeutic categories (the antiinfective/chemotherapeutic, central nervous system (CNS), and respiratory agents) constituted 78.1 percent of the 1402 prescribed medications. The most frequently prescribed agents in each of these categories were, respectively, amoxicillin, aminophylline, and acetaminophen. These agents represent recent advances in drug usage because they became most frequently used only within the past ten years. The age-dependent medication profile indicated that there was a higher prescription rate of antiinfectives and respiratory disorder agents in the younger age groups; in the adolescent group CNS agents were more often prescribed. Drug In tell C/in Pharm 1988;22:999-1002.