Xrx1 controls proliferation and multipotency of retinal progenitors

We investigated the function of Xrx1 during Xenopus retinogenesis. Xrx1 overexpression lengthens mitotic activity and ectopically activates the expression of markers of undifferentiated progenitors in the developing retina. We assayed Xrx1 ability to support proliferation with a cell-autonomous mechanism by in vivo lipofection of single retinal progenitors. Xrx1 overexpression increases clonal proliferation while Xrx1 functional inactivation exerts the opposite effect. We also compared the effects of Xrx1 with those of the cyclin-dependent kinase cdk2, a strong mitotic promoter. Despite the similar increase in clonal proliferation displayed by both factors, Xrx1 and cdk2 act differently on retinal cell fate determination. cdk2/cyclinA2 lipofected retinas show a decrease in early-born cell types as ganglion cells and cones and an increase in late-born types such as bipolar neurons. On the contrary, Xrx1 lipofected retinas show no changes in the proportions of the different cell types, thus suggesting a role in supporting multipotency of retinal progenitors.     

EEG power spectra changes and forebrain ischemia in rats

BACKGROUND: Several animal models of cerebral ischemia have been developed to investigate both pathophysiology and pharmacological treatment. The aim of this study was to verify the prognostic value of EEG power spectra analysis in a two-vessel plus hypotension rat model of transient global ischemia. METHODS: Spontaneously hypertensive rats (SHRs) and Wistar Kyoto rats (WKYs) were subjected to 20 min bilateral common carotid artery occlusion plus hypotension by sodium nitroprusside followed by reperfusion for seven days. Sham-operated animals served as controls. The changes after ischemia in EEG power spectra, and their relations with neuronal damage and astrocytic response were investigated. RESULTS: The EEG analysis revealed that in SHRs and WKYs, ischemia produced a dramatic increase in delta activity and a decrease in theta, beta and alpha activities derived from both cortical and hippocampal areas. EEG activity reverted to normal values more quickly in WKYs than in SHRs which did not recover cortical and hippocampal alpha and beta activities even at six days of reperfusion. SHRs presented more severe damage and intense astrocytosis than WKYs in almost all the brain regions analyzed. In SHRs, hippocampal delta activity was positively correlated with the degree of neuronal necrosis and astrocytic activation, whereas theta, alpha and beta activities correlated negatively. No correlations were found in WKYs. CONCLUSIONS: These data indicate that the hippocampal bioelectrical activity recorded in SHRs from the beginning of reperfusion could be useful for predicting the ischemic outcome and evaluating the effects of pharmacological interventions.     

Age and gender affect the relation between methylenetetrahydrofolate reductase C677T genotype and fasting plasma homocysteine concentrations in the Framingham Offspring Study Cohort

The C677T variant of methylenetetrahydrofolate reductase (MTHFR), a key enzyme in the remethylation of homocysteine to methionine, is a frequent genetic cause of mild hyperhomocysteinemia among individuals with low folate status. However, little is known about the influence of subject characteristics, such as age and sex, on the relation between the C677T MTHFR polymorphism and fasting plasma total homocysteine (tHcy) concentrations. The aim of the present study was to explore the influence of age and gender, together with folate status, on the association between the C677T polymorphism and tHcy concentrations. The C677T genotype was determined for 1820 participants from the fifth examination of the Framingham Offspring Study. Mean age of the participants was 56 y (range 28-82 y). The allelic distribution was not different from the Hardy-Weinberg equilibrium, with a TT frequency comparable in men and women (14%). Geometric mean tHcy was 15% higher in men than in women (P < 0.001), and women had significantly higher plasma folate levels (P < 0.001). Geometric mean tHcy was significantly higher in TT participants (P = 0.001) than in participants with the CC and CT genotypes among those with plasma folate <12.5 nmol/L, but not among those with higher folate status. Because of a significant age and sex interaction (P = 0.02), we further stratified the low folate group by age and sex, and observed that the association between genotype and tHcy was confined to men <55 y old (P < 0.001). Our results suggest that age and sex modify the contribution of the MTHFR C677T mutation to fasting tHcy concentrations.     

Effect of low dose tamoxifen on the insulin-like growth factor system in healthy women

The use of tamoxifen as a preventive agent may be limited by the increased risk of endometrial cancer and venous thromboembolic events observed in postmenopausal women. We have recently shown a comparable activity of lower doses of tamoxifen on several surrogate biomarkers of cardiovascular disease and breast cancer, including Insulin-like Growth Factor-I (IGF-I). To provide further insight into the effect of tamoxifen at low doses on the IGF system, we have correlated the drug serum levels attained after 2 months of either placebo (n=32), tamoxifen 20mg/day (n=26), 10mg/day (n=23) or 10mg/every other day (n=29) with the changes in IGF-I, Insulin-like Growth Factor-II (IGF-II), Insulin-like Growth Factor Binding Protein-1 (IGFBP-1), Insulin-like Growth Factor Binding Protein-3 (IGFBP-3), and IGF-I/IGFBP-3 ratio. Compared with placebo, tamoxifen induced a mean±standard error (SE) reduction of IGF-I of 16.9±7.8%, p0.05, a non-significant increase of 22.9±12.2% in IGF-II, an increase in IGFBP-1 of 49.3±22.7%, p0.05, and a non-significant change of IGFBP-3 (–4.0%±9.2). No significant concentration-response relationship was observed between serum tamoxifen concentrations and the biomarker changes except for the ratio of IGF-I/IGFBP-3, which decreased by 1.53±0.68% for any increase by 10ng/ml of serum tamoxifen concentration (p=0.02). Although low tamoxifen concentrations induce a comparable modulation of the IGF family relative to the conventional dose, the lower decrements in the IGF-I/IGFBP-3 ratio observed at low drug concentrations might be associated with a reduced preventive activity. Further studies on the search of the minimal active dose of tamoxifen are warranted.     

Spatial reorientation decline in aging: the combination of geometry and landmarks

ABSTRACT

Objectives: The study is focused on the assessment of reorientation skills in a sample of community-dwelling elderly people, manipulating landmarks and geometric (layout) information.

Method: A neuropsychological assessment was administered to 286 elderly participants, divided into six groups (healthy controls, HC; four subgroups of participants with mild cognitive impairment, MCI; participants with probable dementia, Prob_D) and tested with the Virtual Reorientation Test (VReoT). VReoT manipulated different spatial cues: geometry and landmarks (proximal and distal).

Result: Compared with HC, participants with MCI and Prob_D showed to be impaired in tasks involving geometry, landmarks and a combination of them. Both single and multiple domain impairment in MCI had an impact on reorientation performance. Moreover, VReoT was marginally able to discriminate between amnesic and non-amnesic MCI. The occurrence of getting lost events seemed to be associated to learning of geometric information.

Conclusion: The associative strength between landmark and target plays an important role in affecting spatial orientation performance of cognitively impaired participants. Geometry significantly supports landmark information and becomes helpful with the increase of cognitive impairment which is linked to a decrement in landmark encoding. VReoT seems to represent a reliable evaluation supplement for spatial orientation deficits in prodromal stages of dementia.     

Menarcheal timing in intensively treated girls with type 1 diabetes mellitus

Background and aimPrevious studies on menarcheal age (MA) in type 1 diabetes mellitus (T1DM) have shown conflicting results about the effects of DM, but most lack a control group. The present study design is peculiar in that it covers a study population of 73 intensively treated menarcheal adolescents with premenarcheal onset of T1DM (Group A), whose MA was compared with that recorded in three control populations: the first one consisting of 280 healthy adolescents, the second one consisting of 20 T1DM adolescents with postmenarcheal DM onset (Group B) and the third one represented by the respective mothers.Methods and resultsMA of Group A patients was significantly delayed when compared with the respective mothers, healthy controls and Group B patients. By contrast MA of Group B girls was superimposable to the one of both their respective mothers and healthy controls. In Group A MA was strongly related (p < 0.0005) to HbA1c at the time of menarche and to average HbA1c concentrations during the last years before menarche. In Group A no relationship between patients' and mothers' MAs was found, whilst such a correlation was significant in Group B.Conclusions(a) MA is significantly delayed in girls with premenarcheal presentation of T1DM, even if intensively treated; (b) menarcheal retardation is more severe in the patients with suboptimal metabolic control at the time of menarche; and (c) MA in premenarcheal presenting T1DM is irrespective of maternal MA, age and HbA1c concentrations at DM presentation, body mass index and daily insulin dose at menarche.     

High accuracy of noninvasive tests to diagnose Helicobacter pylori infection in very young children

OBJECTIVE: To validate the (13)C-urea-breath-test (UBT) and stool antigen test (HpSA) in children aged 5 years or younger, against invasive histologic study and rapid-urease-testing or culture. STUDY DESIGN: On all consecutive children aged 5 years or younger undergoing endoscopy in 1 single center during the last 7.5 years, UBT and HpSA were performed. RESULTS: Of a total of 184 children (median age 2.2 years, range 0.2-5.5), 30 were Helicobacter pylori-positive (16.3%). Sensitivity and specificity of UBT were 93.3% (95%CI 77.9%-99.2%) and 95.5% (90.9-98.2), with a cutoff of 5 per thousand, but specificity increased to 98.1% (94.4%-99.6%) with a cutoff of 8 per thousand. Sensitivity and specificity of HpSA were 93.3% (77.9%-99.2%) and 98.7% (95.4%-99.8%). CONCLUSION: Accuracy of noninvasive tests in our single-center study were satisfactory: specificity of UBT improved with a cutoff at 8%, and sensitivity of HpSA was high when determined locally without transportation after long or inadequate storage that could impair results.     

Antioxidant and free-radical scavenging activity of constituents of the leaves of Tachigalia paniculata

Two new myricetin glycosides, myricetin 7-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside (1) and myricetin 7-O-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-glucopyranoside (2), together with the known compounds quercetin 3-O-beta-D-glucopyranoside (3), quercetin 3-O-alpha-L-rhamnopyranoside (4), quercetin 3-O-beta-D-galactopyranoside (5), methyl gallate (6), isovanillin (7), 4-hydroxymethylbenzoate (8), 3,4-dihydroxymethylbenzoate (9), and caffeoyl aldehyde (10) were isolated from the leaves of Tachigalia paniculata. The structures of these compounds were determined by spectroscopic methods. Their antioxidant activity was determined by measuring free-radical scavenging effects using three different assays, namely, the Trolox Equivalent Antioxidant Capacity (TEAC) assay, the coupled oxidation of beta-carotene and linoleic acid (autoxidation assay), and the inhibition of xanthine oxidase activity. Compounds 1, 2, and 6 showed activity in the TEAC test, compounds 5-7 and 10 were moderately active in the autoxidation assay, while compounds 1 and 2 were the most potent of the isolates in the xanthine oxidase test.