Sertraline and Citalopram Actions on Gut Barrier Function

Introduction

Disruption of intestinal barrier is a key component to various diseases. Whether barrier dysfunction is the cause or effect in these situations is still unknown, although it is believed that translocation of luminal content may initiate gastrointestinal or systemic inflammatory disorders. Since trauma- or infection-driven epithelial permeability depends on Toll-like receptor (TLR) activity, inhibition of TLR signaling has been proposed as a strategy to protect intestinal barrier integrity after infection or other pathological conditions. Recently, selective serotonin recapture inhibitors including sertraline and citalopram were shown to inhibit TLR-3 activity, but the direct effects of these antidepressant drugs on the gut mucosa barrier remain largely unexplored.

Materials and methods

To investigate this, two approaches were used: first, ex vivo studies were performed to evaluate sertraline and citalopram-driven changes in permeability in isolated intestinal tissue. Second, both compounds were tested for their preventive effects in a rat model of disrupted gut barrier, induced by a low protein (LP) diet.

Results

Only sertraline was able to increase transepithelial electrical resistance in the rat colon both when used in an ex vivo (0.8 μg/mL, 180 min) or in vivo (30 mg/kg p.o., 20 days) fashion. However, citalopram (20 mg/kg p.o., 20 days), but not sertraline, prevented the increase in phospho–IRF3 protein, a marker of TLR-3 activation, in LP-rat ileum. Neither antidepressant affected locomotion, anxiety-like behaviours or stress-induced defecation.

Conclusion

Our data provides evidence to support the investigation of sertraline as therapeutic strategy to protect intestinal barrier function under life-threatening situations or chronic conditions associated with gut epithelial disruption.

     

A strategy to improve treatment‐related mortality and abandonment of therapy for childhood ALL in a developing country reveals the impact of treatment delays

Background

Treatment‐related mortality and abandonment of therapy are major barriers to successful treatment of childhood acute lymphoblastic leukemia (ALL) in the developing world.

Procedure

A collaboration was undertaken between Instituto Nacional de Cancerologia (Bogota, Colombia), which serves a poor patient population in an upper‐middle income country, and Dana‐Farber/Boston Children's Cancer and Blood Disorders Center (Boston, USA). Several interventions aimed at reducing toxic deaths and abandonment were implemented, including a reduced‐intensity treatment regimen and a psychosocial effort targeting abandonment. We performed a cohort study to assess impact.

Results

The Study Population comprised 99 children with ALL diagnosed between 2007 and 2010, and the Historic Cohort comprised 181 children treated prior to the study interventions (1995–2004). Significant improvements were achieved in the rate of deaths in complete remission (13% to 3%; P = 0.005), abandonment (32% to 9%; P < 0.001), and event‐free survival with abandonment considered an event (47% to 65% at 2 years; P = 0.016). However, relapse rate did not improve. Medically unnecessary treatment delays were common, and landmark analysis revealed that initiating the PIII phase of therapy ≥4 weeks delayed predicted markedly inferior disease‐free survival (P = 0.016). Conversely, patients who received therapy without excessive delays had outcomes approaching those achieved in high‐income countries.

Conclusions

Implementation of a twinning program was followed by reductions in abandonment and toxic deaths, but relapse rate did not improve. Inappropriate treatment delays were common and strongly predicted treatment failure. These findings highlight the importance of adherence to treatment schedule for effective therapy of ALL. Pediatr Blood Cancer 2015;62:1395–1402. © 2015 Wiley Periodicals, Inc.     

Energy Intake,Profile, and Dietary Sources in the Spanish Population: Findings of the ANIBES Study

Energy intake, and the foods and beverages contributing to that, are considered key to understanding the high obesity prevalence worldwide. The relative contributions of energy intake and expenditure to the obesity epidemic, however, remain poorly defined in Spain. The purpose of this study was to contribute to updating data of dietary energy intake and its main sources from food and beverages, according to gender and age. These data were derived from the ANIBES (“Anthropometry, Intake, and Energy Balance in Spain”) study, a cross-sectional study of a nationally representative sample of the Spanish population (from 9–75 years old). A three-day dietary record, collected by means of a tablet device, was used to obtain information about food and beverage consumption and leftovers. The final sample comprised 2009 individuals (1,013 men, 996 women). The observed mean dietary energy intake was 7.6 ± 2.11 MJ/day (8.2 ± 2.22 MJ/day for men and 6.9 ± 1.79 MJ/day for women). The highest intakes were observed among adolescents aged 13–17 years (8.4 MJ/day), followed by children 9–12 years (8.2 ± 1.80 MJ/day), adults aged 18–64 (7.6 ± 2.14 MJ/day) and older adults aged 65–75 years (6.8 ± 1.88 MJ/day). Cereals or grains (27.4%), meats and derivatives (15.2%), oils and fats (12.3%), and milk and dairy products (11.8%) contributed most to daily energy intake. Energy contributions from non-alcoholic beverages (3.9%), fish and shellfish (3.6%), sugars and sweets (3.3%) and alcoholic beverages (2.6%) were moderate to minor. Contributions to caloric profile were 16.8%E from proteins; 41.1%E from carbohydrates, including 1.4%E from fiber; 38.5%E from fats; and 1.9%E from alcohol intake. We can conclude that energy intake is decreasing in the Spanish population. A variety of food and beverage groups contribute to energy intake; however, it is necessary to reinforce efforts for better adherence to the traditional Mediterranean diet.     

Hyperthyrotropinemia in Mexican newborns

OBJECTIVE: To assess the differences in the blood concentration levels of the thyroid stimulating hormone and their possible use as an indicator of iodine sufficiency, in a sample of Mexican newborns. MATERIAL AND METHODS: A cross-sectional study was conducted from September 1999 to August 2000, among 25,427 Mexican newborns in the Ministry of Health clinics from 5 states. A total of 8,095 heel-prick and 17,332 umbilical cord blood samples were analyzed. Blood samples were collected in filter paper and processed by enzyme-linked immunosorbent assay. The Mann-Whitney U test and the Kruskal-Wallis test were used for statistical analyses. RESULTS: Hyperthyrotropinemia was found in 9.95% of heel samples and in 24.27% of umbilical cord samples (TSH > 5 microUl/ml). CONCLUSIONS: The percentage of hyperthyrotropinemia observed in this study was higher than that expected in a population with sufficient iodine intake; these findings could be due to poor maternal iodine intake.     

Swa: a Subdivision

For some time, anomalous serological reactions have been observed when the same anti-Swa sera are tested against red cells from different individuals reported as Sw(a+). A comparative collaborative study using the same collection of Sw(a+) cells and anti-Swa sera was undertaken by 4 reference laboratories, and it was found that Swa represents a heterogeneous group of antigens that can be subdivided into two categories. Both categories, Sw(a+) 700:41 and Sw(a+) 700:-41, were shown to be inherited.