Comparison of longer-term outcomes after kidney transplantation between Hispanic and non-Hispanic whites in the United States.

Little is known about the longer-term kidney transplant outcomes in the rapidly growing Hispanic population. Using the United States Renal Data System, we identified 105 250 Caucasian patients who received a first kidney transplant between January 1, 1996 and December 31, 2010. We tested for differences between Hispanic and non-Hispanic patients in the outcomes of (1) mortality, (2) all-cause graft failure, and (3) graft failure excluding death with a functioning graft. We used Cox regression to estimate (with 95% confidence intervals) multivariable-adjusted cause-specific hazard ratios (aHRCS ) for mortality and all-cause graft failure and subdistribution hazard ratios (aHRSD ) accounting for death as a competing risk for graft failure excluding death with a functioning graft. Both mortality [aHRCS = 0.69 (0.65-0.73)] and all-cause graft failure [aHRCS = 0.79 (0.75-0.83)] were lower in Hispanics. The association between Hispanic ethnicity and graft failure excluding death was modified by age (p < 0.003). Compared with non-Hispanic whites, graft failure excluding death with a functioning graft did not differ in Hispanics aged 18-39 years [aHRSD = 0.96 (0.89-1.05)] or aged 40-59 years [aHRSD = 1.08 (1.00-1.16)], but was 13% lower in those aged ≥60 years [aHRSD = 0.87 (0.78-0.98)]. In conclusion, once accounting for differences in overall survival, better graft survival was found in older Hispanic patients, but among not those aged <60 years.

Regulation of plasma membrane Ca(2+)-ATPase activity by acetylated tubulin: influence of the lipid environment.

We demonstrated previously that acetylated tubulin inhibits plasma membrane Ca(2+)-ATPase (PMCA) activity in plasma membrane vesicles (PMVs) of rat brain through a reversible interaction. Dissociation of the PMCA/tubulin complex leads to restoration of ATPase activity. We now report that, when the enzyme is reconstituted in phosphatidylcholine vesicles containing acidic or neutral lipids, tubulin not only loses its inhibitory effect but is also capable of activating PMCA. This alteration of the PMCA-inhibitory effect of tubulin was dependent on concentrations of both lipids and tubulin. Tubulin (300µg/ml) in combination with acidic lipids at concentrations >10%, increased PMCA activity up to 27-fold. The neutral lipid diacylglycerol (DAG), in combination with 50µg/ml tubulin, increased PMCA activity >12-fold, whereas tubulin alone at high concentration (≥300µg/ml) produced only 80% increase. When DAG was generated in situ by phospholipase C incubation of PMVs pre-treated with exogenous tubulin, the inhibitory effect of tubulin on PMCA activity (ATP hydrolysis, and Ca(2+) transport within vesicles) was reversed. These findings indicate that PMCA is activated independently of surrounding lipid composition at low tubulin concentrations (<50µg/ml), whereas PMCA is activated mainly by reconstitution in acidic lipids at high tubulin concentrations. Regulation of PMCA activity by tubulin is thus dependent on both membrane lipid composition and tubulin concentration.

Evaluation of hippuric acid content in goat milk as a marker of feeding regimen.

Organic producers, traders, and consumers must address 2 issues related to milk: authentication of the production system and nutritional differentiation. The presence of hippuric acid (HA) in goat milk samples has been proposed as a possible marker to differentiate the feeding regimen of goats. The objective of this work is to check the hypothesis that HA could be a marker for the type of feeding regimen of goats by studying the influence of production system (conventional or organic) and feeding regimen (with or without grazing fodder). With this purpose, commercial cow and goat milk samples (n=27) and raw goat milk samples (n=185; collected from different breeds, localizations, and dates) were analyzed. Samples were grouped according to breed, feeding regimen, production system, and origin to compare HA content by ANOVA and honestly significant difference Tukey test at a confidence level of ≥95%. Hippuric acid content was obtained by analyzing milk samples with capillary electrophoresis. This method was validated by analyzing part of the samples with HPLC as a reference technique. Sixty-nine raw goat milk samples (of the total 158 samples analyzed in this work) were quantified by capillary electrophoresis. In these samples, the lowest average content for HA was 7±3 mg/L. This value corresponds to a group of conventional raw milk samples from goats fed with compound feed. The highest value of this group was 28±10 mg/L, corresponding to goats fed compound feed plus grass. Conversely, for organic raw goat milk samples, the highest concentration was 67±14 mg/L, which corresponds to goats fed grass. By contrast, the lowest value of this organic group was 26±10 mg/L, which belongs to goats fed organic compounds. Notice that the highest HA average content was found in samples from grazing animals corresponding to the organic group. This result suggests that HA is a good marker to determine the type of goats feeding regimen; a high content of HA represents a diet based mainly or exclusively on eating green grass (grazing), independently of the production system. Hence, this marker would not be useful for the actual organic policies to distinguish organic milk under the current regulations, because organic dairy ruminants can be fed organic compound feed and conserved fodder without grazing at all.

Plasma membrane and vesicular glutamate transporter expression in chromaffin cells of bovine adrenal medulla.

The study of the functional expression of glutamate signaling molecules in peripheral tissues has received relatively little attention. However, evidence is increasing for a role of glutamate as an extracellular signal mediator in endocrine systems, in addition to having an excitatory amino acid neurotransmitter role in the CNS. Chromaffin cells are good models of catecholaminergic neurons, in which previous work from our group demonstrated the existence of both functional glutamate receptors and specific exocytotic and nonexocytotic glutamate release. In this work, the presence of specific plasma membrane (EAATs) and vesicular glutamate (VGLUTs) transporters has been investigated by using confocal microscopy, flow cytometric analysis, Western blot, and qRT-PCR techniques. We found specific expression of EAAT3, EAAT2, VGLUT1, and VGLUT3 in about 95%, 65%, 55%, and 25%, respectively, of the whole chromaffin cell population. However, chromaffin cells do not express VGLUT2 and have a very low expression of EAAT1. VGLUTs are localized mainly in the membrane fraction, and EAATs share their subcellular location between membrane and cytosolic fractions. Their estimated molecular weights were about 70 kDa for EAAT2, about 65 kDa for EAAT3, about 50 kDa for VGLUT1, and about 60 kDa for VGLUT3. RT-qPCR techniques confirm the expression of these glutamate transporters at the mRNA level and show a different regulation by cytokines and glucocorticoids between VGLUT1 and -3 and EAAT2 and -3 subfamilies. These interesting results support the participation of these glutamate transporters in the process of glutamate release in chromaffin cells and in the regulation of their neurosecretory function in adrenal medulla.

Involvement of NMDA receptor in the modulation of excitatory and inhibitory amino acid neurotransmitters release in cortical neurons.

The purpose of this paper was to examine the function of N-methyl-D-aspartate (NMDA) glutamate receptor in cortical neurons on amino acid neurotransmitters release as well as the fraction of neurons implicated in the response of this receptor. Local stimulation of these cells at different concentrations of NMDA, agonist of this ionotropic glutamate receptor, produced a dose dependent release of aspartate, glutamate, glycine and GABA. These effects were blocked by DAP5, an antagonist of the NMDA receptor. The amino acid Ca(2+) dependent release mediated by the NMDA receptor, is induced by the opening of voltage-dependent Ca(2+) channels that this receptor promotes. Ca(++) movements were explored in single cells loaded with fura-2. When single cells were stimulated with 100 microM NMDA, the calcium recording performed showed that 82% of the cells responded to this agonist increasing the intracellular calcium concentration, although the amplitude of these increments was variable. The results suggest that NMDA-elicited neurotransmitter release from cortical neurons involves Ca(2+)-dependent and Ca(2+)-independent components, as well as neuron depolarisation, and different VDCC subtypes of N, P/Q or L depending of the amino acid neurotransmitter release elicited by this receptor.

Development of a minimally invasive epidermal abrasion device for clinical skin sampling and its applications in molecular biology.

A new abrasion tool (US patent US7087063 B2) has been developed for collecting skin epidermal samples. This device includes a central shaft that holds the probe in a split chuck. Of the variety of probe designs tested, the laser-cut hollow tube (HT) probe abraded the basal layer of the epidermis most consistently, resulting in representative epidermal skin samples. Compared with traditional clinical methods, the abrasion method allows for high-throughput epidermal skin collection with minimal invasiveness to the volunteer subjects. A large number of abrasion samples have been collected in various clinical studies with no adverse effects observed. Epidermal abrasion, when used appropriately and with the optimized probes, can yield high quality tissue samples that are representative of the epidermis. A sufficient quantity of RNA and protein can be obtained for many subsequent molecular and biochemical applications. Because of its minimal invasiveness and high-throughput nature, the abrasion method can be a valuable tool used to investigate the efficacy of topical applications of skin care products.

Evaluación y detección bioinformática de terpenoides con potencial inhibitorio de la proteína viral 1 (VP1) del virus de la bursitis infecciosa / Evaluation and bioinformatic detection of terpenoids with inhibitory potential of viral protein 1 (VP1) of infectious bursitis virus

El virus de la bursitis infecciosa (IBDV) es el agente causal de la enfermedad de la bursa, la cual afecta principalmente a poblaciones avícolas jóvenes y genera un impacto económico negativo en la producción. La proteína viral (VP1) es una enzima con funciones clave para la replicación del genoma viral, por lo que puede ser considerada blanco para la búsqueda de compuestos con posibles actividades inhibitorias. El objetivo de esta investigación fue evaluar terpenoides con potencial inhibitorio de la proteína VP1 del IBDV mediante herramientas de aproximaciones bioinformáticas. Se seleccionó un total de 52 terpenoides, cuyas propiedades farmacológicas, farmacocinéticas y tóxicas (ADME-Tox) se evaluaron. Las moléculas sin actividades tóxicas y con aptitudes farmacocinéticas fueron sometidas a pruebas exhaustivas de acoplamiento molecular con el sitio catalítico de la VP1 mediante el uso del algoritmo genético y de Broyden-Fletcher-Goldfarb-Shanno junto con el método de optimización local de gradientes. Los datos obtenidos revelaron que la Giberelina A1 presenta valores de energía libre de unión significativamente (p< 0,05) favorables (ΔG=-7,28±0,06 kcal/mol; Kdcalc= 8,62±0,99 µM) en comparación con los sustratos rCTP y rGTP. El complejo Giberelina A1-VP1 presenta puentes de hidrógeno con los residuos Arg335 y Asp402, los cuales cumplen roles importantes en la actividad catalítica en la replicación viral. Estos hallazgos sugieren que el terpenoide Giberelina A1 puede ser considerado como compuesto candidato para estudios in vitro de inhibición de funciones de la VP1 e in vivode actividades antivirales contra el virus de la bursitis infecciosa.

Infectious bursitis virus (IBDV) is the infectious agent of bursal disease, which mainly affects young poultry populations, generating a negative economic impact on productions. The viral protein 1 (VP1) is an enzyme with important functions for the replication of the viral genome, so it could be considered as a target for searching compounds with possible inhibitory activities. The aim of this research was to evaluate terpenoids with inhibitory potential of the VP1 protein of IBDV using computational approximations tools. A total of 52 terpenoids were selected and evaluated for their pharmacological, pharmacokinetic and toxic properties (ADME-Tox). Molecules without toxic activities and with pharmacokinetic competences were subjected to extensive molecular docking tests with the catalytic site of VP1 using the genetic and Broyden-Fletcher-Goldfarb-Shanno algorithms with a local gradient optimization method. Data obtained revealed that Gibberellin A1 exhibits significantly (P < 0.05) favorable binding free energy values (ΔG=-7.28±0.06 kcal/mol; Kdcalc= 8.62±0.99 µM) compared to rCTP and rGTP subs-trates. The Gibberellin A1-VP1 complex exhibits hydrogen bonds with residues Arg335 and Asp402, which play important roles in catalytic activity in viral replication. These findings suggest that the terpenoid Gibberellin A1 could be considered as a candidate compound for in vitro studies of inhibition of VP1 functions and in vivo antiviral activities against infectious bursitis virus.

Ultrasound versus anatomical landmarks: Immediate complications in the central venous catheterization in children under 18 years of age. / Ultrasonido frente a referencias anatómicas: complicaciones inmediatas en la canalización de vía venosa central en menores de 18 años.

INTRODUCTION: The insertion of a central venous line in children and adolescents is technically more difficult, due to the smaller size of the structures. This can lead to an increase in immediate complications, which can be reduced when using ultrasound. In our institution, the percentage of these complications and the use of ultrasound are unknown. OBJECTIVE: To describe the frequency of immediate complications of central venous catheterisation guided by the ultrasound in a general university hospital, compared to the anatomical landmarks technique in children less than 18years of age. MATERIALS AND METHODS: Observational, retrospective, and analytical study, comparing the frequency of complications with two central venous catheterisation techniques: anatomical landmarks and ultrasound, according to the clinical records of procedures performed from June to November 2016. RESULTS: A total of 201 procedural records were analysed, of which 71% were with landmarks, and 29% with ultrasound. The overall incidence of immediate complications was 18.4%, with 12% using ultrasound and 21% using landmarks (OR: 0.5; 95%CI: 0.2-1.2). Children under 5years of age presented with 90% of the complications, the most frequent being the impossibility of passing the guide (29.7%) and multiple punctures (24.3%). There was no arterial puncture with use of ultrasound. Ultrasound was used by 13.4% of paediatric surgeons, by 32.4% of paediatricians, and 46.4% of anaesthetists, with complications of 25%, 19%, and 7%, respectively. The main indication for catheterisation was the need for vasoactive agents (74%), with the procedure being more complicated in patients with no peripheral venous accesses (46%). The success rate with anatomical landmarks was 77.6%, compared to 91.4% with ultrasound. CONCLUSION: Central venous catheterisation with ultrasound guidance in children under 18 reduces immediate complications by 42.8% and improves the success rate by 13.8%.

Self-assembled monolayer-based piezoelectric flow immunosensor for the determination of canine immunoglobulin.

A simple, highly sensitive immunosensor for the direct determination of immunoglobulin (Ig) in canine serum based on a piezoelectric crystal accommodated in a flow-cell was developed and optimized. The new biosensor is also useful for discriminating between Ig subclasses present in canine serum by using specific monoclonal antibodies binding to the coated crystal. Various canine monoclonal anti-IgG were deposited onto the surface of the gold-coated crystal resonator using the self-assembly technique to form a receptor layer. The highly ordered self-assembled monolayers thus obtained provide a well-controlled surface structure and many advantages as regards sensing performance. The results obtained with the proposed immunosensor were compared with those provided by a protein A-based orientation-controlled immobilization method for the same monoclonal antibodies and also with direct physical adsorption of the antibodies. The crystal was accommodated in a flow-cell that was inserted into a buffer flowing stream in order to make resonant frequency measurements.

Within-subject reliability and inter-session stability of EEG power and coherent activity in women evaluated monthly over nine months.

OBJECTIVE: Quantitative EEG parameters during resting conditions are used as baseline in research on cognition and in serial-EEG recordings. Despite its increasing use in cognitive research and the numerous evidences of the existence of sex differences in EEG, EEG stability has been mainly investigated in men. Particularly, studies on stability of coherent activity are scarce. The aim of this study was to investigate within-subject reliability and inter-session stability of resting EEG over a nine-month period in women. METHODS: Within-subject reliability and inter-session stability were analyzed for absolute power and inter- and intrahemispheric coherent activity at central and posterior regions, once a month, in resting conditions, with eyes open and closed. RESULTS: Within-subject reliability was very high (r>0.89) for all subjects and EEG parameters. Inter-session stability was higher with eyes closed and for interhemispheric coherent activity, and poorer with eyes open especially in the alpha band. CONCLUSIONS: Present results indicate high reliability of the pattern of power and coherent activity of each individual woman during rest, and group stability of EEG activity with eyes closed at least over a nine-month period. SIGNIFICANCE: These results provide information on EEG stability in women over a long period.

Cadmium induces reactive oxygen species generation and lipid peroxidation in cortical neurons in culture.

Cadmium is a toxic agent that it is also an environmental contaminant. Cadmium exposure may be implicated in some humans disorders related to hyperactivity and increased aggressiveness. This study presents data indicating that cadmium induces cellular death in cortical neurons in culture. This death could be mediated by an apoptotic and a necrotic mechanism. The apoptotic death may be mediated by oxidative stress with reactive oxygen species (ROS) formation which could be induced by mitochondrial membrane dysfunction since this cation produces: (a) depletion of mitochondrial membrane potential and (b) diminution of ATP levels with ATP release. Necrotic death could be mediated by lipid peroxidation induced by cadmium through an indirect mechanism (ROS formation). On the other hand, 40% of the cells survive cadmium action. This survival seems to be mediated by the ability of these cells to activate antioxidant defense systems, since cadmium reduced the intracellular glutathione levels and induced catalase and SOD activation in these cells.

Value of high-performance liquid chromatographic analysis of amino acids in the determination of Panax ginseng radix extract effect in cultured neurons.

The present research describes a reversed-phase high-performance liquid chromatographic (RP-HPLC) method that allows the determination of several amino acids in primary cultured cortical neurons of rats. The concentration of amino acids was determined by using pre-column derivatization with dansyl chloride and UV-diode array detection. Data show that Panax ginseng radix extract (GS) can modulate amino acid release in neurons. The levels of glutamate (Glu), aspartate (Asp), gamma-aminobutyric acid (GABA) and glycine (Gly) in the GS-treated groups were higher than in the non-treated groups dose-dependentwise. In this case, Glu and GABA were the most released amino acids (74.43% +/- 0.97 and 88.41% +/- 4.12 at ginseng dose 0.01 mg/ml after 1h from treatment, respectively). The values obtained in the determination of the analytical parameters (linearity, precision, limit of detection and accuracy) confirm the quality of the method. The average recoveries for intra and inter-day assay (n = 5) were 101.18 and 102.38 for Asp, 99.35 and 98.44 for Glu, 99.59 and 99.66 for Gly, and 100.06 and 100.37 for GABA. These data proved that the method yields accurate results, with RSD lower than 2.2%. The precision of the method was estimated on the basis of RSD of six injections at two different concentrations of amino acids. This technique is useful in studying the GS-mediated modulation of the dynamic equilibrium of amino acids and neurotransmission in neurons.

Enhanced repair of O6-methylguanine DNA adducts in the liver of transgenic mice expressing the ada gene.

The capacity to repair O6-methylguanine-DNA adducts was measured in the liver of transgenic mice expressing a chimeric gene consisting of the inducible P-enolpyruvate carboxykinase (GTP) promoter linked to the bacterial O6-alkylguanine-DNA alkyltransferase (ada) gene. Under induced conditions, total hepatic alkyltransferase reached 32.8 +/- 4.2 (SE) fmol/micrograms DNA compared to 7.8 +/- 1.1 fmol/micrograms DNA in nontransgenic mice. Administration of methylnitrosourea or nitrosodimethylamine to both groups of mice produced O6-methylguanine-DNA adducts which resulted in repair-mediated depletion of total hepatic alkyltransferase in a dose-dependent fashion. In nontransgenic mice, depletion of hepatic alkyltransferase occurred at lower doses of carcinogen, and recovery of alkyltransferase activity occurred later than in ada+ transgenic mice. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of residual alkyltransferase activity after methylating agent exposure indicated that the bacterial as well as endogenous mammalian alkyltransferases were functioning as DNA repair proteins in hepatocytes in vivo. Analysis of O6-methylguanine- and N7-methylguanine-DNA adducts in the liver of transgenic and nontransgenic mice after treatment with one dose of 50 mg/kg methylnitrosourea i.p. revealed that transgenic mice repaired in situ O6-methylguanine-DNA adducts approximately 3 times faster than nontransgenic mice, commensurate with the increase in alkyltransferase activity. Thus, ada+ transgenic mice treated with methylnitrosourea have lower levels of persistent mutagenic O6-methylguanine adducts than ada- nontransgenic mice. Hepatic expression of bacterial alkyltransferase appears to protect mice from the DNA-damaging effects of N-nitroso compounds in vivo.

Estimating Waiting Time for Deceased Donor Renal Transplantion in the Era of New Kidney Allocation System.

BACKGROUND: On December 4, 2014, a new deceased donor kidney allocation system (KAS) was implemented. The KAS was designed to improve organ equity and graft-recipient longevity matching. However, estimated wait-time to deceased donor transplantation is difficult to predict post-KAS. METHODS: Using the Kidney-Pancreas Simulated Allocation Model software (KPSAM), a program that the Organ Procurement and Transplant Network uses to assess policy proposals, we compared the kidney allocations of both the new (post-KAS) and old policies (pre-KAS) (10 iterations for each group; total N = 204,148) and estimated wait-time based on blood type, duration of dialysis exposure, and calculated panel-reactive antibody (CPRA). RESULTS: The simulations revealed that estimated median (25(th) and 75(th) percentile) waiting time in transplanted recipients decreased from 2.3 (1.2, 3.8) years in the old allocation to 1.8 (0.8, 3.4) years in the new allocation system. The rate of transplantations performed within the first year of wait-listing increased from 20.7% to 31.3%. The KPSAM resulted in more transplantations in recipients with more than 5 years of dialysis exposure (26.5% to 37.4%), longevity matching (12.2% to 17.5%), blood group B (12.6% to 17.2%), and high CPRA ≥98% (1.9% to 4.3%) in post-KAS compared with pre-KAS simulations. CONCLUSIONS: Based on the KPSAM results, it was projected that post-KAS wait-time in transplanted recipients might decrease approximately 6 months (22%) across all CPRA categories. It might be related to the KAS awarding waiting time points for prelisting dialysis time and priority points awarded based on CPRA (bolus effect).

Effect of polyanions and polycations on detyrosination of tubulin and microtubules at steady state.

Microtubule protein preparations purified from rat brain were used to study the effect of polycations and polyanions on the release of the COOH-terminal tyrosine of the alpha-chain of tubulin catalyzed by tubulin carboxypeptidase. (1) Most of the polycations and polyanions tested, independently of the ionogenic group, inhibited the reaction in a concentration-dependent fashion. Under steady-state conditions, detyrosination of the microtubule pool was inhibited to the same degree as occurred with the non-assembled tubulin pool, except in the case of chondroitin sulphate. This compound inhibited detyrosination of the non-assembled tubulin pool, but not that of microtubules. (2) Heparin, the most potent inhibitor tested, produced the dissociation of the carboxypeptidase from microtubules. Many, but not all, of the other microtubule-associated polypeptides were also dissociated by heparin. (3) Polylysine counteracted the inhibitory and dissociating effects of heparin. (4) Heparin protected tubulin carboxypeptidase against inactivation. Our results and previous reports describing, in nervous tissue, the presence of proteoglycans, RNA and basic proteins that inhibit detyrosination, suggest that tubulin carboxypeptidase might be physiologically modulated by electrically charged macromolecules.

Tyrosinatable and non-tyrosinatable tubulin subpopulations in rat muscle in comparison with those in brain.

Using immunobinding and enzymatic assays we determined in rat muscle extracts the proportion of tyrosinatable tubulin, that is, tubulin that participates in the tyrosination/detyrosination cycle. We found that in muscle, in contrast with nervous tissue, practically all tubulin molecules are tyrosinatable. In the case of rat brain the non-tyrosinatable tubulin pool accounts for about 50% of the tubulin. In addition, isolectrofocusing of 14C-tyrosinated tubulin from brain and muscle extracts revealed a different composition in tyrosinatable tubulin isotypes. One of the isotypes, which in muscle accounts for 86% of the 14C-tyrosinated tubulin species, was detyrosinated by the action of tubulin carboxypeptidase faster than the rest of the 14C-tyrosinated tubulin isotypes taken in whole. In the case of brain extract, that isotype accounts for only 16% of the labeled tubulin.

SNAP, a NO donor, induces cortical neuron death by a mechanism in which the caspase pathway is implicated.

In this paper, we present data which demonstrate that, in cortical neurons, SNAP induces loss in cell viability as evaluated by the XTT test. This cell death started at 250 microM SNAP when the treatment was performed in a serum-free medium and at 10 microM when the treatment was given in the presence of serum. This death was mediated, at least in part, by an apoptotic mechanism detected by flow cytometry and DNA fractionation. The highest SNAP concentrations induced a dual behavior on caspase-3 activity. Concentrations of 250 microM in the absence of serum and 10 microM to 300 microM in the presence of serum produced caspase-3 activation. This indicates that NO induces neuronal death by an apoptotic mechanism in which the caspase pathway is implicated. Higher SNAP concentrations (500 microM to 1 mM) diminished the caspase-3 activity to levels similar or even lower than control values. This profile was observed in the absence as well as in the presence of serum in the medium. The caspase-3 inhibition mediated by the highest SNAP concentrations did not imply NO cellular protection since the caspase-3 inhibition mediated by these SNAP concentrations neither correlated with cellular viability nor with cellular apoptosis. The possible mechanism of caspase-3 inhibition at the highest SNAP concentrations used is discussed.

SNAP, a NO donor, induces cellular protection only when cortical neurons are submitted to some aggression process.

Nitric oxide is a versatile molecule, which plays important physiological and pathological roles. Its protective and toxic actions have been already evidenced in several cell types. However, the protective effect in cortical neurons remains elusive. In this work, we demonstrate that the NO-donor SNAP may induce both neuroprotection and neurotoxicity in this sort of cells. The protective effect of NO was evidenced when cortical neurons were exposed to deleterious conditions, such as serum deprivation. Serum deprivation induces apoptotic cortical neuron death through a caspase-dependent mechanism. Under these conditions, SNAP was able to oppose cell death through both caspase-3 inhibition and/or increase of antiapoptotic protein levels (Bcl-2 and Bcl-x(L)). On the other hand, in a normally serum-supplemented medium, high dose of SNAP behaves as a neurotoxic agent, through a mechanism which involves caspase-3 activation.

Secretory carcinoma of the breast containing the ETV6-NTRK3 fusion gene in a male: case report and review of the literature.

BACKGROUND: Secretory carcinoma (SC) of the breast is a rare and indolent tumor. Although originally described in children, it is now known to occur in adults of both sexes. Recently, the tumor was associated with the ETV6-NTRK3 gene translocation. CASE PRESENTATION: A 52-year-old male was diagnosed with secretory breast carcinoma and underwent a modified radical mastectomy. At 18 months the tumor recurred at the chest wall and the patient developed lung metastases. He was treated concurrently with radiation and chemotherapy without response. His tumor showed the ETV6-NTRK3 translocation as demonstrated by fluorescent in situ hybridization (FISH). CONCLUSION: SC is a rare slow-growing tumor best treated surgically. There are insufficient data to support the use of adjuvant radiation or chemotherapy. Its association with the ETV6-NTRK3 fusion gene gives some clues for the better understanding of this neoplasm and eventually, the development of specific therapies.