tin-mesoporphyrin and Sepsis

It is estimated that about two thirds of newborns will appear clinically jaundiced during their first weeks of life. As newborns and their mothers spend fewer days in the hospital after birth, the number of infants readmitted yearly in the United States for neonatal jaundice over the last 10 years has increased by 160%. A portion of these infants present to the emergency department, requiring a careful history and physical examination assessing them for the risk factors associated with pathologic bilirubin levels. Although the spectrum of illness may be great, the overwhelming etiology of neonatal jaundice presenting to an emergency department is physiologic and not due to infection or isoimmunization. Therefore, a little more than a good history, physical examination, and indirect/direct bilirubin levels are needed to evaluate an otherwise well-appearing jaundiced newborn. The American Academy of Pediatrics' 2004 clinical practice guidelines for "Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation" are a helpful and easily accessible resource when evaluating jaundiced newborns (available at http://aappolicy.aappublications.org/cgi/content/full/pediatrics;114/1/297). There are several exciting developments on the horizon for the diagnosis and management of hyperbilirubinemia including increasing use of transcutaneous bilirubin measuring devices and medications such as tin mesoporphyrin and intravenous immunoglobulin that may decrease the need for exchange transfusions.

Topics: Bilirubin; Blood Group Incompatibility; Breast Feeding; Diagnosis, Differential; Emergencies; Erythroblastosis, Fetal; Exchange Transfusion, Whole Blood; Female; Hemoglobinopathies; Humans; Hyperbilirubinemia, Neonatal; Immunoglobulins, Intravenous; Infant, Newborn; Jaundice, Neonatal; Kernicterus; Male; Metabolism, Inborn Errors; Metalloporphyrins; Phototherapy; Practice Guidelines as Topic; Pregnancy; Rh Isoimmunization; Sepsis

The aim of this study was to examine the role of heme oxygenase-1 induction in the intestinal tissue injury in a rat model of sepsis.. Randomized, masked, controlled animal study.. University-based animal research facility.. Sprague-Dawley male rats, weighing 220-250 g (n = 126).. Rats were injected with lipopolysaccharide (10 mg/kg) intraperitoneally. Another group of rats was injected with interleukin-6 (10 microg/kg) intravenously. In some rats, tin mesoporphyrin (1 micromol/kg) was administered intravenously 1 hr before lipopolysaccharide treatment.. Following lipopolysaccharide treatment, expression of heme oxygenase-1 and nonspecific delta-aminolevulinate synthase (ALAS-N), the rate-limiting enzymes of heme catabolism and biosynthesis, respectively, was examined in various regions of the intestine. Lipopolysaccharide treatment markedly increased heme oxygenase-1 messenger RNA and protein concentrations in the mucosal epithelial cells in the duodenum and the jejunum, whereas its expression in the ileum and the colon was hardly detectable and was not influenced by the treatment. ALAS-N messenger RNA was also more markedly increased in the duodenum, the jejunum, and the ileum than in the colon following lipopolysaccharide treatment. Interleukin-6 administration also induced heme oxygenase-1 and ALAS-N gene expression in a pattern similar to that following lipopolysaccharide treatment. In contrast to the marked heme oxygenase-1 expression in the upper intestine, lipopolysaccharide-induced mucosal injury and inflammation in the upper intestine were far less than observed in the lower intestine as judged both by tumor necrosis factor-alpha gene expression and by histologic analysis. Of note, inhibition of heme oxygenase activity by tin mesoporphyrin produced a significant tissue injury in the upper intestine of the lipopolysaccharide-treated animals.. Intestinal heme oxygenase-1 and ALAS-N gene expression was regulated in a site-specific manner in a rat model of sepsis. Our findings also suggest that heme oxygenase-1 induction may play a fundamental role in protecting mucosal epithelial cells of the intestine from oxidative damages that occur in sepsis.

Topics: 5-Aminolevulinate Synthetase; Animals; Disease Models, Animal; Gene Expression Regulation; Heme Oxygenase (Decyclizing); Heme Oxygenase-1; Inflammation; Interleukin-6; Intestinal Mucosa; Intestines; Lipopolysaccharides; Male; Metalloporphyrins; Oxidative Stress; Random Allocation; Rats; Rats, Sprague-Dawley; RNA, Messenger; Sepsis; Tumor Necrosis Factor-alpha