Fear of injections may interfere with receipt of vaccines. The frequency, associations, and precipitators of fear-provoking factors of 400 travelers visiting a travel health clinic were evaluated. The median age of this group was 25, 7% were medical staff members, and 2.8% were regular injectors (insulin). Eighty-five (21.7%; 95% confidence interval, 17.3-25.6%) of the travelers indicated that they were afraid of injections, and in 8.2%, the fear was unreasonably intense. Multivariate analysis revealed that watching other people being vaccinated, fear of pain, needle size, and a history of fainting were highly and independently associated with injection phobia. The sensitivity, specificity, and discrimination accuracy of this model were 79.5%, 78.0%, and 78.3%, respectively. Injection phobia and a bad past vaccination experience were significantly associated with fainting. Perceived empathy, on the other hand, was a significant protective factor. Fear of injections was common in this cohort and was highly associated with past fainting after vaccination.

. Effects of hyperoxia on local and remote microcirculatory inflammatory response after splanchnic ischemia and reperfusion. Am J Physiol Heart Circ Physiol 285: H643-H652, 2003. First published April 24, 2003 10.1152/ajpheart.00900.2002-Splanchnic ischemia-reperfusion (I/R) causes tissue hypoxia that triggers local and systemic microcirculatory inflammatory responses. We evaluated the effects of hyperoxia in I/R induced by 40-min superior mesenteric artery (SMA) occlusion and 120-min reperfusion in four groups of rats: 1) control (anesthesia only), 2) sham operated (all surgical procedures without vascular occlusion; air ventilation), 3) SMA I/R and air, 4) SMA I/R and 100% oxygen ventilation started 10 min before reperfusion. Leukocyte rolling and adhesion in mesenteric microvessels, pulmonary microvascular blood flow velocity (BFV), and macromolecular (FITC-albumin) flux into lungs were monitored by intravital videomicroscopy. We also determined pulmonary leukocyte infiltration. SMA I/R caused marked decreases in mean arterial blood pressure (MABP) and blood flow to the splanchnic and hindquarters vascular beds and pulmonary BFV and shear rates, followed by extensive increase in leukocyte rolling and adhesion and plugging of Ͼ50% of the mesenteric microvasculature. SMA I/R also caused marked increase in pulmonary sequestration of leukocytes and macromolecular leak with concomitant decrease in circulating leukocytes. Inhalation of 100% oxygen maintained MABP at significantly higher values (P Ͻ 0.001) but did not change regional blood flows. Oxygen therapy attenuated the increase in mesenteric leukocyte rolling and adherence (P Ͻ 0.0001) and maintained microvascular patency at values not significantly different from sham-operated animals. Hyperoxia also attenuated the decrease in pulmonary capillary BFV and shear rates, reduced leukocyte infiltration in the lungs (P Ͻ 0.001), and prevented the increase in pulmonary macromolecular leak (P Ͻ 0.001), maintaining it at values not different from sham-operated animals. The data suggest that beneficial effects of normobaric hyperoxia in splanchnic I/R are mediated by attenuation of both local and remote inflammatory microvascular responses. reperfusion injury; acute lung injury; reoxygenation injury; intravital videomicroscopy; multiorgan failure; systemic inflammatory response syndrome HYPOPERFUSION AND ISCHEMIA of the bowel is a common, important pathological process that affects adults and infants. In both groups the morbidity and mortality related to these processes are high. In adults, occlusive and nonocclusive conditions may reduce splanchnic blood flow (8,35

Oxidative stress has a complex effect on cancer development. To further study this process, we induced colon tumors with azoxymethane (AOM) in mice deficient for uncoupling protein-2 (UCP2). UCP2 has recently emerged as a negative regulator of mitochondrial oxidant production. When overexpressed, UCP2 protects cells from oxidative stress, while its absence may cause abundance of reactive oxygen species, release of pro-inflammatory cytokines and persistent activation of nuclear factor kappaB (NF-kappaB), a pleiotropic transcription factor with an increasingly recognized role in cancer. Here we show that Ucp2-/- mice develop more aberrant crypt foci and colon tumors than Ucp2+/+ littermates when examined 24 weeks after the completion of treatment with AOM (10 mg/kg i.p. weekly for a total of 6 weeks, n = 8-12). This effect is primarily seen in the proximal colon of Ucp2-/- mice (P < 0.05), in association with changes indicative of increased oxidative stress (increased staining for malondialdehyde and inducible nitric oxide synthase), enhanced NF-kappaB activation (increased levels of phosphorylated IkappaB and increased nuclear presence of p65) and a disrupted balance between intestinal epithelial cell proliferation (greater 5-bromo-2'-deoxy-uridine incorporation rates and increased phosphorylation of ERK1/2 and AKT) and apoptosis (decreased number of terminal deoxynucleotidyltransferase-mediated nick-end-labeling (TUNEL)-positive cells and increased expression of Bcl-2). In conclusion, our findings provide the first in vivo evidence for a link between UCP2 and tumorigenesis and indicate the need for additional studies to assess the role of mitochondrial uncoupling in cancer development.

Sheets AR, Fülöp P, Derdák Z, Kassai A, Sabo E, Mark NM, Paragh G, Wands JR, Baffy G. Uncoupling protein-2 modulates the lipid metabolic response to fasting in mice. Am J Physiol Gastrointest Liver Physiol 294: G1017-G1024, 2008. First published February 21, 2008 doi:10.1152/ajpgi.00016.2008.-Uncoupling protein-2 (UCP2) regulates insulin secretion by controlling ATP levels in ␤-cells. Although UCP2 deficiency improves glycemic control in mice, increased expression of UCP2 interferes with glucose-stimulated insulin secretion. These observations link UCP2 to ␤-cell dysfunction in type 2 diabetes with a perplexing evolutionary role. We found higher residual serum insulin levels and blunted lipid metabolic responses in fasted ucp2 Ϫ/Ϫ mice, supporting the concept that UCP2 evolved to suppress insulin effects and to accommodate the fuel switch to fatty acids during starvation. In the absence of UCP2, fasting initially promotes peripheral lipolysis and hepatic fat accumulation at less than expected rates but culminates in protracted steatosis, indicating diminished hepatic utilization and clearance of fatty acids. We conclude that UCP2-mediated control of insulin secretion is a physiologically relevant mechanism of the metabolic response to fasting. prolonged fasting; lipolysis; steatosis; insulin secretion UNCOUPLING PROTEIN (UCP) 2, a member of the anion carrier protein superfamily, is a widely distributed constituent of the mitochondrial inner membrane (6, 35). Although UCP2 was identified over 10 years ago by molecular cloning, its biological role and evolutionary aspects remain debated (6,29,35,40). Based on its significant homology with the brown adipose tissue-specific UCP1 (thermogenin), UCP2 was predicted to regulate energy balance. Subsequent observations did not confirm this prediction, and UCP2 appears to have a complex function yet to be fully explored (6,29,35,40). Similar to other uncoupling proteins, UCP2 lowers the mitochondrial membrane potential by mediating proton leak across the inner membrane (6). As a result, UCP2 has the ability to interfere with the function of F 1 F 0 ATP synthase and to alter the matrix ATP-to-ADP ratio (6).Soon after its discovery, the importance of UCP2 was recognized in pancreatic ␤-cells, where UCP2 acts as a negative regulator of glucose-stimulated insulin secretion (GSIS) (30, 51). Pancreatic ␤-cells sense blood glucose through its metabolism that results in increased levels of intracellular ATP and triggers GSIS to maintain glucose homeostasis (41). Because of more efficient oxidative phosphorylation and increased rates of mitochondrial ATP synthesis, UCP2 deficiency is associated with enhanced ␤-cell insulin secretory capacity in ucp2 Ϫ/Ϫ mice and allows the partial correction of diabetes in leptin-deficient ob/ob mice (51). In contrast, overexpression of UCP2 in ␤-cells reduces intracellular ATP levels, leading to diminished GSIS (21). Because increased UCP2 expression of ␤-cells is associated with obesity, UCP2 has been linked to impaired insulin production in typ...

These results support a direct linkage between diabetic vascular disease and the Hp genotype. These Hp-modified mice may serve as a platform on which to test a variety of pharmacological agents in order to decrease diabetic vascular disease.