The Spanish flu as a worst case scenario?

References

• Mounier-Jack S, Coker RJ. How prepared is Europe for pandemic influenza? Analysis of national plans. Lancet 2006; 367: 1405–11
   PubMed Web of Science ®Google Scholar
• Taubenberger JK, Reid AH, Janczewski TA, Fanning TG. Integrating historical, clinical and molecular genetic data in order to explain the origin and virulence of the 1918 Spanish influenza virus. Philos Trans R Soc Lond B Biol Sci 2001; 356: 1829–39
   PubMed Web of Science ®Google Scholar
• Osterholm MT. Preparing for the next pandemic. Foreign Affairs 2005; July/August:24–37.
   Google Scholar
• Johnson NP, Mueller J. Updating the accounts: global mortality of the 1918–1920 “Spanish” influenza pandemic. Bull Hist Med 2002; 76: 105–15
   PubMed Web of Science ®Google Scholar
• Murray CJ, Lopez AD, Chin B, Feehan D, Hill KH. Estimation of potential global pandemic influenza mortality on the basis of vital registry data from the 1918–20 pandemic: a quantitative analysis. Lancet 2006; 368: 2211–18
   PubMed Web of Science ®Google Scholar
• Mamelund S-E. Spanish Influenza and beyond: The case of Norway. Dr. polit. Thesis, Department of Economics, University of Oslo, September 2004.
   Google Scholar
• Oxford JS, Lambkin R, Sefton A, Daniels R, Elliot A, Brown R, et al. A hypothesis: the conjunction of soldiers, gas, pigs, ducks, geese and horses in Northern France during the Great War provided the conditions for the emergence of the “Spanish” influenza pandemic of 1918–1919. Vaccine 2005; 23: 940–5
   PubMed Web of Science ®Google Scholar
• Mamelund S-E. Spanish influenza mortality of ethnic minorities in Norway 1918–1919. Eur J Population 2003; 19: 83–102
   Web of Science ®Google Scholar
• Smith FB. The Russian influenza in the United Kingdom, 1889–1894. Soc Hist Med 1995; 8: 55–73
   Web of Science ®Google Scholar
• World Health Organization. Influenza research at the human and animal interface. Report of a WHO working group. Geneva, Switzerland, 21–22 September 2006. WHO/EPR/GIP/2006.3. Available online on WHO home site.
   Google Scholar
• Sompayrac L. How the immune system works2nd edn. Blackwell Publishing, Oxford 2003
   Google Scholar
• Qureshi K, Molbak K, Sandström A, Kofoed PE, Rodrigues A, Dias F, et al. Breast milk reduces the risk of illness in children of mothers with cholera: observations from an epidemic of cholera in Guinea-Bissau. Pediatr Infect Dis J 2006; 25: 1163–6
   PubMed Web of Science ®Google Scholar
• Ballabio C, Bertino E, Coscia A, Fabris C, Fuggetta D, Molfino S, et al. Immunoglobulin-A profile in breast milk from mothers delivering full term and preterm infants. Int J Immunopathol Pharmacol 2007; 20: 119–28
   Web of Science ®Google Scholar
• Severin S, Wenshui X. Milk biologically active components as nutraceuticals: review. Crit Rev Food Sci Nutr 2005; 45: 645–56
   PubMed Web of Science ®Google Scholar
• Morrow AL, Rangel JM. Breast milk reduces the risk of illness in children of mothers with cholera: observations from an epidemic of cholera in Guinea-Bissau. Pediatr Infect Dis J. 2006; 25: 1163–6
   Web of Science ®Google Scholar
• Coppa GV, Bruni S, Morelli L, Soldi S, Gabrielli O. The first prebiotics in humans: human milk oligosaccharides. J Clin Gastroenterol 2004;38(6 Suppl):S80–S83.
   Web of Science ®Google Scholar
• Coppa GV, Zampini L, Galeazzi T, Gabrielli O. Prebiotics in human milk: a review. Dig Liver Dis 2006; 38(Suppl 2)S291–S294
   PubMedGoogle Scholar
• Picard C, Fioramonti J, Francois A, Robinson T, Neant F, Matuchansky C. Review article: bifidobacteria as probiotic agents – physiological effects and clinical benefits. Aliment Pharmacol Ther 2005; 22: 495–512
   PubMed Web of Science ®Google Scholar
• Bruzzese E, Volpicelli M, Squaglia M, Tartaglione A, Guarino A. Impact of prebiotics on human health. Dig Liver Dis 2006; 38(Suppl 2)S283–S287
   Google Scholar
• Leakey R, Lewins R. People of the lake. Mankind & its beginnings. Dutton, New York 1977
   Google Scholar
• Woldemaria A, Norwegian University of Life Sciences (personal communication).
   Google Scholar
• McKeon T. The modern rise of population. Academic Press, New York 1976
   Google Scholar
• Scrimshaw NS, Taylor CE, Gordon JE. Interactions of nutrition and infection. WHO, Geneva 1968
   Google Scholar
• Scrimshaw NS, SanGiovanni JP. Synergism of nutrition, infection, and immunity: an overview. Am J Clin Nutr 1997; 66: 464S–477S
   PubMed Web of Science ®Google Scholar
• Leung AK, Kellner JD, Davies HD. Rotavirus gastroenteritis. Adv Ther 2005; 22: 476–87
   PubMed Web of Science ®Google Scholar
• Christophersen OA, Haug A. More about hypervirulent avian influenza: is the world now better prepared? Microb Ecol Health Dis 2007;19:78–121.
   Google Scholar
• Hannappel E, Huff T. The thymosins. Prothymosin alpha, parathymosin, and beta-thymosins: structure and function. Vitam Horm 2003; 66: 257–96
   PubMed Web of Science ®Google Scholar
• Cordero OJ, Sarandeses CS, Lopez JL, Nogueria M. Prothymosin alpha enhances human natural killer cell cytotoxicity: role in mediating signals for NK activity. Lymphokine Cytokine Res 1992; 11: 277–85
   PubMedGoogle Scholar
• Saha AR, Hadden EM, Hadden JW. Zinc induces thymulin secretion from human thymic epithelial cells in vitro and augments splenocyte and thymocyte responses in vivo. Int J Immunopharmacol 1995; 17: 729–33
   PubMed Web of Science ®Google Scholar
• Geneser F. Histologi – på molekylærbiologisk grundlag. [Histology – on basis of molecular biology.] 1st edn, 4th reprint. København: Munksgaard, 2004 (in Danish).
   Google Scholar
• Min H, Montecino-Rodriguez E, Dorshkind K. Reassessing the role of growth hormone and sex steroids in thymic involution. Clin Immunol 2006; 118: 117–23
   PubMed Web of Science ®Google Scholar
• Bellamy D, Hinsull SM, Phillips JG. Factors controlling growth and age involution of the rat thymus. Age Ageing 1976; 5: 12–19
   Google Scholar
• Fahy GM. Apparent induction of partial thymic regeneration in a normal human subject: a case report. J Anti Aging Med 2003; 6: 219–27
   Google Scholar
• Zoller AL, Kersh GJ. Estrogen induces thymic atrophy by eliminating early thymic progenitors and inhibiting proliferation of beta-selected thymocytes. J Immunol 2006; 176: 7371–8
   PubMed Web of Science ®Google Scholar
• Hareramadas B, Rai U. Cellular mechanism of estrogen-induced thymic involution in wall lizard: caspase-dependent action. J Exp Zool A Comp Exp Biol 2006; 305: 396–409
   Google Scholar
• Yao G, Hou Y. Thymic atrophy via estrogen-induced apoptosis is related to Fas/FasL pathway. Int Immunopharmacol 2004; 4: 213–21
   PubMed Web of Science ®Google Scholar
• Kim DH, Kim CH, Kim MS, Kim JY, Jung KJ, Chung JH, et al. Suppression of age-related inflammatory NF-kappaB activation by cinnamaldehyde. Biogerontology 2007; 8: 545–54
   PubMed Web of Science ®Google Scholar
• Peng Y, Gallagher SF, Haines K, Baksh K, Murr MM. Nuclear factor-kappaB mediates Kupffer cell apoptosis through transcriptional activation of Fas/FasL. J Surg Res 2006; 130: 58–65
   PubMed Web of Science ®Google Scholar
• Yao PL, Lin YC, Sawhney P, Richburg JH. Transcriptional regulation of FasL expression and participation of sTNF-alpha in response to Sertoli cell injury. J Biol Chem 2007; 282: 5420–31
   PubMed Web of Science ®Google Scholar
• Davis BH, Chen A, Beno DW. Raf and mitogen-activated protein kinase regulate stellate cell collagen gene expression. J Biol Chem 1996; 271: 11039–42
   PubMed Web of Science ®Google Scholar
• Berra E, Pages G, Pouyssegur J. MAP kinases and hypoxia in the control of VEGF expression. Cancer Metastasis Rev 2000; 19: 139–45
   PubMed Web of Science ®Google Scholar
• Pages G, Milanini J, Richard DE, Berra E, Gothie E, Vinals F, et al. Signaling angiogenesis via p42/p44 MAP kinase cascade. Ann N Y Acad Sci 2000; 902: 187–200
   PubMed Web of Science ®Google Scholar
• Moon SK, Jung SY, Kim CH. Transcription factor Sp1 mediates p38MAPK-dependent activation of the p21WAF1 gene promoter in vascular smooth muscle cells by pyrrolidine dithiocarbamate. Biochem Biophys Res Commun 2004; 316: 605–11
   Web of Science ®Google Scholar
• D'Addario M, Arora PD, McCulloch CA. Role of p38 in stress activation of Sp1. Gene 2006; 379: 51–61
   Web of Science ®Google Scholar
• Dasari A, Bartholomew JN, Volonte D, Galbiati F. Oxidative stress induces premature senescence by stimulating caveolin-1 gene transcription through p38 mitogen-activated protein kinase/Sp1-mediated activation of two GC-rich promoter elements. Cancer Res 2006; 66: 10805–14
   PubMed Web of Science ®Google Scholar
• Gee K, Angel JB, Mishra S, Blahoianu MA, Kumar A. IL-10 regulation by HIV-Tat in primary human monocytic cells: involvement of calmodulin/calmodulin-dependent protein kinase-activated p38 MAPK and Sp-1 and CREB-1 transcription factors. J Immunol 2007; 178: 798–807
   PubMed Web of Science ®Google Scholar
• Tu VC, Bahl JJ, Chen QM. Distinct roles of p42/p44(ERK) and p38 MAPK in oxidant-induced AP-1 activation and cardiomyocyte hypertrophy. Cardiovasc Toxicol 2003; 3: 119–33
   Google Scholar
• Zdanov S, Debacq-Chainiaux F, Remacle J, Toussaint O. Identification of p38MAPK-dependent genes with changed transcript abundance in H2O2-induced premature senescence of IMR-90 hTERT human fibroblasts. FEBS Lett 2006; 580: 6455–63
   Web of Science ®Google Scholar
• Kim DH, Kim HK, Park S, Kim JY, Zou Y, Cho KH, et al. Short-term feeding of baicalin inhibits age-associated NF-kappaB activation. Mech Ageing Dev 2006; 127: 719–25
   PubMed Web of Science ®Google Scholar
• Lee HC, Wei YH. Oxidative stress, mitochondrial DNA mutation, and apoptosis in aging. Exp Biol Med (Maywood) 2007; 232: 592–606
   PubMed Web of Science ®Google Scholar
• Barja G. Mitochondrial free radical production and aging in mammals and birds. Ann N Y Acad Sci 1998; 854: 224–38
   PubMed Web of Science ®Google Scholar
• Barja G. Rate of generation of oxidative stress-related damage and animal longevity. Free Radic Biol Med 2002; 33: 1167–72
   PubMed Web of Science ®Google Scholar
• Pamplona R, Portero-Otin M, Riba D, Ledo F, Gredilla R, Herrero A, et al. Heart fatty acid unsaturation and lipid peroxidation, and aging rate, are lower in the canary and the parakeet than in the mouse. Aging (Milano) 1999; 11: 44–9
   Google Scholar
• Bodey B, Bodey B, Jr, Siegel SE, Kaiser HE. The role of zinc in pre- and postnatal mammalian thymic immunohistogenesis. In Vivo 1998; 12: 695–722
   Web of Science ®Google Scholar
• Bodey B, Bodey B, Jr, Siegel SE, Kaiser HE. Involution of the mammalian thymus, one of the leading regulators of aging. In Vivo 1997; 11: 421–40
   PubMed Web of Science ®Google Scholar
• Goya RG, Gagnerault MC, De Moraes MC, Savino W, Dardenne M. In vivo effects of growth hormone on thymus function in aging mice. Brain Behav Immun 1992; 6: 341–54
   PubMed Web of Science ®Google Scholar
• Yamada M, Hato F, Kinoshita Y, Tominaga K, Tsuji Y. The indirect participation of growth hormone in the thymocyte proliferation system. Cell Mol Biol (Noisy-le-grand) 1994; 40: 111–21
   Web of Science ®Google Scholar
• De Mello-Coelho V, Savino W, Postel-Vinay MC, Dardenne M. Role of prolactin and growth hormone on thymus physiology. Dev Immunol 1998; 6: 317–23
   PubMedGoogle Scholar
• Vigano A, Saresella M, Trabattoni D, Giacomet V, di Natale B, Merlo M, et al. Growth hormone in T-lymphocyte thymic and postthymic development: a study in HIV-infected children. J Pediatr 2004; 145: 542–8
   PubMed Web of Science ®Google Scholar
• Polgreen L, Steiner M, Dietz CA, Manivel JC, Petryk A. Thymic hyperplasia in a child treated with growth hormone. Growth Horm IGF Res 2007; 17: 41–6
   Web of Science ®Google Scholar
• Brunton LL, Lazo JS, Parker KL. Goodman & Gilman's The pharmacological basis of therapeutics, 11th edn. New York: McGraw-Hill, 2006.
   Google Scholar
• Huang Y, Chen Z, Zhou C, Yao H, Li M, Xu C. The modulation of thymosin alpha 1 in the maturation, differentiation and function of murine bone marrow-derived dendritic cells in the absence or presence of tumor necrosis factor-alpha. Int Immunopharmacol 2004; 4: 539–46
   PubMed Web of Science ®Google Scholar
• Yang YM, Lu XY, Huang WD, Shen MY. [Effect of thymosin alpha 1 on cellular immune function in elderly patients with malignant tumor.]. Zhejiang Da Xue Xue Bao Yi Xue Ban 2003; 32: 339–41 (in Chinese)
   Google Scholar
• Lauria F, Raspadori D, Tura S. Effect of a thymic factor on T lymphocytes in B cell chronic lymphocytic leukemia: in vitro and in vivo studies. Blood 1984; 64: 667–71
   PubMed Web of Science ®Google Scholar
• Wespes E, Schulman CC. Male andropause: myth, reality, and treatment. Int J Impot Res 2002; 14(Suppl 1)S93–S98
   Google Scholar
• Moxnes JE, Christophersen OA. Counter-attacking pandemic H5N1 bird influenza by counter-pandemic. Microb Ecol Health Dis 2006; 18: 4–25
   Google Scholar
• Ronichevskaya GM, Smirnov PN, Goncharova NB, Zlobina GA. [The biological activity of chalone-like proteoglycans isolated from the spleen and thymus at various periods of ontogeny.]. Ontogenez 1989; 20: 409–15 (in Russian)
   Google Scholar
• Liang J, Yao G, Yang L, Hou Y. Dehydroepiandrosterone induces apoptosis of thymocyte through Fas/Fas-L pathway. Int Immunopharmacol 2004; 4: 1467–75
   Web of Science ®Google Scholar
• Yao G, Shang XJ. A comparison of modulation of proliferation of thymocyte by testosterone, dehydroisoandrosterone and androstenedione in vitro. Arch Androl 2005; 51: 257–65
   Web of Science ®Google Scholar
• Yan CH, Jiang XF, Pei X, Dai YR. The in vitro antiapoptotic effect of dehydroepiandrosterone sulfate in mouse thymocytes and its relation to caspase-3/caspase-6. Cell Mol Life Sci 1999; 56: 543–7
   Web of Science ®Google Scholar
• Molinero P, Soutto M, Benot S, Hmadcha A, Guerrero JM. Melatonin is responsible for the nocturnal increase observed in serum and thymus of thymosin alpha1 and thymulin concentrations: observations in rats and humans. J Neuroimmunol 2000; 103: 180–8
   PubMed Web of Science ®Google Scholar
• Sainz RM, Mayo RC, Reiter RJ, Antolin I, Esteban MM, Rodriguez C. Melatonin regulates glucocorticoid receptor: an answer to its antiapoptotic action in thymus. FASEB J 1999; 13: 1547–56
   PubMed Web of Science ®Google Scholar
• Hoijman E, Rocha Viegas L, Keller Sarmiento MI, Rosenstein RE, Pecci A. Involvement of Bax protein in the prevention of glucocorticoid-induced thymocytes apoptosis by melatonin. Endocrinology 2004; 145: 418–25
   Web of Science ®Google Scholar
• Oner H, Kus I, Oner J, Ogeturk M, Ozan E, Ayar A. Possible effects of melatonin on thymus gland after pinealectomy in rats. Neuro Endocrinol Lett 2004; 25: 115–18
   Web of Science ®Google Scholar
• Pertsov SS. Effect of melatonin on the thymus, adrenal glands, and spleen in rats during acute stress. Bull Exp Biol Med 2006; 141: 292–5
   Web of Science ®Google Scholar
• Presman DM, Hoijman E, Ceballos NR, Galigniana MD, Pecci A. Melatonin inhibits glucocorticoid receptor nuclear translocation in mouse thymocytes. Endocrinology 2006; 147: 5452–9
   PubMed Web of Science ®Google Scholar
• Naranjo MC, Guerrero JM, Rubio A, Lardone PJ, Carillo-Vico A, Carrascosa-Salmoral MP, et al. Melatonin biosynthesis in the thymus of humans and rats. Cell Mol Life Sci 2007; 64: 781–90
   PubMed Web of Science ®Google Scholar
• Dardenne M, Savino W, Gagnerault MC, Itoh T, Bach JF. Neuroendocrine control of thymic hormonal production. I. Prolactin stimulates in vivo and in vitro the production of thymulin by human and murine thymic epithelial cells. Endocrinology 1989; 125: 3–12
   PubMed Web of Science ®Google Scholar
• McNeill WH. Plagues and peoples. Anchor Books, New York 1998
   Google Scholar
• Maestroni GJ, Covacci V, Conti A. Hematopoietic rescue via T-cell-dependent, endogenous granulocyte-macrophage colony-stimulating factor induced by the pineal neurohormone melatonin in tumor-bearing mice. Cancer Res 1994; 54: 2429–32
   PubMed Web of Science ®Google Scholar
• Maestroni GJ. kappa-Opioid receptors in marrow stroma mediate the hematopoietic effects of melatonin-induced opioid cytokines. Ann N Y Acad Sci 1998; 840: 411–19
   Web of Science ®Google Scholar
• Maestroni GJ, Zammaretti F, Pedrinis E. Hematopoietic effect of melatonin involvement of type 1 kappa-opioid receptor on bone marrow macrophages and interleukin-1. J Pineal Res 1999; 27: 145–53
   PubMed Web of Science ®Google Scholar
• Srinavasan V, Maestroni G, Cardinali D, Esquifino A, Perumal SP, Miller S. Melatonin, immune function and aging. Immun Ageing 2005; 2: 17
   Google Scholar
• Tan DX, Manchester LC, Reiter RJ, Qi WB, Karbownik M, Calvo JR. Significance of melatonin in antioxidative defense system: reactions and products. Biol Signals Recept 2000; 9: 137–59
   PubMedGoogle Scholar
• Tan DX, Manchester LC, Terron MP, Flores LJ, Reiter RJ. One molecule, many derivatives: a never-ending interaction of melatonin with reactive oxygen and nitrogen species?. J Pineal Res 2007; 42: 28–42
   PubMed Web of Science ®Google Scholar
• Reiter RJ, Carneiro RC, Oh CS. Melatonin in relation to cellular antioxidative defense mechanisms. Horm Metab Res 1997; 29: 363–72
   PubMed Web of Science ®Google Scholar
• Maldonado MD, Murillo-Cabezas F, Terron MP, Flores LJ, Tan DX, Manchester LC, et al. The potential of melatonin in reducing morbidity-mortality after craniocerebral trauma. J Pineal Res 2007; 42: 1–11
   PubMed Web of Science ®Google Scholar
• Maldonado MD, Murillo-Cabezas F, Calvo JR, Lardone PJ, Tan DX, Guerrero JM, et al. Melatonin as pharmacologic support in burn patients: a proposed solution to thermal injury-related lymphocytopenia and oxidative damage. Crit Care Med 2007; 35: 1177–85
   Web of Science ®Google Scholar
• Sandyk PR. Possible role of pineal melatonin in the mechanisms of aging. Int J Neurosci 1990; 52: 85–92
   PubMed Web of Science ®Google Scholar
• Reiter RJ. Pineal function during aging: attenuation of the melatonin rhythm and its neurobiological consequences. Acta Neurobiol Exp (Wars) 1994; 54(Suppl)31–9
   PubMedGoogle Scholar
• Ruzsas C, Mess B. Melatonin and aging. A brief survey. Neuro Endocrinol Lett 2000; 21: 17–23
   PubMed Web of Science ®Google Scholar
• Kuhn DM, Ruskin B, Lovenberg W. Tryptophan hydroxylase. The role of oxygen, iron, and sulfhydryl groups as determinants of stability and catalytic activity. J Biol Chem 1980; 255: 4137–43
   PubMed Web of Science ®Google Scholar
• Johnson M, Hanson GR, Gibb JW. Characterization of acute N-ethyl-3,4-methylenedioxyamphetamine (MDE) action on the central serotonergic system. Biochem Pharmacol 1989; 38: 4333–8
   PubMed Web of Science ®Google Scholar
• Stone DM, Johnson M, Hanson GR, Gibb JW. Acute inactivation of tryptophan hydroxylase by amphetamine analogs involves the oxidation of sulfhydryl sites. Eur J Pharmacol 1989; 172: 93–7
   PubMed Web of Science ®Google Scholar
• Kuhn DM, Arthur RE, Jr. Inactivation of brain tryptophan hydroxylase by nitric oxide. J Neurochem 1996; 67: 1072–7
   PubMed Web of Science ®Google Scholar
• Kuhn DM, Arthur RE, Jr. Inactivation of tryptophan hydroxylase by nitric oxide: enhancement by tetrahydrobiopterin. J Neurochem 1997; 68: 1495–502
   PubMed Web of Science ®Google Scholar
• Kuhn DM, Geddes TJ. Peroxynitrite inactivates tryptophan hydroxylase via sulfhydryl oxidation. Coincident nitration of enzyme tyrosyl residues has minimal impact on catalytic activity. J Biol Chem 1999; 274: 29726–32
   PubMed Web of Science ®Google Scholar
• Mohan PF, Jacobson MS. Inhibition of macrophage superoxide generation by dehydroepiandrosterone. Am J Med Sci 1993; 306: 10–15
   PubMed Web of Science ®Google Scholar
• Padgett DA, Loria RM. In vitro potentiation of lymphocyte activation by dehydroepiandrosterone, androstenediol, and androstenetriol. J Immunol 1994; 153: 1544–52
   PubMed Web of Science ®Google Scholar
• Loria RM. Antiglucocorticoid function of androstenetriol. Psychoneuroendocrinology 1997; 22(Suppl 1)S103–S108
   Web of Science ®Google Scholar
• Hernandez-Pando R, De La Luz Streber M, Orozco H, Arriaga K, Pavon L, Al-Nakhli SA, et al. The effects of androstenediol and dehydroepiandrosterone on the course and cytokine profile of tuberculosis in BALB/c mice. Immunology 1998; 95: 234–41
   PubMed Web of Science ®Google Scholar
• Loria RM, Padgett DA. Control of the immune response by DHEA and its metabolites. Rinsho Byori 1998; 46: 505–17
   Google Scholar
• Padgett DA, Loria RM. Endocrine regulation of murine macrophage function: effects of dehydroepiandrosterone, androstenediol, and androstenetriol. J Neuroimmunol 1998; 84: 61–8
   PubMed Web of Science ®Google Scholar
• Loria RM, Conrad DH, Huff T, Carter H, Ben-Nathan D. Androstenetriol and androstenediol. Protection against lethal radiation and restoration of immunity after radiation injury. Ann N Y Acad Sci 2000; 917: 860–7
   PubMed Web of Science ®Google Scholar
• Whitnall MH, Elliott TB, Harding RA, Inal CE, Landauer MR, Wilhelmsen CL, et al. Androstenediol stimulates myelopoiesis and enhances resistance to infection in gamma-irradiated mice. Int J Immunopharmacol 2000; 22: 1–14
   PubMed Web of Science ®Google Scholar
• Loria RM. Immune up-regulation and tumor apoptosis by androstene steroids. Steroids 2002; 67: 953–66
   PubMed Web of Science ®Google Scholar
• Chahal HS, Drake WM. The endocrine system and ageing. J Pathol 2007; 211: 173–80
   PubMed Web of Science ®Google Scholar
• Ben-Nathan D, Lachmi B, Lustig S, Feuerstein G. Protection by dehydroepiandrosterone in mice infected with viral encephalitis. Arch Virol 1991; 120: 263–71
   PubMed Web of Science ®Google Scholar
• Ben-Nathan D, Lustig S, Kobiler D, Danenberg HD, Lupu E, Feuerstein G. Dehydroepiandrosterone protects mice inoculated with West Nile virus and exposed to cold stress. J Med Virol 1992; 38: 159–66
   PubMed Web of Science ®Google Scholar
• Loria RM, Padgett DA. Androstenediol regulates systemic resistance against lethal infections in mice. Arch Virol 1992; 127: 103–15
   PubMed Web of Science ®Google Scholar
• Carr DJ. Increased levels of IFN-gamma in the trigeminal ganglion correlate with protection against HSV-1-induced encephalitis following subcutaneous administration with androstenediol. J Neuroimmunol 1998; 89: 160–7
   PubMed Web of Science ®Google Scholar
• Daigle J, Carr DJ. Androstenediol antagonizes herpes simplex virus type 1-induced encephalitis through the augmentation of type I IFN production. J Immunol 1998; 160: 3060–6
   PubMed Web of Science ®Google Scholar
• Padgett DA, Loria RM, Sheridan JF. Endocrine regulation of the immune response to influenza virus infection with a metabolite of DHEA-androstenediol. J Neuroimmunol 1997; 78: 203–11
   PubMed Web of Science ®Google Scholar
• Padgett DA, Sheridan JF. Androstenediol (AED) prevents neuroendocrine-mediated suppression of the immune response to an influenza viral infection. J Neuroimmunol 1999; 98: 121–9
   PubMed Web of Science ®Google Scholar
• Padgett DA, Loria RM, Sheridan JF. Steroid hormone regulation of antiviral immunity. Ann N Y Acad Sci 2000; 917: 935–43
   Web of Science ®Google Scholar
• Carroll J, Fearnley IM, Shannon RJ, Hirst J, Walker JE. Analysis of the subunit composition of complex I from bovine heart mitochondria. Mol Cell Proteomics 2003; 2: 117–26
   PubMed Web of Science ®Google Scholar
• Mansouri A, Muller FL, Liu Y, Ng R, Faulkner J, Hamilton M, et al. Alterations in mitochondrial function, hydrogen peroxide release and oxidative damage in mouse hind-limb skeletal muscle during aging. Mech Ageing Dev 2006; 127: 298–306
   PubMed Web of Science ®Google Scholar
• Jornot L, Petersen H, Junod AF. Hydrogen peroxide-induced DNA damage is independent of nuclear calcium but dependent on redox-active ions. Biochem J 1998; 335: 85–94
   PubMed Web of Science ®Google Scholar
• Lloyd DR, Carmichael PL, Phillips DH. Comparison of the formation of 8-hydroxy-2′-deoxyguanosine and single- and double-strand breaks in DNA mediated by Fenton reactions. Chem Res Toxicol 1998; 11: 420–7
   PubMed Web of Science ®Google Scholar
• Barbouti A, Doulias PT, Zhu BZ, Frei B, Galaris D. Intracellular iron, but not copper, plays a critical role in hydrogen peroxide-induced DNA damage. Free Radic Biol Med 2001; 31: 490–8
   PubMed Web of Science ®Google Scholar
• Messina SA, Dawson R, Jr. Attenuation of oxidative damage to DNA by taurine and taurine analogs. Adv Exp Med Biol 2000; 483: 355–67
   Web of Science ®Google Scholar
• Rodriguez B, Sethi AK, Cheruvu VK, Mackay W, Bosch RJ, Kitahata M, et al. Predictive value of plasma HIV RNA level on rate of CD4 T-cell decline in untreated HIV infection. JAMA 2006; 296: 1498–506
   PubMed Web of Science ®Google Scholar
• Di Marzio L, Alesse E, Roncaioli P, Muzi P, Moretti S, Marcellini S, et al. Influence of L-carnitine on CD95 cross-lining-induced apoptosis and ceramide generation in human cell lines: correlation with its effects on purified acidic and neutral sphingomyelinases in vitro. Proc Assoc Am Physicians 1997; 109: 154–63
   Google Scholar
• Di Marzio L, Moretti S, D'Alo S, Zazzeroni F, Marcellini S, Smacchia C, et al. Acetyl-L-carnitine administration increases insulin-like growth factor 1 levels in asymptomatic HIV-1-infected subjects: correlation with its suppressive effect on lymphocyte apoptosis and ceramide generation. Clin Immunol 1999; 92: 103–10
   PubMed Web of Science ®Google Scholar
• Christophersen OA, Haug A. Possible roles of oxidative stress, local circulatory failure and nutrition factors in the pathogenesis of hypervirulent influenza: implications for therapy and global emergency preparedness. Microb Ecol Health Dis 2005; 17: 189–99
   Google Scholar
• Chatterjee S. Sphingolipids in atherosclerosis and vascular biology. Arterioscler Thromb Vasc Biol 1998; 18: 1523–33
   PubMed Web of Science ®Google Scholar
• Corda S, Laplace C, Vicaut E, Duranteau J. Rapid reactive oxygen species production by mitochondria in endothelial cells exposed to tumor necrosis factor-alpha is mediated by ceramide. Am J Respir Cell Mol Biol 2001; 24: 762–8
   PubMed Web of Science ®Google Scholar
• Suematsu N, Tsutsui H, Wen J, Kang D, Ikeuchi M, Ide T, et al. Oxidative stress mediates tumor necrosis factor-alpha-induced mitochondrial DNA damage and dysfunction in cardiac myocytes. Circulation 2003; 107: 1418–23
   PubMed Web of Science ®Google Scholar
• Martin SF, Williams N, Chatterjee S. Lactosylceramide is required in apoptosis induced by N-Smase. Glycoconj J 2006; 23: 147–57
   PubMed Web of Science ®Google Scholar
• Garcia-Ruiz C, Colell A, Mari M, Morales A, Fernandez-Checa JC. Direct effect of ceramide on the mitochondrial electron transport chain leads to generation of reactive oxygen species. Role of mitochondrial glutathione. J Biol Chem 1997; 272: 11369–77
   PubMed Web of Science ®Google Scholar
• Garcia-Ruiz C, Colell A, Morales A, Calvo M, Enrich C, Fernandez-Checa JC. Trafficking of ganglioside GD3 to mitochondria by tumor necrosis factor-alpha. J Biol Chem 2002; 277: 36443–8
   Web of Science ®Google Scholar
• Garcia-Ruiz C, Colell A, Paris R, Fernandez-Checa JC. Direct interaction of GD3 ganglioside with mitochondria generates reactive oxygen species followed by mitochondrial permeability transition, cytochrome c release, and caspase activation. FASEB J 2000; 14: 847–58
   PubMed Web of Science ®Google Scholar
• Goldfeld AE, Doyle C, Maniatis T. Human tumor necrosis factor alpha gene regulation by virus and lipopolysaccharide. Proc Natl Acad Sci U S A 1990; 87: 9769–73
   PubMed Web of Science ®Google Scholar
• Yao J, Mackman N, Edgington TS, Fan ST. Lipopolysaccharide induction of the tumor necrosis factor-alpha promoter in human monocytic cells. Regulation by Egr-1, c-Jun, and NF-kappaB transcription factors. J Biol Chem 1997; 272: 17795–801
   PubMed Web of Science ®Google Scholar
• Liu H, Sidiropoulos P, Song G, Pagliari LJ, Birrer MJ, Stein B, et al. TNF-alpha gene expression in macrophages: regulation by NF-kappa B is independent of c-Jun or C/EBP beta. J Immunol 2000; 164: 4277–85
   PubMed Web of Science ®Google Scholar
• Steer JH, Kroeger KM, Abraham LJ, Joyce DA. Glucocorticoids suppress tumor necrosis factor-alpha expression by human monocytic THP-1 cells by suppressing transactivation through adjacent NF-kappa B and c-Jun-activating transcription factor-2 binding sites in the promoter. J Biol Chem 2000; 275: 18432–40
   PubMed Web of Science ®Google Scholar
• Sanceau J, Kaisho T, Hirano T, Wietzerbin J. Triggering of the human interleukin-6 gene by interferon-gamma and tumor necrosis factor-alpha in monocytic cells involves cooperation between interferon regulatory factor-1, NF kappa B, and Sp1 transcription factors. J Biol Chem 1995; 270: 27920–31
   PubMed Web of Science ®Google Scholar
• Zhang X, Wu K, Wang D, Yue X, Song D, Zhu Y, et al. Nucleocapsid protein of SARS-CoV activates interleukin-6 expression through cellular transcription factor NF-kappaB. Virology 2007; 365: 324–35
   Web of Science ®Google Scholar
• Yang CM, Chien CS, Hsiao LD, Luo SF, Wang CC. Interleukin-1beta-induced cyclooxygenase-2 expression is mediated through activation of p42/44 and p38 MAPKs, and NF-kappaB pathways in canine tracheal smooth muscle cells. Cell Signal 2002; 14: 899–911
   PubMed Web of Science ®Google Scholar
• Luo SF, Wang CC, Chien CS, Hsiao LD, Yang CM. Induction of cyclooxygenase-2 by lipopolysaccharide in canine tracheal smooth muscle cells: involvement of p42/p44 and p38 mitogen-activated protein kinases and nuclear factor-kappaB pathways. Cell Signal 2003; 15: 497–509
   PubMed Web of Science ®Google Scholar
• Lin CC, Hsiao LD, Chien CS, Lee CW, Hsieh JT, Yang CM. Tumor necrosis factor-alpha-induced cyclooxygenase-2 expression in human tracheal smooth muscle cells: involvement of p42/p44 and p38 mitogen-activated protein kinases and nuclear factor-kappaB. Cell Signal 2004; 16: 597–607
   PubMed Web of Science ®Google Scholar
• Si J, Fu X, Behar J, Wands J, Beer DG, Souza RF, et al. NADPH oxidase NOX5-S mediates acid-induced cyclooxygenase-2 expression via activation of NF-kappa B in Barrett's esophageal adenocarcinoma cells. J Biol Chem 2007; 282: 16244–55
   PubMed Web of Science ®Google Scholar
• Leonarduzzi G, Scavazza A, Biasi F, Chiarpotto E, Camandola S, Vogel S, et al. The lipid peroxidation end product 4-hydroxy-2,3-nonenal up-regulates transforming growth factor beta1 expression in the macrophage lineage: a link between oxidative injury and fibrosclerosis. FASEB J 1997; 11: 851–7
   PubMed Web of Science ®Google Scholar
• Chiarpotto E, Allasia C, Biasi F, Leonarduzzi G, Ghezzo F, Berta G, et al. Down-modulation of nuclear localisation and pro-fibrogenic effect of 4-hydroxy-2,3-nonenal by thiol- and carbonyl-reagents. Biochim Biophys Acta 2002; 1584: 1–8
   PubMed Web of Science ®Google Scholar
• Chiarpotto E, Castello L, Leonarduzzi G, Biasin And F, Poli G. Role of 4-hydroxy-2,3-nonenal in the pathogenesis of fibrosis. Biofactors 2005; 24: 229–36
   Web of Science ®Google Scholar
• Jarnicki AG, Lysaght J, Todryk S, Mills KH. Suppression of antitumor immunity by IL-10 and TGF-beta-producing T cells infiltrating the growing tumor: influence of tumor environment on the induction of CD4+ and CD8+ regulatory T cells. J Immunol 2006; 177: 896–904
   PubMed Web of Science ®Google Scholar
• Kriegel MA, Li MO, Sanjabi S, Wan YY, Flavell RA. Transforming growth factor-beta: recent advances on its role in immune tolerance. Curr Rheumatol Rep 2006; 8: 138–44
   PubMedGoogle Scholar
• Li MQ, Sanjabi S, Flavell RA. Transforming growth factor-beta controls development, homeostasis, and tolerance of T cells by regulatory T cell-dependent and -independent mechanisms. Immunity 2006; 25: 455–71
   PubMed Web of Science ®Google Scholar
• Kojima M, Morisaki T, Uchiyama A, Doi F, Mibu R, Katano M, et al. Association of enhanced cyclooxygenase-2 expression with possible local immunosuppression in human colorectal carcinomas. Ann Surg Oncol 2001; 8: 458–65
   PubMed Web of Science ®Google Scholar
• Harizi H, Juzan M, Pitard V, Moreau JF, Gualde N. Cyclooxygenase-2-issued prostaglandin E2 enhances the production of endogenous IL-10, which down-regulates dendritic cell functions. J Immunol 2002; 168: 2255–63
   PubMed Web of Science ®Google Scholar
• Akasaki Y, Liu G, Chung NH, Ehtesham M, Black KL, Yu JS. Induction of a CD4+ T regulatory type 1 response by cyclooxygenase-2-overexpressing glioma. J Immunol 2004; 173: 4352–9
   PubMed Web of Science ®Google Scholar
• Landino LM, Crews BC, Gierse JK, Hauser SD, Marnett LJ. Mutational analysis of the role of the distal histidine and glutamine residues of prostaglandin-endoperoxide synthase-2 in peroxidase catalysis, hydroperoxide reduction, and cyclooxygenase activation. J Biol Chem 1997; 272: 21565–74
   PubMed Web of Science ®Google Scholar
• Goodwin DC, Rowlinson SW, Marnett LJ. Substitution of tyrosine for the proximal histidine ligand to the heme of prostaglandin endoperoxide synthase 2: implications for the mechanism of cyclooxygenase activation and catalysis. Biochemistry 2000; 39: 5422–32
   Web of Science ®Google Scholar
• Seibold SA, Ball T, Hsi LC, Mills DA, Abeysinghe RD, Micielli R, et al. Histidine 386 and its role in cyclooxygenase and peroxidase catalysis by prostaglandin-endoperoxide H synthases. J Biol Chem 2003; 278: 46163–70
   Web of Science ®Google Scholar
• Rogge CE, Liu W, Wu G, Eang LH, Kulmacz RJ, Tsai AL. Identification of Tyr504 as an alternative tyrosyl radical site in human prostaglandin H synthase-2. Biochemistry 2004; 43: 1560–8
   Web of Science ®Google Scholar
• Rogge CE, Ho B, Liu W, Kulmacz RJ, Tsai AL. Role of Tyr348 in Tyr385 radical dynamics and cyclooxygenase inhibitor interactions in prostaglandin H synthase-2. Biochemistry 2006; 45: 523–32
   Web of Science ®Google Scholar
• Morse DE, Duncan H, Hooker N, Morse A. Hydrogen peroxide induces spawning in mollusks, with activation of prostaglandin endoperoxide synthetase. Science 1977; 196: 298–300
   PubMed Web of Science ®Google Scholar
• Seregi A, Serfozo P, Mergl Z. Evidence for the localization of hydrogen peroxide-stimulated cyclooxygenase activity in rat brain mitochondria: a possible coupling with monoamine oxidase. J Neurochem 1983; 40: 407–13
   PubMed Web of Science ®Google Scholar
• Hecker G, Utz J, Kupferschmidt RJ, Ullrich V. Low levels of hydrogen peroxide enhance platelet aggregation by cyclooxygenase activation. Eicosanoids 1991; 4: 107–13
   PubMedGoogle Scholar
• Im JW, Kim HK, Kim ND, Choi JS, Yu BP, Yang HS, et al. Activation of cyclooxygenases by H2O2 and t-butylhydroperoxide in aged rat lung. Biotechnol Lett 2004; 26: 1665–9
   PubMed Web of Science ®Google Scholar
• Lands WEM, Rome LH. Inhibition of prostaglandin biosynthesis. Prostaglandins: chemical and biochemical aspects, SMM Karim. MTP Press, LancasterUK 1976; 87–137
   Google Scholar
• Hemler ME, Lands WE. Evidence for a peroxide-initiated free radical mechanism of prostaglandin biosynthesis. J Biol Chem 1980; 255: 6253–61
   PubMed Web of Science ®Google Scholar
• Kulmacz RJ, Lands WE. Requirements for hydroperoxide by the cyclooxygenase and peroxidase activities of prostaglandin H synthase. Prostaglandins 1983; 25: 531–40
   PubMed Web of Science ®Google Scholar
• Kulmacz RJ, Wang LH. Comparison of hydroperoxide initiator requirements for the cyclooxygenase activities of prostaglandin H synthase-1 and -2. J Biol Chem 1995; 270: 24019–23
   PubMed Web of Science ®Google Scholar
• Kulmacz RJ. Regulation of cyclooxygenase catalysis by hydroperoxides. Biochem Biophys Res Commun 2005; 338: 25–33
   Web of Science ®Google Scholar
• Landino LM, Crews BC, Timmons MD, Morrow JD, Marnett LJ. Peroxynitrite, the coupling product of nitric oxide and superoxide, activates prostaglandin biosynthesis. Proc Natl Acad Sci U S A 1996; 93: 15069–74
   PubMed Web of Science ®Google Scholar
• Goodwin DC, Landino LM, Marnett LJ. Effects of nitric oxide and nitric oxide-derived species on prostaglandin endoperoxide synthase and prostaglandin biosynthesis. FASEB J 1999; 13: 1121–36
   PubMed Web of Science ®Google Scholar
• Upmacis RK, Deeb RS, Hajjar DP. Regulation of prostaglandin H2 synthase activity by nitrogen oxides. Biochemistry 1999; 38: 12505–13
   PubMed Web of Science ®Google Scholar
• Bachschmid M, Schildknecht S, Ullrich V. Redox regulation of vascular prostanoid synthesis by the nitric oxide-superoxide system. Biochem Biophys Res Commun 2005; 338: 536–42
   PubMed Web of Science ®Google Scholar
• Schildknecht S, Bachschmid M, Ullrich V. Peroxynitrite provides the peroxide tone for PGHS-2-dependent prostacyclin synthesis in vascular smooth muscle cells. FASEB J 2005; 19: 1169–71
   PubMed Web of Science ®Google Scholar
• Kulmacz RJ. Prostaglandin H synthase and hydroperoxides: peroxidase reaction and inactivation kinetics. Arch Biochem Biophys 1986; 249: 273–85
   PubMed Web of Science ®Google Scholar
• Wu G, Wei C, Kulmacz RJ, Osawa Y, Tsai AL. A mechanistic study of self-inactivation of the peroxidase activity in prostaglandin H synthase-1. J Biol Chem 1999; 274: 9231–7
   Web of Science ®Google Scholar
• Wu G, Kulmacz RJ, Tsai AL. Cyclooxygenase inactivation kinetics during reaction of prostaglandin H synthase-1 with peroxide. Biochemistry 2003; 42: 13772–7
   Web of Science ®Google Scholar
• Wu G, Rogge CE, Wang JS, Kulmacz RJ, Palmer G, Tsai AL. Oxyferryl heme and not tyrosyl radical is the likely culprit in prostaglandin H synthase-1 peroxidase inactivation. Biochemistry 2007; 46: 534–42
   Web of Science ®Google Scholar
• Hayama M, Inoue R, Akiba S, Sato T. ERK and p38 MAP kinase are involved in arachidonic acid release induced by H2O2 and PDGF in mesangial cells. Am J Physiol Renal Physiol 2002; 282: F485–91
   Web of Science ®Google Scholar
• Coulon L, Calzada C, Moulin P, Vericel E, Lagarde M. Activation of p38 mitogen-activated protein kinase/cytosolic phospholipase A2 cascade in hydroperoxide-stressed platelets. Free Radic Biol Med 2003; 35: 616–25
   PubMed Web of Science ®Google Scholar
• Shit S, Atreja SK. Phospholipase A2 activation by hydrogen peroxide during in vitro capacitation of buffalo spermatozoa. Indian J Exp Biol 2004; 42: 486–90
   Google Scholar
• van Rossum GS, Drummen GP, Verkleij AJ, Post JA, Boonstra J. Activation of cytosolic phospholipase A2 in Her14 fibroblasts by hydrogen peroxide: a p42/44(MAPK)-dependent and phosphorylation-independent mechanism. Biochim Biophys Acta 2004; 1636: 183–95
   Web of Science ®Google Scholar
• Colston JT, de la Rosa SD, Strader JR, Anderson MA, Freeman GL. H2O2 activates Nox4 through PLA2-dependent arachidonic acid production in adult cardiac fibroblasts. FEBS Lett 2005; 579: 2533–40
   Web of Science ®Google Scholar
• Cui XL, Ding Y, Alexander LD, Bao C, Al-Khalili OK, Simonson M, et al. Oxidative signaling in renal epithelium: critical role of cytosolic phospholipase A2 and p38(SAPK). Free Radic Biol Med 2006; 41: 213–21
   Web of Science ®Google Scholar
• Nimmerjahn F, Dudziak D, Dirmeier U, Hobom G, Riedel A, Schlee M, et al. Active NF-kappaB signalling is a prerequisite for influenza virus infection. J Gen Virol 2004; 85: 2347–56
   PubMed Web of Science ®Google Scholar
• Wurzer WJ, Ehrhardt C, Pleschka S, Berberich-Siebelt F, Wolff T, Walczak H, et al. NF-kappaB-dependent induction of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas/FasL is crucial for efficient influenza virus propagation. J Biol Chem 2004; 279: 30931–7
   PubMed Web of Science ®Google Scholar
• Abdala-Valencia H, Cook-Mills JM. VCAM-1 signals activate endothelial cell protein kinase Calpha via oxidation. J Immunol 2006; 177: 6379–87
   PubMed Web of Science ®Google Scholar
• Wu WS, Tsai RK, Chang CH, Wang S, Wu JR, Chang YX. Reactive oxygen species mediated sustained activation of protein kinase C alpha and extracellular signal-regulated kinase for migration of human hepatoma cell Hepg2. Mol Cancer Res 2006; 4: 747–58
   PubMed Web of Science ®Google Scholar
• Lin D, Lobell S, Jewell A, Takemoto DJ. Differential phosphorylation of connexin46 and connexin50 by H2O2 activation of protein kinase Cgamma. Mol Vis 2004; 10: 688–95
   PubMed Web of Science ®Google Scholar
• Lin D, Takemoto DJ. Oxidative activation of protein kinase Cgamma through the C1 domain. Effects on gap junctions. J Biol Chem 2005; 280: 13682–93
   PubMed Web of Science ®Google Scholar
• Zhang Y, McPherson BC, Liu H, Baman TS, Rock P, Yao Z. H2O2 opens mitochondrial K(ATP) channels and inhibits GABA receptors via protein kinase C-epsilon in cardiomyocytes. Am J Physiol Heart Circ Physiol 2002; 282: H1395–403
   Web of Science ®Google Scholar
• Dina OA, Chen X, Reichling D, Levine JD. Role of protein kinase Cepsilon and protein kinase A in a model of paclitaxel-induced painful peripheral neuropathy in the rat. Neuroscience 2001; 108: 507–15
   PubMed Web of Science ®Google Scholar
• Amadesi S, Cottrell GS, Divino L, Chapman K, Grady EF, Bautista F, et al. Protease-activated receptor 2 sensitizes TRPV1 by protein kinase Cepsilon- and A-dependent mechanisms in rats and mice. J Physiol 2006; 575: 555–71
   PubMed Web of Science ®Google Scholar
• Mao J, Price DD, Phillips LL, Lu J, Mayer DJ. Increases in protein kinase C gamma immunoreactivity in the spinal cord dorsal horn of rats with painful mononeuropathy. Neurosci Lett 1995; 198: 75–8
   PubMed Web of Science ®Google Scholar
• Dina OA, Barletta J, Chen X, Mutero A, Martin A, Messing RO, et al. Key role for the epsilon isoform of protein kinase C in painful alcoholic neuropathy in the rat. J Neurosci 2000; 20: 8614–19
   Web of Science ®Google Scholar
• Olah Z, Karai L, Iadarola MJ. Protein kinase Calpha is required for vanilloid receptor 1 activation. Evidence for multiple signaling pathways. J Biol Chem 2002; 277: 35752–9
   PubMed Web of Science ®Google Scholar
• Sweitzer SM, Wong SM, Tjolsen A, Allen CP, Mochly-Rosen D, Kendig JJ. Exaggerated nociceptive responses on morphine withdrawal: roles of protein kinase C epsilon and gamma. Pain 2004; 110: 281–9
   Web of Science ®Google Scholar
• Sweitzer SM, Wong SM, Peters MC, Mochly-Rosen D, Yeomans DC, Kendig JJ. Protein kinase C epsilon and gamma: involvement in formalin-induced nociception in neonatal rats. J Pharmacol Exp Ther 2004; 309: 616–25
   Web of Science ®Google Scholar
• Shumilla JA, Liron T, Mochly-Rosen, Kendig JJ, Sweitzer SM. Ethanol withdrawal-associated allodynia and hyperalgesia: age-dependent regulation by protein kinase C epsilon and gamma isoenzymes. J Pain 2005; 6: 535–49
   Web of Science ®Google Scholar
• Hartung HP, Toyka KV. Activation of macrophages by substance P: induction of oxidative burst and thromboxane release. Eur J Pharmacol 1983; 89: 301–5
   PubMed Web of Science ®Google Scholar
• Peck R. Neuropeptides modulating macrophage function. Ann N Y Acad Sci 1987; 496: 264–70
   PubMed Web of Science ®Google Scholar
• Serra MC, Bazzoni F, Della Bianca V, Greskowiak M, Rossi F. Activation of human neutrophils by substance P. Effect on oxidative metabolism, exocytosis, cytosolic Ca2+ concentration and inositol phosphate formation. J Immunol 1988; 141: 2118–24
   PubMed Web of Science ®Google Scholar
• Perianin A, Snyderman R, Malfroy B. Substance P primes human neutrophil activation: a mechanism for neurological regulation of inflammation. Biochem Biophys Res Commun 1989; 161: 520–4
   PubMed Web of Science ®Google Scholar
• Brunelleschi S, Vanni L, Ledda F, Giotti A, Maggi CA, Fantozzi R. Tachykinins activate guinea-pig alveolar macrophages: involvement of NK2 and NK1 receptors. Br J Pharmacol 1990; 100: 417–20
   PubMed Web of Science ®Google Scholar
• Brunelleschi S, Tarli S, Giotti A, Fantozzi R. Priming effects of mammalian tachykinins on human neutrophils. Life Sci 1991; 48: PL1–5
   PubMed Web of Science ®Google Scholar
• Boichot E, Lagente V, Paubert-Braquet M, Frossard N. Inhaled substance P induces activation of alveolar macrophages and increases airway responses in the guinea-pig. Neuropeptides 1993; 25: 307–13
   Web of Science ®Google Scholar
• Berman AS, Chancellor-Freeland C, Zhu G, Black PH. Substance P primes murine peritoneal macrophages for an augmented proinflammatory cytokine response to lipopolysaccharide. Neuroimmunomodulation 1996; 3: 141–9
   PubMed Web of Science ®Google Scholar
• Tanabe T, Otani H, Zeng XT, Mishima K, Ogawa R, Inagaki C. Inhibitory effects of calcitonin gene-related peptide on substance-P-induced superoxide production in human neutrophils. Eur J Pharmacol 1996;314:175–83 [Erratum in: Eur J Pharmacol 1997;321:137–41].
   Web of Science ®Google Scholar
• Tanabe T, Otani H, Bao L, Mikami Y, Yasukura T, Ninomiya T, et al. Intracellular signaling pathway of substance P-induced superoxide production in human neutrophils. Eur J Pharmacol 1996; 299: 187–95
   PubMed Web of Science ®Google Scholar
• Brunelleschi S, Nicali R, Lavagno L, Viano I, Pozzi E, Gagliardi L, et al. Tachykinin activation of human monocytes from patients with interstitial lung disease, healthy smokers or healthy volunteers. Neuropeptides 2000; 34: 45–50
   PubMed Web of Science ®Google Scholar
• Marriott I, Mason MJ, Elhofy A, Most KL. Substance P activates NF-kappaB independent of elevations in intracellular calcium in murine macrophages and dendritic cells. J Neuroimmunol 2000; 102: 163–71
   PubMed Web of Science ®Google Scholar
• Lavagno L, Bordin G, Colangelo D, Viano I, Brunelleschi S. Tachykinin activation of human monocytes from patients with rheumatoid arthritis: in vitro and ex-vivo effects of cyclosporin A. Neuropeptides 2001; 35: 92–9
   Web of Science ®Google Scholar
• Marriott I, Bost KL. Substance P receptor mediated macrophage responses. Adv Exp Med Biol 2001; 493: 247–54
   PubMed Web of Science ®Google Scholar
• Delgado AV, McManus AT, Chambers JP. Production of tumor necrosis factor-alpha, interleukin 1-beta, interleukin 2, and interleukin 6 by rat leukocyte subpopulations after exposure to substance P. Neuropeptides 2003; 37: 355–61
   PubMed Web of Science ®Google Scholar
• Weinstock JV. The role of substance P, hemokinin and their receptor in governing mucosal inflammation and granulomatous responses. Front Biosci 2004; 9: 1936–43
   Google Scholar
• Bardelli C, Gunella G, Varsaldi F, Balbo P, Del Boca E, Bernardone IS, et al. Expression of functional NK1 receptors in human alveolar macrophages: superoxide anion production, cytokine release and involvement of NF-kappaB pathway. Br J Pharmacol 2005; 145: 385–96
   PubMed Web of Science ®Google Scholar
• Koon HW, Pothoulakis C. Immunomodulatory properties of substance P: the gastrointestinal system as a model. Ann N Y Acad Sci 2006; 1088: 23–40
   PubMed Web of Science ®Google Scholar
• Longhurst JC, Dittman LE. Hypoxia, bradykinin, and prostaglandins stimulate ischemically sensitive visceral afferents. Am J Physiol 1987; 253: H556–67
   Google Scholar
• Martin HA, Basbaum AI, Kwiat GC, Goetzl EJ, Levine JD. Leukotriene and prostaglandin sensitization of cutaneous high-threshold C- and A-delta mechanonociceptors in the hairy skin of rat hindlimbs. Neuroscience 1987; 22: 651–9
   PubMed Web of Science ®Google Scholar
• Martin HA, Basbaum AI, Goetzl EJ, Levine JD. Leukotriene B4 decreases the mechanical and thermal thresholds of C-fiber nociceptors in the hairy skin of the rat. J Neurophysiol 1988; 60: 438–45
   PubMed Web of Science ®Google Scholar
• Devor M, White DM, Goetzl EJ, Levine JD. Eicosanoids, but not tachykinins, excite C-fiber endings in rat sciatic nerve-end neuromas. Neuroreport 1992; 3: 21–4
   Web of Science ®Google Scholar
• Karla W, Shams H, Orr JA, Scheid P. Effects of the thromboxane A2 mimetic, U46,619, on pulmonary vagal afferents in the cat. Respir Physiol 1992; 87: 383–96
   Google Scholar
• Rueff A, Dray A. Sensitization of peripheral afferent fibres in the in vitro neonatal rat spinal cord-tail by bradykinin and prostaglandins. Neuroscience 1993; 54: 527–35
   PubMed Web of Science ®Google Scholar
• Khasar SG, Ouseph AK, Chou B, Ho T, Green PG, Levine JD. Is there more than one prostaglandin E receptor subtype mediating hyperalgesia in the rat hindpaw?. Neuroscience 1995; 64: 1161–5
   PubMed Web of Science ®Google Scholar
• Ouseph AK, Khasar SG, Levine JD. Multiple second messenger systems act sequentially to mediate rolipram-induced prolongation of prostaglandin E2-induced mechanical hyperalgesia in the rat. Neuroscience 1995; 64: 769–76
   Web of Science ®Google Scholar
• Wang JF, Khasar SG, Ahlgren SC, Levine JD. Sensitization of C-fibres by prostaglandin E2 in the rat is inhibited by guanosine 5′-O-(2-thiodiphosphate), 2′,5′-dideoxyadenosine and Walsh inhibitor peptide. Neuroscience 1996; 71: 259–63
   Web of Science ®Google Scholar
• Petho G, Derow A, Reeh PW. Bradykinin-induced nociceptor sensitization to heat is mediated by cyclooxygenase products in isolated rat skin. Eur J Neurosci 2001; 14: 210–18
   PubMed Web of Science ®Google Scholar
• Bergren DR. Prostaglandin involvement in lung C-fiber activation by substance P in guinea pigs. J Appl Physiol. 2006; 100: 1918–27
   Web of Science ®Google Scholar
• Frassetto L, Morris RC, Jr, Sellmeyer DE, Todd K, Sebastian A. Diet, evolution and aging – the pathophysiologic effects of the post-agricultural inversion of the potassium-to-sodium and base-to-chloride ratios in the human diet. Eur J Nutr 2001; 40: 200–13
   PubMed Web of Science ®Google Scholar
• Gorman Hills A. Acid-base balance. Chemistry, physiology, pathophysiology. Williams & Wilkins, Baltimore 1993
   Google Scholar
• Maurer M, Riesen W, Muser J, Hulter HN, Krapf R. Neutralization of Western diet inhibits bone resorption independently of K intake and reduces cortisol secretion in humans. Am J Physiol Renal Physiol 2003; 284: F32–40
   PubMed Web of Science ®Google Scholar
• Lembeck F, Amann R. The influence of capsaicin sensitive neurons on stress-induced release of ACTH. Brain Res Bull 1986; 16: 541–3
   Web of Science ®Google Scholar
• Amann R, Lembeck F. Stress induced ACTH release in capsaicin treated rats. Br J Pharmacol 1987; 90: 727–31
   Web of Science ®Google Scholar
• Donnerer J, Amann R, Skofitsch G, Lembeck F. Substance P afferents regulate ACTH-corticosterone release. Ann N Y Acad Sci 1991; 632: 296–303
   Web of Science ®Google Scholar
• Watanabe T, Morimoto A, Tan N, Makisumi T, Shimada SG, Nakamori T, et al. ACTH response induced in capsaicin-desensitized rats by intravenous injection of interleukin-1 or prostaglandin E. J Physiol 1994; 475: 139–45
   PubMed Web of Science ®Google Scholar
• Franco-Cereceda A, Kallner G, Lundberg JM. Capsazepine-sensitive release of calcitonin gene-related peptide from C-fibre afferents in the guinea-pig heart by low pH and lactic acid. Eur J Pharmacol 1993; 238: 311–16
   PubMed Web of Science ®Google Scholar
• Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, et al. The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 1998; 21: 531–43
   PubMed Web of Science ®Google Scholar
• Auberson S, Lacroix JS, Lundberg JM. Modulation of capsaicin-sensitive nerve activation by low pH solutions in guinea-pig lung. Pharmacol Toxicol 2000; 86: 16–23
   Google Scholar
• Fischer MJ, Reeh PW, Sauer SK. Proton-induced calcitonin gene-related peptide release from rat sciatic nerve axons, in vitro, involving TRPV1. Eur J Neurosci 2003; 18: 803–10
   Web of Science ®Google Scholar
• Geppetti P, Materazzi S, Nicoletti P. The transient receptor potential vanilloid 1: role in airway inflammation and disease. Eur J Pharmacol 2006; 533: 207–14
   PubMed Web of Science ®Google Scholar
• van der Merwe MT, Jansson PA, Crowther NJ, Boyd IH, Gray IP, Joffe BI, et al. Lactate and glycerol release from subcutaneous adipose tissue in black and white lean men. J Clin Endocrinol Metab 1999;84:2888–95 [Erratum in: J Clin Endocrinol Metab 2000;85:1670–1].
   Web of Science ®Google Scholar
• Kerckhoffs DA, Arner P, Bolinder J. Lipolysis and lactate production in human skeletal muscle and adipose tissue following glucose ingestion. Clin Sci (Lond) 1998; 94: 71–7
   Web of Science ®Google Scholar
• van der Merwe MT, Crowther NJ, Schlaphoff GP, Boyd IH, Gray IP, Joffe BI, et al. Lactate and glycerol release from the subcutaneous adipose tissue of obese urban women from South Africa; important metabolic implications. J Clin Endocrinol Metab 1998; 83: 4084–91
   Web of Science ®Google Scholar
• Gustafsson J, Eriksson J, Marcus C. Glucose metabolism in human adipose tissue studied by 13C-glucose and microdialysis. Scand J Clin Lab Invest 2007; 67: 155–64
   PubMed Web of Science ®Google Scholar
• Kobasa D, Jones SM, Shinya K, Kash JC, Copps J, Ebihara H, et al. Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus. Nature 2007; 445: 319–23
   PubMed Web of Science ®Google Scholar
• Fabris N, Mocchegiani E, Amadio L, Zannotti M, Licastro F, Franceschi C. Thymic hormone deficiency in normal ageing and Down's syndrome: is there a primary failure of the thymus?. Lancet 1984; 1: 983–6
   PubMed Web of Science ®Google Scholar
• Mocchegiani E, Fabris N, Travaglini P, Sartorio A, Travaglini P, Sartorio A, et al. Thymic endocrine activity in children with idiopathic growth-hormone deficiency. Int J Neurosci 1991; 59: 151–7
   PubMed Web of Science ®Google Scholar
• Mocchegiani E, Paolucci P, Granchi D, Cavalazzi L, Santarelli L, Fabris N. Plasma zinc level and thymic hormone activity in young cancer patients. Blood 1994; 83: 749–57
   PubMed Web of Science ®Google Scholar
• Mocchegiani E, Fabris N. Age-related thymus involution: zinc reverses in vitro the thymulin secretion defect. Int J Immunopharmacol 1995; 17: 745–9
   Web of Science ®Google Scholar
• Mocchegiani E, Santarelli L, Muzzioli M, Fabris N. Reversibility of the thymic involution and of age-related peripheral immune dysfunctions by zinc supplementation in old mice. Int J Immunopharmacol 1995; 17: 703–18
   Web of Science ®Google Scholar
• Mocchegiani E, Santarelli L, Costarelli L, Cipriano C, Muti E., Giacconi R, et al. Plasticity of neuroendocrine-thymus interactions during ontogeny and ageing: role of zinc and arginine. Ageing Res Rev 2006; 5: 281–309
   Web of Science ®Google Scholar
• Dardenne M, Boukaiba N, Gagnerault MC, Homo-Delarche F, Chappuis P, Lemonnier D, et al. Restoration of the thymus in aging mice by in vivo zinc supplementation. Clin Immunol Immunopathol 1993; 66: 127–35
   PubMedGoogle Scholar
• Dardenne M, Savino W, Wade S, Kaiserlian D, Lemonnier D, Bach JF. In vivo and in vitro studies of thymulin in marginally zinc-deficient mice. Eur J Immunol 1984; 14: 454–8
   Web of Science ®Google Scholar
• Prasad AS, Meftah S, Abdallah J, Kaplan J, Brewer GJ, Bach JF, et al. Serum thymulin in human zinc deficiency. J Clin Invest 1988; 82: 1202–10
   PubMed Web of Science ®Google Scholar
• Prasad AS. Zinc: an overview. Nutrition 1995;11(1 Suppl):93–9.
   PubMed Web of Science ®Google Scholar
• Prasad AS. Zinc and immunity. Mol Cell Biochem 1998; 188: 63–9
   PubMed Web of Science ®Google Scholar
• Prasad AS. Zinc: mechanisms of host defense. J Nutr 2007; 137: 1345–9
   PubMed Web of Science ®Google Scholar
• Consolini R, Cei B, Cini P, Bottone E, Casarosa L. Circulating thymic hormone activity in young cancer patients. Clin Exp Immunol 1986; 66: 173–80
   Web of Science ®Google Scholar
• Consolini R, Legitimo A, Giorgianni A, Putti MC. Thymic dysfunction in childhood T-acute lymphoblastic leukemia: a possible linkage with a primary thymus involvement. Haematologica 1992; 77: 243–7
   Web of Science ®Google Scholar
• Mocchegiani E, Ciavattini A, Santarelli L, Tibaldi A, Muzzioli M, Bonazzi P, et al. Role of zinc and alpha2 macroglobulin on thymic endocrine activity and on peripheral immune efficiency (natural killer activity and interleukin 2) in cervical carcinoma. Br J Cancer 1999; 79: 244–50
   Web of Science ®Google Scholar
• Mocchegiani E, Perissin L, Santarelli L, Tibaldi A, Zorzet S, Rapozzi V, et al. Melatonin administration in tumor-bearing mice (intact and pinealectomized) in relation to stress, zinc, thymulin and IL-2. Int J Immunopharmacol 1999; 21: 27–46
   Web of Science ®Google Scholar
• Mocchegiani E, Provinciali M, Di Stefano G, Nobilini A, Caramia G, Santarelli L, et al. Role of the low zinc bioavailability on cellular immune effectiveness in cystic fibrosis. Clin Immunol Immunopathol 1995; 75: 214–24
   Google Scholar
• Franceschi C, Chiricolo M, Licastro F, Zannotti M, Masi M, Mocchegiani E, et al. Oral zinc supplementation in Down's syndrome: restoration of thymic endocrine activity and of some immune defects. J Ment Defic Res 1988; 32: 169–81
   PubMedGoogle Scholar
• Licastro F, Mocchegiani E, Zannotti M, Arena G, Masi M, Fabris N. Zinc affects the metabolism of thyroid hormones in children with Down's syndrome: normalization of thyroid stimulating hormone and of reversal triiodothyronine plasmic levels by dietary zinc supplementation. Int J Neurosci 1992; 65: 259–68
   PubMed Web of Science ®Google Scholar
• Licastro F, Mocchegiani E, Masi M, Fabris N. Modulation of the neuroendocrine system and immune functions by zinc supplementation in children with Down's syndrome. J Trace Elem Electrolytes Health Dis 1993; 7: 237–9
   Web of Science ®Google Scholar
• Licastro F, Chiricolo M, Mocchegiani E, Fabris N, Zannoti M, Beltrandi E, et al. Oral zinc supplementation in Down's syndrome subjects decreased infections and normalized some humoral and cellular immune parameters. J Intellect Disabil Res 1994; 38: 149–62
   Web of Science ®Google Scholar
• Mocchegiani E, Brignola C, Iannone P, Campieri M, Pasquali M, Lanfranchi GA, et al. Levels of zinc and thymulin in plasma from patients with Crohn's disease. J Clin Lab Immunol 1990; 32: 79–84
   Google Scholar
• Brignola C, Belloli C, De Simone G, Evangelisti A, Parente R, Mancini R, et al. Zinc supplementation restores plasma concentrations of zinc and thymulin in patients with Crohn's disease. Aliment Pharmacol Ther 1993; 7: 275–80
   Web of Science ®Google Scholar
• Mocchegiani E, Veccia S, Ancarani F, Scalise G, Fabris N. Benefit of oral zinc supplementation as an adjunct to zidovudine (AZT) therapy against opportunistic infections in AIDS. Int J Immunopharmacol 1995; 17: 719–27
   PubMed Web of Science ®Google Scholar
• Mocchegiani E, Muzzioli M. Therapeutic application of zinc in human immunodeficiency virus against opportunistic infections. J Nutr 2000;130(5S Suppl):1424S–1431S.
   Google Scholar
• Mocchegiani E, Boemi M, Fumelli P, Fabris N. Zinc-dependent low thymic hormone level in type I diabetes. Diabetes 1989; 38: 932–7
   Web of Science ®Google Scholar
• Travaglini P, Moriondo P, Togni E, Venegoni P, Bochicchio D, Conti A, et al. Effect of oral zinc administration on prolactin and thymulin circulating levels in patients with chronic renal failure. J Clin Endocrinol Metab 1989; 68: 186–90
   PubMed Web of Science ®Google Scholar
• Muzzioli M, Mocchegiani E, Bressani N, Bevilacqua P, Fabris N. In vitro restoration by thymulin of NK activity of cells from old mice. Int J Immunopharmacol 1992; 14: 57–61
   PubMed Web of Science ®Google Scholar
• Giacconi R, Cipriano C, Muzzioli M, Gasparini N, Orlando F, Mocchegiani E. Interrelationships among brain, endocrine and immune response in ageing and successful ageing: role of metallothionein III isoform. Mech Ageing Dev 2003; 124: 371–8
   Web of Science ®Google Scholar
• Licastro F, Savorani G, Sarti G, Salsi A, Cavazzuti F, Zanichelli L, et al. Zinc and thymic hormone-dependent immunity in normal ageing and in patients with senile dementia of the Alzheimer type. J Neuroimmunol 1990; 27: 201–8
   Web of Science ®Google Scholar
• Licastro F, Davis LJ, Mocchegiani E, Fabris N. Impaired peripheral zinc metabolism in patients with senile dementia of probable Alzheimer's type as shown by low plasma concentrations of thymulin. Biol Trace Elem Res 1996; 51: 55–62
   PubMed Web of Science ®Google Scholar
• Mocchegiani E, Verbanac D, Santarelli L, Tibaldi A, Muzzioli M, Radosevic-Stasic B, et al. Zinc and metallothioneins on cellular immune effectiveness during liver regeneration in young and old mice. Life Sci 1997; 61: 1125–45
   Web of Science ®Google Scholar
• Mocchegiani E, Muzzioli M, Cipriano C, Giacconi R. Zinc, T-cell pathways, aging: role of metallothioneins. Mech Ageing Dev 1998; 106: 183–204
   PubMed Web of Science ®Google Scholar
• Mocchegiani E, Muzzioli M, Giacconi R. Zinc, metallothioneins, immune responses, survival and ageing. Biogerontology 2000; 1: 133–43
   PubMed Web of Science ®Google Scholar
• Mocchegiani E, Giacconi R, Cipriano C, Muzzioli M, Fattoretti P, Bertoni-Freddari C, et al. Zinc-bound metallothioneins as potential biological markers of ageing. Brain Res Bull 2001; 55: 147–53
   Web of Science ®Google Scholar
• Mocchegiani E, Giacconi R, Cipriano C, Gasparini N, Orlando F, Stecconi R, et al. Metallothioneins (I + II) and thyroid-thymus axis efficiency in old mice: role of corticosterone and zinc supply. Mech Ageing Dev 2002; 123: 675–94
   Web of Science ®Google Scholar
• Mocchegiani E, Giacconi R, Cipriano C, Muzzioli M, Gasparini N, Moresi R, et al. MtmRNA gene expression, via IL-6 and glucocorticoids, as potential genetic marker of immunosenescence: lessons from very old mice and humans. Exp Gerontol 2002; 37: 349–57
   Web of Science ®Google Scholar
• Cipriano C, Giacconi R, Muzzioli M, Gasparini N, Orlando F, Corradi A, et al. Metallothionein (I + II) confers, via c-myc, immune plasticity in oldest mice: model of partial hepatectomy/liver regeneration. Mech Ageing Dev 2003; 124: 877–86
   Web of Science ®Google Scholar
• Mocchegiani E, Muzzioli M, Giacconi R, Cipriano C, Gasparini N, Franceschi C, et al. Metallothioneins/PARP-1/IL-6 interplay on natural killer cell activity in elderly: parallelism with nonagenarians and old infected humans. Effect of zinc supply. Mech Ageing Dev 2003; 124: 459–68
   PubMed Web of Science ®Google Scholar
• Mocchegiani E, Giacconi R, Cipriano C, Gasparini N, Bernardini G, Malavolta M, et al. The variations during the circadian cycle of liver CD1d-unrestricted NK1.1+TCR gamma/delta+ cells lead to successful ageing. Role of metallothionein/IL-6/gp130/PARP-1 interplay in very old mice. Exp Gerontol 2004; 39: 775–88
   PubMed Web of Science ®Google Scholar
• Mocchegiani E, Giacconi R, Cipriano C, Muti E, Gasparini N, Malavolta M. Are zinc-bound metallothionein isoforms (I + II and III) involved in impaired thymulin production and thymic involution during ageing?. Immun Ageing 2004; 1: 5
   Google Scholar
• Mocchegiani E, Giacconi R, Fattoretti P, Casoli T, Cipriano C, Muti E, et al. Metallothionein isoforms (I + II and III) and interleukin-6 in the hippocampus of old rats: may their concomitant increments lead to neurodegeneration?. Brain Res Bull 2004; 63: 133–42
   Web of Science ®Google Scholar
• Mocchegiani E, Giacconi R, Muti E, Rogo C, Bracci M, Muzzioli M, et al. Zinc, immune plasticity, aging, and successful aging: role of metallothionein. Ann N Y Acad Sci 2004; 1019: 127–34
   PubMed Web of Science ®Google Scholar
• Mocchegiani E, Bertoni-Freddari C, Marcellini F, Malavolta M. Brain, aging and neurodegeneration: role of zinc ion availability. Prog Neurobiol 2005; 75: 367–90
   PubMed Web of Science ®Google Scholar
• Mocchegiani E, Costarelli L, Giacconi R, Cipriano C, Muti E, Malavolta M. Zinc-binding proteins (metallothionein and alpha-2 macroglobulin) and immunosenescence. Exp Gerontol 2006; 41: 1094–107
   Web of Science ®Google Scholar
• Mocchegiani E, Paolucci E, Balsamo A, Cacciari E, Fabris N. Influence of growth hormone on thymic endocrine activity in humans. Horm Res 1990; 33: 248–55
   PubMedGoogle Scholar
• Mocchegiani E, Sartorio A, Santarelli L, Ferrero S, Fabris N. Thymulin, zinc and insulin-like growth factor-I (IGF-I) activity before and during recombinant growth hormone (rec-GH) therapy in children and adults with GH deficiency. J Endocrinol Invest 1996; 19: 630–7
   PubMed Web of Science ®Google Scholar
• Dardenne M. Role of thymic peptides as transmitters between the neuroendocrine and immune systems. Ann Med 1999; 31(Suppl 2)34–9
   Google Scholar
• Mocchegiani E, Bulian D, Santarelli L, Tibaldi A, Muzzioli M, Pierpaoli W, et al. The immuno-reconstituting effect of melatonin or pineal grafting and its relation to zinc pool in aging mice. J Neuroimmunol 1994; 53: 189–201
   PubMed Web of Science ®Google Scholar
• Mocchegiani E, Bulian D, Santarelli L, Tibaldi A, Muzzioli M, Lesnikov V, et al. The zinc pool is involved in the immune-reconstituting effect of melatonin in pinealectomized mice. J Pharmacol Exp Ther 1996; 277: 1200–8
   PubMed Web of Science ®Google Scholar
• Fabris N, Mocchegiani E, Provinciali M. Plasticity of neuro-endocrine-thymus interactions during aging – a minireview. Cell Mol Biol (Noisy-le-grand) 1997; 43: 529–41
   PubMed Web of Science ®Google Scholar
• Fabris N, Mocchegiani E, Provinciali M. Plasticity of neuroendocrine-thymus interactions during aging. Exp Gerontol 1997; 32: 415–29
   PubMed Web of Science ®Google Scholar
• Mocchegiani E, Santarelli L, Tibaldi A, Muzzioli M, Bulian D, Cipriano K, et al. Presence of links between zinc and melatonin during the circadian cycle in old mice: effects on thymic endocrine activity and on the survival. J Neuroimmunol 1998; 86: 111–22
   Web of Science ®Google Scholar
• Dalton T, Palmiter RD, Andrews GK. Transcriptional induction of the mouse metallothionein-I gene in hydrogen peroxide-treated Hepa cells involves a composite major late transcription factor/antioxidant response element and metal response promoter elements. Nucleic Acids Res 1994; 22: 5016–23
   PubMed Web of Science ®Google Scholar
• Ren Y, Smith A. Mechanism of metallothionein gene regulation by heme-hemopexin. Roles of protein kinase C, reactive oxygen species, and cis-acting elements. J Biol Chem 1995; 270: 23988–95
   PubMed Web of Science ®Google Scholar
• Dalton TP, Li Q, Bittel D, Liang L, Andrews GK. Oxidative stress activates metal-responsive transcription factor-1 binding activity. Occupancy in vivo of metal response elements in the metallothionein-I gene promoter. J Biol Chem 1996; 271: 26233–41
   PubMed Web of Science ®Google Scholar
• Andrews GK. Regulation of metallothionein gene expression by oxidative stress and metal ions. Biochem Pharmacol 2000; 59: 95–104
   PubMed Web of Science ®Google Scholar
• McAleer MF, Tuan RS. Metallothionein protects against severe oxidative stress-induced apoptosis of human trophoblastic cells. In Vitro Mol Toxicol 2001; 14: 219–31
   Google Scholar
• Datta J, Majumder S, Kutay H, Motiwala T, Frankel W, Costa R, et al. Metallothionein expression is suppressed in primary human hepatocellular carcinomas and is mediated through inactivation of CCAAT/enhancer binding protein alpha by phosphatidylinositol 3-kinase signaling cascade. Cancer Res 2007; 67: 2736–46
   PubMed Web of Science ®Google Scholar
• Hernandez J, Carrasco J, Belloso E, Giralt M, Bluethmann H, Kee Lee D, et al. Metallothionein induction by restraint stress: role of glucocorticoids and IL-6. Cytokine 2000; 12: 791–6
   PubMed Web of Science ®Google Scholar
• Kobayashi K, Himeno S, Satoh M, Kuroda J, Shibata N, Seko Y, et al. Pentavalent vanadium induces hepatic metallothionein through interleukin-6-dependent and -independent mechanisms. Toxicology 2006; 228: 162–70
   PubMed Web of Science ®Google Scholar
• Ashino T, Arima Y, Shioda S, Iwakura Y, Numasawa S, Yoshida T. Effect of interleukin-6 neutralization on CYP3A11 and metallothionein-1/2 expressions in arthritic mouse liver. Eur J Pharmacol 2007; 558: 199–207
   Web of Science ®Google Scholar
• Kobayashi K, Kuroda J, Shibata N, Hasegawa T, Seko Y, Satoh M, et al. Induction of metallothionein by manganese is completely dependent on interleukin-6 production. J Pharmacol Exp Ther 2007; 320: 721–7
   PubMed Web of Science ®Google Scholar
• Ginn-Pease ME, Whisler RL. Redox signals and NF-kappaB activation in T cells. Free Radic Biol Med 1998; 25: 346–61
   PubMed Web of Science ®Google Scholar
• Kabe Y, Ando K, Hirao S, Yoshida M, Handa H. Redox regulation of NF-kappaB activation: distinct redox regulation between the cytoplasm and the nucleus. Antioxid Redox Signal 2005; 7: 395–403
   PubMed Web of Science ®Google Scholar
• Cai L, Tsiapalis G, Cherian MG. Protective role of zinc-metallothionein on DNA damage in vitro by ferric nitrilotriacetate (Fe-NTA) and ferric salts. Chem Biol Interact 1998; 115: 141–51
   PubMed Web of Science ®Google Scholar
• Iqbal M, Noor R, Mizuno R, Okada S. Protective role of zinc-metallothionein (Zn-MT) in iron nitrilotriacetate (Fe-NTA)-induced renal oxidative damage. Redox Rep 2003; 8: 163–7
   PubMed Web of Science ®Google Scholar
• Min KS, Morishita F, Tetsuchikawahara N, Onosaka S. Induction of hepatic and renal metallothionein synthesis by ferric nitrilotriacetate in mice: the role of MT as an antioxidant. Toxicol Appl Pharmacol 2005; 204: 9–17
   PubMed Web of Science ®Google Scholar
• Min KS. [The physiological significance of metallothionein in oxidative stress.] Yakugaku Zasshi 2007;127:695–702 (in Japanese).
   Web of Science ®Google Scholar
• Sun Y, Tan M, Duan H, Swaroop M. SAG/ROC/Rbx/Hrt, a zinc RING finger gene family: molecular cloning, biochemical properties, and biological functions. Antioxid Redox Signal 2001; 3: 635–50
   PubMed Web of Science ®Google Scholar
• Cragg RA, Phillips SR, Piper JM, Varma JS, Campbell FC, Mathers JC, et al. Homeostatic regulation of zinc transporters in the human small intestine by dietary zinc supplementation. Gut 2005; 54: 469–78
   Web of Science ®Google Scholar
• Mason B. Victor Moritz Goldschmidt: father of modern geochemistry. Special Publication No. 4. Geochemical Society, 1992.
   Google Scholar
• Goldschmidt VM. Geochemistry. Clarendon Press, Oxford 1954
   Google Scholar
• Houston MC. The role of mercury and cadmium heavy metals in vascular disease, hypertension, coronary heart disease, and myocardial infarction. Altern Ther Health Med 2007; 13: S128–S133
   PubMed Web of Science ®Google Scholar
• Lopez-Alonso M, Prieto F, Miranda M, Castillo C, Hernandez JR, Benedito JL. Intracellular distribution of copper and zinc in the liver of copper-exposed cattle from northwest Spain. Vet J 2005; 170: 332–8
   Web of Science ®Google Scholar
• Sienko NJ, Plane RA. Chemical principles and properties2nd edn. McGraw-Hill, New York 1974
   Google Scholar
• Underwood EJ. Trace elements in human and animal nutrition4th edn. Academic Press, New York 1977
   Google Scholar
• Karimbakas J, Langkamp-Henken B, Percival SS. Arrested maturation of granulocytes in copper deficient mice. J Nutr 1998; 128: 1855–60
   PubMed Web of Science ®Google Scholar
• Percival SS. Copper and immunity. Am J Clin Nutr 1998;67(5 Suppl):1064S–1068S.
   PubMed Web of Science ®Google Scholar
• Lominadze D, Saari JT, Percival SS, Schuschke DA. Proinflammatory effects of copper deficiency on neutrophils and lung endothelial cells. Immunol Cell Biol 2004; 82: 231–8
   PubMed Web of Science ®Google Scholar
• Davis GK, Mertz W. Copper. In: Mertz W. Trace elements in human and animal nutrition, 5th edn, Vol 1. New York: Academic Press, 1987:301–64.
   Google Scholar
• Lentsch AB, Kato A, Saari JT, Schuschke DA. Augmented metalloproteinase activity and acute lung injury in copper-deficient rats. Am J Physiol Lung Cell Mol Physiol 2001; 281: L387–93
   Web of Science ®Google Scholar
• Chowell G, Ammon CE, Hengartner NW, Hyman JM. Estimation of the reproductive number of the Spanish flu epidemic in Geneva, Switzerland. Vaccine 2006; 24: 6747–50
   PubMed Web of Science ®Google Scholar
• Chowell G, Ammon CE, Hengartner NW, Hyman JM. Transmission dynamics of the great influenza pandemic of 1918 in Geneva, Switzerland: assessing the effects of hypothetical interventions. J Theor Biol 2006; 241: 193–204
   PubMed Web of Science ®Google Scholar