Psilocybin restrains activity-based anorexia in female rats by enhancing cognitive flexibility: contributions from 5-HT1A and 5-HT2A receptor mechanisms.

Psilocybin has shown promise for alleviating symptoms of depression and is currently in clinical trials for the treatment of anorexia nervosa (AN), a condition that is characterised by persistent cognitive inflexibility. Considering that enhanced cognitive flexibility after psilocybin treatment is reported to occur in individuals with depression, it is plausible that psilocybin could improve symptoms of AN by breaking down cognitive inflexibility. A mechanistic understanding of the actions of psilocybin is required to tailor the clinical application of psilocybin to individuals most likely to respond with positive outcomes. This can only be achieved using incisive neurobiological approaches in animal models. Here, we use the activity-based anorexia (ABA) rat model and comprehensively assess aspects of reinforcement learning to show that psilocybin (post-acutely) improves body weight maintenance in female rats and facilitates cognitive flexibility, specifically via improved adaptation to the initial reversal of reward contingencies. Further, we reveal the involvement of signalling through the serotonin (5-HT) 1 A and 5-HT2A receptor subtypes in specific aspects of learning, demonstrating that 5-HT1A antagonism negates the cognitive enhancing effects of psilocybin. Moreover, we show that psilocybin elicits a transient increase and decrease in cortical transcription of these receptors (Htr2a and Htr1a, respectively), and a further reduction in the abundance of Htr2a transcripts in rats exposed to the ABA model. Together, these findings support the hypothesis that psilocybin could ameliorate cognitive inflexibility in the context of AN and highlight a need to better understand the therapeutic mechanisms independent of 5-HT2A receptor binding.

Pentoxifylline and tocopherol for the treatment of osteoradionecrosis of the jaws. A systematic review.

BACKGROUND: Osteoradionecrosis of the jaws (ORNJ) is a severe and challenging complication of head and neck radiation therapy. Despite its aggressiveness and controversy respect to its efficacy, surgical intervention remains the main treatment modality. Nevertheless, due to advances in the understanding of ORNJ physiopathology, new treatment alternatives such as the combination of pentoxifylline with tocopherol (PENTO) have emerged. The aim of this systematic review was to assess the reported efficacy of PENTO for the treatment of ORNJ.  Material and Methods: Studies were search using Pubmed, The Cochrane Library, Scopus, and Web of Science data bases following the PRISMA guidelines. Inclusion criteria were cohort, case series, randomized or non-randomized clinical studies published in English including human subjects who received PENTO as treatment for ORN of the jaws.  Results: Eleven articles met the inclusion criteria and were included for data analysis. All studies reported patients with complete mucosal coverage with no exposed bone (considered healthy) after PENTO treatment, ranging from 16.6% to 100% of the patients, depending on the study. Clinical improvement or disease stabilization was reported between 7.6% and 66.6% of studied individuals, while disease progression was seen in only 5 studies involving 7.6 - 32% of patients. CONCLUSIONS: PENTO treatment achieved a complete disease control in a significant number of patients in all studies. However, there is no standardized protocol for administering the therapy. It is necessary to determine the pharmacological doses and to evaluate the benefits of adding antibiotics and clodronate. Good quality clinical trials are needed to develop a successful algorithm for the management of ORN of the jaws.

Glutamatergic Receptor Activation in the Commisural Nucleus Tractus Solitarii (cNTS) Mediates Brain Glucose Retention (BGR) Response to Anoxic Carotid Chemoreceptor (CChr) Stimulation in Rats.

Glutamate, released from central terminals of glossopharyngeal nerve, is a major excitatory neurotransmitter of commissural nucleus tractus solitarii (cNTS) afferent terminals, and brain derived neurotrophic factor (BDNF) has been shown to attenuate glutamatergic AMPA currents in NTS neurons. To test the hypothesis that AMPA contributes to glucose regulation in vivo modulating the hyperglycemic reflex with brain glucose retention (BGR), we microinjected AMPA and NBQX (AMPA antagonist) into the cNTS before carotid chemoreceptor stimulation in anesthetized normal Wistar rats, while hyperglycemic reflex an brain glucose retention (BGR) were analyzed. To investigate the underlying mechanisms, GluR2/3 receptor and c-Fos protein expressions in cNTS neurons were determined. We showed that AMPA in the cNTS before CChr stimulation inhibited BGR observed in aCSF group. In contrast, NBQX in similar conditions, did not modify the effects on glucose variables observed in aCSF control group. These experiments suggest that glutamatergic pathways, via AMPA receptors, in the cNTS may play a role in glucose homeostasis.

Mechanisms underlying the efficacy of a rodent model of vertical sleeve gastrectomy - A focus on energy expenditure.

OBJECTIVE: Bariatric surgery remains the only effective and durable treatment option for morbid obesity. Vertical Sleeve Gastrectomy (VSG) is currently the most widely performed of these surgeries primarily because of its proven efficacy in generating rapid onset weight loss, improved glucose regulation and reduced mortality compared with other invasive procedures. VSG is associated with reduced appetite, however, the relative importance of energy expenditure to VSG-induced weight loss and changes in glucose regulation, particularly that in brown adipose tissue (BAT), remains unclear. The aim of this study was to investigate the role of BAT thermogenesis in the efficacy of VSG in a rodent model. METHODS: Diet-induced obese male Sprague-Dawley rats were either sham-operated, underwent VSG surgery or were pair-fed to the food consumed by the VSG group. Rats were also implanted with biotelemetry devices between the interscapular lobes of BAT to assess local changes in BAT temperature as a surrogate measure of thermogenic activity. Metabolic parameters including food intake, body weight and changes in body composition were assessed. To further elucidate the contribution of energy expenditure via BAT thermogenesis to VSG-induced weight loss, a separate cohort of chow-fed rats underwent complete excision of the interscapular BAT (iBAT lipectomy) or chemical denervation using 6-hydroxydopamine (6-OHDA). To localize glucose uptake in specific tissues, an oral glucose tolerance test was combined with an intraperitoneal injection of 14C-2-deoxy-d-glucose (14C-2DG). Transneuronal viral tracing was used to identify 1) sensory neurons directed to the stomach or small intestine (H129-RFP) or 2) chains of polysynaptically linked neurons directed to BAT (PRV-GFP) in the same animals. RESULTS: Following VSG, there was a rapid reduction in body weight that was associated with reduced food intake, elevated BAT temperature and improved glucose regulation. Rats that underwent VSG had elevated glucose uptake into BAT compared to sham operated animals as well as elevated gene markers related to increased BAT activity (Ucp1, Dio2, Cpt1b, Cox8b, Ppargc) and markers of increased browning of white fat (Ucp1, Dio2, Cited1, Tbx1, Tnfrs9). Both iBAT lipectomy and 6-OHDA treatment significantly attenuated the impact of VSG on changes in body weight and adiposity in chow-fed animals. In addition, surgical excision of iBAT following VSG significantly reversed VSG-mediated improvements in glucose tolerance, an effect that was independent of circulating insulin levels. Viral tracing studies highlighted a patent neural link between the gut and BAT that included groups of premotor BAT-directed neurons in the dorsal raphe and raphe pallidus. CONCLUSIONS: Collectively, these data support a role for BAT in mediating the metabolic sequelae following VSG surgery, particularly the improvement in glucose regulation, and highlight the need to better understand the contribution from this tissue in human patients.

Vanadium inhalation in a mouse model for the understanding of air-suspended particle systemic repercussion.

There is an increased concern about the health effects that air-suspended particles have on human health which have been dissected in animal models. Using CD-1 mouse, we explore the effects that vanadium inhalation produce in different tissues and organs. Our findings support the systemic effects of air pollution. In this paper, we describe our findings in different organs in our conditions and contrast our results with the literature.

Palliative gastrojejunostomy in unresectable cancer and gastric outlet obstruction: a retrospective cohort study.

INTRODUCTION: Palliative gastrojejunostomy is a surgical technique that allows restoration of oral intake among patients with gastric outlet obstruction (GOO) caused by unresectable neoplasms. Research suggests standard treatment for malignant GOO should be laparoscopic gastrojejunostomy (LGJ). This study presents the clinical outcomes of palliative gastrojejunostomy and compares results from LGJ and open gastrojejunostomy (OGJ) at our centre. METHODS: We performed a retrospective analysis on patients who underwent palliative gastrojejunostomy for GOO caused by unresectable neoplasms between 2008 and 2018. We included demographic variables, time to recover intestinal transit, time to recover oral intake, hospital stay, complications and global survival. RESULTS: A total of 39 patients underwent palliative gastrojejunostomy (20 OGJ, 19 LGJ). Patients in the LGJ group recovered oral intake and intestinal transit faster than those in the OGJ group (3 vs 5 days, p<0.05). There were no statistically significant differences in median operating time, hospital stay or postoperative complications between the two groups. No intraoperative complications occurred. The estimated global survival was 178 days, with no significant difference between the groups. CONCLUSIONS: Palliative LGJ allows earlier restoration of oral intake and does not increase morbidity or mortality. Palliative LGJ should be considered the standard treatment for these patients.

Classification of antineoplastic drug-induced tissue damage: a Consensus of the Spanish Oncology Pharmacy Group.

OBJECTIVE: To reach at an expert consensus, using the Delphi method, for classifying the tissue-damaging potential of antineoplastic drugs, in  order to facilitate the decision-making process in the event of  extravasations. METHOD: The panel of expert evaluators was made up of seven  pharmacists belonging to the working group on extravasations. Other  member served as coordinator. The likelihood of tissue damage was  reviewed on the basis of eight reference documents. Four categories of  drugs were established: vesicant (V); high risk irritant (HRI); low risk  irritant (LRI) and non-irritant (NI). Two rounds of surveys were performed. The drugs with an agreement of less than 70% after the two rounds were  discussed non-anonymously by the group. For each of the rounds the  following was analysed: median of the degree of consensus and the  interquartile range (IQR25-75), degree of agreement by tissue damage  category, and percentage of antineoplastics reaching a degree of  consensus of over 85% and of 100%. Drugs whose classification differed in the various reference documents were assessed separately. SPSS v23.0  statistical software was used. RESULTS: Seventy-one antineoplastics were evaluated. In the first round, the median for degree of consensus was 100.0% (IQR25-75: 71.4- 100.0%). In the second round, the median was 100.0% (IQR25-75: 85.7- 100.0%). The percentage of antineoplastics with a consensus of 85.7% or  above increased from 66.7% to 85.9% in the second round. For the 30  antineoplastics whose values differed in the reference documents, the  degree of agreement increased from 71.4% (IQR25-75: 57.1-87.7%) to  100.0% (IQR25-75: 85.7-100.0%) in the second round. The percentage of antineoplastics with a consensus of 85.7% or above increased from 40.0%  to 76.7%. Four antineoplastics had a degree of agreement of less  than 70.0%. The final classification of drugs per category, was: 17  vesicants; 15 HRI; 13 LRI; and 26 NI. The final degree of consensus was  85.7% or above for 90.1% of antineoplastics, and 100.0% for 74.6% of  the same. CONCLUSIONS: In this area of scarce evidence and high variability, the Delphi method allows for consensus in classifying tissue damage risk,  thus making it easier to reach clinical decisions. In approximately 90% of  the antineoplastics, the degree of consensus reached by the expert panel  was 85% or above. In 74% of the antineoplastics, it was 100%. This  provides solid ground for management decisions.

Objetivo: Realizar un consenso de expertos utilizando el método Delphi para la clasificación del potencial de daño tisular de los  antineoplásicos que facilite la toma de decisiones ante una extravasación.Método: El panel de evaluadores estaba formado por siete farmacéuticos del grupo de trabajo de extravasaciones. Otro actuó como coordinador. Se revisó la probabilidad de daño tisular a partir de  ocho documentos de referencia. Se clasificaron en cuatro categorías:  vesicante, irritante de alto riesgo, irritante de bajo riesgo y no irritante. Se realizaron dos rondas; tras éstas los fármacos con consenso < 70% se discutieron en grupo de forma no anónima. Se analizó para cada ronda: la mediana del grado de consenso y ámbito intercuartílico (AIQ25- 75), el grado de concordancia por categoría de daño tisular y el porcentaje de antineoplásicos con grado de consenso > 85% y del 100%. Se analizaron de forma separada los fármacos con discordancias de clasificación entre los documentos consultados. Se utilizó el programa estadístico SPSS v23.0.Resultados: Se evaluaron 71 antineoplásicos. En la primera ronda la mediana del grado de consenso fue 100% (AIQ25-75: 71,4-100,0%) y  en la segunda ronda 100% (AIQ25-75: 85,7-100,0%). El porcentaje de  antineoplásicos con consenso ≥ 85,7% aumentó del 66,7% al 85,9% en la segunda ronda. Para los 30 antineoplásicos con discrepancias entre los  documentos revisados, el grado de consenso aumentó del 71,4% (AIQ25- 75: 57,1-87,7%) al 100% (AIQ25-75: 85,7-100,0%) en la segunda ronda. El porcentaje de antineoplásicos con concordancia ≥ 85,7% pasó del  40,0% al 76,7%. Cuatro antineoplásicos presentaron consenso < 70%. La  clasificación final incluyó 17 fármacos como vesicantes, 15 como irritantes  de alto riesgo, 13 como irritantes de bajo riesgo y 26 como no irritantes. El grado de acuerdo final fue ≥ 85,7% en el 90,1% de los antineoplásicos y  del 100% en el 74,6%.Conclusiones: En este área de escasa evidencia y variabilidad la metodología Delphi permite alcanzar un consenso de clasificación del riesgo de daño tisular que facilita la toma de decisiones.  Aproximadamente para el 90% de los antineoplásicos el grado de  concordancia alcanzado por el panel de expertos fue > 85%, y para el  74% de los antineoplásicos la concordancia fue del 100%, aportando una  base sólida para las decisiones de manejo.

Nitric oxide in the hypothalamus-pituitary axis mediates increases in brain glucose retention induced by carotid chemoreceptor stimulation with cyanide in rats.

Neuronal nitric oxide synthase (nNOS), which catalyzes the generation of nitric oxide (NO), is expressed by neuron subpopulations in the CNS. Nitric oxide is involved in neurotransmission and central glucose homeostasis. Our prior studies have shown that carotid body receptors participate in brain glucose regulation in vivo, and suggest the presence of a NO tonic mechanism in the solitary tract nucleus (STn). However, the role of NO within STn in glucose control remains unknown. In this study, we explored the potential regulatory role of NO on brain glucose retention induced by carotid body chemoreceptor anoxic stimulation with sodium cyanide (NaCN) which inhibits oxidative metabolism. Intracisternal infusions of nitroxidergic drugs before carotid chemoreceptor stimulation in anesthetized rats, elicited changes in nitrite concentration in plasma and hypothalamus-pituitary (H-P) tissue, as well as in gene expression of neuronal and inducible isoforms (nNOS and iNOS) in H-P tissue. The changes observed in above variables modified brain glucose retention in an opposite direction. When the NO donor, sodium nitroprusside (SNP), was given before carotid stimulation, nitrite concentration in plasma and H-P tissue, and gene expression of nNOS and iNOS in H-P tissue increased, whereas brain glucose retention decreased. In contrast, when the NOS inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME) was infused immediately before carotid chemoreceptor stimulation, nitrite levels and nNOS expression decreased in plasma and H-P tissue, whereas brain glucose retention increased. Anoxic stimulation by itself induced an increase in the expression of both genes studied. All these results indicate that de novo expression of the nNOS gene in H-P tissue may be critically involved in central glucose changes observed after anoxic carotid chemoreceptor stimulation in conjunction with NO.

Endogenous antioxidants and nasal human epithelium response to air pollutants: genotoxic and inmmuno-cytochemical evaluation.

Nasal epithelium is a source for identifying atmospheric pollution impact. Antioxidants play a relevant role in the protection of the cells from environmental injury, but scarce information is available about the interaction of endogenous antioxidants and genotoxic damage in nasal epithelium from urban populations highly exposed to traffic-generated air pollutants. An immunocytochemical and genotoxic evaluation was implemented in nasal cell epithelium in a population chronically exposed to atmospheric pollution from autumn 2004 to autumn 2005. Superoxide dismutase (SOD) and Catalase (CAT) were evaluated in nasal scrapings by morphometry and genotoxicity by comet assay. An increase in DNA damage correlates with a decrease in SOD and CAT in nasal cells during autumn and the inverse result was observed during summer (R = 0.88). Not only should exogenous antioxidant supplements be encouraged, but also a healthy diet to strengthen intracellular defenses against oxidative stress induced by exposure to air pollutants.

Reliability of CT Angiography in Cerebral Vasospasm: A Systematic Review of the Literature and an Inter- and Intraobserver Study.

BACKGROUND AND PURPOSE: Computed tomography angiography offers a non-invasive alternative to DSA for the assessment of cerebral vasospasm following subarachnoid hemorrhage but there is limited evidence regarding its reliability. Our aim was to perform a systematic review (Part I) and to assess (Part II) the inter- and intraobserver reliability of CTA in the diagnosis of cerebral vasospasm. MATERIALS AND METHODS: In Part I, articles reporting the reliability of CTA up to May 2018 were systematically searched and evaluated. In Part II, 11 raters independently graded 17 arterial segments in each of 50 patients with SAH for the presence of vasospasm using a 4-category scale. Raters were additionally asked to judge the presence of any moderate/severe vasospasm (≥ 50% narrowing) and whether findings would justify augmentation of medical treatment or conventional angiography ± balloon angioplasty. Four raters took part in the intraobserver reliability study. RESULTS: In Part I, the systematic review revealed few studies with heterogeneous vasospasm definitions. In Part II, we found interrater reliability to be moderate at best (κ ≤ 0.6), even when results were stratified according to specialty and experience. Intrarater reliability was substantial (κ > 0.6) in 3/4 readers. In the per arterial segment analysis, substantial agreement was reached only for the middle cerebral arteries, and only when senior raters' judgments were dichotomized (presence or absence of ≥50% narrowing). Agreement on the medical or angiographic management of vasospasm based on CTA alone was less than substantial (κ ≤ 0.6). CONCLUSIONS: The diagnosis of vasospasm using CTA alone was not sufficiently repeatable among observers to support its general use to guide decisions in the clinical management of patients with SAH.

Effect of the degree of oxidation of graphene oxide on As(III) adsorption.

The study of the interaction between graphene oxide (GO) and arsenic is of great relevance not only in the design of adsorbent materials to remove this contaminant but also in the understanding of its combined nanotoxicity. In this work, we show that As(III) adsorption, primarily H3AsO3, by graphene oxide is affected by its degree of oxidation. Three types of GO with C/O ratios between 1.35 and 1.98 were produced, resulting in important variations in the concentration of COH and COC functional groups. The less oxidized material reached a maximum As(III) adsorption capacity of 123 mg/g, whereas the GO with the highest degree of oxidation reached a value of 288 mg/g at pH 7, the highest reported in the literature. We also show that sulfates and carbonates present in water strongly inhibit As(III) adsorption. The interaction between graphene oxide and As(III) was also studied by Density Functional Theory (DFT) computer models showing that graphene oxide interacts with As(III) primarily through hydrogen bonds, having interaction energies with the hydroxyl and epoxide groups of 1508.6 and 1583.6 kJ/mol, respectively. Finally, cytotoxicity tests showed that the graphene oxide maintained cellular viability of 57% with 50 µg/ml, regardless of its degree of oxidation.

Nitric oxide in the solitary tract nucleus (STn) modulates glucose homeostasis and FOS-ir expression after carotid chemoreceptor stimulation.

We evaluate in rats the role of NO in the solitary tract nucleus (STn) after an anoxic stimulus to carotid body chemoreceptor cells (CChrc) with cyanide (NaCN), on the hyperglycemic reflex with glucose retention by the brain (BGR) and FOS expression (FOS-ir) in the STn. The results suggest that nitroxidergic pathways in the STn may play an important role in glucose homeostasis. A NO donor such as sodium nitroprusside (NPS) in the STn before CChrc stimulation increased arterial glucose level and significantly decreased BGR. NPS also induced a higher FOS-ir expression in STn neurons when compared to neurons in control rats that only received artificial cerebrospinal fluid (aCSF) before CChrc stimulation. In contrast, a selective NOS inhibitor such as Nomega-nitro-L-arginine methyl ester (L-NAME) in the STn before CChrc stimulation resulted in an increase of both, systemic glucose and BGR above control values. In this case, the number of FOS-ir positive neurons in the STn decreased when compared to control or to NPS experiments. FOS-ir expression in brainstem cells suggests that CChrc stimulation activates nitroxidergic pathways in the STn to regulate peripheral and central glucose homeostasis. The study of these functionally defined cells will be important to understand brain glucose homeostasis.

A randomized trial of endovascular versus surgical management of ruptured intracranial aneurysms: Interim results from ISAT2.

BACKGROUND AND PURPOSE: Appropriate management of ruptured intracranial aneurysm (RIA) in patients eligible for surgical clipping but under-represented in or excluded from previous randomized trials remains undetermined. METHODS: The International Subarachnoid Aneurysm Trial-2 (ISAT-2) is a randomized care trial comparing surgical versus endovascular treatment (EVT) of RIA. All patients considered for surgical clipping but eligible for endovascular treatment can be included. The primary endpoint is death or dependency on modified Rankin score (mRS>2) at 1 year. Secondary endpoints are 1 year angiographic results and length of hospital stay. RESULTS: An interim analysis was performed after 103 patients were treated from November 2012 to July 2017 in 4 active centers. Fifty-two of the 55 patients allocated to surgery were treated by clipping, and 45 of the 48 allocated to EVT were treated by coiling, with 3 crossovers in each arm. The main endpoint (1 year mRS>2), available for 76 patients, was reached in 16/42 patients allocated to clipping (38%; 95%CI: 25%-53%), and 10/34 patients allocated to coiling (29%; 17%-46%). One year imaging results were available in 54 patients: complete aneurysm occlusion was found in 23/27 patients allocated to clipping (85%; 67%-94%), and 18/27 patients allocated to coiling (67%; 47%-81%). Hospital stay exceeding 20 days was more frequent in surgery (26/55 [47%; 34%-60%]) than EVT (9/48 [19%; 10%-31%]). CONCLUSION: Ruptured aneurysm patients for whom surgical clipping may still be best can be managed in a randomized care trial, which is feasible in some centers. More participating centers are needed.

[Syndrome of vertebral destruction: understanding to practice]. / Síndrome de destrucción vertebral: del entendimiento a la práctica.

The term «vertebral destruction syndrome¼ comprises pathologies causing structural changes in the spine, mainly in the vertebral body, producing mechanical deformity and neurological involvement. The pathologies found in this definition may be infectious, metabolic or tumoral. Vertebral osteomyelitis is a disease that occurs mainly in adults > 50 years; we speak of spondylodiscitis when the condition affects the disc and vertebral body. The most important organism in vertebral osteomyelitis is Staphylococcus aureus, seen in over 50% of cases. Tumors of the spine can start from local or adjacent spinal injuries or distant ones, and spread through the blood or lymphatic system. Metastases account for about 97% of all tumors of the spine. Primary tumors that most commonly spread to the spine are lung, prostate, breast and kidney. Metabolic bone diseases are a group of disorders that occur as a result of changes in the calcium metabolism. The spine contains large amounts of metabolically active cancellous bone, which must withstand axial loads during stance. Osteoporosis is a metabolic disease that most commonly affects the spine; it is characterized by low bone mass. The diagnosis of these entities is important for the treatment and prognosis of the patient. The term «vertebral destruction syndrome¼ proposes a notarized scheme aimed at improving the patients prognosis and his/her prompt treatment.

El término «síndrome de destrucción vertebral¼ engloba patologías que causan alteraciones estructurales en la columna en particular, en el cuerpo vertebral, produciendo deformidad con afectación neurológica y/o mecánica. Dentro de las patologías que se encuentran en esta definición están la infecciosa, tumoral y metabólica. La osteomielitis vertebral es una enfermedad que se da sobre todo en adultos > 50 años; se habla de espondilodiscitis cuando hay afección del disco y cuerpo vertebral. El más importante organismo en la osteomielitis vertebral es el Staphylococcus aureus, visto en más de 50% de los casos. Los tumores de la columna vertebral pueden iniciar desde lesiones locales o adyacentes a la columna o a distancia, diseminados por vía hematógena o linfática; las lesiones por metástasis abarcan cerca de 97% de todos los tumores de la columna. Los tumores primarios que con mayor frecuencia se diseminan a columna vertebral son pulmonar, de próstata, mama y riñón. Las enfermedades metabólicas óseas son un grupo de desórdenes que ocurren como resultado de cambios en el metabolismo del calcio. La columna vertebral contiene grandes cantidades de hueso esponjoso metabólicamente activo que debe resistir cargas axiales durante la postura. La osteoporosis es la enfermedad metabólica que con más frecuencia afecta la columna vertebral; se caracteriza por disminución en la masa ósea. El diagnóstico de estas entidades es importante para el tratamiento y pronóstico del paciente; el término «síndrome de destrucción vertebral¼ propone un esquema protocolizado encaminado a mejorar el pronóstico del paciente, así como su pronto tratamiento.

BDNF and AMPA receptors in the cNTS modulate the hyperglycemic reflex after local carotid body NaCN stimulation.

The application of sodium cyanide (NaCN) to the carotid body receptors (CBR) (CBR stimulation) induces rapid blood hyperglycemia and an increase in brain glucose retention. The commissural nucleus tractus solitarius (cNTS) is an essential relay nucleus in this hyperglycemic reflex; it receives glutamatergic afferents (that also release brain derived neurotrophic factor, BDNF) from the nodose-petrosal ganglia that relays CBR information. Previous work showed that AMPA in NTS blocks hyperglycemia and brain glucose retention after CBR stimulation. In contrast, BDNF, which attenuates glutamatergic AMPA currents in NTS, enhances these glycemic responses. Here we investigated the combined effects of BDNF and AMPA (and their antagonists) in NTS on the glycemic responses to CBR stimulation. Microinjections of BDNF plus AMPA into the cNTS before CBR stimulation in anesthetized rats, induced blood hyperglycemia and an increase in brain arteriovenous (a-v) of blood glucose concentration difference, which we infer is due to increased brain glucose retention. By contrast, the microinjection of the TrkB antagonist K252a plus AMPA abolished the glycemic responses to CBR stimulation similar to what is observed after AMPA pretreatments. In BDNF plus AMPA microinjections preceding CBR stimulation, the number of c-fos immunoreactive cNTS neurons increased. In contrast, in the rats microinjected with K252a plus AMPA in NTS, before CBR stimulation, c-fos expression in cNTS decreased. The expression of AMPA receptors GluR2/3 did not change in any of the studied groups. These results indicate that BDNF in cNTS plays a key role in the modulation of the hyperglycemic reflex initiated by CBR stimulation.

Acyl ghrelin improves cognition, synaptic plasticity deficits and neuroinflammation following amyloid ß (Aß1-40) administration in mice.

Ghrelin is a metabolic hormone that has neuroprotective actions in a number of neurological conditions, including Parkinson's disease (PD), stroke and traumatic brain injury. Acyl ghrelin treatment in vivo and in vitro also shows protective capacity in Alzheimer's disease (AD). In the present study, we used ghrelin knockout (KO) and their wild-type littermates to test whether or not endogenous ghrelin is protective in a mouse model of AD, in which human amyloid ß peptide 1-40 (Aß1-40 ) was injected into the lateral ventricles i.c.v. Recognition memory, using the novel object recognition task, was significantly impaired in ghrelin KO mice and after i.c.v. Aß1-40 treatment. These deficits could be prevented by acyl ghrelin injections for 7 days. Spatial orientation, as assessed by the Y-maze task, was also significantly impaired in ghrelin KO mice and after i.c.v. Aß1-40 treatment. These deficits could be prevented by acyl ghrelin injections for 7 days. Ghrelin KO mice had deficits in olfactory discrimination; however, neither i.c.v. Aß1-40 treatment, nor acyl ghrelin injections affected olfactory discrimination. We used stereology to show that ghrelin KO and Aß1-40 increased the total number of glial fibrillary acidic protein expressing astrocytes and ionised calcium-binding adapter expressing microglial in the rostral hippocampus. Finally, Aß1-40 blocked long-term potentiation induced by high-frequency stimulation and this effect could be acutely blocked with co-administration of acyl ghrelin. Collectively, our studies demonstrate that ghrelin deletion affects memory performance and also that acyl ghrelin treatment may delay the onset of early events of AD. This supports the idea that acyl ghrelin treatment may be therapeutically beneficial with respect to restricting disease progression in AD.

A method based on infrared detection for determining the moisture content of ceramic plaster materials.

In this work, we describe a methodology for developing a mathematical model based on infrared (IR) detection to determine the moisture content (M) in solid samples. For this purpose, an experimental setup was designed, developed and calibrated against the gravimetric method. The experimental arrangement allowed for the simultaneous measurement of M and the electromotive force (EMF), fitting the experimental variables as much as possible. These variables were correlated by a mathematical model, and the obtained correlation was M=1.12×exp(3.47×EMF), ±2.54%. This finding suggests that it is feasible to measure the moisture content when it has greater values than 2.54%. The proposed methodology could be used for different conditions of temperature, relative humidity and drying rates to evaluate the influence of these variables on the amount of energy received by the IR detector.

Arginine-vasopressin in nucleus of the tractus solitarius induces hyperglycemia and brain glucose retention.

Hypothalamic arginine-vasopressin (AVP) plays an important role both as a neurotransmitter and hormone in the regulation of blood glucose and feeding behavior. AVP-containing axons from the parvocellular subdivision of paraventricular nucleus of the hypothalamus terminate in the nucleus of the tractus solitarius (NTS), but the function of this projection is not known. Interestingly, the NTS also receives afferent information from the carotid body and other peripheral receptors involved in glucose homeostasis. We have previously reported that stimulation of the carotid body receptors initiates a hyperglycemic reflex and increases brain glucose retention. Here we show that direct administration of micro-doses of AVP into the NTS of anesthetized or awake rats rapidly increased the levels of blood glucose concentration and brain arterio-venous (A-V) glucose difference. This effect was not observed when the same doses of AVP were injected in the brainstem outside NTS. Arginine-vasopressin antagonist microinjections alone produced a small but significant reduction in brain A-V glucose. Pre-administered VP1-receptor antagonist [beta-mercapto-beta,beta-cyclopentamethylene-propionyl(1),O-Me-Tyr(2),Arg(8)]vasopressin blocked the effects of AVP. These results indicate that AVP acting on its receptors locally within the NTS participates in glucose homeostasis, increasing both blood glucose concentration and brain A-V glucose differences. Hypothalamic AVP may facilitate hyperglycemic responses initiated by peripheral signals processed at the level of the NTS.

Electrochemical behavior of different preparations of plasma-sprayed hydroxyapatite coatings on Ti6Al4V substrate.

The corrosion behavior of four different preparations of plasma-sprayed hydroxyapatite (HA) coatings on Ti6Al4V substrates in static Hank's balanced salt solution was investigated using dc potentiodynamic and ac impedance techniques. Two different nominal thicknesses, 50 microm and 200 microm, and two different spraying conditions, were considered. The electrochemical impedance experiments proved this technique to be very suitable for the investigation of the electrochemical behavior of surgical implant alloys when they are coated with HA, which is characterized by the dissolution and passivation characteristics of the underlying metal substrate. Because the coatings are porous, ionic paths between the electrolytic medium and the base material can eventually be produced, resulting in the corrosion of the coated metal. Differences in the corrosion resistance of the coated materials were detected, and a relevant model for the description of the coating degradation in the biosimulating solution was proposed. The model consisted of the description of the coated system in terms of a two-layer model of the surface film. Significant differences in electrochemical behavior for similar nominal thicknesses of HA coatings obtained under different spraying conditions were found.

[Kinetic incorporation of mercury in Emerita portoricensis (Crustacea: Decapoda)]. / Cinética de incorporación del mercurio en Emerita portoricensis (Crustacea: Decapoda).

Benthic test species used in toxicity assays are the best indicators of sediment toxicity because they live in direct contact with sediments and the water column. Mercury chloride is one the most toxic metallic salts. Its strong affinity for particles explains the high Hg content found in benthic populations. The genus Emerita is abundantly found in Venezuelan coasts and is a good bioaccumulator of pollutants, but the toxicological assays performend on this genus are scarce. The present experimental test reports on the distribution of mercury in the water column and sediment, using static bioassay in short term (24 hr) and the ability of Emerita portoricensis to bioconcentrate mercury under experimental conditions. Our results suggest that the Hg transference from water to sediment is enhanced in the presence of Emerita. The kinetic uptake of Hg in Emerita portoricensis shows a mechanism of rapid absorption reaching high metal concentrations in short exposure times.