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- Faa, G., et al.
(author)
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A Developmental Approach to Drug-induced Liver Injury in Newborns and Children
- 2012
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In: Current Medicinal Chemistry. - 0929-8673. ; 19:27, s. 4581-4594
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Research review (peer-reviewed)abstract
- The liver represents the major site of drug metabolism in humans. The developmental changes that occur in the liver's metabolic activity during fetal life and in the perinatal period are at the basis of the varied sensitivity of human newborns to many drugs. The decreased capacity of the fetal and newborn liver to metabolize, detoxify, and excrete drugs - total cytochrome P450 content in the fetal liver being 30% to 60% of adult values - may explain the prolonged actions of many drugs in the newborn, as well as less their potential toxicity. On the other hand, the low levels of phase I (activation) enzymes, producing more polar reactive and often toxic metabolites, could explain the lower incidence of adverse effects of some drugs reported in newborns. Moreover, the greater capacity of newborns to synthesize glutathione is at the basis of their ability in inactivating many toxic metabolites. Here we review the acute and chronic liver toxicity due to the most widely used drugs in the neonate. We will discuss in detail the biochemical profile of the fetal and neonatal liver, and the toxic metabolites formed during the metabolism of the most widely used drugs in the neonate. The histological picture of liver disease related to the therapeutic use of drugs will be discussed, with particular emphasis on the mode of cell death involved in hepatitis induced by different drugs most frequently utilized in the neonatal intensive care units.
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- Cabras, T., et al.
(author)
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Top-down HPLC-ESI-MS characterization of rat gliadoralin A, a new member of the family of rat submandibular gland glutamine-rich proteins and potential substrate of transglutaminase
- 2013
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In: Journal of Separation Science. - : Wiley. - 1615-9306. ; 36:17, s. 2848-2861
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Journal article (peer-reviewed)abstract
- During HPLC-ESI-MS/MS analysis of rat submandibular saliva secreted under isoprenaline stimulation, a protein with an experimental [M+H](1+) = 10544.24 m/z was detected (17.5 +/- 0.7 min). The MS/MS fragmentation pattern, manually investigated, allowed establishing an internal sequence in agreement with a DNA-derived sequence of an unknown rat protein coded D3Z9M3 (Swiss-Prot). To match the experimental MS/MS fragmentation pattern and protein mass with theoretical data, the removal from the N terminus of the signal peptide and from the C terminus of three amino acid (a.a.) residues (Arg-Ala-Val) and the cyclization of the N-terminal glutamine in pyroglutamic had to be supposed, resulting in a mature protein of 90 a.a. HPLC-ESI-MS/MS of the trypsin digest ensured 100% sequence coverage. For the high glutamine content (34/90 = 37.8%) we propose to name this protein rat gliadoralin A 1-90. Low amounts of five different isoforms were sporadically detected, which did not significantly change their relative amounts after stimulation. Gliadoralin A is substrate for transglutaminase-2, having Lys 60 and different Gln residues as major determinants for enzyme recognition. In silico investigation of superior structures evidenced that a small part of the protein adopts an -helical fold, whereas large segments are unfolded, suggesting an unordered conformation.
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- Nemolato, S., et al.
(author)
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Immunoreactivity for thymosin beta 4 and thymosin beta 10 in the adult rat oro-gastrointestinal tract
- 2013
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In: European Journal of Histochemistry. - : PAGEPress Publications. - 1121-760X .- 2038-8306. ; 57:2, s. 106-111
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Journal article (peer-reviewed)abstract
- Thymosin beta 4 (T beta 4) and thymosin beta 10 (T beta 10) are two members of the beta-thymosin family, involved in multiple cellular activities in different organs in multiple animal species. Here we report the expression pattern of T beta 4 and T beta 10 in rat tissues, in the gut and in annexed glands. The two peptide were differently expressed: T beta 4 was absent in salivary glands whereas T beta 10 was expressed in parotid and in submandibular glands. T beta 4 was mildly expressed in the tongue and in the oesophagus, where T beta 10 was absent. A similar expression was found in the stomach, ileum and colon mucosa. In pancreas T beta 4 reactivity was restricted to the Langerhans islet cells; T beta 4 was also detected in the exocrine cells. Both peptide were not expressed in liver cells. When the rat expression pattern in rat organs was compared to reactivity for T beta 4 and T beta 10 in humans, marked differences were found. Our data clearly indicate a species-specific expression of T beta 4 and T beta 10, characterized by the actual unpredictability of the expression of these peptides in different cells and tissues. The common high expression of T beta 4 in mast cells, both in humans and in rats, represents one of the few similarities between these two species.
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