Self-rated health in individuals with and without disease is associated with multiple biomarkers representing multiple biological domains.

Self-rated health (SRH) is one of the most frequently used indicators in health and social research. Its robust association with mortality in very different populations implies that it is a comprehensive measure of health status and may even reflect the condition of the human organism beyond clinical diagnoses. Yet the biological basis of SRH is poorly understood. We used data from three independent European population samples (N approx. 15,000) to investigate the associations of SRH with 150 biomolecules in blood or urine (biomarkers). Altogether 57 biomarkers representing different organ systems were associated with SRH. In almost half of the cases the association was independent of disease and physical functioning. Biomarkers weakened but did not remove the association between SRH and mortality. We propose three potential pathways through which biomarkers may be incorporated into an individual's subjective health assessment, including (1) their role in clinical diseases; (2) their association with health-related lifestyles; and (3) their potential to stimulate physical sensations through interoceptive mechanisms. Our findings indicate that SRH has a solid biological basis and it is a valid but non-specific indicator of the biological condition of the human organism.

Correlation between erythropoietin serum levels and erythrocyte susceptibility to lipid peroxidation in elderly with type 2 diabetes.

Erythropoietin (EPO), a key hormone involved in red blood cell formation has been recently acknowledged for its pleiotropic actions and protective role in ageing and various pathological conditions concurrent with oxidative stress, vascular diseases and metabolic abnormalities such as diabetes mellitus. The aim of the study was to evaluate the relationship between circulating erythropoietin levels and oxidative stress biomarkers, in elderly with type 2 diabetes (T2DM). The study was carried out in 67 subjects with T2DM (69 ± 5 years; n = 37) without anemia, and aged-matched controls (70 ± 6 years; n = 30). EPO serum levels, erythrocyte susceptibility to lipid peroxidation (ESP) and total antioxidant capacity (TAC) were evaluated. Lower EPO levels (p < 0.01) and higher ESP values (p < 0.001) were found in T2DM group, compared to healthy subjects. EPO levels showed significant negative associations with ESP, both in T2DM subjects (r = -0.565; p < 0.001) and in all study population (r = -0,600; p < 0,001; n = 67). In conclusion, we provide new data regarding the cytoprotective effect of EPO exerted at systemic level on erythrocyte membrane, in the particular state of impaired glucose metabolism associated with oxidative stress, in the elderly.

Correlations between eyelid tumors and tear lipocalin, lysozyme and lactoferrin concentrations in postmenopausal women.

RATIONALE: Common ophthalmological problems are found in patients with eyelid tumors and include ocular surface diseases, such as dry eyes, eyelid disorders, excessive tearing and ocular inflammation. OBJECTIVE: The potential correlation between the symptomatology, tear break-up time (TBUT) and lipocalin, lactoferrin and lysozyme concentrations in the tear film were investigated in a group of symptomatic dry-eyed postmenopausal (PM) women compared to age-matched controls, considering the patients with eyelid tumors. METHODS AND RESULTS: 66 females were divided into two groups of 33 females each, one group having dry eye (DE) and one asymptomatic group (non-dry eye) (NDE), based on their responses to the OSDI questionnaire, TBUT and Schirmer test evaluation. Tears were collected via capillary tubes. Tear lysozyme, lactoferrin and lipocalin concentrations were determined via electrophoresis and the results for patients with or without eyelid tumors were compared. The results revealed significant differences in lysozyme concentration between patients with or without eyelid tumors in the DE group (p = 0.004). Lower levels for TBUT and lactoferrin in the DE group were also found, compared to the NDE group for eyelid tumors patients. Tear lipocalins were in the same range in both groups. DISCUSSION: Within a PM population, some components of the tear film were found to be at lower levels in patients with eyelid tumors, compared to patients without this pathology, which resulted in the development of DE or in the enhancement of the symptoms of an existing DE.

Redox state alteration modulates astrocyte glucuronidation.

We have investigated the effects of mild oxidative conditions on drug-metabolizing enzyme activity in rat cultured astrocytes. These experimental conditions promoting an oxidative environment were obtained by short exposure to a low concentration of menadione (5 microM) for a short duration (15 min). This resulted in the rapid and transient production of reactive oxygen species (+130%), associated with a decrease in GSH cellular content (-24%), and an increase in total protein oxidation (+26%), but promoted neither PGE(2) nor NO production. This treatment induced a rapid and persistent decrease in astrocyte glucuronidation activities, which was totally prevented by N-acetyl-l-cysteine. These oxidative conditions also affected the specific UGT1A6 activity measured in transfected V79-1A6 cells. Finally, the subsequent recovery of astrocyte glucuronidation activity may result from upregulation of UGT1A6 expression (+62%) as shown by RT-PCR and gene reporter assay. These results show that the catalytic properties and expression of cerebral UGT1A6 are highly sensitive to the redox environment. The protective effect of N-acetyl-l-cysteine suggests both a direct action of reactive oxygen species on the protein and a more delayed action on the transcriptional regulation of UGT1A6. These results suggest that cerebral metabolism can be altered by physiological or pathological redox modifications.

Rat olfactory bulb and epithelium UDP-glucuronosyltransferase 2A1 (UGT2A1) expression: in situ mRNA localization and quantitative analysis.

UDP-glucuronosyltransferases (UGTs) form a multigenic family of enzymes involved in the biotransformation and elimination of numerous endo- and xenobiotic compounds. Beside the diverse UGT isoforms present in the liver as well as in other tissues, the UGT2A1 isoform, also called olfactory UGT, was initially thought to be expressed in the nasal epithelium only. In this work, we demonstrate the UGT2A1 mRNA expression in the olfactory bulb, using in situ hybridization and quantitative reverse transcription-polymerase chain reaction (RT-PCR) techniques. Within the epithelium, UGT2A1 mRNA is mainly found in the sustentacular cells and to a lesser extent in Bowman's gland cells. Moreover, in situ hybrization staining reveals UGT2A1 mRNA expression in the olfactory sensory neuron nuclei. Neuronal localization of UGT2A1 mRNA within the olfactory bulb is mainly found in the deeper granular cells. The development of the quantitative multistandard RT-PCR method firstly required characterization of the mouse Ugt2A1 cDNA by rapid amplification of cDNA ends (RACE)-PCR. UGT2A1 mRNA levels appear quantitatively six-fold lower in the olfactory bulb than in the epithelium, in both the rat and mouse. The expression of UGT2A1 in the olfactory bulb, which directly connects the nasal epithelium to the brain, emphasizes the potential role of this enzyme in the protection of the brain against airborne hazardous chemicals.

UDP-glucuronosyltransferase in the rat olfactory bulb: identification of the UGT1A6 isoform and age-related changes in 1-naphthol glucuronidation.

Xenobiotic glucuronidation represents a major metabolic protection of the brain against chemical aggressions at blood-brain interfaces. We previously observed that glucuronidation of 1-naphthol was very effective in olfactory bulb, which is a pathway for the entry of foreign molecules into the brain. In this work, we showed that 1-naphthol glucuronidation varied according to age. It was very high at birth, then decreased markedly in 3-month-old rats and increased again significantly during aging. By Western blot and reverse transcription-polymerase chain reaction (RT-PCR), we demonstrated the presence in the olfactory bulb of the UDP-glucuronosyltransferase (UGT) 1A6 isoform, which catalyzes the glucuronidation of phenols, such as 1-naphthol. Quantitative RT-PCR indicated that the mRNA levels encoding UGT1A6 did not significantly change according to age, thus suggesting that other differently regulated UGT isoforms were present and would account for the variations of 1-naphthol glucuronidation observed.

Identification of the uridine diphosphate glucuronosyltransferase isoform UGT1A6 in rat brain and in primary cultures of neurons and astrocytes.

The expression of a phenol uridine diphosphate glucuronosyltransferase (UGT) was investigated in rat brain homogenate and in primary cultures of astrocytes and neurons, by means of model substrates (1-naphthol and 4-methylumbelliferone) assays, Western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) experiments. Glucuronidation of these substances occurred in cerebral cell or brain homogenates, although to different extents. The specific activity was the highest in astrocytes, with values more than 10- and 100-fold those found in neurons or total brain, respectively. Using antibodies able to recognize several rat liver UGT isoforms, only one protein with an apparent molecular mass of 54 kDa was detected in astrocyte and neuron homogenates and brain microsomes. RT-PCR experiments run with primers specifically designed for the rat liver UGT1A6 revealed amplificons of the expected sizes in accordance with the presence of UGT1A6 mRNA. The nucleotide sequence of the 330-base pair product was 100% homologous to that of exon 1 of rat liver isoform UGT1A6. In conclusion, this work allowed us to identify for the first time a constitutive cerebral UGT isoform identical to rat liver UGT1A6, which glucuronidates planar phenolic substances in cultured astrocytes, neurons, and the entire brain.

Production and characterization of monoclonal antibodies against Taylorella equigenitalis.

Monoclonal antibodies were produced against Taylorella equigenitalis using two reference strains. Out of the 79 hybridoma clones shown to express antibodies to T equigenitalis by indirect immunofluorescence assay, 16 were selected for monoclonal antibody production and characterization. These clones recognized different field strains of T equigenitalis isolated in France. They showed no cross-reaction with bacterial strains with previously reported antigenic cross-reactivity, nor did they react with other bacteria commonly found in genital flora. The epitopes recognized by eight of the monoclonal antibodies were situated in proteins of 150, 120, 52.7 and 22 kDa. These epitopes were resistant to the extraction denaturing conditions. These monoclonal antibodies could be used as reagents for specific detection of T equigenitalis.

Propagation of equine infectious anemia virus in horse cell cultures.

The Wyoming strain of equine infectious anemia virus was adapted to cell cultures by 7 passages in horse leukocytes and 14 passages in fetal equine dermal and kidney cells. The virus was made evident by electron microscopy and immunodiffusion tests with antigens prepared from culture fluids.