Alpha‐Tocopherol during lactation and after weaning alters the programming effect of prenatal high salt intake on cardiac and renal functions of adult male offspring

Maternal salt overload programs cardiovascular and renal alterations in the offspring. However, beneficial and harmful effects of high dose vitamin E supplementation have been described in humans and animals. We investigated the hypothesis as to whether cardiac and renal alterations can be programmed by gestational salt overload, and can become further modified during lactation and after weaning. Male Wistar rats were used, being the offspring of mothers that drank either tap water or 0.3 mol/L NaCl for 20 days before and during pregnancy. α‐Tocopherol (0.35 g/kg) was administered to mothers daily during lactation or to their offspring for 3 weeks post‐weaning. Systolic blood pressure (tcSBP) was measured in juvenile rats aged 210 days. The response of mean arterial pressure (MAP) and heart rate (HR) to intravenous infusion of angiotensin II (Ang II) was also examined. Left ventricle plasma membrane (PMCA) and sarcoplasmic reticulum Ca²⁺‐ATPase (SERCA) activities, and certain parameters of renal function, were measured. Maternal saline programmed for increased body mass and kidney mass/body mass ratio, increased tcSBP, increased mean arterial pressure and heart rate with anomalous response to infused Ang II. In the heart, saline increased PMCA and α‐Tocopherol per se increased PMCA/SERCA. In the kidney, the most remarkable result was the silent saline programming of Cr_Cl, which was sensitized for a sharp decrease after α‐Tocopherol. In conclusion, the combination of maternal saline overload and high α‐Tocopherol immediately after birth leads to simultaneous cardiovascular and renal alterations in the young offspring, like those encountered in type V cardiorenal syndrome.     

Increase in the Expression of CD4 + CD25+ Lymphocytic T Cells in the Indeterminate Clinical Form of Human Chagas Disease After Stimulation With Recombinant Antigens of Trypanosoma cruzi

Purpose

Regulatory T cells are involved in the clinical course of chronic Chagas disease, possibly because they exercise a control in the patient’s inflammatory response to Trypanosoma cruzi. This study analyzed the levels of CD4?+?CD25+ T cells in chronic Chagas disease patients after in vitro stimulation of the peripheral blood mononuclear cells with CRA (Cytoplasmic Repetitive Antigen) or FRA (Flagellar Repetitive Antigen) T. cruzi antigens.

Methods

Groups of patients with the cardiac form and indeterminate form; and non-infected individuals, were selected. The CD4?+?CD25+ T lymphocyte population, as well as the FoxP3 expression and the IL10 production, were evaluated by flow cytometry after stimulation with CRA or FRA.

Result

The IND group presented higher levels of CD4?+?CD25+ T cells than the CARD group. However, there was no evidence of a relationship between FoxP3 and IL10 with any of the chronic forms.

Conclusions

Our results suggest the possible involvement of CD4?+?CD25+ T cells specific to CRA and FRA in controlling the progression of clinical outcomes. Though, further studies are needed to define which mechanisms activate regulatory T cells and lead to pathology control in chronic human Chagas disease.     

Susceptibility of As-yet-uncultivated and Difficult-to-culture Bacteria to Chemomechanical Procedures

Introduction

A significant portion of the bacteria taking part of the microbiome associated with apical periodontitis still remain to be cultivated and phenotypically characterized. This molecular study evaluated the prevalence of selected as-yet-uncultivated and difficult-to-culture bacterial taxa in infected root canals and their susceptibility to chemomechanical procedures.

Methods

Root canals of single-rooted teeth with apical periodontitis were prepared using rotary nickel-titanium instruments and 2.5% sodium hypochlorite as the irrigant. DNA extracts from samples taken before (S1) and after (S2) chemomechanical preparation were surveyed for the presence of 7 as-yet-uncultivated phylotypes and 1 difficult-to-culture species using end-point polymerase chain reaction. Samples were also subjected to quantitative analysis of total bacteria and levels of the 2 most prevalent taxa.

Results

Bacteroidaceae sp. HOT-272 (24%) and Fretibacterium fastidiosum (20%) were the most prevalent taxa in S1. Their mean counts in S1 were 8.25 × 10³ and 2.13 × 10³ rRNA gene copies, corresponding to 0.18% and 0.55% of the total bacteria. Chemomechanical debridement promoted a highly statistically significant reduction in total bacterial counts (P < .001), but 64% of the canals were still positive for bacterial presence. Of the target taxa, only Bacteroidaceae sp. HOT-272 and F. fastidiosum were detected in S2 (each one in 1 sample). The reduction in counts of both taxa was also highly significant (P < .001).

Conclusions

Findings confirmed that several as-yet-uncultivated and difficult-to-grow bacterial taxa can participate in the microbiome associated with apical periodontitis. Two of them were found in relatively high prevalence but rarely as a dominant species. Chemomechanical procedures were highly effective in completely eliminating these taxa or at least substantially reducing their numbers.     

The role of IL‐6 on apical periodontitis: a systematic review

The aim of this review was to examine current knowledge of the role of interleukin‐6 (IL‐6) in apical periodontitis (AP) pathogenesis as an inflammatory or pro‐inflammatory cytokine. It also looked at whether IL‐6 could serve as a measure for differential diagnosis or as a biomarker that can further predict the progression of bone resorption. A systematic review relating to AP and IL‐6 was made via PubMed, BIOSIS, Cochrane, EMBASE and Web of Science databases using keywords and controlled vocabulary. Two independent reviewers first screened titles and abstracts and then the full texts. The reference lists of the identified publications were examined for additional titles. Eighteen papers were studied in total. In vitro studies (n = 6) revealed that IL‐6 is present in AP, and its levels are proportional to the size of the periapical lesions. Neutrophils and macrophages resident in these lesions can produce IL‐6 in vitro after a bacterial stimulus. Animal studies (n = 5) showed that IL‐6 is present in AP and that osteoblasts can produce IL‐6 in vivo. On the other hand, two studies using IL‐6 knockout mice revealed larger periapical lesions when compared with control groups, demonstrating IL‐6's role as an anti‐inflammatory cytokine. In human studies (n = 7), IL‐6 was identified in AP, and its levels were higher in symptomatic, epithelialized and large lesions than in asymptomatic and small lesions. These data lead to the conclusion that IL‐6 may play a pro‐inflammatory role, increasing its levels and reabsorbing bone in the presence of infections. When IL‐6 is not present, other cytokines such as IL‐1 and TNF‐α induce bone resorption. Further studies about the relationship between AP development and the cytokine network must be performed to establish the exact role of each cytokine in the inflammatory process.     

Neuroprotective effect of epidural hypothermia after spinal cord lesion in rats

OBJECTIVES

: To evaluate the neuroprotective effect of epidural hypothermia in rats subjected to experimental spinal cord lesion.

METHODS:

Wistar rats (n = 30) weighing 320-360 g were randomized to two groups (hypothermia and control) of 15 rats per group. A spinal cord lesion was induced by the standardized drop of a 10-g weight from a height of 2.5 cm, using the New York University Impactor, after laminectomy at the T9-10 level. Rats in the hypothermia group underwent epidural hypothermia for 20 minutes immediately after spinal cord injury. Motor function was assessed for six weeks using the Basso, Beattie and Bresnahan motor scores and the inclined plane test. At the end of the final week, the rats'' neurological status was monitored by the motor evoked potential test and the results for the two groups were compared.

RESULTS:

Analysis of the Basso, Beattie and Bresnahan scores obtained during the six-week period indicated that there were no significant differences between the two groups. There was no significant difference between the groups in the inclined plane test scores during the six-week period. Furthermore, at the end of the study, the latency and amplitude values of the motor evoked potential test were not significantly different between the two groups.

CONCLUSION:

Hypothermia did not produce a neuroprotective effect when applied at the injury level and in the epidural space immediately after induction of a spinal cord contusion in Wistar rats.     

Risk Factors for Development of Rectal Neuroendocrine Tumors Longer Than 9 mm: Retrospective Cohort

BackgroundRectal neuroendocrine tumors (R-NET) represent the most frequent of gastroenteropancreatic neuroendocrine neoplasms (NEN-GEP) according to the United States Surveillance, Epidemiology, and End Results database. With an annual percentage of occurrence increasing to 8.2% of all rectal neoplasms, R-NET affect less than 2% and are reported in only 0.05% to 0.07% of patients undergoing colorectal cancer (CRC) screening. The primary objective of this study was to assess the risk factors associated with R-NET greater than 10 mm. As a secondary objective, it was also aimed to evaluate the response to endoscopic treatment.Methods: This was a retrospective study, using data collected through the analysis of medical records of colonoscopies performed from January 2008 to December 2014. Records of polypectomies were identified, and the results were searched for pathological findings of R-NET. We also gathered epidemiological data and outcomes as risk factors for lesions greater than or equal to 10 mm, with local and distant recurrence.Results: During the study period, 18 218 colonoscopies were performed and 10 865 polypoid lesions were detected and removed, 20 with R-NET anatomopathology. The detection rate was 0.1%. The risk factors associated with major lesions were Japanese ethnicity, the lack of previous cancer diagnosis, and a Ki67 index > 2%. The mean follow-up was 56.6 months, and there was no local lymph node recurrence or distant relapse.ConclusionThis study concludes that endoscopic resection is a good and effective method for treatment of Grade 1 rectal NET smaller than 11 mm, with high cure rates and low rates of local or distant relapse.