NO enhances presynaptic currents during cerebellar mossy fiber-granule cell LTP

Nitric oxide (NO) is a candidate retrograde messenger in long-term potentiation (LTP). The NO metabolic pathway is expressed in the cerebellar granule cell layer but its physiological role remained unknown. In this paper we have investigated the role of NO in cerebellar mossy fiber-granule cell LTP, which has postsynaptic N-methyl-d-aspartate (NMDA) receptor-dependent induction. Pre- and postsynaptic current changes were simultaneously measured by using extracellular focal recordings, and NO release was monitored with an electrochemical probe in P21 rat cerebellar slices. High-frequency mossy fiber stimulation induced LTP and caused a significant NO release (6.2 +/- 2.8 nM; n = 5) in the granular layer that was dependent on NMDA receptor as well as on nitric oxide synthase (NOS) activation. Preventing NO production by perfusing the NOS inhibitor 100 microM NG-nitro-l-arginine (L-NNA), blocking extracellular NO diffusion by 10 microM MbO2, or inhibiting the NO target guanylyl cyclase (sGC) with 10 microM 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-dione (ODQ) prevented LTP. Moreover, the NO donor 10 microM 2-(N,N-diethylamino)-diazenolate-2-oxide.Na (DEA-NO) induced LTP, which was mutually occlusive with LTP generated by high-frequency stimulation, prevented by ODQ, and insensitive to NMDA channel blockade (50 microM APV + 25 microM 7-Cl-kyn) or interruption of mossy fiber stimulation. Thus NO is critical for LTP induction at the cerebellar mossy fiber-granule cell relay. Interestingly, LTP manipulations were accompanied by consensual changes in the presynaptic current, suggesting that NO acts as a retrograde signal-enhancing presynaptic terminal excitability.     

Immune response induction and new effector mechanisms possibly involved in protection conferred by the Cuban anti-meningococcal BC vaccine

This report explores the participation of some afferent mechanisms in the immune response induced by the Cuban anti-meningococcal vaccine VA-MENGOC-BC. The induction of delayed-type hypersensitivity in nursing babies and lymphocyte proliferation after immunization is demonstrated. The presence of gamma interferon IFN-gamma and interleukin-2 (IL-2) mRNAs but absence of IL-4, IL-5, and IL-10 mRNAs were observed in peripheral blood mononuclear cells from immunized subjects after in vitro challenge with outer membrane vesicles. In addition, some effector functions were also explored. The presence of opsonic activity was demonstrated in sera from vaccinees. The role of neutrophils as essential effector cells was shown. In conclusion, we have shown that, at least in the Cuban adult population, VA-MENGOC-BC induces mechanisms with a T-helper 1 pattern in the afferent and effector branches of the immune response.     

Cow’s Milk Protein Allergy as a Model of Food Allergies

Cow’s milk allergy (CMA) is one of the most common food allergies in infants, and its prevalence has increased over recent years. In the present paper, we focus on CMA as a model of food allergies in children. Understanding the diagnostic features of CMA is essential in order to manage patients with this disorder, guide the use of an elimination diet, and find the best moment to start an oral food challenge (OFC) and liberalize the diet. To date, no shared tolerance markers for the diagnosis of food allergy have been identified, and OFC remains the gold standard. Recently, oral immunotherapy (OIT) has emerged as a new therapeutic strategy and has changed the natural history of CMA. Before this, patients had to strictly avoid the food allergen, resulting in a decline in quality of life and subsequent nutritional, social, and psychological impairments. Thanks to the introduction of OIT, the passive approach involving rigid exclusion has changed to a proactive one. Both the heterogeneity in the diagnostic process among the studies and the variability of OIT data limit the comprehension of the real epidemiology of CMA, and, consequentially, its natural history. Therefore, well-planned randomized controlled trials are needed to standardize CMA diagnosis, prevention, and treatment strategies.     

Prenatal Exposure to BPA: The Effects on Hepatic Lipid Metabolism in Male and Female Rat Fetuses

Bisphenol A (BPA) is an organic chemical compound widely used for manufacturing plastics. BPA exposure originates principally from the diet, but it can also originate from dermal contact. In over 90% of individuals, including pregnant women, BPA is detectable in several body fluids. The effects of this exposure on the fetus are under active investigation in several research laboratories. The aim of our work was to study the impact of prenatal exposure to BPA in the liver of rat fetuses from a sex-dependent point of view. We particularly investigated the effects of prenatal BPA exposure on hepatic lipids because of their crucial role, not only for the liver, but also for the whole-body functions. Our results demonstrate that the liver of rat fetuses, in utero exposed to a very low dose of BPA (2.5 µg/kg/day), displays significant modulations with regard to proteins involved in cholesterol and fatty acid biosynthesis and trafficking. Moreover, an impact on inflammatory process has been observed. All these effects are dependent on sex, being observable only in female rat fetuses. In conclusion, this work demonstrates that maternal exposure to BPA compromises hepatic lipid metabolism in female offspring, and it also reveals the perspective impact of BPA on human health at doses currently considered safe.     

Complicaciones durante la intubación traqueal repetida en la unidad de cuidados intensivos. Estudio prospectivo,observacional comparando primera intubación y reintubación

Background of the studyThe goal of the study was to compare the incidence of complications, technical difficulty of intubation and physiologic pre-intubation status between the first intubation and reintubation performed on the same patient in an ICU.Materials and methodsThe study was approved by the ethics committee of Galicia (Santiago-Lugo, code No. 2015-012). Due to the observational, noninterventional, and noninvasive design of this study, the need for written consent was waived by the ethics committee of Galicia. Patients requiring tracheal intubation and reintubation in the ICU were included in this prospective observational study. Main endpoint was to compare the incidence of complications, physiologic pre-intubation status, and the rate of technical difficulty of intubation between the first intubation and reintubation performed on the same patient in an ICU.Results and discussion504 patients were intubated in our ICU during the study period, and 82 (16%) required reintubation. There was no difference between the first intubation and reintubation regarding number of total complication (35% vs 33%; P = .86), hypotension (24% vs 24%; P = 1), hypoxia (26% vs 26%; P = 1), esophageal intubation (1% vs 1%; P = 1), and bronchoaspiration (2% vs 1%; P = .86). Physiologic pre-intubation status and technical difficulty of intubation did not differ between the first intubation and reintubation.ConclusionsIn our ICU patients requiring tracheal reintubation, incidence of complications, physiologic pre-intubation status, and technical difficulty of intubation did not differ between the first intubation and reintubation.     

Meta-analysis and meta-regression of outcomes for adult living donor liver transplantation versus deceased donor liver transplantation

Prior single center or registry studies have shown that living donor liver transplantation (LDLT) decreases waitlist mortality and offers superior patient survival over deceased donor liver transplantation (DDLT). The aim of this study was to compare outcomes for adult LDLT and DDLT via systematic review. A meta-analysis was conducted to examine patient survival and graft survival, MELD, waiting time, technical complications, and postoperative infections. Out of 8600 abstracts, 19 international studies comparing adult LDLT and DDLT published between 1/2005 and 12/2017 were included. U.S. outcomes were analyzed using registry data. Overall, 4571 LDLT and 66,826 DDLT patients were examined. LDLT was associated with lower mortality at 1, 3, and 5 years posttransplant (5-year HR 0.87 [95% CI 0.81–0.93], p < .0001), similar graft survival, lower MELD at transplant (p < .04), shorter waiting time (p < .0001), and lower risk of rejection (p = .02), with a higher risk of biliary complications (OR 2.14, p < .0001). No differences were observed in rates of hepatic artery thrombosis. In meta-regression analysis, MELD difference was significantly associated with posttransplant survival (R² 0.56, p = .02). In conclusion, LDLT is associated with improved patient survival, less waiting time, and lower MELD at LT, despite posing a higher risk of biliary complications that did not affect survival posttransplant.     

Clivus ependymoma

Summary An 8-month-old girl had an ependymoma in the clivus, 2x6 cm in size, connected with the fourth ventricle by a cord of tissue 0.5 cm thick. There were no indications to make us suspect the origin of the tumour in the fourth ventricle, or that it was a case of ependymoma.     

Occlusion of the cerebral arteries in Recklinghausen's disease

Summary Two children, aged 18 months and 6 years, who had Recklinghausen's disease, had occlusion of cerebral arteries. One child had no motor deficit but the other had right hemiparesis and partial occlusion of the left posterior cerebral artery, a fact not found in the literature.