Th17 cells have been associated with immune-mediated diseases in humans but it has still not been determined whether they play a role in immune thrombocytopenia. We evaluated representative cytokines ...of the Th17, Th1, Th2 and Treg cell commitment in the serum of patients with chronic immune thrombocytopenia, as well as the cell source of IL-17A. Higher levels of IL-17A and Th17-related cytokines, and an increased percentage of IL-17A producing CD4+ and neutrophils were observed in patients. The levels of cytokines involved in Th1 cell commitment IFN-γ, IL-2, IL12-p70 and the percentages of Th1 cells were also increased, but IL-4 was not detected. Although the concentrations of IL-10 were higher, the levels of TGF-β were similar in both groups. In conclusion, our results point to a putative role for Th-17 cells/IL-17A cytokine in the pathogenesis of chronic immune thrombocytopenia.
Intracerebroventricular (icv) streptozotocin (STZ) administration induces pathological and behavioral alterations similar to those observed in Alzheimer's disease (AD) and is thus considered an ...experimental model of sporadic AD. Since caffeine (an adenosine receptor antagonist) and selective antagonists of adenosine A2A receptors modify the course of memory impairment in different amyloid-β-based experimental models of AD, we now tested the impact of caffeine on STZ-induced dementia and associated neurodegeneration in the hippocampus as well as on the expression and density of adenosine receptors. Adult male rats received a bilateral infusion of saline or STZ (3 mg/kg, icv), which triggered memory deficits after four weeks, as gauged by impaired object recognition memory. This was accompanied by a reduced NeuN immunoreactivity in the hippocampal CA1 region and an increased expression and density of adenosine A2A receptors (A2AR), but not A1R, in the hippocampus. Caffeine consumption (1 g/L in the drinking water starting 2 weeks before the STZ challenge) prevented the STZ-induced memory impairment and neurodegeneration as well as the upregulation of A2AR. These findings provide the first demonstration that caffeine prevents sporadic dementia and implicate the control of central A2AR as its likely mechanism of action.
Abstract Duodenal ulcer-promoting gene ( dupA ) was recently described as a new putative Helicobacter pylori virulence marker associated with an increased risk for duodenal ulcer and reduced risk for ...gastric carcinoma in Japan and Korea. Since differences regarding the association among H. pylori markers and H. pylori -associated diseases have been demonstrated around the world, we evaluated the presence of the gene in 482 strains from Brazilian children (34 with duodenal ulcer and 97 with gastritis) and adults (126 with duodenal ulcer, 144 with gastritis and 81 with gastric carcinoma) by PCR using the described primers and an additional set of primers based on Brazilian strain sequences. The results were confirmed by sequencing. The presence of cagA was investigated by PCR and also included in the analysis. dupA was present in 445 (92.32%) and absent in 29 (6.02%) strains. All samples from children with and without duodenal ulcer were dupA -positive ( p =1.0). No association was observed among the strains from adults with gastritis (92.36%), duodenal ulcer (87.30%, p =0.30) and gastric carcinoma (87.65%, p =0.31). Conversely, cagA- positve status remained independently associated with duodenal ulcer (children: odds ratios (OR)=5.58, 95% confidence intervals (CI)=1.67–18.50; adults: OR=3.33, 95% CI=2.14–5.19) and gastric carcinoma (OR=6.58, 95% CI=3.51–12.30) in multivariate analyses. The presence of dupA was significantly higher in strains from children than in those from adults ( p =0.01). In conclusion, dupA is highly frequent and not associated with H. pylori -associated diseases in both Brazilian adults and children, which points to regional differences in the distribution of the gene.
The influence of temperature on the speed of an electrochemical coloration process of AISI 304 and AISI 430 stainless steel was investigated in temperature ranging from 25 °C to 40 °C. The surface ...properties of the interference colored nanofilms obtained in both types of stainless steel substrates, were also evaluated. A higher coloring speed was observed for AISI 304. The coloring time to obtain a gold color decreased with increasing temperature for both steels. This effect was stronger on the AISI 430 substrate, with a decrease of 36.6% in the coloration time for the samples colored at 40 °C and 25 °C. The Arrhenius model was applied to estimate the equations of colored films growth rate. The films porous fractions evaluated by SEM were in the range of 27–29%, without relevant variation with the coloring temperature. The nanohardness of the conjugated film-substrate obtained in a nanoindenter coupled to an AFM shows lower values than the uncolored substrates, and this reduction is more significant for the films grown on the AISI 430 ferritic specimens. The wettability of the surface to water and oil increased after coloring. The amplification effect of the hydrophilic effect can be associated with the increased AFM nanorugosity values.
Objective
Sleep disturbances are prevalent in human tauopathies yet despite the importance of sleep, little is known about its relationship with tau pathology. Here, we investigate this interaction ...by analyzing sleep and tau pathology throughout tauopathy disease progression in P301S human tau transgenic mice.
Methods
P301S and wild‐type mice were analyzed by electroencephalography (EEG)/electromyography at 3, 6, 9, and 11 months of age for sleep/wake time, EEG power, and homeostatic response. Cortical volume and tau pathology was also assessed by anti‐phospho‐tau AT8 staining.
Results
P301S tau mice had significantly decreased rapid eye movement (REM) sleep at 9 months of age and decreased REM and non‐REM (NREM) sleep as well as increased wakefulness at 11 months. Sleep loss was characterized by fewer wake, REM, and NREM bouts, increased wake bout duration, and decreased sleep bout duration. Decreased REM and NREM sleep was associated with increased brainstem tau pathology in the sublaterodorsal area and parafacial zone, respectively. P301S mice also showed increased EEG power at 6 and 9 months of age and decreased power at 11 months. Decreased EEG power was associated with decreased cortical volume. Despite sleep disturbances, P301S mice maintained homeostatic response to sleep deprivation.
Interpretation
Our results indicate that tau pathology is associated with sleep disturbances that worsen with age and these changes may be related to tau pathology in brainstem sleep regulating regions as well as neurodegeneration. Tau‐induced sleep changes could affect disease progression and be a marker for therapeutic efficacy in this and other tauopathy models.
Background: Helicobacter pylori infection is acquired predominantly in childhood. There is also evidence that children loss the infection. Therefore, factors that account for children remain ...infected need to be investigated because once established the infection persists throughout the life unless treated.
Methods: This study aimed to evaluate the H. pylori infection in children of a low‐income community at baseline and 8 years later to determine the predictor factors linked to the maintenance, acquisition, and loss of the infection using regression models of generalized estimating equations. H. pylori status was determined by 13C‐urea breath test.
Results: Data from 37.7% (133/353) of the children were available. No difference between the characteristics of the included and nonincluded children was observed. The prevalence of infection increased from 53.4 to 64.7%. Thirty‐nine children (29.3%) remained noninfected, 47.4% remained infected, 17.3% became infected, and 6.0% lost the infection. Factors associated with to remain infected compared with to remain noninfected included the age, increased number of children in the household, and the use of well water instead of municipal water. The acquisition of the infection was associated with the male gender.
Conclusion: Factors linked to remain and to gain H. pylori infection in a poor region were increased number of children in the household and the male gender. Also, the acquisition rates were higher than the loss rates, which lead to an increase in the infection prevalence with age.
Abstract Caffeine is the psychostimulant most consumed worldwide. Anxiogenic effects
of caffeine
have
been described in adult animals
with controversial findings about its anxiogenic potential. ...Besides, the effects of caffeine on anxiety with aging are still poorly known. In this study, adult mice (6 months old) started to receive caffeine (0.3 and 1.0 mg/mL, drinking water) during 12
–
14 months only in the light cycle and at weekdays. The open field (OF) and elevated plus maze (EPM) testing were used to determine the effects of caffeine on anxiety-related behavior in adult and aged mice (18
–
20 months old). Because aging alters synaptic proteins, we also evaluated SNAP-25 (as a nerve terminals marker), GFAP (as an astrocyte marker) and adenosine A1 and A2A receptors levels in the cortex. According to the OF analysis, caffeine did not change both hypolocomotion and anxiety with aging. However, aged mice showed less anxiety behavior in the EPM, but after receiving caffeine (0.3 mg/mL) during adulthood they were anxious as adult mice. While SNAP-25 and adenosine A2A receptors increased with aging, both GFAP and adenosine A1 receptors were not affected. Caffeine at moderate dose prevented the age-related increase of the SNAP-25, with no effect on adenosine A2A receptors. The absence of effect for the highest dose suggests that tolerance to caffeine may have developed over time. Aged mice showed high responsiveness to the OF, being difficult to achieve any effect of caffeine. On the other hand this substance sustained the adult anxious behavior over time in a less stressful paradigm, and this effect was coincident with changes in the SNAP-25, suggesting the involvement of this synaptic protein in the ability of caffeine to preserve changes related to emotionality with aging.
The
dupA of
Helicobacter pylori has been suggested as a virulence marker associated with the development of duodenal ulcer disease. However, the studies performed in different geographical areas have ...shown that there are variations in the prevalence of
dupA and its association with
H. pylori clinical outcomes. Our group did not observe associations between the presence of
dupA and
H. pylori clinical outcomes in Brazil. On the other hand, we observed 2 mutations in the sequence of
dupA that lead to stop codons: a deletion of an adenine at position 1311 and an insertion of an adenine at position 1426 of the gene. Our aim was to evaluate associations of the presence of
dupA with duodenal ulcer and gastric cancer, considering
dupA-positive only those
H. pylori strains that do not have the mutations in the gene sequence. We also evaluated the effect of infection with a strain carrying an intact
dupA on the gastric mucosa histology and IL-8 gastric levels. Colonization with strains that had the intact
dupA was negatively associated with gastric carcinoma (
p
=
0.001, OR
=
0.32, 95% CI
=
0.16–0.66). The presence of
dupA was also associated with an increased degree of antral mucosa inflammation (
p
=
0.01) and with decreased corpus atrophy (
p
<
0.01) as well as with increased gastric mucosa IL-8 levels (
p
=
0.04). In conclusion, the infection with a
H. pylori strain containing the
dupA without the stop codon polymorphisms is associated with a lower risk of development of gastric carcinoma in Brazilian subjects.
The possible role of RET variants in modifying the natural course of medullary thyroid carcinoma (MTC) is still a matter of debate. Here, we investigate whether the RET variants L769L, S836S, and ...G691S/S904S influence disease presentation in hereditary or sporadic MTC patients. One hundred and two patients with hereditary MTC and 81 patients with sporadic MTC attending our institution were evaluated. The frequencies of RET polymorphisms in hereditary MTC were as follows: L769L, 17.3%; S836S, 7.95%; and S904S/G691S, 18.2%. No associations were observed between these polymorphisms and pheochromocytoma, hyperparathyroidism, lymph node, or distant metastasis. However, patients harboring the S836S variant were younger than those without this allele (17±8.2 vs 28.6±14.4 years, P=0.01), suggesting that these patients had metastases at a young age. Accordingly, the cumulative frequency of local and/or distant metastases as estimated by Kaplan–Meier curves showed that lymph node and distant metastases occurred earlier in patients harboring the S836S variant (P=0.003 and P=0.026 respectively). The S836S allele frequency was higher in sporadic MTC patients than in controls (10.5 vs 3.1%, P=0.01). Individuals harboring the S836S variant were younger (38.6±13.3 vs 48.5±16.7 years, P=0.02) and showed a higher percentage of lymph node and distant metastases (P=0.02 and P=0.04 respectively). Kaplan–Meier estimates of lymph node and distant metastases yielded distinct curves for patients with or without the S836S allele (P=0.002 and P=0.001 respectively). Additional analyses using a COX regression model showed that the S836S variant was independently associated with metastatic disease (hazard ratio 2.82 (95% confidence interval 1.51–5.26), P=0.001). In conclusion, the RET S836S variant is associated with early onset and increased risk for metastatic disease in patients with hereditary or sporadic MTC.
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