Lipopolysaccharide-responsive beige-like anchor is involved in regulating NF-κB activation in B cells.

Introduction: Lipopolysaccharide-responsive and beige-like anchor (LRBA) is a scaffolding protein that interacts with proteins such as CTLA-4 and PKA, the importance of which has been determined in various cell types, including T regulatory cells, B cells, and renal cells. LRBA deficiency is associated with an inborn error in immunity characterized by immunodeficiency and autoimmunity. In addition to defects in T regulatory cells, patients with LRBA deficiency also exhibit B cell defects, such as reduced cell number, low memory B cells, hypogammaglobulinemia, impaired B cell proliferation, and increased autophagy. Although Lrba-/- mice do not exhibit the immunodeficiency observed in humans, responses to B cell receptors (BCR) in B cells have not been explored. Therefore, a murine model is for elucidating the mechanism of Lrba mechanism in B cells. Aim: To compare and evaluate spleen-derived B cell responses to BCR crosslinking in C57BL6 Lrba-/- and Lrba+/+ mice. Materials and methods: Spleen-derived B cells were obtained from 8 to 12-week-old mice. Subpopulations were determined by immunostaining and flow cytometry. BCR crosslinking was assessed by the F(ab')2 anti-µ chain. Activation, proliferation and viability assays were performed using flow cytometry and protein phosphorylation was evaluated by immunoblotting. The nuclear localization of p65 was determined using confocal microscopy. Nur77 expression was evaluated by Western blot. Results: Lrba-/- B cells showed an activated phenotype and a decreased proportion of transitional 1 B cells, and both proliferation and survival were affected after BCR crosslinking in the Lrba-/- mice. The NF-κB pathway exhibited a basal activation status of several components, resulting in increased activation of p50, p65, and IκBα, basal p50 activation was reduced by the Plcγ2 inhibitor U73122. BCR crosslinking in Lrba-/ - B cells resulted in poor p50 phosphorylation and p65 nuclear localization. Increased levels of Nur77 were detected. Discussion: These results indicate the importance of Lrba in controlling NF-κB activation driven by BCR. Basal activation of NF-κB could impact cellular processes, such as, activation, differentiation, proliferation, and maintenance of B cells after antigen encounter.

Lianas in tropical dry seasonal forests have a high hydraulic efficiency but not always a higher embolism resistance than lianas in rainforests.

BACKGROUND AND AIMS: Lianas have higher relative abundance and biomass in drier seasonal forests than in rainforests, but whether this difference is associated with their hydraulic strategies is unclear. Here, we investigate whether lianas of seasonally dry forests are safer and more efficient in water transport than rainforest lianas, explaining patterns of liana abundance. METHODS: We measured hydraulic traits on five pairs of congeneric lianas of the tribe Bignonieae in two contrasting forest sites: the wet 'Dense Ombrophilous Forest' in Central Amazonia (~2 dry months) and the drier 'Semideciduous Seasonal Forest' in the inland Atlantic Forest (~6 dry months). We also gathered a broader database, including 197 trees and 58 liana species from different tropical forests, to compare hydraulic safety between habits and forest types. KEY RESULTS: Bignonieae lianas from both forests had high and similar hydraulic efficiency but exhibited variability in resistance to embolism across forest types when phylogenetic relationships were taken into account. Three genera had higher hydraulic safety in the seasonal forest than in the rainforest, but species across both forests had similar positive hydraulic safety margins despite lower predawn water potential values of seasonal forest lianas. We did not find the safety-efficiency trade-off. Merging our results with previously published data revealed a high variability of resistance to embolism in both trees and lianas, independent of forest types. CONCLUSIONS: The high hydraulic efficiency of lianas detected here probably favours their rapid growth across tropical forests, but differences in hydraulic safety highlight that some species are highly vulnerable and may rely on other mechanisms to cope with drought. Future research on the lethal dehydration threshold and the connection between hydraulic resistance strategies and liana abundance could offer further insights into tropical forest dynamics under climatic threats.

Leaf thermotolerance of Hevea brasiliensis clones: intra- versus interclonal variation and relationships with other functional traits.

Land surface temperature is predicted to increase by 0.2 °C per decade due to climate change, although with considerable regional variability, and heatwaves are predicted to increase markedly in the future. These changes will affect where crops can be grown in the future. Understanding the thermal limits of plant physiological functioning and how flexible such limits are is thus important. Here, we report on the measurements of a core foliar thermotolerance trait, T50, defined as the temperature at which the maximum quantum yield (Fv/Fm) of photosystem II declines by 50%, across nine different Malaysian Hevea brasiliensis clones. We explore the relative importance of interclonal versus intraclonal variation in T50 as well as its association with leaf and hydraulic traits. We find very low variation in T50 within individual clones (mean intraclonal coefficient of variation (CoV) of 1.26%) and little variation across clones (interclonal CoV of 2.1%). The interclonal variation in T50 was lower than for all other functional traits considered. The T50 was negatively related to leaf mass per area and leaf dry matter content, but it was not related to hydraulic traits such as embolism resistance (P50) or hydraulic safety margins (HSM50). The range of T50 observed (42.9-46.2 °C) is well above the current maximum air temperatures Tmax,obs (T50 - Tmax,obs >5.8 °C), suggesting that H. brasiliensis is likely thermally safe in this south-east Asian region of Malaysia.

The Effect of Magneto-Priming on the Physiological Quality of Soybean Seeds.

Microwaves have been applied to the drying of seeds of several species due to their maintenance of the quality of the seeds and reduction of time and costs. However, few is known about the effect of microwaves on the increase of the physiological quality of soybean seeds and especially their effects on longevity. Therefore, the use of microwaves as magneto-priming in soybean seeds was the object of study in this work. For this purpose, two soybean cultivars were selected and submitted to the ultra-high frequency (UHF) microwave exposure of 2.45 GHz, in the wavelength of 11 cm, and power of 0.2 W/g, for 15 min. The results showed that this condition of exposure to the microwave brought benefits in both cultivars after treatment. Incremental improvements were observed in the germinability indexes, the seedling length, the water absorption by the seeds, the fresh mass, dry mass, and longevity. The genes related to seed germination and longevity showed superior expression (HSFA3, HSP21, HSP17.6b, EXP, ABI3) with magneto-priming treatment. The data found ensure the use of the technique as a viable option for pre-treatment as magneto-priming in soybean seeds in order to improve seed quality.

Variaciones fenotípicas relacionadas a respuestas hipóxicas entre andinos a distintas altitudes / Phenotypic variations related to hypoxic responses among Andeans at different altitudes

Introducción. La adaptación a grandes altitudes implica cambios evolutivos que conllevan respuestas adaptativas, como a la hipoxia. Los andinos desarrollaron fenotipos eritroides diferentes en relación con otras poblaciones a gran altitud que pueden variar dependiendo la altitud. Objetivo. Determinar las variaciones fenotípicas de hemoglobina (Hb), saturación de oxígeno (SpO2), P50 y lactato en andinos bolivianos con radicatorias entre 400, 4000 y 5000 msnm. Material y métodos. Estudio descriptivo transversal de tipo prospectivo. Se recolectó sangre venosa periférica de andinos bolivianos (n=124) nacidos a 4000 m, pero con radicatoria en altitudes diferentes (400 m, 4000 m, 5000 m), así como de aquellos con eritrocitosis patológicas. Adicionalmente, se recolectó muestras de europeos residentes a 4000 m (n=11). Se realizó estudios de hemograma, oximetría y gasometría. La P50 fue calculada con fórmula de Lichtman. Resultados. Los andinos sanos, comparados entre distintas altitudes, reflejaron aumento de Hb al ser mayor la altitud (p: 0,001), empero disminución de SpO2 (p: 0,001) y P50 (p: 0,001); sin variaciones en lactato. Los europeos a 4000 m, en relación con andinos a la misma altitud, presentaron Hb incrementada (p: 0,01), SpO2 y P50 sin variaciones, pero lactato significativamente aumentado (p: 0,001). Los pacientes con eritrocitosis comparados con sujetos sanos, a 4000 m y 5000 m respectivamente, presentaron Hb aumentada (p: 0,001); SpO2 disminuida (p: 0,001); P50 sin variaciones, pero lactato incrementado (p: 0,01). El lactato elevado en sujetos a 5000 m con eritrocitosis fue llamativo (1,7 mmol/L). Conclusiones. Las variaciones fenotípicas observadas entre andinos en diferentes altitudes constituyen una expresión de una adaptación parcial a la altura.

Introduction. Human adaptation to high altitude involves evolutionary changes leading adaptive responses, such as to hypoxia. Andeans developed different erythroid phenotypes in relation to other populations at high altitude, which can vary depending on the altitude. Objective. To determine the phenotypic variations of hemoglobin (Hb), oxygen saturation (SpO2), P50 and lactate in Bolivian Andeans residing between 400, 4000 or 5000 masl. Material and methods. Prospective cross-sectional descriptive study. Peripheral venous blood from Bolivian Andeans (n=124) born at 4000 m, but residing at different altitudes (400 m, 4000 m, 5000 m), likewise from those with pathological erythrocytosis were collected. Additionally, samples from Europeans residing at 4000 m (n=11) were collected. CBC, oximetry and blood gas studies were performed. P50 was calculated using the Lichtman formula. Results. Healthy Andeans, compared between different altitudes, reflected an increased Hb (p: 0.001), but a decreased SpO2 (p: 0.001) and P50 (p: 0.001) as the altitude was higher; without variations in lactate. Europeans at 4000 m, related to Andeans at the same altitude, presented increased Hb (p: 0.01), SpO2 and P50 without variations, but significantly increased lactate (p: 0.001). Patients with erythrocytosis compared to healthy subjects, at 4000 m and 5000 m respectively, depicted increased Hb (p: 0.001); decreased SpO2 (p: 0.001); P50 without changes, but increased lactate (p: 0.01). Increased lactate in subjects with erythrocytosis at 5000 m was remarkable (1.7 mmol/L). Conclusion. The phenotypic variations observed among Andeans residing at different altitudes constitute an expression of partial adaptation to altitude.

Small understorey trees have greater capacity than canopy trees to adjust hydraulic traits following prolonged experimental drought in a tropical forest.

Future climate change predictions for tropical forests highlight increased frequency and intensity of extreme drought events. However, it remains unclear whether large and small trees have differential strategies to tolerate drought due to the different niches they occupy. The future of tropical forests is ultimately dependent on the capacity of small trees (<10 cm in diameter) to adjust their hydraulic system to tolerate drought. To address this question, we evaluated whether the drought tolerance of neotropical small trees can adjust to experimental water stress and was different from tall trees. We measured multiple drought resistance-related hydraulic traits across nine common neotropical genera at the world's longest-running tropical forest throughfall-exclusion experiment and compared their responses with surviving large canopy trees. Small understorey trees in both the control and the throughfall-exclusion treatment had lower minimum stomatal conductance and maximum hydraulic leaf-specific conductivity relative to large trees of the same genera, as well as a greater hydraulic safety margin (HSM), percentage loss of conductivity and embolism resistance, demonstrating that they occupy a distinct hydraulic niche. Surprisingly, in response to the drought treatment, small trees increased specific hydraulic conductivity by 56.3% and leaf:sapwood area ratio by 45.6%. The greater HSM of small understorey trees relative to large canopy trees likely enabled them to adjust other aspects of their hydraulic systems to increase hydraulic conductivity and take advantage of increases in light availability in the understorey resulting from the drought-induced mortality of canopy trees. Our results demonstrate that differences in hydraulic strategies between small understorey and large canopy trees drive hydraulic niche segregation. Small understorey trees can adjust their hydraulic systems in response to changes in water and light availability, indicating that natural regeneration of tropical forests following long-term drought may be possible.

In vitro effect of dibenzyl trisulfide on the p50 of the oxygen haemoglobin dissociation curve.

OBJECTIVES: Dibenzyl trisulfide (DTS) has been reported to have cytotoxic and anti-inflammatory effects. It also affects erythrocyte deformability. We investigated the effects of DTS on the p50 of the oxygen haemoglobin dissociation curve. METHODS: Blood samples from 10 healthy male volunteers with normal haemoglobin AA were exposed to 50, 100, 200 and 400 ng/mL, respectively, of DTS. A hemox-analyzer was used to obtain the p50 values. RESULTS: The mean p50 value for the control samples was 25.89 ± 2.18 mm Hg. The values for the samples exposed to 50, 100, 200 and 400 ng/mL were 23.53 ± 1.81 mm Hg, 22.62 ± 1.61 mm Hg, 21.88 ± 1.67 mm Hg and 21.68 ± 1.88 mm Hg, respectively. CONCLUSIONS: DTS caused a significant (p<0.001) reduction in p50 values indicating a shift of the oxygen- haemoglobin dissociation curve to the left in all the samples compared with control, suggesting that the administration of DTS could result in decrease in oxygen supply to tissues.

Pharmacological safety of Plinia cauliflora (Mart.) Kausel in rabbits.

Fruit peels of Plinia cauliflora (Mart.) Kausel are widely used in Brazilian traditional medicine, but no studies have proved the safety of its pharmacological effects on the respiratory, cardiovascular, and central nervous systems. The present study assessed the safety pharmacology of P. cauliflora in New Zealand rabbits. First, an ethanol extract (EEPC) was selected for the pharmacological experiments and chemical characterization. Then, different groups of rabbits were orally treated with EEPC (200 and 2000 mg/kg) or vehicle. Acute behavioral and physiological alterations in the modified Irwin test, respiratory rate, arterial blood gas, and various cardiovascular parameters (i.e., heart rate, blood pressure, and electrocardiography) were evaluated. The main secondary metabolites that were identified in EEPC were ellagic acid, gallic acid, O-deoxyhexosyl quercetin, and the anthocyanin O-hexosyl cyanidin. No significant behavioral or physiological changes were observed in any of the groups. None of the doses of EEPC affected respiratory rate or arterial blood gas, with no changes on blood pressure or electrocardiographic parameters. The present study showed that EEPC did not cause any significant changes in respiratory, cardiovascular, or central nervous system function. These data provide scientific evidence of the effects of this species and important safety data for its clinical use.

The hydraulic efficiency-safety trade-off differs between lianas and trees.

Hydraulic traits are important for woody plant functioning and distribution. Associations among hydraulic traits, other leaf and stem traits, and species' performance are relatively well understood for trees, but remain poorly studied for lianas. We evaluated the coordination among hydraulic efficiency (i.e., maximum hydraulic conductivity), hydraulic safety (i.e., cavitation resistance), a suite of eight morphological and physiological traits, and species' abundances for saplings of 24 liana species and 27 tree species in wet tropical forests in Panama. Trees showed a strong trade-off between hydraulic efficiency and hydraulic safety, whereas efficiency and safety were decoupled in lianas. Hydraulic efficiency was strongly and similarly correlated with acquisitive traits for lianas and trees (e.g., positively with gas exchange rates and negatively with wood density). Hydraulic safety, however, showed no correlations with other traits in lianas, but with several in trees (e.g., positively with leaf dry matter content and wood density and negatively with gas exchange rates), indicating that in lianas hydraulic efficiency is an anchor trait because it is correlated with many other traits, while in trees both efficiency and safety are anchor traits. Traits related to shade tolerance (e.g., low specific leaf area and high wood density) were associated with high local tree sapling abundance, but not with liana abundance. Our results suggest that different, yet unknown mechanisms determine hydraulic safety and local-scale abundance for lianas compared to trees. For trees, the trade-off between efficiency and safety will provide less possibilities for ecological strategies. For lianas, however, the uncoupling of efficiency and safety could allow them to have high hydraulic efficiency, and hence high growth rates, without compromising resistance to cavitation under drought, thus allowing them to thrive and outperform trees under drier conditions.

Embolism resistance drives the distribution of Amazonian rainforest tree species along hydro-topographic gradients.

Species distribution is strongly driven by local and global gradients in water availability but the underlying mechanisms are not clear. Vulnerability to xylem embolism (P50 ) is a key trait that indicates how species cope with drought and might explain plant distribution patterns across environmental gradients. Here we address its role on species sorting along a hydro-topographical gradient in a central Amazonian rainforest and examine its variance at the community scale. We measured P50 for 28 tree species, soil properties and estimated the hydrological niche of each species using an indicator of distance to the water table (HAND). We found a large hydraulic diversity, covering as much as 44% of the global angiosperm variation in P50 . We show that P50 : contributes to species segregation across a hydro-topographic gradient in the Amazon, and thus to species coexistence; is the result of repeated evolutionary adaptation within closely related taxa; is associated with species tolerance to P-poor soils, suggesting the evolution of a stress-tolerance syndrome to nutrients and drought; and is higher for trees in the valleys than uplands. The large observed hydraulic diversity and its association with topography has important implications for modelling and predicting forest and species resilience to climate change.

Sildenafil Increases the p50 and Shifts the Oxygen-Hemoglobin Dissociation Curve to the Right.

INTRODUCTION: Sildenafil (Viagra®) is a selective phosphodiesterase type 5 (PDE5) inhibitor that block the breakdown of cyclic guanyl monophosphate (cGMP) leading to relaxation of the smooth muscles of the corpus cavernous and an increase in blood flow resulting in penile erection. It is hypothesized that sildenafil will increase the release of oxygen from erythrocytes and shift the oxygen-hemoglobin curve to the right. AIM: The aim of this study was to investigate the effect of varying doses of sildenafil on the p50 of the oxygen-hemoglobin dissociation curve in blood samples from eight (8) healthy adult male volunteers with normal hemoglobin HbAA. METHOD: The hemox-analyzer was used to generate the p50 and the oxygen-hemoglobin dissociation curves. MAIN OUTCOME MEASURES: The effect of different doses of sildenafil on the p50 values and shift of the oxygen-hemoglobin curve were the main outcome measures. RESULT: Sildenafil caused a statistically significant increase in the p50 values and rightward shift of the oxygen-hemoglobin dissociation curve. CONCLUSION: Sildenafil caused a dose-dependent increase in the release of oxygen from the erythrocytes as shown by the increased p50 values and rightward shift of the oxygen-hemoglobin dissociation curve. Ellis SS and Pepple DJ. Sildenafil increases the p50 and shifts the oxygen-hemoglobin dissociation curve to the right.

Effect of cilostazol on the p50 of the oxygen-hemoglobin dissociation curve.

Cilostazol is a drug used for the treatment of intermittent claudication caused by narrowing of the blood vessels and reduced oxygen supply, characterized by intense pain in the leg when walking. This study was designed to investigate the effect of cilostazol on the P50 of the oxygen hemoglobin dissociation curve. A total of eight healthy adult subjects were studied. Blood samples (0.5 mL) from each subject were mixed with 5, 10, and 20 µL of the 0.5 mg/mL stock solution of cilostazol to give concentrations of 10, 20, and 40 µg/mL equivalent to adult doses of 50, 100, and 200 mg, respectively. The control sample had no drug added. The oxygen hemoglobin dissociation curve of each sample was plotted and the P50 determined with a Hemox-Analyzer (TCS, Medical Products Division, Southampton, PA). The mean P50 for the control samples was 28.27 ± 0.43 mm Hg. The values of the samples exposed to 10, 20, and 40 µg/mL cilostozol were 29.63 ± 0.66, 30.15 ± 0.77, and 31.66 ± 0.62 mm Hg, respectively. There was a statistically significant difference (p < 0.01) between the control and samples exposed to 40 µg/mL cilostazol. This study suggests that cilostazol caused an increase in the release of oxygen from hemoglobin as shown in the P50 values. This effect was significant at the highest concentration of 40 µg/mL.

Involvement of the NF-кB/p50/Bcl-3 complex in response to antiangiogenic therapy in a mouse model of metastatic renal cell carcinoma.

Renal cell carcinoma (RCC) represents approximately 2-3% of human malignancies. Nuclear transcription factor кB (NF-кB) is composed of a family of transcription factors that have been associated with the development and progression of RCC. Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. In this study, we evaluated the expression of NF-кB in metastatic tumor cells from animals treated with ES. Balb/c-bearing Renca-EGFP cells were treated with NIH/3T3-LendSN or NIH/3T3-LXSN cells as a control. At the end of the in vivo experiment, plasma Renca-EGFP-sorted cells and tissue lung samples were collected. A real-time PCR array for NF-κB target genes revealed that ES therapy led to down regulation of Bcl-3 (P<0.031), NF-кB1 (P<0.001) and c-Rel (P<0.004) in the ES-treated group. Using an electrophoretic mobility shift assay (EMSA), we observed a reduction in NF-kB binding activity in ES-treated Renca-EGP cells. Furthermore, a supershift assay showed a clear shift of the NF-кB DNA band in samples incubated with a p50 antibody. By immunohistochemistry analysis, ES treatment resulted in a significant reduction in expression of p50. (ES vs. control P<0.05). The immunoprecipitation experiments confirmed the presence of a p50/Bcl-3 complex in nuclear extracts from cells of metastatic lung tissues. Our findings indicate that p50 and Bcl-3 plays a regulatory role in gene transcription in RCC.

Pattern of P50 suppression deficit in patients with epilepsy and individuals with schizophrenia / Padrão do déficit de supressão do P50 em pacientes com epilepsia e em indivíduos com esquizofrenia

OBJECTIVE: To identify P50 suppression in patients with epilepsy, to investigate the effect of seizure control on P50 suppression, and to compare epilepsy patients with individuals with schizophrenia and healthy volunteers. METHOD: P50 evoked potential parameters and P50 suppression were studied crossectionally in patients with uncontrolled or controlled epilepsy, in individuals with schizophrenia and in healthy volunteers. RESULTS: Individuals with schizophrenia had significantly smaller conditioning stimulus (S1) amplitude, and patients with epilepsy had larger test stimulus (S2) amplitude. Mean S2/S1 ratio was 0.71±0.33 for patients with uncontrolled epilepsy; 0.68±0.36 for patients with controlled epilepsy; 0.96±0.47 for individuals with schizophrenia, and 0.42±0.24 for healthy volunteers. CONCLUSION: The sensory filter of patients with epilepsy is altered, and this alteration is not associated with seizure control. Also, it works differently from the sensory filter of individuals with schizophrenia.

OBJETIVO: Identificar se existe déficit de supressão do P50 em pacientes com epilepsia, verificar a influência do controle das crises nesse déficit, comparando com pacientes com esquizofrenia e com voluntários saudáveis. MÉTODO: Os parâmetros do potencial evocado P50 e sua supressão foram estudados, com um corte transversal, em pacientes com epilepsia controlada ou não, esquizofrenia e em voluntários saudáveis. RESULTADOS: Indivíduos com esquizofrenia apresentam uma amplitude de S1 significativamente menor que os demais, sendo que os pacientes com epilepsia apresentavam uma resposta S2 de maior amplitude. A média da razão S2/S1 foi de 0,71±0,33 nos pacientes com epilepsia não controlada; 0,68±0,36 naqueles com epilepsia controlada; 0,96±0,47 nos com esquizofrenia e 0,42±0,24 nos controles normais. CONCLUSÃO: O filtro sensitivo de pacientes com epilepsia é alterado, e essa alteração não está associada com o controle das crises. Além disso, ele funciona de forma diferente do filtro sensitivo dos indivíduos com esquizofrenia.

Filtrado sensorial y P50: implicaciones para la neurobiología de la esquizofrenia

Resumen: El estudio del filtrado sensorial mediante potenciales evocados ha marcado una línea de investigación en la esquizofrenia que plantea explicaciones alternativas a la presencia de la sintomatología, y que bien merecen atención y estudio. La P50 es un potencial evocado con respuesta de latencia media que se origina en el lóbulo temporal medio, en el hipocampo y cerca de éste. Mediante estudios con magnetoencefalografía, se ha propuesto que las células piramidales situadas en el giro temporal son la fuente más probable de la P50 en el registro electroencefalográfico, correspondiente al electrodo CZ situado en el vértex, de acuerdo con el sistema internacional 10-20. En este paradigma se presentan ensayos con dos estímulos auditivos con sonido de "clic": el primero es condicionante (E1) y el segundo, de prueba (E2), y pueden tener parámetros variables de duración, intensidad, intervalo interestímulo e intervalo interensayo. Cuando existe variación en los valores de estos parámetros, se obtiene como resultado una respuesta facilitada o suprimida al segundo estímulo. La P50 es una onda con amplitud no mayor a 50 -i.V ni menor a 0.5 -i.V. Para su análisis, se saca un promedio de entre 30 y 180 ensayos de cada estímulo y finalmente se analiza mediante la comparación del porcentaje de disminución de la amplitud de E1 y de E2, también con el resultado de la diferencia de E1 menos E2, o con el porcentaje de disminución en el área de la P50 de E2 comparada con la disminución de Et Los estudios que documentan la eficacia de los antipsicóticos para normalizar el defecto en el filtrado sensorial no brindan información concluyente. Algunos estudios han observado que los pacientes sin medicación antipsicótica no presentan supresión de la respuesta a E2, o la presentan muy disminuida. Otros estu dios han documentado la repuesta no suprimida de la P50 en un grupo de esquizofrénicos bajo tratamiento antipsicótico. En ellos se observó un aumento en las latencias y amplitudes del trazo casi idénticas que las presentadas por los controles sanos. Se ha descri to que la mejoría en el déficit sensorial que presentan los esquizofrénicos bajo tratamiento antipsicótico se debe al bloqueo de la transmisión dopaminérgica. Se ha observado que algunos de los familiares en primer grado de los pacientes con esquizofrenia muestran también alteraciones en la inhibición del segundo estímulo auditivo del paradigma P50. Asimismo, en familiares sanos no fumadores que presentaban el defecto de filtrado se ha reportado una normalización transitoria del déficit sensorial registrado después de dosificar nicotina me diante goma de mascar. De acuerdo con estos datos, se ha propuesto la importancia que tiene la nicotina para el filtrado sensorial. En el paradigma de la P50, el fenómeno de habituación se produce cuando E1 activa las interneuronas a través de los receptores nicotínicos, que provocan la liberación de GABA, con la cual las células piramidales del hipocampo no logran ser excitadas por E2 y por lo tanto no responden a éste. En la esquizofrenia, la falta de habituación puede explicarse por una disminución en el número de interneuronas inhibitorias que muestran una alta ex presión de receptores nicotínicos.

Abstract: In the search for etiologic and physiologic keys to increase the knowledge about schizophrenia, research focused in the assessment of sensory gating by the use of event-related potentials has been considered an alternative to explain the presence of cognitive and positive symptoms. The P50 is a middlelatency-evoked potential originated in the temporal lobe, in the hippocampus and close to this. Through magnetoencephalographic studies, it has been hypothesized that piramidal cells located in the temporal gyrus are the most suitable source of the P50 wave present in electroencephalographic recordings. Therefore, the main wave for the obtention of the P50 is located in the vertex, which corresponds to the CZ electrode, in agreement with the 10-20 International System. The P50 paradigm is evoked by two auditory stimuli with the sound of a click, where the first stimulus is labelled conditioning (S1) and the second one, testing (S2). Both of them may have variable values for duration, intensity, inter-stimulus interval and inter-testing interval. Any variation on these parameter values leads to a suppressed or a facilitated response of the second stimulus. The amplitude established for the P50 paradigm is smaller than 50 [íV and greater than 0.5 -iV. Once the recording is acquired, the analysis of the P50 wave must be done with an average of 30 to 180 tests of S1 and S2. Results from the average can be analyzed by: a) a comparison of the amplitude's diminution percentage of S1 and S2, b) the difference between the substraction of the S1 value minus the S2 value, or c) the mean reduction of the P50 area of S1 compared with the mean reduction of the P50 area of S2. Different pharmacological assays had shown evidence of changes in sensory gating performance by means of the mechanism of action of some antipsychotics. Although some studies had shown a normalizing effect of antipsychotics over the sensory gating deficit in schizophrenic patients, the results are not conclusive. Some studies have reported that schizophrenic patients under antipsychotic treatment suppress the S2, while patients without antipsychotic treatment showed a lack of suppression of the S2. Nevertheless, other studies had reported a minor suppression of the second stimulus in groups of schizophrenic patients under antipsychotic treatment. Moreover, other studies had observed increased latencies and almost identical amplitudes of the outline between schizophrenic patients and normal healthy controls. The dopamine hypothesis has been one of the most important physiopathologic explanations for schizophrenia and the dopaminergic transmission blockade has also been implicated in the improvement of sensory gating in schizophrenic patients under antipsychotic treatment. Furthermore, a familiar pattern of sensory gating dysfunction has been found in healthy first-degree relatives of schizophrenic patients, whose response to the P50 paradigm has shown the lack of inhibition to the second auditory stimulus. This deficit is mainly observed in the parent having a greater familiar history for schizophrenia and also in half of the patient's healthy sibs. It is important to consider that although some relatives display an abnormal performance of the P50 wave, in general their cognitive performance is higher than the one showed by the schizophrenic patient. Likewise, some healthy non-smoker relatives, whose previous recordings displayed abnormal P50 waves, showed a transitory normalization of their sensory gating after nicotine administration by means of a nicotine chewing gum. It has been postulated that nicotine has a primary effect over the sensory gating performance. Hippocampal neurons receiving the originating stimuli from the medial septal nucleus are densely concentrated with nicotinic receptors. This inervation has been described as the main filter of repetitive auditory stimuli in the hippocampus. Following the hypothesis of the influence of nicotine over the sensory gating performance, it has been proposed that the habituation phenomenon occuring in the P50 paradigm takes place when interneurons are activated by nicotinic receptors after the first auditory stimuli. This activation causes a liberation of GABA, which avoids hippocampal piramidal cells excitation by S2, and therefore they do not respond to this stimulus. In schizophrenic patients, the lack of habituation can be explained by histochemical evidencies which suggest a smaller number of inhibitory interneurons with a higher expression of OC-7 nicotinic receptors. Based on these data, the actual background of the P50 paradigm brings out the possibility of including it as an important biological marker for the early detection of schizophrenia between high-risk relatives of schizophrenic patients. Further research is required to fully understand the potential advantages offered by the P50 sensory gating study. It is important to develop pharmacological studies focused on the role of specific antipsychotics over cognitive functions in schizophrenic patients. Also, future research should be addressed to the assessment of the influence of nicotinic receptors in attentional proceses and in the etiopathology of schizophrenia in order to explore O -7 nicotinic receptor selective agonists as candidates for the treatment of cognitive and perceptual disturbances in schizophrenia. The aim of this review is to give an introduction to the auditory sensory gating studies applied to schizophrenia research by means of event-related potentials.