Lipid and protein oxidation in newborn infants after lutein administration.

OBJECTIVES: To test the hypothesis that neonatal supplementation with lutein in the first hours of life reduces neonatal oxidative stress (OS) in the immediate postpartum period. METHODS: A randomized controlled, double-blinded clinical trial was conducted among 150 newborns divided into control group, not supplemented (n = 47), and test group, supplemented with lutein on the first day postpartum (n = 103). Blood Samples were collected at birth from cord and at 48 hrs postpartum while routine neonatal metabolic screenings were taking place. Total hydroperoxide (TH), advanced oxidation protein products (AOPP), and biological antioxidant potential (BAP) were measured by spectrophotometry and data were analyzed by Wilcoxon rank sum test and by multivariate logistic regression analysis. RESULTS: Before lutein supplementation, the mean blood concentrations of AOPP, TH, and BAP were 36.10 umol/L, 156.75 mmol/H2O2, and 2361.04 umol/L in the test group. After lutein supplementation, significantly higher BAP increment (0.17 ± 0.22 versus 0.06 versus ± 0.46) and lower TH increment (0.46 ± 0.54 versus 0.34 ± 0.52) were observed in the test group compared to controls. CONCLUSION: Neonatal supplementation with lutein in the first hours of life increases BAP and reduces TH in supplemented babies compared to those untreated. The generation of free radical-induced damage at birth is reduced by lutein. This trial is registered with ClinicalTrials.gov NCT02068807.

Distortion-product otoacoustic emissions: a useful test for monitoring ototoxicity induced by pegylated interferon and ribavirin treatment in patients with chronic hepatitis C.

Pegylated-interferon (peg-IFN) and ribavirin combination therapy for the treatment of hepatitis C virus (HCV) infection is well known to be associated with significant adverse effects. Several studies have investigated a possible auditory pathway involvement during IFN therapy, but a method to monitor the potential auditory involvement during treatment has not yet been described. The aim of this study is to evaluate possible modifications of the outer hair cell (OHC) function in HCV patients receiving peg-IFN and ribavirin combination therapy. Thirteen adult HCV patients (8 F/5 M, mean age 52∓12 years) treated with peg-IFN and ribavirin combination therapy underwent Pure Tone Audiogram and Distortion Product Otoacoustic Emission (DPOAE) tests. We compared mean auditory thresholds (PTA) and mean DPOAE amplitude before, at month 3 during, and at the end of treatment (T0, T3, and Tend, respectively), and 3 months after treatment discontinuation (Tfu). No significant differences were found in hearing levels at the different time points analyzed. During treatment, three patients developed tinnitus, which in 2 cases resolved spontaneously after the end of therapy. Compared to T0 (19.5±0.83), a statistically significant DPOAE increase at T3 (30±1,26) and Tend (28.6±2.16) was found (p<0.05 at both time points), while DPOAEs returned to pre-treatment levels at Tfu (19.3±1.3). In our group, none of the patients reported a permanent auditory impairment, excluding one patient with persistent tinnitus. Peg-IFN could produce an increase of motility of the OHCs by means of intracellular pathways. DPOAE test could be considered a new method for monitoring ototoxicity induced by IFN. On the basis of recent literature and our audiological results, physicians should be aware of the possible ototoxic effects of peg-IFN, requiring appropriate surveillance, and the patient should be informed of the potential side effects of IFN therapy on the auditory pathway.

Low levels of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 in patients with newly diagnosed type 1 diabetes.

BACKGROUND AND AIMS: An epidemiological retrospective study and a recent prospective study from Finland have both concluded that vitamin D3 supplementation at birth protects individuals from type 1 diabetes later in life. Moreover, it is thought that vitamin D3 supplementation, in particular its activated form, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], may act as an immunomodulator, facilitating the shift from a Th1 to a Th2 immune response. The aim of this surveillance study was to measure levels of both 25-hydroxyvitamin D3 (25OHD3) and 1,25-dihydroxyvitamin D3 in patients with newly diagnosed type 1 diabetes as compared to normal subjects. METHODS: We measured plasma levels of 25-hydroxyvitamin D3 [25OHD3] and 1,25-dihydroxyvitamin D3 by radioimmunoassay in 88 consecutive patients with newly diagnosed type 1 diabetes (mean age 14.6 years; diagnosis within the last week), and in 57 healthy age and sex-matched subjects (mean age 16.5 years) born and residing in the Lazio region of continental Italy. RESULTS: Mean levels of both 25OHD3 and 1,25-(OH)2D3 were significantly lower in patients compared to controls (p < 0.01 and p < 0.03, respectively). There was no correlation between 1,25-(OH)2D3 plasma level and metabolic control status at disease diagnosis, age, gender, or most importantly, seasonality of disease diagnosis. This new observation endorses the findings of the Finnish study, even though Italy is a geographic area with more hours of sunlight than Finland. CONCLUSIONS: These findings suggest that vitamin D3 may be an important pathogenic factor in type 1 diabetes independent of geographical latitude, and that its supplementation should be considered not only at birth, but also at diagnosis of type 1 diabetes with the aim of favouring a Th2 immune response and protecting residual beta cells from further destruction.

HLA-DRB1* and allergy to Parietaria: linkage and association analyses.

In this study, we used the affected sibling-pairs approach to investigate the linkage of HLA (human leukocyte antigen)-DRB* with phenotypes related to allergy to Parietaria, the most common pollinosis in Mediterranean countries. The study population consisted of 51 nuclear families (235 subjects). Linkage was detected with Parietaria skin test positivity (p < (0.01), presence of IgG and IgE antibodies specific for the major allergen Par o 1 (p < 0.020 and p < 0.025, respectively), and absence of Par o 1-specific IgE (p < 0.020). High levels of Par o 1-specific IgG were associated with DRB1*1101 and/or DRB1*1104 (p < 0.0001 and p < 0.0119, respectively) in parents and probands. High levels of Par o 1-specific IgE were associated with DRB*1104 in parents (p < 0.017) and with DRB1*1101 in probands (p < 0.0146). When siblings were categorized according to high/low total IgE levels (> or =125 IU/ml and <125 IU/ml, respectively), high IgE antibody response was associated with DRB1*1104 in siblings with low total IgE (p < 0.034) and with DRB1*1101 in siblings with high total IgE (p < 0.05). These results demonstrate that HLA-DRB1*, or genes in linkage disequilibrium, contributes to susceptibility to Parietaria allergy and that total IgE levels can discriminate population subsets where different alleles (at the HLA region or at loci in linkage disequilibrium) contribute to control allergen-specific IgE synthesis.

Clinical and biological aspects of bereavement and loss-induced depression: a reappraisal.

Loss and bereavement can be regarded as risk factors for the development of psychiatric and medical illness. Vulnerability to physical illness and mortality are increased during the first 2 years of bereavement, with men at higher risk than women. Symptoms of anxiety and a frank depressive syndrome are common during the first months of bereavement and, although depressive symptoms are usually transient and self-limited, bereaved individuals not rarely go on to develop major depression. In our perspective, loss perceived as irreparable, and persistence of perceived loss may favour the development of complicated grief and depression. Factors such as unexpectedness, absence of social support, concurrent loss or illness, and grief proneness may predict poor adjustment after bereavement. Complicated bereavement should be distinguished from uncomplicated bereavement, because patients with the latter need no treatment. In humans, there is evidence of increased adrenocortical activity and altered immune function following bereavement, whereas in non-human primates, biogenic amine systems appear to be involved in the response to maternal or social separation. According to a 'psychosomatic view of the brain', critical life events can both affect brain neurotransmitters and contribute to psychological and somatic symptoms of depression. Emotional events may be transduced into long-lasting brain changes, involving neurotransmitters, neuropeptides and receptors. Although only very limited evidence exists, long-term consequences could involve changes at the gene expression level.