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Eighteen non-institutionalized Down's syndrome (DS) children (mean age: 7.0 +/- 10/12 years) with a history of respiratory tract, auditory and skin infections, low plasma levels of a nonapeptide thymic hormone, i.e. Serum Thymic Factor (STF), high plasma levels of inactive zinc-unbound STF molecules, and reduced absolute number of circulating T-lymphocytes, were given an oral non-pharmacological supplementation of zinc sulphate (1 mg Zn++/kg body weight/day for 2 months; two cycles, 10 months apart) and monitored immunologically before and after each cycle. A dramatic increase of plasma STF level and concomitantly an almost complete disappearance of inactive STF molecules was observed after each cycle. The absolute number of circulating T-lymphocytes was significantly increased by zinc treatment. The marginal zinc deficiency was also corrected without any appreciable influence on copper plasma levels. A reduction of recurrent infections and an improvement in school attendance after zinc supplementation were recorded. These beneficial effects of zinc supplementation were also noted in those DS children who did not show an apparent zinc deficiency, as assessed by measuring zinc plasma level. The reduced number of circulating B lymphocytes and the impaired lymphocyte responsiveness to phytohaemagglutinin and concanavalin A were not restored. On the whole, these findings suggest that there exists a defect in the bio-availability and/or in the utilization of zinc in DS. This alteration, of unknown origin, can be underestimated on the simple basis of the zinc plasma level and can be corrected with moderate nutritional zinc supplementation.

Down syndrome critical region gene 1-like 2 (DSCR1L2) belongs to the human DSCR1-like gene family, which also includes DSCR1 and DSCR1L1. Both DSCR1 and DSCR1L1 proteins interact with calcineurin, a calcium/calmodulin-dependent phosphatase. To date, no interactor has been described for DSCR1L2. The aim of this work was to perform a first functional study of DSCR1L2 using yeast two-hybrid analysis conducted on a human heart cDNA library. Here, we report the interaction between DSCR1L2 and the human cardiac troponin I (TNNI3), the heart-specific inhibitory subunit of the troponin complex, a central component of the contractile apparatus. This interaction was confirmed by both yeast cotransformation and GST (glutathione-sepharose transferase) fusion protein assay. Moreover, a new DSCR1L2 mRNA isoform, generated by alternative splicing, was identified and cloned in different tissues: it lacks two central exons, encoding the most conserved domains among the DSCR1-like protein family. A quantitative relative reverse transcription-polymerase chain reaction (RT-PCR) assay showed that in heart tissue the normalized expression level ratio for DSCR1L2 and DSCR1L2-E2E5 mRNA isoforms is 3.5 : 1, respectively. The yeast cotransformation and GST fusion protein assay demonstrated the interaction between this new DSCR1L2 variant and the human cardiac troponin I and the prominent role of DSCR1L2 exon 2 in determining binding between both DSCR1L2 isoforms and TNNI3. These data indicate an entirely new role for a DSCR1-like family gene, suggesting a possible involvement of DSCR1L2 in cardiac contraction.

Metabolic activation of peripheral blood leukocytes (chemiluminescence) from 27 children with Down syndrome (DS) and 23 age and sex-matched control children after phagocytic stimulation by opsonized zymosan particles was investigated through a chemiluminescence assay. Using autologous plasma or serum as opsonizing media, phagocytic activity of circulating leukocytes was significantly decreased in DS subjects. A further decrease of phagocytic activity was found in neutrophils from DS children, when normal heterologous plasma or sera were used. On the other hand, sera or plasma from DS subjects significantly increased phagocytic activation of leukocytes from normal donors. In DS subjects opsonizing agents such as serum immunoglobulins and complement fractions were in the normal ranges of concentration. Thus, the impaired chemiluminescence of neutrophils was mainly due to a metabolic impairment at the cellular level. A decreased production of radicals derived from the oxygen metabolism in neutrophils may be an important step of immune derangement leading to the increased incidence of infectious diseases frequently associated with DS.

A novel human gene has been identified by in-depth bioinformatics analysis of chromosome 21 segment 40/105 (21q21.1), with no coding region predicted in any previous analysis. Brain-derived DNA complementary to RNA (cDNA) sequencing predicts a 154-amino acid product with no similarity to any known protein. The gene has been named cysteine and tyrosine-rich protein 1 gene (symbol cysteine and tyrosine-rich 1, CYYR1). The CYYR1 messenger RNA was found by Northern blot analysis in a broad range of tissues (two transcripts of 3.4 and 2.2 kb). The gene consists of four exons and spans about 107 kb, including a very large intron of 85.8 kb. Analysis of expressed sequence tags shows high CYYR1 expression in cells belonging to the amine precursor uptake and decarboxylation system. We also cloned the cDNA of the murine ortholog Cyyr1, which was mapped by a radiation hybrid panel on chromosome 16 within the region corresponding to that containing the respective human homolog on chromosome 21. Sequence and phylogenetic analysis led to identification of several genes encoding CYYR1 homologous proteins. The most prominent feature identified in the protein family is a central, unique cysteine and tyrosine-rich domain, which is strongly conserved from lower vertebrates (fishes) to humans but is absent in bacteria and invertebrates.

A recently recognized gene family, conserved from yeast to humans, includes Down syndrome candidate region 1 gene (DSCR1), Adapt78 (recognized as the hamster ortholog of the DSCR1 isoform 4), ZAKI-4 (renamed DSCR1-like 1, DSCR1L1) and DSCR1L2 (a novel gene on human chromosome 1), along with yeast and C. elegans single members (Strippoli P., Lenzi L., Petrini M., Carinci P., Zannotti M., 2000. A new gene family including DSCR1 (Down Syndrome Candidate Region 1) and ZAKI-4: characterization from yeast to human and identification of DSCR1-like 2, a novel human member. Genomics 64, 252-263). The proposed family labels were a putative single-strand nucleic acid binding domain similar to the RNA recognition motif, and a unique, highly-conserved serine-proline motif. We have used a bioinformatics-driven molecular biology approach to characterize the murine members of DSCR1-like gene family. Systematic expressed-sequence-tags (EST) database search and reverse-transcription polymerase chain rection (RT-PCR) product sequencing allowed identification of the murine DSCR1, DSCR1L1 and DSCR1L2. The sequences of the respective protein products are of 198, 197 and 241 amino acids, respectively, and are very similar to the corresponding human proteins. The very broad expression pattern of the murine DSCR1 genes is similar to that of the human genes. Using a radiation hybrid panel, we mapped the murine DSCR1-like family members. The murine DSCR1 ortholog is located on the chromosome 16, in a region corresponding to that on human chromosome 21 just upstream of the Down syndrome candidate region. DSCR1L1 and DSCR1L2 murine genes are also located in chromosomal segments of chromosome 17 and 4, respectively, exactly corresponding to those containing the respective human homologs on chromosomes 6 and 1. Description of the mouse orthologs for DSCR1-like genes will allow knockout mice to be obtained for specific family members.

Summary: Extracting the desired data from a database entry for later analysis is a constant need in the biological sequence analysis community; GeneRecords 1.0 is a solution for GenBank biological flat file parsing, as it implements a structured representation of each feature and feature qualifier in GenBank following import in a common database managing system usable in a personal computer (Macintosh and Windows environments). This collection of related databases enables the local management of GenBank records, allowing indexing, retrieval and analysis of both information and sequences on a personal computer. Availability: the current release, including the FileMaker Pro runtime application (built for Windows and Macintosh environments), is freely available at http://apollo11.isto.unibo.it/software/

Peripheral blood lymphocytes from 7 patients with Down's syndrome (DS; trisomy 21) and 14 healthy age-matched controls were studied for the induction of micronuclei (MN) by the cytokinesis-block method. The spontaneous incidence of MN in lymphocytes from DS subjects was lower than that of control cultures. When lymphocytes were treated with mitomycin C (MMC) at the beginning of the culture period, an increase in MN formation was found in cells from both DS and control subjects. In DS subjects this increase was much more marked than in control donors. This effect had to be ascribed to cells from older DS subjects (37–55 years old), which showed an MMC-induced MN formation that was markedly and significantly higher than that observed in cells from younger (9–16 years old) DS subjects. These data indicate that age has to be considered a major variable when studies on the genetic instability of DS subjects are performed.

Background CYYR1 is a recently identified gene located on human chromosome 21 whose product has no similarity to any known protein and is of unknown function. Analysis of expressed sequence tags (ESTs) have revealed high human CYYR1 expression in cells belonging to the diffuse neuroendocrine system (DNES). These cells may be the origin of neuroendocrine (NE) tumors. The aim of this study was to conduct an initial analysis of sequence, splicing and expression of the CYYR1 mRNA in human NE tumors. Methods The CYYR1 mRNA coding sequence (CDS) was studied in 32 NE tumors by RT-PCR and sequence analysis. A subtle alternative splicing was identified generating two isoforms of CYYR1 mRNA differing in terms of the absence (CAG- isoform, the first described mRNA for CYYR1 locus) or the presence (CAG+ isoform) of a CAG codon. When present, this specific codon determines the presence of an alanine residue, at the exon 3/exon 4 junction of the CYYR1 mRNA. The two mRNA isoform amounts were determined by quantitative relative RT-PCR in 29 NE tumors, 2 non-neuroendocrine tumors and 10 normal tissues. A bioinformatic analysis was performed to search for the existence of the two CYYR1 isoforms in other species. Results The CYYR1 CDS did not show differences compared to the reference sequence in any of the samples, with the exception of an NE tumor arising in the neck region. Sequence analysis of this tumor identified a change in the CDS 333 position (T instead of C), leading to the amino acid mutation P111S. NE tumor samples showed no significant difference in either CYYR1 CAG- or CAG+ isoform expression compared to control tissues. CYYR1 CAG- isoform was significantly more expressed than CAG+ isoform in NE tumors as well as in control samples investigated. Bioinformatic analysis revealed that only the genomic sequence of Pan troglodytes CYYR1 is consistent with the possible existence of the two described mRNA isoforms. Conclusion A new "subtle" splicing isoform (CAG+) of CYYR1 mRNA, the sequence and the expression of this gene were defined in a large series of NE tumors.

Background All standard methods for cDNA cloning are affected by a potential inability to effectively clone the 5' region of mRNA. The aim of this work was to estimate mRNA open reading frame (ORF) 5' region sequence completeness in the model organism Danio rerio (zebrafish). Results We implemented a novel automated approach (5'_ORF_Extender) that systematically compares available expressed sequence tags (ESTs) with all the zebrafish experimentally determined mRNA sequences, identifies additional sequence stretches at 5' region and scans for the presence of all conditions needed to define a new, extended putative ORF. Our software was able to identify 285 (3.3%) mRNAs with putatively incomplete ORFs at 5' region and, in three example cases selected (selt1a, unc119.2, nppa), the extended coding region at 5' end was cloned by reverse transcription-polymerase chain reaction (RT-PCR). Conclusion The implemented method, which could also be useful for the analysis of other genomes, allowed us to describe the relevance of the "5' end mRNA artifact" problem for genomic annotation and functional genomic experiment design in zebrafish. Open peer review This article was reviewed by Alexey V. Kochetov (nominated by Mikhail Gelfand), Shamil Sunyaev, and Gáspár Jékely. For the full reviews, please go to the Reviewers' Comments section.

The activation of the insulin-like growth factor 1/IGF1 receptor system (IGF1/IGF1R) is a critical event in the transformation and tumorigenicity processes in a wide variety of human tumors. The IGF1/IGF1R system has been recently studied in carcinoid tumors that often arise in the gastrointestinal tract; these tumors are characterized by hypersecretion of bioamines and neuropeptides, leading to functional tumor disease. Two alternatively spliced IGF1R mRNA transcripts have been described to differ by only three nucleotides (CAG) in the coding sequence, resulting in an amino-acid change from the originally described Thr-Gly to an Arg in the extracellular portion of the receptor beta subunit. In transfected Chinese hamster ovary cells, the form without CAG (CAG-) exhibited an approximate 2-fold increase in IGF1 stimulation of activities required for its mitogenic properties. In this study, we examine the relative expression of the two IGF1R mRNA isoforms by a semiquantitative RT-PCR approach using highly standardized conditions, beta-2 microglobulin (B2M) as a reference gene and gel imaging analysis. We analyzed a large series of human neuroendocrine tumors (32 samples) and 9 normal tissues. A significant higher expression of both isoforms in the tumor samples (approximately 2-fold increase) was found, while a constant CAG+/CAG- IGF1R mRNA isoforms of an approximate 3:1 ratio was observed in all tumoral and normal cell types studied. The phylogenetic study of the IGF1R locus in several species suggests that human IGF1R CAG- mRNA isoform is evolutionarily more recent compared to the IGF1R CAG+ mRNA isoform and it could be used by the splicing apparatus at this intron/exon junction with a lower efficiency. This study highlights the relevance of IGF1R mRNA expression in neuroendocrine tumor cells, and the constant presence of 'subtle' alternative splicing for the IGF1R locus.

Summary: UniGene Tabulator 1.0 provides a solution for full parsing of UniGene flat file format; it implements a structured graphical representation of each data field present in UniGene following import into a common database managing system usable in a personal computer. This database includes related tables for sequence, protein similarity, sequence-tagged site (STS) and transcript map interval (TXMAP) data, plus a summary table where each record represents a UniGene cluster. UniGene Tabulator enables full local management of UniGene data, allowing parsing, querying, indexing, retrieving, exporting and analysis of UniGene data in a relational database form, usable on Macintosh (OS X 10.3.9 or later) and Windows (2000, with service pack 4, XP, with service pack 2 or later) operating systems-based computers. Availability: The current release, including both the FileMaker runtime applications, is freely available at Contact: pierluigi.strippoli@unibo.it Supplementary information: We also distribute a precalculated implementation for current Homo sapiens (build #190, March 2006) and Danio rerio (zebrafish, build #90, March 2006) UniGene data.

Background Formal description of a cell's genetic information should provide the number of DNA molecules in that cell and their complete nucleotide sequences. We pose the formal problem: can the genome sequence forming the genotype of a given living cell be known with absolute certainty so that the cell's behaviour (phenotype) can be correlated to that genetic information? To answer this question, we propose a series of thought experiments. Results We show that the genome sequence of any actual living cell cannot physically be known with absolute certainty, independently of the method used. There is an associated uncertainty, in terms of base pairs, equal to or greater than μs (where μ is the mutation rate of the cell type and s is the cell's genome size). Conclusion This finding establishes an "uncertainty principle" in genetics for the first time, and its analogy with the Heisenberg uncertainty principle in physics is discussed. The genetic information that makes living cells work is thus better represented by a probabilistic model rather than as a completely defined object.

The amino acid sequence of gene products is routinely deduced from the nucleotide sequence of the relative cloned cDNA, according to the rules for recognition of start codon (first-AUG rule, optimal sequence context) and the genetic code. From this prediction stem most subsequent types of product analysis, although all standard methods for cDNA cloning are affected by a potential inability to effectively clone the 5′ region of mRNA. Revision by bioinformatics and cloning methods of 109 known genes located on human chromosome 21 (HC 21) shows that 60 mRNAs lack any in-frame stop upstream of the first-AUG, and that in five cases (DSCR1, KIAA0184, KIAA0539, SON, and TFF3) the coding region at the 5′ end was incompletely characterized in the original descriptions. We describe the respective consequences for genomic annotation, domain and ortholog identification, and functional experiments design. We have also analyzed the sequences of 13,124 human mRNAs (RefSeq databank), discovering that in 6448 cases (49%), an in-frame stop codon is present upstream of the initiation codon, while in the other 6676 mRNAs (51%), identification of additional bases at the mRNA 5′ region could well reveal some new upstream in-frame AUG codons in the optimal context. Proportionally to the HC 21 data, about 550 known human genes might thus be affected by this 5′ end mRNA artifact. © 2003 Elsevier B.V. All rights reserved.

Background : The ADARB1 gene is located in 21q22.3 region, previously linked to familial bipolar disorder, and its product has a documented action in the editing of the pre-mRNA of glutamate receptor B subunit. Dysfunction of glutamatergic neurotransmission could play an important role in the patophysiology of bipolar disorder (BD). Glutamate excitatory neurotransmission regulation is a possible mechanism of the initial effect of anticonvulsants in regulating mood. Methods : To investigate the hypothesis of an involvement of ADARB1 gene in the BD, the ADARB1 cDNA has been cloned and sequenced in seven selected bipolar I disorder patients with evidence of familiarity of mood disorders. A detailed investigation of the gene nucleotide sequence in the open reading frame has been performed. Results : No alteration in the sequence of the ADARB1 gene cDNA was found in any patient, except a common neutral polymorphism in three out of seven patients. Conclusions : Mutations in ADARB1 gene are not commonly associated with bipolar I disorder, therefore other genes in the 21q22 region could be associated with bipolar illness in some families, likely in the context of a multifactorial transmission model.

A new gene family has been identified on the basis of in-depth bioinformatics analysis of the Down syndrome candidate region 1 ( DSCR1 ) gene, located on 21q22.1. We have determined the complete coding sequences of similar genes in Saccharomyces cerevisiae and Caenorhabditis elegans, as well as that of a novel human gene, named DSCR1L2 ( DSCR1 -like 2). Peripheral blood leukocyte cDNA sequencing predicts as its product a 241-amino-acid protein highly similar to products of the human genes DSCR1 and ZAKI-4 (HGMW-approved symbol DSCR1L1 ). The highest level of expression of DSCR1L2 mRNA was found by Northern blot analysis in heart and skeletal muscles, liver, kidney, and peripheral blood leukocytes (three transcripts of 3.2, 5.2, and 7.5 kb). The gene consists of four exons and spans about 22 kb on chromosome 1 (1p33–p35.3) (Human Chromosome 1, Sanger Centre). Exon/intron organization is highly conserved between DSCR1 and DSCR1L2. Two alternative DSCR1L2 mRNA splicing forms have been recognized, with one lacking 10 amino acids in the middle of the protein. Analysis of expressed sequence tags (ESTs) shows DSCR1L2 expression in fetal tissues (heart, liver, and spleen) and in adenocarcinomas. ESTs related to the murine DSCR1L2 orthologue are found in the 2-cell stage mouse embryo, in developing brain stem and spinal cord, and in thymus and T cells. The most prominent feature identified in the protein family is a central short, unique serine–proline motif (including an ISPPXSPP box), which is strongly conserved from yeast to human but is absent in bacteria. Moreover, homology with the RNA-binding domain was weakly but consistently detected in a stretch of 80 amino acids at the amino-terminus by fine sequence analysis based on tools utilizing both hidden Markov models and BLAST. The identification of this new gene family should allow a better understanding of the functions of the genes belonging to it.

Levels of circulating thyroid stimulating hormone (TSH), tetraiodothyronine (T4), 3,5,3'-triiodothyronine (T3), and 3,3',5' triiodothyronine (reversal T3 or rT3) were measured in 25 children with trisomy of chromosome 21, also known as Down's syndrome (DS), and in 14 normal children. In subjects with DS TSH levels were increased, while plasmic levels of rT3 were decreased. No alteration in T3 and T4 levels was observed. Before zinc supplementation, plasmic levels of zinc and thymulin, a zinc dependent thymic hormone, were significantly decreased in DS children. After four months of dietary supplementation with zinc sulphate, a normalization of plasmic zinc, thymulin and TSH levels was observed. Plasmic levels of rT3 significantly increased, and after zinc treatment no difference was detectable between DS children and normal children. Clinical evaluation of the health status of DS children showed that zinc supplementation decreased the incidence of infectious diseases and improved school attendance. Thus, the increased efficiency of the immune system and the normalization of some endocrine parameters by zinc supplementation suggests that zinc deficiency may play a crucial role in some of the pathological manifestations associated with the syndrome, such as infections and malfunctioning of the thyroid gland.

The fingerprints of 162 children with Cooley’s trait were analyzed. Statistically significant differences in thalassemic children in comparison with controls were observed especially with regards to fingerprint type frequency and their distribution on each sex.

Normal individuals aged over 50 and most young Down's syndrome (DS) subjects had markedly reduced concentrations of circulating thymic hormone (facteur thymique sérique, FTS). Plasma from these two groups contained factors capable of inhibiting biological activity of FTS in vitro. Addition of zinc sulphate to plasma samples from DS subjects or the older individuals induced concentrations of FTS comparable to those observed in young healthy people and completely prevented FTS-inhibitory activity. These findings suggest that biologically active circulating thymic hormone is bound to zinc. The decline in thymic hormone activity in older individuals and DS subjects may be the result of changes in the mechanism of zinc-dependent activation of FTS molecules, which are probably associated with marginal zinc deficiency rather than with a primary failure of the thymus. Addition of zinc salt to plasma samples unmasks the presence of inactive FTS molecules.

Five unrelated patients with a supernumerary chromosome derivative of chromosome 15 are described. The clinical findings in the present series of cases show a gross concordance with the data previously reported in subjects with similar aberrations and allow the delineation of a distinct syndrome. Although undetermined variation in the structure of these extra chromosomes may contribute significantly to phenotypic heterogeneity, the patients display a rather common constellation of findings, which include: absence of major malformations, mental and developmental retardation, seizures, hypotonia, behavioural disturbances, and reduced total ridge count on fingertips. Patients with partial trisomy 15q- resulting from dicentric chromosomes bear little resemblance to patients carrying 15q- chromosomes arising de novo or due to unbalanced translocations.

The effect of different concentrations of LiCl or KCl (0.6-20 meq/liter) on PHA-stimulated lymphocytes from young, old, and Down's syndrome subjects was studied. LiCl showed a dramatic enhancing effect on [3H]thymidine incorporation induced by a suboptimal dose of PHA in old subjects and Down's syndrome patients. An increase of [3H]thymidine incorporation in human lymphocytes stimulated by a suboptimal dose of PHA was also observed with KCl. This effect was higher in old subjects than that observed in young and Down's subjects. LiCl and KCl can modulate and partially restore the derangement in early events of mitogen stimulation which seems to be present in lymphocytes from both old and Down's syndrome subjects.

The redistribution with the time of concanavalin A (Con A) receptors at one pole of the cell after addition of FITC-Con A - so-called capping - in the peripheral blood lymphocytes from 13 aged subjects (mean: 84 +/- 1 years old), and of 16 noninstitutionalized patients affected by a syndrome of precocious aging, such as Down's syndrome (mean: 17 +/- 2 years old), was studied and compared with a group of 15 normal young people (mean: 23 +/- 2 years old). An opposite alteration in the percentage of capped cells, i.e. a decrease in aged subjects and an increase in Down's syndrome patients, was observed. A derangement of lymphocyte membrane fluidity appears to be present in both groups even if the underlying biochemical defect may be different. However, a similar alteration of the kinetics of the phenomenon was present either in aged or in Down's syndrome subjects. Both groups did not show any significant increase with time of the percentage of capped cells, suggesting that they were lacking a lymphocyte subpopulation(s) which start capping later.

Phenotype and proliferative ability of peripheral blood lymphocytes from 15 noninstitutionalized children affected with Down Syndrome (DS), in apparently good health, were studied and compared with those of 16 healthy control children of the same age. A complex derangement of all the major peripheral blood cell subsets, i.e., B cells, T cells, and natural killer (NK) cells, was present in DS children. A significant decrease of the absolute number of circulating lymphocytes, a marked and significant decrease of B lymphocyte absolute number and percentage, and dramatic modifications of the T-cell subsets were observed. The absolute number of CD4+ cells was significantly decreased, whereas CD8+ cells increased significantly in percentage but not in absolute number. A derangement of cells bearing markers associated with NK activity, such as CD57, CD16, and CD56, was observed. Among the most important alterations, the presence of a high number of CD57+, CD16- cells, of CD57+, CD8+ lymphocytes, and of CD3+, CD56+ lymphocytes was seen. Many of these alterations are similar to those characteristic of chromosomally normal subjects of advanced age. The hypothesis that the reduced thymic endocrine activity and the zinc deficiency characteristic of DS are responsible for the derangement of T and NK subsets is discussed.

1. 1. The sensitivity of ubiquinol:cytochrome c reductase to its most powerful inhibitors has been characterized in mitochondria from three ciliate and two trypanosome protozoans and compared with that in mitochondria of animals and plants. 2. 2. Mitochondria of ciliates, particularly those of Tetrahymena pyriformis , are resistant to antimycin. 3. 3. Mitochondria of trypanosomes are quite resistant to stigmatellin, as they exhibit a 40-fold higher titer than that in ciliate or animals mitochondria. 4. 4. Both ciliates and trypanosomes are highly resistant to myxothiazol. 5. 5. Correlations have been drawn between the natural resistance of the protozoan mitochondria to antimycin, stigmatellin and myxothiazol and peculiar features in the structure of their apocytochrome b , on the basis of an accurate alignment of the sequences of this protein.

Free radicals are formed in the body as a consequence of aerobic metabolism. Cells have developed a variety of antioxidant systems, that include classical antioxidant enzymes (superoxide dismutase, glutathione peroxidase, and catalase) as well as nonenzymatic oxy-radicals scavengers (vitamin E, urea, s-carotene and some more recently described substances such as carnosine) (1). However, a certain fraction of active oxygen species escapes the cellular defence and may cause transient or permanent damage to cellular components. According to one of the most interesting theory of aging is the “free radical theory of aging”, proposed by D. Harman (2) more than thirty years ago, where oxidative damage has been suggested as a major cause of aging. One of the prediction of this theory is an age-related decrease of the efficiency of antioxidant defence mechanisms.