Association of SOD1 gene variants (50 bp Ins/Del, rs4817415, rs2070424, rs1041740, rs17880135) with plasma protein levels in vitiligo patients and their analysis in silico.

OBJECTIVE: Vitiligo is a common systemic, idiopathic autoimmune disease. The aim of this study was to analyze the frequency of variants of the superoxide dismutase 1 (SOD1) gene (50 bp Ins/Del, rs4817415, rs2070424, rs1041740, rs17880135) and circulating plasma protein levels through in-silico analysis. PATIENTS AND METHODS: Blood samples were collected from adult patients of both sexes with a clinical diagnosis of vitiligo. ELISA tests for SOD and analysis of gene variants by qPCR were compared to a disease-free reference group. RESULTS: The population analyzed was young people between 29 and 37 years old, with a higher percentage of women. The population was found in the Hardy-Weinberg equilibrium (HWE). The 50 bp Ins/Del, rs4817415, and rs2070424 variants showed no significant difference between groups (p > 0.05). Although, in the dominant model, the CT and CTTT genotypes of the rs1041740 and rs17880135 variants showed an association with susceptibility to vitiligo compared to the control. Plasma SOD levels showed significant differences between the groups, and when stratified according to the genotypes of each variant, there was a significant difference, except with the rs17880135 variant. The haplotypes InsCGTC and InsAGCC are shown to be risk factors for susceptibility to vitiligo. The in-silico analysis demonstrated that the rs4817415, rs2070424, rs1041740, and rs17880135 variants of the SOD1 gene participate in the modification of selected regulatory elements for differentiating the protein, transcription factors, and long non-coding RNA. CONCLUSIONS: Information regarding the pathogenesis of vitiligo helps recognize risk factors and identify the relationship of diagnostic markers of cell damage inherent to the disease. This will help improve aspects of prevention and the choice of treatment alternatives appropriate to each case.

[Impact of the Interdisciplinary Chronic Pain Rehabilitation Programme in patients with and without sleep disorders]. / Impacto del Programa de Rehabilitación Interdisciplinario de Dolor Crónico en pacientes sin y con trastornos del sueño.

INTRODUCTION: Sleep disorders and chronic pain are linked to each other bidirectionally. Both are related to affective disorders, fatigue, depression, anxiety and drug abuse, and have a significant effect on quality of life. The Interdisciplinary Pain Programme (IDP) aims to relieve the patients' pain and improve their functionality by incorporating healthy postural, sleep and nutritional habits, relaxation techniques, physical exercise and cognitive-behavioural mechanisms. PATIENTS AND METHODS: A retrospective, observational, cross-sectional study was conducted. A total of 323 patients with chronic pain who completed the IDP were examined. They were assessed at the beginning and at the end of the programme with pain, depression, quality of life and insomnia scales, and were then compared between groups with and without insomnia, that is, with an insomnia severity index (ISI) less than 15 versus greater than or equal to 15. Fifty-eight patients were studied by means of polysomnography. RESULTS: A significant improvement (p < 0.0001) in pain, depression and quality of life, as assessed by the visual analogue scale (VAS), the Beck inventory and the Short Form-36 (SF-36) questionnaire was observed in chronic pain patients with an ISI below 15 and in those with an ISI greater than or equal to 15. The results were superior in the group of patients with insomnia. The presence of a high apnoea and hypopnoea index and periodic lower limb movements in patients was not related to improvements on the Beck, SF-36, ISI and VAS scales. CONCLUSIONS: In conclusion, IDP benefits patients with chronic non-cancer-induced pain in several affected areas, in addition to pain, due to a comprehensive treatment. Polysomnography can help diagnose specific pathologies and individualise pharmacological treatment.

TITLE: Impacto del Programa de Rehabilitación Interdisciplinario de Dolor Crónico en pacientes sin y con trastornos del sueño.Introducción. Los trastornos del sueño y el dolor crónico están relacionados bidireccionalmente. Ambos están relacionados con trastornos afectivos, fatiga, depresión, ansiedad y abuso de fármacos, y afectan significativamente a la calidad de vida. El objetivo del Programa Interdisciplinario de Dolor (PRID) es aliviar el dolor del paciente y mejorar su funcionalidad a través de la incorporación de hábitos posturales, del sueño y nutricionales saludables, técnicas de relajación, ejercicio físico y mecanismos cognitivoconductuales. Pacientes y métodos. Se realizó un estudio retrospectivo, observacional y transversal. Se examinó a 323 pacientes con dolor crónico que completaron el PRID. Se les evaluó al principio y al final del programa con escalas de dolor, depresión, calidad de vida e insomnio, y se les comparó entre grupos con y sin insomnio ­índice de gravedad del insomnio (ISI) menor de 15 frente a mayor o igual a 15­. Se estudió a 58 pacientes con polisomnografía. Resultados. Se observó una mejoría significativa (p < 0,0001) del dolor, la depresión y la calidad de vida evaluados mediante la escala analógica visual (EVA), el inventario de Beck y el cuestionario Short Form-36 (SF-36), tanto en pacientes con dolor crónico con ISI menor de 15 como ISI mayor o igual a 15. Los resultados fueron superiores en el grupo de pacientes con insomnio. La presencia de un índice de apneas e hipopneas elevado y movimientos periódicos de los miembros inferiores en los pacientes no se relacionó con la mejoría de las escalas de Beck, SF-36, ISI y EVA. Conclusiones. En conclusión, el PRID beneficia a los pacientes con dolor crónico no oncológico en varias esferas afectadas, además del dolor, mediante un tratamiento integral. La polisomnografía puede ayudar a diagnosticar patologías específicas e individualizar el tratamiento farmacológico.

Carcinoma papilar tiroideo con invasión locorregional: reporte de caso / Papillary thyroid crcinoma with locoregional invasion: case report

El cáncer diferenciado de tiroides incluye el tipo papilar y folicular que representan más del 80% de los casos y tienen un excelente pronóstico. Existen varios subtipos histológicos y las variantes foliculares son probablemente las más comunes. La incidencia de cáncer papilar variante folicular ha ido en aumento. En un reporte de un solo centro, cerca del 40% de los cánceres papilares eran variantes foliculares1. El subtipo infiltrativo de la variante folicular presenta sectores que invaden el parénquima tiroideo no neoplásico y carece de una cápsula tumoral bien definida. Tiene un comportamiento biológico y un perfil molecular que es más similar al tumor papilar clásico2. Existen características clínicas y patológicas asociadas con riesgo más alto de recurrencia tumoral y mortalidad; entre ellos se describen el tamaño del tumor primario y la presencia de invasión de tejidos blandos3. En la invasión de estructuras adyacentes, los sitios más comprometidos incluyen los músculos pretiroideos, el nervio laríngeo recurrente, el esófago, la faringe, laringe y la tráquea. Además, puede haber otras estructuras involucradas como: la vena yugular interna, la arteria carótida y los nervios vago, frénico y espinal4. El compromiso de los ganglios linfáticos y la incidencia de metástasis ganglionares en adultos depende de la extensión de la cirugía. Entre los que se realizan una disección radical modificada del cuello, hasta el 80% tienen metástasis en los ganglios linfáticos y el 50% de ellas son microscópicas5. Clínicamente los tumores localmente avanzados cursan con disfonía, disfagia, disnea, tos o hemoptisis, pero la ausencia de síntomas no descarta la invasión local. Según las guías de la American Thyroid Association6 son variables de mal pronóstico: la edad del paciente, el tamaño del tumor primario, la extensión extra tiroidea y la resección quirúrgica incompleta.

Differentiated thyroid cancer includes papillary and follicular types that represent more than 80% of cases and have an excellent prognosis. There are several histologic subtypes, and follicular variants are probably the most common. The incidence of papillary follicular variant cancer has been increasing. In a singlecenter report, about 40% of papillary cancers were follicular variants1. The infiltrative subtype of the follicular variant presents sectors that invade the non-neoplastic thyroid parenchyma and lacks a well-defined tumor capsule. It has a biological behavior and a molecular profile that is more similar to the classic papillary tumor2. There are clinical and pathological characteristics associated with a higher risk of tumor recurrence and mortality; These include the size of the primary tumor and the presence of soft tissue invasion3. In the invasion of adjacent structures, the most compromised sites include the pre-thyroid muscles, the recurrent laryngeal nerve, the esophagus, the pharynx, larynx and trachea. In addition, there may be other structures involved such as: the internal jugular vein, the carotid artery and the vagus, phrenic and spinal nerves4. The involvement of the lymph nodes and the incidence of lymph node metastases in adults depends on the extent of the surgery. Among those who undergo a modified radical neck dissection, up to 80% have lymph node metastases and 50% of them are microscopic5. Clinically locally advanced tumors present with dysphonia, dysphagia, dyspnea, cough, or hemoptysis, but the absence of symptoms does not rule out local invasion. According to the American Thyroid Association guidelines6, there are variables with a poor prognosis: the age of the patient, the size of the primary tumor, the extra-thyroid extension, and incomplete surgical resection.

Variante células altas de cáncer papilar de tiroides: reporte de casos / Tall cell variant of papillary thyroid cancer: case report

El cáncer papilar constituye aproximadamente el 80% de todos los casos de cáncer de tiroides y el 85% de los tumores diferenciados. La variante de células altas representa el 1,3 al 12% del cáncer papilar siendo la variante agresiva más común de estos tumores. Posee un comportamiento agresivo, con mayor incidencia de invasión extratiroidea, linfovascular y metástasis a distancia, responsables de tasas de recurrencia más altas y peor pronóstico. Los casos aquí reportados reflejan las características que hacen sospechar mayor agresividad tumoral, desde el diagnóstico. Describimos dos pacientes de sexo femenino, entre 40 y 50 años, con historia de corta evolución, cuya presentación fue con síntomas de compresión locorregional y adenopatías metastásicas en cuello. Con hallazgos ecográficos e intraoperatorios de relevancia en cuanto la agresividad tumoral que hicieron sospechar la presencia de una variante agresiva del cáncer papilar. La histopatología de la variante de células altas posee una base molecular diferente respecto al papilar clásico que le confiere mayor morbi-mortalidad, constituyendo un factor de pronóstico independiente para la recurrencia. El tratamiento quirúrgico es la tiroidectomía total con vaciamiento profiláctico de los ganglios linfáticos centrales y eventualmente vaciamiento lateral de cuello según valoración preoperatoria, con posterior ablación postoperatoria de restos tiroideos mediante yodo radiactivo.

Papillary cancer constitutes approximately 80% of all thyroid cancer cases and 85% of differentiated tumors. The tall cell variant represents 1.3 to 12% of papillary cancers, being the most common aggressive variant of these tumors. It has an aggressive behavior, showing a higher incidence of extrathyroid and lymphovascular invasion and distant metastasis, responsible for higher recurrence rates and a worse prognosis. The cases reported here reflect characteristics that make us suspect tumor aggressiveness. These are female patients, between 40 and 70 years old, with a history of short evolution. They present locoregional symptoms or metastatic adenopathies, with ultrasound and intraoperative findings of relevance in terms of tumor aggressiveness that led to the suspicion of the presence of an aggressive variant of papillary cancer. The histopathology of the tall cell variant has a different molecular basis that confers its own morbidity and mortality, being an independent prognostic factor for recurrence. Total thyroidectomy is recommended with prophylactic dissection of the central lymph nodes and eventually lateral neck dissection according to preoperative evaluation followed by postoperative ablation with radioactive iodine.

Downstream effects of polypathology on neurodegeneration of medial temporal lobe subregions.

The medial temporal lobe (MTL) is a nidus for neurodegenerative pathologies and therefore an important region in which to study polypathology. We investigated associations between neurodegenerative pathologies and the thickness of different MTL subregions measured using high-resolution post-mortem MRI. Tau, TAR DNA-binding protein 43 (TDP-43), amyloid-ß and α-synuclein pathology were rated on a scale of 0 (absent)-3 (severe) in the hippocampus and entorhinal cortex (ERC) of 58 individuals with and without neurodegenerative diseases (median age 75.0 years, 60.3% male). Thickness measurements in ERC, Brodmann Area (BA) 35 and 36, parahippocampal cortex, subiculum, cornu ammonis (CA)1 and the stratum radiatum lacunosum moleculare (SRLM) were derived from 0.2 × 0.2 × 0.2 mm3 post-mortem MRI scans of excised MTL specimens from the contralateral hemisphere using a semi-automated approach. Spearman's rank correlations were performed between neurodegenerative pathologies and thickness, correcting for age, sex and hemisphere, including all four proteinopathies in the model. We found significant associations of (1) TDP-43 with thickness in all subregions (r = - 0.27 to r = - 0.46), and (2) tau with BA35 (r = - 0.31) and SRLM thickness (r = - 0.33). In amyloid-ß and TDP-43 negative cases, we found strong significant associations of tau with ERC (r = - 0.40), BA35 (r = - 0.55), subiculum (r = - 0.42) and CA1 thickness (r = - 0.47). This unique dataset shows widespread MTL atrophy in relation to TDP-43 pathology and atrophy in regions affected early in Braak stageing and tau pathology. Moreover, the strong association of tau with thickness in early Braak regions in the absence of amyloid-ß suggests a role of Primary Age-Related Tauopathy in neurodegeneration.

Skin cancer prevention campaign in childhood: survey based on 3676 children in Brazil.

BACKGROUND AND OBJECTIVES: Primary skin cancer prevention campaigns are essential and more effective among children, not only because of the importance of sun exposure effects during this period, but also because this age is when individuals are developing behaviours. The Brazilian Society of Dermatology - Regional State of Sao Paulo developed and conducted the programme named 'The Sun, Friend of Childhood', a school health education and disease prevention project for children and parents. Our objective was to evaluate the cognitive and behavioural effects of the children and parents before and after an education model-based intervention of sun protection. METHODS: We carried out a study on a school population of Social Service of Industry - Regional State of São Paulo, from the first to the fifth years of the regular course (6-10 years). Our educational project was planned to be based on two children's learning tools (comic magazine and a DVD cartoon). Questionnaires in relation to habits and knowledge in sun exposure were applied to the children (3776) before and (2748) after the intervention. A questionnaire was applied to 3663 parents regarding personal details and habits of their children. RESULTS: According to the McNemar's statistical test, all changes in the children in acquiring new knowledge about good practices for sun exposure were statistically significant. CONCLUSIONS: Educative sun exposure programmes in childhood are a relevant tool to modify the history of life for next generations, to concern the skin cancer and good health practices.

Buccal micronucleus cytome assay of populations under chronic heavy metal and other metal exposure along the Santiago River, Mexico.

The Santiago River is one of the most contaminated rivers in Mexico, with heavy metal levels above the allowed limits. Scientific evidence indicates that chronic heavy metal exposure leads to cytogenotoxic effects. The aims of this study were to evaluate the genotoxic and cytotoxic effects of such exposure in buccal mucosa cells by micronucleus (MN) assay and to identify other nuclear abnormalities (NAs), such as nuclear buds (NBUDs), binucleated cells (BNs), pyknotic nuclei (PNs), karyorrhexis (KX), karyolysis (KL), and abnormally condensed chromatin (CC). Assays were performed on samples from four populations located alongside the Santiago River that are under chronic exposure to heavy metals and other metals (HMMs), and the results were compared with those of a population without exposure to HMMs. The exposed group showed increased frequencies of NAs (KX, CC, and KL), which are associated with cytotoxic damage, and NBUDs, which are associated with genotoxic damage. Increased frequencies of NBUDs and CC were observed in subjects from El Salto/Juanacatlán, Ocotlán, and Paso de Guadalupe, and an increase in KX frequency was observed in subjects from El Salto/Juanacatlán. Significant differences in KL frequency were observed in subjects from La Barca, El Salto/Juanacatlán, Paso de Guadalupe, and Ocotlán. Predictors for increased development of MNs and NBUDs were high concentrations of Al, Zn, and Cu. In conclusion, chronic exposure to HMMs, especially Al, Cu, and Zn, in the studied population could be related to increased frequencies of NAs, such as NBUDs, KX, CC, and KL, in the buccal mucosa cells.

Anatomical segmentation of the human medial prefrontal cortex.

The medial prefrontal areas 32, 24, 14, and 25 (mPFC) form part of the limbic memory system, but little is known about their functional specialization in humans. To add anatomical precision to structural and functional magnetic resonance imaging (MRI) data, we aimed to identify these mPFC subareas in histological preparations of human brain tissue, determine sulci most consistently related with mPFC areal boundaries, and use these sulci to delineate mPFC areas in MRIs. To achieve this, we obtained three-dimensional MRI data from 11 ex vivo hemispheres and processed them for cyto- and myelo-architectonic analysis. The architectonic boundaries of mPFC areas were identified in histology and cortical surface length and volumes were measured. Unfolded maps of histologically determined boundaries were generated to identify the association of mPFC areal boundaries with sulci across cases. This analysis showed that cingulate and superior rostral were the sulci most consistently related to mPFC areal boundaries. Based on presence/absence and anastomosis between such sulci, 6 sulci patterns in the 11 hemispheres were found. A further analysis of 102 hemispheres of in vivo MRI scans (N = 51 males, mean ± SD 24.1 ± 3.1 years of age) showed similar sulci patterns, which allowed us to delineate the mFPC areas in them. The volumes of mPFC areas across histological, ex vivo and in vivo MRI delineations were comparable and probabilistic maps generated from the MRIs of the102 hemispheres. Probabilistic maps of mPFC areas were registered to MNI space and are available for regional analysis of functional magnetic resonance imaging data.

Nuclear abnormalities in buccal mucosa cells of patients with type I and II diabetes treated with folic acid.

Diabetes mellitus (DM) is characterized by high blood glucose. Excessive production of free radicals may cause oxidative damage to DNA and other molecules, leading to complications of the disease. It may be possible to delay or reduce such damage by administration of antioxidants such as folic acid (FA). The objective of this study was to determine the effect of FA on nuclear abnormalities (NAs) in the oral mucosa of patients with DM. NAs (micronucleated cells, binucleated cells, pyknotic nuclei, karyorrhexis, karyolysis, abnormally condensed chromatin, and nuclear buds) were analyzed in 2000 cells from 45 healthy individuals (control group) and 55 patients with controlled or uncontrolled type I or II DM; 35 patients in the latter group were treated with FA. Samples were taken from the FA group before and after treatment. An increased rate of NAs was found in patients with DM in comparison with that of the control group (P<0.001). FA supplementation in patients with DM reduced the frequency of NAs (20.4 ± 8.0 before treatment vs. 10.5 ± 5.2 after treatment; P<0.001). The type I and type II DM and controlled and uncontrolled DM subgroups were analyzed in terms of sex, age, and smoking habit. The significantly reduced frequencies of buccal mucosa cells with micronuclei, binucleation, pyknosis, karyorrhexis, karyorrhexis+abnormally condensed chromatin, karyolysis, and nuclear buds produced by FA supplementation in DM patients (P<0.02) are consistent with the idea that free radicals are responsible for the increased frequency of NAs in DM patients.

Are white-rot fungi a real biotechnological option for the improvement of environmental health?

The use of white-rot fungi as a biotechnological tool for cleaning the environment of recalcitrant pollutants has been under evaluation for several years. However, it is still not possible to find sufficiently detailed investigations of this subject to conclude that these fungi can decontaminate the environment. In the present review, we have summarized and discussed evidence about the potential of white-rot fungi to degrade such pollutants as polycyclic aromatic hydrocarbons, dyes or antibiotics as an example of the complex structures that these microorganisms can attack. This review also discusses field experiment results and limitations of white-rot fungi trials from contaminated sites. Moreover, the use of catabolic potential of white-rot fungi in biopurification systems (biobeds) is also discussed. The current status and future perspectives of white-rot fungi, as a viable biotechnological alternative for improvement of environmental health are noted.

Treatment with pirfenidone for two years decreases fibrosis, cytokine levels and enhances CB2 gene expression in patients with chronic hepatitis C.

BACKGROUND: The aim of this study was to assess whether two-years treatment with Pirfenidone influences necroinflammation, fibrosis and steatosis, serum levels of TGF-ß1, IL-6, TNF-α and CB1 and CB2 gene expression, in patients with chronic hepatitis C (CHC). METHODS: Twenty-eight patients out of 34 with CHC virus infection were enrolled in the study and received Pirfenidone (1200 mg/day) for 24 months. Six patients dropped out after 12 months of PFD. Liver biopsies and serum samples were obtained at the beginning and end of treatment. Modified HAI was calculated. CB1 and CB2 gene expression was correlated with fibrosis progression alongside with necroinflammation and steatosis. TGF-ß1, IL-6, TNF-α and liver transaminases were measured in serum at two-months intervals. HCV genotype and viral load were also assessed. Quality of life was evaluated by SF36 questionnaires and the prognosis of disease was assessed with Child-Pugh score. The Wilcoxon test matched-pair signed ranks were used to analyze the outcomes. RESULTS: Intention to treat analyses were performed for biochemistry and clinical parameters. At the end of treatment, necroinflammation grading was reduced in an average of 3.2 points in 82% of patients (p < 0.05) and Ishak's fibrosis stage decreased 2-points average in 67% of patients (p < 0.05). Steatosis decreased in 61% of patients. IL-6 and TGF-ß1 serum levels decreased significantly in 93% and 67% of patients (p < 0.05), respectively, while TNF-α diminished in 47% of patients. ALT and AST tended to normalize in 81% of patients; CB2 mRNA levels increased in 86% and CB1 expression diminished in 29% of patients. Both, quality of life and Child-Pugh score improvements were reported in all patients. CONCLUSIONS: Pirfenidone for two years benefits CHC patients and improves inflammation, fibrosis and steatosis in higher number of patients as previously shown for 12-months treatment with PFD. Additionally, PFD improved TGFß1 and IL-6 levels and diminished liver expression of anti-fibrogenic receptor CB2. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02161952. Protocol Registration Date: 06/11/2014.

Clitoral anesthesia disrupts paced copulation in the female rat.

Clitoral stimulation produced by sexual contact with a partner or during manual stimulation is associated with pleasure in humans, and produces conditioned place preference in rats. The present experiment investigated the effect of blocking genitosensory stimulation of the clitoris with lidocaine during copulation in female rats on a measure of female sexual motivation: pacing behavior. Sexually naïve, ovariectomized female rats were treated with 10µg estradiol benzoate 48h and 500µg progesterone 4h prior to a 30-min copulatory trial with a sexually vigorous stimulus male scheduled every 4days. A total of 10 copulatory sessions were divided into two phases of 5 trails each. In the first phase, females received an injection (0.05ml) of either 2% lidocaine, saline, or no injection to the clitoral sheath under isoflurane anesthesia immediately prior to the start of a copulatory session, and were then placed on one side of a paced mating chamber and allowed to copulate for 30min. In the second phase, females previously injected with lidocaine were switched to saline and vice versa, and the no injection group remained the same. Variables measured included overall time spent with the males, number of solicitations, contact-return latencies following male mounts, intromissions, and ejaculations; the frequency of entrances and exits from the male chamber, and frequency of mounts, intromissions, ejaculations. Sexual behavior was examined at session 1, session 5, and session 10. At test 5, females that received LID had a greater number of entrances/exits but spent significantly less time in the presence of the male during the copulatory bout than CNTL animals. These females also displayed a trend for longer contact return latencies s after ejaculations than VEH and CNTL groups. On session 10, females that received LID and subsequently switched to VEH treatment no longer differed from controls in entrance/exit numbers, time spent with males or ejaculation contact return latency. They did however, receive a greater number of intromissions and displayed shorter inter intromission intervals compared to CNTLs. We suggest that clitoral stimulation in the rat serves as both a reward signal and may contribute to the detection of differences in copulatory stimuli that are critical to pacing and potentially, the initiation of pregnancy.

Sexual experience blocks the ability of clitoral stimulation to induce a conditioned place preference in the rat.

We have previously established the rewarding value of clitoral stimulation (CLS) through the demonstration that manual, distributed, CLS induces a significant conditioned place preference (CPP) and conditioned partner preference in naïve, hormonally primed and non-hormonally primed rats. The present experiment asks whether previous sexual experience might inhibit the ability of clitoral stimulation to induce a conditioned place preference. Female Long-Evans rats were ovariectomized and treated with 10 µg of estradiol benzoate (EB) 48 h and 500 µg of progesterone (P) 4h prior to receiving either 0, 1, or 5 consecutive copulatory sessions with a sexually vigorous male. Each copulatory session ended when females received at least 1 ejaculation. Females then experienced 10 alternating trials of distributed CLS or no CLS paired with one side of a non-biased CPP box under the same hormone-priming regimen. Females that experienced 5 consecutive copulatory sessions did not develop a significant place preference indicated by both a preference score (the proportion of time spent in the reinforced chamber) and a difference score (time in the non-reinforced chamber minus the time in the reinforced chamber) compared prior to and following the 10 conditioning trials. This suggests that repeated copulatory experience might induce a desensitization of the genitosensory circuit since copulation includes both clitoral, and vaginocervical stimulation from mounts plus intromissions. Alternatively, repeated sexual experience prior to conditioning may generate a UCS pre-exposure effect that cannot be altered when manual clitoral stimulation is paired with a new environment.

Acutely applied MDMA enhances long-term potentiation in rat hippocampus involving D1/D5 and 5-HT2 receptors through a polysynaptic mechanism.

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a drug of abuse that induces learning and memory deficit. However, there are no experimental data that correlate the behavioral evidence with models of synaptic plasticity such as long-term potentiation (LTP) or long-term depression (LTD). Using field potential recordings in rat hippocampal slices of young rats, we found that acute application of MDMA enhances LTP in CA3-CA1 synapses without affecting LTD. Using specific antagonists and paired-pulse facilitation protocols we observed that the MDMA-dependent increase of LTP involves presynaptic 5-HT2 serotonin receptors and postsynaptic D1/D5 dopamine receptors. In addition, the inhibition of PKA suppresses the MDMA-dependent increase in LTP, suggesting that dopamine receptor agonism activates cAMP-dependent intracellular pathways. We propose that MDMA exerts its LTP-altering effect involving a polysynaptic interaction between serotonergic and dopaminergic systems in hippocampal synapses. Our results are compatible with the view that the alterations in hippocampal LTP could be responsible for MDMA-dependent cognitive deficits observed in humans and animals.

Trastornos del sueño en los pacientes críticos / Sleep disorders in critically ill patients

Sleep disorders are common in critically ill patients, and its consequences still insufficiently clarified. An environment with multiple noxious stimuli, light and hearing, admission for severe acute illness with multisystem disease, and the need for drugs that can disrupt sleep physiology, lead to this situation. We will review the epidemiology and risk factors for these disorders, and its possible consequences. Finally we discuss potential strategies for prevention of sleep disorders in this patient population.

Long-term use of everolimus in lung transplant patients.

Everolimus has been successfully used in solid organ transplantation, especially of the heart and kidney, but much less often in lung transplantation. The aim of this study was to evaluate the efficacy and safety of long-term use of everolimus in lung transplantation in Chile. We retrospectively analyzed patients receiving everolimus between 2005 and 2010 in terms of indication, lung and kidney function, rejection episodes, infections, malignancy appearance, and adverse events. Ten of 60 lung transplant recipients were converted to everolimus (16%) at some point after transplantation: four due to calcineurin inhibitor nephropathy (RD); four bronchiolitis obliterans syndrome (BOS); one lymphoma; and one, graft pulmonary fibrosis. Among patients with RD, at a mean follow-up of 25 months (range = 3-60), renal function remained stable with baseline of 42.7 mL/min and final creatinine clearance of 45.7 mL/min; lung function did not deteriorate. BOS patients, with an average of 30 months' follow-up (range = 12-48), showed baseline forced expiratory volume in the first second of 49% (r: 41-57) without variation in three patients, but with a decrease in another one after 12 months. One patient discontinued everolimus due to intolerance after 1 year. Two patients developed neoplasias: skin cancer and multiple myeloma. There were 14 infection episodes in seven patients, including 10 involving the respiratory tract infections. Only one patient developed dyslipidemia after everolimus initiation. Two patients died: one due to multiple myeloma and another to BOS. There was no rejection episode. Everolimus was effective and safe when used in combination with low doses of calcineurin inhibitor over long-term follow-up of lung transplant patients.

Malignancy development in lung transplant patients.

INTRODUCTION: The most common neoplasias among transplant patients are skin cancers and lymphoproliferative disorders. OBJECTIVE: To characterize lung transplanted recipients who developed malignancies. METHODS: A retrospective analysis of clinical records of our patients. RESULTS: Seven patients developed malignancies: skin cancer (n = 5; 71%), and adenocarcinomas of prostatic, gastric, and lung (n = 1 each). One patient developed two hematologic malignancies: T-cell lymphoma and multiple myeloma. Among five patients who died (71%), 3 were due to advanced neoplasia. The mean presentation time was 4.3 years. Skin cancers were resected. The patient with lung adenocarcinoma developed pleural involvement and died. The patient with T-cell lymphoma was treated, but succumbed afterward due to multiple myeloma. The patient with gastric adenocarcinoma died at 3 months after the diagnosis, and the patient with prostate cancer underwent surgery without disease recurrence. CONCLUSION: Malignancies are a late complication of transplant recipients that require a prompt diagnosis and treatment to improve outcomes.

Estrés oxidativo en el trastorno afectivo bipolar / Oxidative stress in bipolar disorder

The pathogenesis of psychiatric disorders have not been fully unravelled. Several theories have been proposed, from those focused on psychosocial aspects to those with a biological basis. Mood disorders are a group of psychiatric disorders with a chronic and recurrent fashion. Therefore these disorders could have molecular etiological basis prompted to be described and typified and currently there is a growing interest to unravel the role of oxidative damage in bipolar disorder and how it could be compensated by the enzymatic antioxidant system. The assessment of both oxidative damage and antioxidant enzyme system s allow us propose some theories that might explain a possible etiologic origin of this disease. Nevertheless, no consensus exists about this proposal. Published studies how an increased oxidative damage in cells from bipolar cases. It produces lipid and protein alterations that could potentially lead to DNA damage, and therefore their repair mechanisms.

La etiopatogenia de los diferentes trastornos psiquiátricos no está completamente dilucidada, se han propuesto diversas teorías que se basan en múltiples enfoques que van desde aquellos centrados en aspectos psicosociales hasta los netamente biologicistas. Los trastornos del ánimo no han estado ajenos a estos estudios, entre ellos el trastorno bipolar se muestra cómo uno de los cuadros que por su carácter crónico y recurrente podría tener su génesis a nivel de alteraciones moleculares posibles de ser definidas y tipificadas. En el último tiempo se ha prestado una importancia creciente a la determinación del rol del daño oxidativo en el trastorno bipolar y de cómo dichas alteraciones generan cambios compensatorios en los sistemas enzimáticos antioxidantes. Su cuantificación ha permitido formular algunas teorías para explicar un posible origen de éste cuadro, sin embargo, hasta la fecha aun no existe un consenso al respecto. Los estudios existentes demuestran categóricamente que existe en pacientes bipolares hay un claro aumento del daño oxidativo, provocando alteración en lípidos y proteínas, que pueden llevar potencialmente a una alteración sobre el ADN y sus mecanismos de reparación.

Everolimus in lung transplantation in Chile.

UNLABELLED: Everolimus has shown good results in kidney and heart transplantation, achieving low rates of rejection, of infections, and of tumors compared with calcineurin inhibitors (CNI). Some publications have shown beneficial effects in bronchiolitis obliterans syndrome (BOS). We have presented herein the initial experience with everolimus among lung allograft recipients in Chile. METHODS: We retrospectively evaluated, charts of lung-transplanted patients who used everolimus (Certican) based on 2 years' follow-up, evaluating the indication for therapy; blood levels, rejection episodes, lung and kidney function, and side effects. RESULTS: Eight of 55 lung transplantation patients were switched to everolimus, targeting a (mean drug level of 4.2 ng/dL), in combination with low-dose tacrolimus (mean levels 5.5 ng/dL) and steroids. The Reasons for conversion were: CNI nephropathy (n = 3), BOS (n = 4), and lymphoma (n = 1). In patients with renal dysfunction, serum creatinine had risen from 1.1 to 1.8 mg/dl, but at 3 months after everolimus conversion, they had returned to baseline values, maintaining that level for at least 2 years' follow-up. Patients with BOS had decreased their ventricular ejection fraction (VEF(1)) by 50%. Using everolimus, they maintained that VEF(1) with little improvement. The patient with lymphoma died 11 months after conversion. No patient experienced a rejection episode, and they suffered from fewer infections than the other lung allograft recipients. There were no adverse events related to everolimus, but one patient discontinued the drug after 1 year owing to intolerance. CONCLUSION: Everolimus was effective to reverse CNI renal dysfunction in lung transplantation patients, possibly retarding the progression of BOS, without side effects over a 2-year follow-up.