The efficiency of glutamate uptake differs between neonatal and adult cortical microvascular endothelial cells

Glutamate transporters (excitatory amino-acid transporters (EAATs)) are essential for brain homeostasis. While previous studies indicate that the vascular endothelium contributes to glutamate efflux in the adult brain, little information is available regarding glutamate uptake in the immature brain. The present study shows a differential expression pattern of EAATs between cortical microvessels in adults and newborns. In addition, adult cortical endothelial cells take up glutamate more efficiently than neonatal cells. Our findings indicate age-specific changes in extracellular glutamate regulation by brain endothelial cells, suggesting differences in the efficiency of glutamate efflux during an excitotoxic process that, in turn, may contribute to age-specific brain vulnerability.     

Effects of Cognitive–Behavioral Conjoint Therapy for PTSD on Partners’ Psychological Functioning

A number of studies have documented that posttraumatic stress disorder (PTSD) symptoms in “one” partner are negatively associated with their intimate partner's psychological functioning. The present study investigated intimate partners’ mental health outcomes (i.e., depression, anxiety, and anger) in a sample of 40 partners of individuals with PTSD within a randomized waitlist controlled trial of cognitive–behavioral conjoint therapy for PTSD (Monson & Fredman, 2012 ). There were no significant differences between active treatment and waitlist in intimate partners’ psychological functioning at posttreatment. Subgroup analyses, however, of partners exhibiting clinical levels of distress at pretreatment on several measures showed reliable and clinically significant improvements in their psychological functioning at posttreatment and no evidence of worsening. Results suggest that cognitive–behavioral conjoint therapy for PTSD may have additional benefits for partners presenting with psychological distress.     

Effects of sleeve gastrectomy in high fat diet-induced obese mice: respective role of reduced caloric intake,white adipose tissue inflammation and changes in adipose tissue and ectopic fat depots

Background

Sleeve gastrectomy (SG) has become a popular bariatric procedure. The mechanisms responsible for weight loss and improvement of metabolic disturbances have still not been completely elucidated. We investigated the effect of SG on body weight, adipose tissue depots, glucose tolerance, and liver steatosis independent of reduced caloric intake in high-fat-diet-induced obese mice.

Methods

C57BI/6 J mice fed a high fat diet (45 %) for 33 weeks were divided into three groups: sleeve gastrectomy (SG, 13 mice), sham-operated ad libitum fed (SALF, 13 mice) and sham-operated pair fed (PFS, 13 mice). The animals were humanely killed 23 days after surgery.

Results

In SG mice, food intake was reduced transiently, but weight loss was significant and persistent compared to controls (SG vs. PFS, P < 0.05; PFS vs. SALF, P < 0.05). SG mice showed improved glucose tolerance and lower levels of liver steatosis compared with controls (area under the curve, SG vs. PFS, P < 0.01; PFS vs. SALF, P < 0.05) (liver steatosis, SG vs. PFS, P < 0.05; PFS vs. SALF, P < 0.01). This was associated with a decrease in the ratios of the weight of pancreas, epididymal and inguinal adipose tissues to body weight, and an increase in the ratio of brown adipose tissue weight to body weight. Epididymal adipose tissue was also infiltrated by fewer activated T cells and by more anti-inflammatory regulatory T cells. Serum levels of fasting acyl ghrelin were still significantly decreased 3 weeks after surgery in SG mice compared to PFS mice (P < 0.05).

Conclusions

Reduced white adipose tissue inflammation, modification of adipose tissue development (brown vs. white adipose tissue), and ectopic fat are potential mechanisms that may account for the reduced caloric intake independent effects of SG.     

Surgery for small-bowel neuroendocrine tumors: Is there any benefit of the laparoscopic approach?

Background

Surgery of small-bowel neuroendocrine (SBNE) tumors is demanding because of the need for associated extensive node dissection and assessment of possible synchronous lesions. For this reason, possible benefit of laparoscopy in SBNE tumors has not been reported to date.

Methods

From 1996, all patients operated on in Beaujon Hospital for SBNE tumors were retrospectively extracted from a prospectively maintained database of intestinal resections.

Results

Overall, 73 patients [55 % males, median age 55 years (range 27–79)] underwent small bowel resection (n = 38; 54 %), ileocolectomy (n = 25; 36 %), or both (n = 7; 10 %). In 18 patients, resection of synchronous liver metastasis was performed simultaneously. Resection was performed laparoscopically in 12 patients (16 %). Resection was R0 in 40 patients (55 %), R1 in 1 patient (1 %), and R2 in 32 patients (44 %) because of unresectable liver metastases (n = 29), nodal involvement (n = 1), or both (n = 2). Laparoscopy was associated with similar R0 (p = 0.06) and morbidity (p = 0.95) rates, but a shorter hospital stay (p = 0.003) compared with laparotomy. Median follow-up was 39 months. Progression-free survival (PFS) at 1, 3, and 5 years were 95, 83 and 75 %, respectively, for R0 patients without liver metastasis; 92, 83, and 57 %, respectively, for R0 patients with resected liver metastasis; and 82, 58 and 30 %, respectively, for R2 patients (p = 0.045). Overall survival and PFS did not show any difference when comparing the laparoscopic and open groups.

Conclusion

Complete resection of primary SBNE tumors with or without liver metastasis is associated with good long-term survival. In selected patients, laparoscopy for SBNE tumors is feasible and associated with a shorter hospital stay than laparotomy.     

Molecular Absorbent Recirculating System therapy (MARS®) in pediatric acute liver failure: a single center experience

Background

Supportive care as a bridge to transplant or recovery remains challenging in children suffering from acute liver failure (ALF). We report our experience in children using the Molecular Absorbent Recirculating System (MARS®).

Methods

Retrospective data from children receiving therapy using MARS® from October 2009 to October 2012 were included in this single-center retrospective study. Patient characteristics, clinical presentation and complications of ALF, clinical and biological data before and after each MARS® session, technical modalities and adverse events were recorded.

Results

A total of six children underwent 17 MARS® sessions during the study period. Two adolescents were treated with the adult filter MARSFLUX® and four infants were treated with the MiniMARS® filter. The mean PEdiatric Logistic Dysfunction (PELOD) score at admission was 19 (range 11–33). All patients were mechanically ventilated, and four had acute kidney injury. The neurological course improved in one case, judged as stable in two cases and worsened in one case; data were unavailable in two cases. Mean serum ammonia levels decreased significantly following treatment with MARS® from an initial 89?±?29 to 58?±?35 mcmol/L (p?=?0.02). No other significant biological improvement was observed. Hemodynamic status improved/remained unchanged in the adolescent group, but in the infants four of the seven sessions were poorly tolerated and two sessions were aborted. Three patients died, two were successfully transplanted and one recovered without transplantation.

Conclusion

In our experience, treatment with MARS® is associated with encouraging results in adolescents, but it needs modification for very sick infants to improve tolerance.     

Islet of Langerhans isolation from pediatric and juvenile donor pancreases

Islet grafts isolated from young donors allow superior functional outcomes but are often associated with poor islet isolation yields. The objective of this study was to comparatively analyze the outcomes of islet isolation between young and older donors. We retrospectively analyzed 564 pancreas isolations performed at our institution. Isolation outcomes were compared between donors aged ≤20 years (n = 42, YD) and >20 years (n = 522, OD). Isolation procedure was identical in both groups. Prepurification percentage of embedded islets was higher in YD (44.3 ± 22.7% vs. 24.9 ± 20.9%, P < 0.001). This led to a lower recovery rate in YD (48% vs. 76%, P = 0.002) and hence lower postpurification IEQ/g pancreas in YD (2 412 ± 1 789 IEQ/g vs. 3 194 ± 1 892 IEQ/g, P = 0.01). Final yield was 180 982 ± 128 073 IEQ in YD and 244 167 ± 134 137 IEQ in OD, (P = 0.006). In vitro function was markedly, albeit nonsignificantly, higher in YD (SI: 4.5 ± 5.1 vs. 3.0 ± 5.7, P = 0.350). Proportion of transplanted preparations was similar in both groups, 38% (16/42) in YD vs. 43% (224/522) in OD, P = 0.628. In spite of isolation and purification difficulties, pancreases from young donors allowed similar islet transplantation rates as older donors. Efforts should be directed at improving islet extraction in these donors to realize their full potential for islet transplantation.