PDA-Based Glyconanomicelles for Hepatocellular Carcinoma Cells Active Targeting Via Mannose and Asialoglycoprotein Receptors.

Hepatocellular carcinoma (HCC) is the sixth most common neoplasia and the fourth most common cause of cancer-related mortality worldwide. Sorafenib is the first-line molecular therapy for patients in an advanced stage of HCC. However, the recommended clinical dose of Sorafenib is associated with several complications, which derive from its lack of cell specificity and its very low water solubility. To circumvent these drawbacks, in the present study we developed two sugar-coated polydiacetylene-based nanomicelles-Sorafenib carriers targeting mannose and asialoglycoprotein receptors (MR and ASGPR, respectively). The strategies allowed the inducement of apoptosis and reduction of cell proliferation at a nanomolar, instead of micromolar, range in liver cancer cells. The study showed that, contrary to literature data, Sorafenib included into the pMicMan (Man = mannose) vector (targeting MR) is more efficient than pMicGal (Gal = galactose) (targeting ASGPR). Indeed, pMicMan increased the endosomal incorporation with an increased intracellular Sorafenib concentration that induced apoptosis and reduced cell proliferation at a low concentration range (10-20 nM).

Self-perceived health in psychiatrists and psychiatry trainees. The role of perfectionism and distress / Autopercepción de la salud en psiquiatras y residentes de psiquiatría. El rol del perfeccionismo y el distrés

Abstract Introduction Self-perceived health (SPH) is related to disease and well-being. Psychiatrists report burnout and mental disorders more frequently than other physicians, while personality traits related to perfectionism may influence the perception of well-being and health in these professionals. Objective To compare and determine the association between demographic variables, health conditions, perceived distress, perfectionism, and SPH. Method A cross-sectional, retrospective, comparative study was performed through an online survey. Psychiatrists and psychiatry trainees who were willing and able to participate were included. Demographic variables and self-reports of mental and physical conditions were examined. SPH was rated on a 10-point visual analogue scale and perfectionism through the Multidimensional Perfectionism Scale. Comparative analyses and multiple linear regression models were performed. Results Three hundred and thirty psychiatry trainees and 355 psychiatrists were recruited. Psychiatrists reported more physical conditions (32.4% vs. 15%, p < .001), distress (p < .001), and perfectionism (p < .001). Major depression and anxiety were present over 50% of all participants. A higher SPH was associated with being partnered and having higher distress levels in psychiatry trainees and with the absence of a physical health condition, less concern over errors, and higher personal standards in psychiatrists. Discussion and conclusion Self-oriented perfectionism may have a significant motivational component, accentuated by competitiveness and individualism. Being married and having higher levels of distress in psychiatry trainees appears to create a sense of satisfaction with achievements. The implementation of strategies to prioritize and meet goals is necessary to have an adequate work-life balance without affecting personal satisfaction or the sense of achievement.

Resumen Introducción La autopercepción de la salud (APS) se relaciona con enfermedad y bienestar. Los psiquiatras reportan desgaste emocional y trastornos mentales con mayor frecuencia que otros médicos. El perfeccionismo puede influir en la percepción de la salud en estos profesionistas. Objetivo Comparar y determinar la asociación de variables demográficas, condiciones de salud, distrés y perfeccionismo con la APS. Método Se realizó un estudio transversal, retrospectivo y comparativo mediante una encuesta en línea. Se incluyeron psiquiatras y residentes de psiquiatría que participaron voluntariamente. Se registraron variables demográficas, enfermedades médicas y psiquiátricas (autorreporte). La APS se evaluó con una escala análogo-visual de 10 puntos y el perfeccionismo con la Escala Multidimensional de Perfeccionismo. Se realizaron análisis comparativos y modelos de regresión lineal múltiple. Resultados Se reclutaron 330 residentes y 355 psiquiatras. Los psiquiatras reportaron más enfermedades físicas (32.4% vs. 15%, p < .001), distrés (p < .001) y perfeccionismo (p < .001). Más del 50% de los participantes reportaron ansiedad y depresión. Una mayor APS se asoció con tener pareja y mayor distrés en los residentes, y con la ausencia de una enfermedad física, menor preocupación por errores y mayores estándares personales en los psiquiatras. Discusión y conclusión El perfeccionismo orientado hacía sí mismo puede tener un componente motivacional acentuado por la competitividad y el individualismo. Tener una pareja y presentar mayor distrés en los residentes pudiera crear una sensación de satisfacción por logros. La creación de estrategias para priorizar y alcanzar objetivos es necesaria para tener un equilibrio de vida sin afectar la satisfacción personal y la sensación de logro.

Integrated molecular signaling involving mitochondrial dysfunction and alteration of cell metabolism induced by tyrosine kinase inhibitors in cancer.

Cancer cells have unlimited replicative potential, insensitivity to growth-inhibitory signals, evasion of apoptosis, cellular stress, and sustained angiogenesis, invasiveness and metastatic potential. Cancer cells adequately adapt cell metabolism and integrate several intracellular and redox signaling to promote cell survival in an inflammatory and hypoxic microenvironment in order to maintain/expand tumor phenotype. The administration of tyrosine kinase inhibitor (TKI) constitutes the recommended therapeutic strategy in different malignancies at advanced stages. There are important interrelationships between cell stress, redox status, mitochondrial function, metabolism and cellular signaling pathways leading to cell survival/death. The induction of apoptosis and cell cycle arrest widely related to the antitumoral properties of TKIs result from tightly controlled events involving different cellular compartments and signaling pathways. The aim of the present review is to update the most relevant studies dealing with the impact of TKI treatment on cell function. The induction of endoplasmic reticulum (ER) stress and Ca2+ disturbances, leading to alteration of mitochondrial function, redox status and phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt)-mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) signaling pathways that involve cell metabolism reprogramming in cancer cells will be covered. Emphasis will be given to studies that identify key components of the integrated molecular pattern including receptor tyrosine kinase (RTK) downstream signaling, cell death and mitochondria-related events that appear to be involved in the resistance of cancer cells to TKI treatments.

Differential effectiveness of tyrosine kinase inhibitors in 2D/3D culture according to cell differentiation, p53 status and mitochondrial respiration in liver cancer cells.

Sorafenib and Regorafenib are the recommended first- and second-line therapies in patients with advanced hepatocellular carcinoma (HCC). Lenvatinib and Cabozantinib have shown non-inferior antitumoral activities compared with the corresponding recommended therapies. The clinical trials have established recommended doses for each treatment that lead different blood concentrations in patients for Sorafenib (10 µM), Regorafenib (1 µM), Lenvatinib (0.1 µM), and Cabozantinib (1 µM). However, very low response rates are observed in patients attributed to intrinsic resistances or upregulation of survival signaling. The aim of the study was the comparative dose-response analysis of the drugs (0-100 µM) in well-differentiated (HepG2, Hep3B, and Huh7), moderately (SNU423), and poorly (SNU449) differentiated liver cancer cells in 2D/3D cultures. Cells harbors wild-type p53 (HepG2), non-sense p53 mutation (Hep3B), inframe p53 gene deletion (SNU423), and p53 point mutation (Huh7 and SNU449). The administration of regular used in vitro dose (10 µM) in 3D and 2D cultures, as well as the dose-response analysis in 2D cultures showed Sorafenib and Regorafenib were increasingly effective in reducing cell proliferation, and inducing apoptosis in well-differentiated and expressing wild-type p53 in HCC cells. Lenvatinib and Cabozantinib were particularly effective in moderately to poorly differentiated cells with mutated or lacking p53 that have lower basal oxygen consumption rate (OCR), ATP, and maximal respiration capacity than observed in differentiated HCC cells. Sorafenib and Regorafenib downregulated, and Lenvatinib and Cabozantinib upregulated epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor receptor (c-Met) in HepG2 cells. Conclusions: Sorafenib and Regorafenib were especially active in well-differentiated cells, with wild-type p53 and increased mitochondrial respiration. By contrast, Lenvatinib and Cabozantinib appeared more effective in moderately to poorly differentiated cells with mutated p53 and low mitochondrial respiration. The development of strategies that allow us to deliver increased doses in tumors might potentially enhance the effectiveness of the treatments.

Molecular Pathways Leading to Induction of Cell Death and Anti-Proliferative Properties by Tacrolimus and mTOR Inhibitors in Liver Cancer Cells.

BACKGROUND/AIMS: Orthotopic liver transplantation (OLT) is the recommended treatment for patients at early stages of hepatocarcinoma (HCC) with portal hypertension and/or increased bilirubinemia, but without vascular-associated diseases. Tumor recurrence, which is the main drawback for the survival of patients submitted to OLT for HCC, has been related to tumor-related variables and the immunosuppressive therapies. We have previously shown that Tacrolimus (FK506) exerts a more potent pro-apoptotic and anti-proliferative effects than the mammalian target of rapamycin (mTOR) inhibitors (Sirolimus and Everolimus) in liver cancer cells. This study identified the role of the immunosuppressant partners such as FK506-binding proteins (FKBPs) in the induction of cell death and arrest of cell proliferation by immunosuppressants in two representative liver cancer cells. METHODS: The regulation of endoplasmic reticulum (ER) stress, apoptosis/autophagy, cell proliferation, and FKBPs expression was determined in Tacrolimus-, Sirolimus- and Everolimus-treated primary human hepatocytes, and hepatoma HepG2 and Huh7 cell lines. The functional repercussion of FKBPs on cell death and proliferation was also addressed using the siRNA technology. The assessed antitumoral properties of the immunosuppressants were associated to microRNAs (miRNAs) pattern. RESULTS: The enhanced pro-apoptotic and anti-proliferative properties of Tacrolimus versus mTOR inhibitors were associated with increased protein kinase RNA-like endoplasmic reticulum kinase (PERK)-related ER stress, Ser15P-p53/p53 ratio and p21 protein expression that may counterbalance the risk of proliferative upregulation caused by enhanced Thr172P-Cdk4/Cdk4 activation in liver cancer cells. The inhibition of the mTOR pathway by Sirolimus and Everolimus was related to an induction of autophagy; and at a high dose, these drugs impaired translation likely at a very early step of the elongation phase. Tacrolimus and mTOR inhibitors increased the protein expression of FKBP12 and FKBP51 that appeared to play pro-survival role. Interestingly, the administration of immunosuppressants yields a specific pattern of miRNAs. Tacrolimus and mTOR inhibitors decreased miR-92a-1-5p, miR-197-3p, miR-483-3p and miR-720, and increased miR-22-3p, miR-376a-3p, miR-663b, miR-886-5p, miR-1300 and miR-1303 expressions in HepG2 cells. CONCLUSION: The more potent pro-apoptotic and anti-proliferative properties of Tacrolimus versus mTOR inhibitors were associated with an increased activation of PERK and p53 signaling, and p21 protein expression. FKBP12 and FKBP51 appeared to be the most relevant partners of Tacrolimus and mTOR inhibitors exerting a pro-survival effect in HepG2 cells. The observed effects of immunosuppressants were related to a specific miRNA signature in liver cancer cells.

Downregulation of thioredoxin-1-dependent CD95 S-nitrosation by Sorafenib reduces liver cancer.

Hepatocellular carcinoma (HCC) represents 80% of the primary hepatic neoplasms. It is the sixth most frequent neoplasm, the fourth cause of cancer-related death, and 7% of registered malignancies. Sorafenib is the first line molecular targeted therapy for patients in advanced stage of HCC. The present study shows that Sorafenib exerts free radical scavenging properties associated with the downregulation of nuclear factor E2-related factor 2 (Nrf2)-regulated thioredoxin 1 (Trx1) expression in liver cancer cells. The experimental downregulation and/or overexpression strategies showed that Trx1 induced activation of nitric oxide synthase (NOS) type 3 (NOS3) and S-nitrosation (SNO) of CD95 receptor leading to an increase of caspase-8 activity and cell proliferation, as well as reduction of caspase-3 activity in liver cancer cells. In addition, Sorafenib transiently increased mRNA expression and activity of S-nitrosoglutathione reductase (GSNOR) in HepG2 cells. Different experimental models of hepatocarcinogenesis based on the subcutaneous implantation of HepG2 cells in nude mice, as well as the induction of HCC by diethylnitrosamine (DEN) confirmed the relevance of Trx1 downregulation during the proapoptotic and antiproliferative properties induced by Sorafenib. In conclusion, the induction of apoptosis and antiproliferative properties by Sorafenib were related to Trx1 downregulation that appeared to play a relevant role on SNO of NOS3 and CD95 in HepG2 cells. The transient increase of GSNOR might also participate in the deactivation of CD95-dependent proliferative signaling in liver cancer cells.

Dermatofitos y hongos levaduriformes causantes de micosis superficiales de piel lampiña en un centro dermatológico, San Lorenzo-Paraguay / Dermatophytes and levaduriform fungi causing superficial mycoses of skin in a dermatological center, San Lorenzo-Paraguay

Introducción: las micosis superficiales o dermatomicosis se encuentran entre las enfermedades infecciosas de piel más comunes. Se localizan en las capas superficiales de la piel y sus anexos (pelo y uñas), por esta razón son motivo de consulta dermatológica. De estas micosis, las dermatofitosis, las malasseziosis y las candidiasis cutáneas son las más frecuentes. Objetivo: describir las características epidemiológicas de las micosis superficiales de piel lampiña. Metodología: estudio observacional, retrospectivo y de corte transverso, donde se analizaron fichas epidemiológicas de pacientes que acudieron al Centro de Especialidades Dermatológicas en el periodo comprendido entre julio del 2017 hasta agosto del 2019, con diagnóstico presuntivo de micosis superficiales de piel lampiña. Resultados: se observaron 341 casos de micosis superficiales de piel lampiña. Entre los agentes causales, los dermatofitos fueron los responsables del 56 % (190/341) de los casos; Malassezia spp. 42 % (142/341) y Candida spp. 2 % 9/341. Se observaron 3 casos de micosis mixtas, donde Candida spp. y dermatofitos fueron los agentes causales. Conclusión: entre las micosis superficiales que afectan piel lampiña, se encuentran en primer lugar los dermatofitos seguidos por las malasseziosis. Este reporte constituye un aporte importante para el conocimiento de la epidemiología de las micosis superficiales en nuestro país.

Introduction: superficial mycoses or dermatomycosis are among the most common skin infectious diseases. These are located in the superficial layers of the skin and its annexes (hair and nails), for this reason it´s a frecuent cause of medical consult. Of these mycoses, dermatophytosis, malasseziosis and cutaneous candidiasis are the most frequent. Objectives: describe the epidemiological characteristics of superficial mycoses of skin. Methodology: observational, retrospective and cross-sectional study, where epidemiological records of patients who were attended at the Dermatological Specialties Center were analyzed in the period from July 2017 to August 2019, with presumptive diagnosis of superficial mycoses of skin. Results: 341 cases of superficial mycosis of skin were observed. Among the causative agents, dermatophytes were responsible for 56 % (190/341) of the cases; Malassezia sp. 42 % (142/341) and Candida sp. 2 % (9/341). Three cases of mixed mycosis were observed; Candida spp. and Dermatophytes were the causative agents. Conclusion: among the superficial mycoses of skin, dermatophytes followed by malaseziosis are in the first places. This report constitutes an important contribution to the knowledge of the epidemiology of superficial mycoses in our country.

Tiña de la cabeza: características epidemiológicas de 132 casos / Tinea capitis: epidemiological characteristics of 132 cases

Introducción: la tiña de la cabeza es una micosis superficial producida por dermatofitos, más común en niños y excepcional en los adultos. Objetivo: conocer las características epidemiológicas y micológicas de la tiña de la cabeza en pacientes que acudieron al Centro de Especialidades Dermatológicas en la ciudad de San Lorenzo. Metodología: estudio observacional retrospectivo de corte transverso, donde se analizaron fichas y registros de todos los pacientes con sospecha clínica de tiña de la cabeza remitidos al laboratorio del Centro de Especialidades Dermatológicas en el periodo julio 2017 - agosto 2019. Los pacientes fueron sometidos a estudios micológicos directos y cultivos para la confirmación del diagnóstico e identificación del agente etiológico. Se consideró el sexo, edad, residencia, posesión de mascotas domésticas y agente etiológico aislado. Resultados: se estudiaron 132 pacientes con diagnóstico de tiña de la cabeza, 69 (52.3 %) varones y 63 (47.7 %) mujeres. La edad de presentación fue desde 1 año hasta 14 años, con una media de 5 años. El principal agente etiológico aislado fue Microsporum canis 99/132 (75 %) seguido de Trichophyton tonsurans 29/132 (22 %). Conclusiones: los hallazgos epidemiológicos obtenidos coinciden con otros trabajos científicos, destacándose M. canis y T. tonsurans como los principales agentes etiológicos.

Introduction: tinea capitis is a superficial mycosis produced by dermatophytes, more common in children and exceptional in adults. Objectives: to know the epidemiological and mycological characteristics of tinea capitis in patients who were attended in the Dermatological Specialties Center of San Lorenzo. Methodology: retrospective, observational and cross-sectional study, in which the files and records of all patients with clinical suspicion of tinea capitis, referred to the laboratory of the Dermatological Specialties Center in the period july 2017 - august 2019 were analyzed. The patients underwent direct mycological studies and cultures for confirmation of the diagnosis and identification of the etiologic agent. The sex, age, residence, possession of domestic pets and isolated etiological agent were considered. Results: 132 patients with a diagnosis of tinea capitis, 69 (52.3 %) men and 63 (47.7 %) women were studied. The age of presentation was from 1 year to 14 years, with an average of 5 years. The main etiological agent isolated was Microsporum canis 99/132 (75 %) followed by Trichophyton tonsurans 29/132 (22 %). Conclusions: the epidemiological findings obtained are agree with other scientific studies, highlighting M. canis and T. tonsurans as the main etiological agents.

Características epidemiológicas de las onicomicosis en la consulta dermatológica / Epidemiological characteristics of onychomycosis in dermatological consultation

Introducción: la onicomicosis es la infección del aparato ungueal causada por hongos dermatofitos, no dermatofitos o levaduras. Constituye una enfermedad frecuente en la práctica médica, con impacto considerable en lo emocional, social, laboral y económico. Objetivo: describir las características epidemiológicas de la onicomicosis en pacientes que consultaron en un servicio dermatológico. Materiales y Métodos: estudio observacional retrospectivo de corte transverso, donde se analizaron fichas epidemiológicas de pacientes que acudieron al servicio de Dermatología del Hospital Nacional de Itauguá y el Centro de Especialidades Dermatológicas en el periodo comprendido entre julio del 2016 a agosto del 2019. Resultados: se analizaron 464 pacientes con onicomicosis. El cultivo fue positivo en el 83 % (385/464) de los casos. Se observó preferentemente en mujeres 72 % (276/385), franja etaria entre los 31 y 65 años 70,1 % (270/385), de procedencia urbana 76 % (292/385) y actividad quehaceres domésticos 41 % (157/385). El 23 % (87/385) presentó una o más comorbilidades asociadas a la aparición de onicomicosis, siendo la diabetes en el 70 % (61/385) de éstas. La localización fue en uñas de pies en 58,2 % (259/ 400), uña de manos en 31,2 % (141/400) y en el 10,1 % (45/400) de los casos se observó onicomicosis en ambas localizaciones. Los géneros aislados con mayor frecuencia fueron Trichophyton y Candida, y las especies fueron T. rubrum y Candida parapsilosis. En las onicomicosis de uñas de los pies se aislaron dermatofitos en un 63,7 % (165/259), mientras que en uñas de las manos se aislaron Candida spp. en el 77,3 % (107/141). Conclusión: la onicomicosis produce una afectación que se observa mayoritariamente en pacientes adultos, generalmente mujeres que se dedican a los quehaceres domésticos, procedentes de áreas urbanas, con afectación principal de las uñas de los pies, siendo los agentes causales más frecuentes, T. rubrum y C. parapsilosis.

Introduction: onychomycosis is an infection of nails caused by dermatophyte fungi, not dermatophytes or yeasts. It constitutes a frequent disease in medical practice, with considerable emotional, social, labor and economic impact. Objective: to describe the epidemiological characteristics of onychomycosis in patients who attended in a dermatological service. Materials and Methods: a retrospective cross-sectional observational study, where epidemiological records of patients who attended the Dermatology service of the Itauguá National Hospital and the Dermatological Specialties Center in the period from july 2016 to august 2019 were analyzed. Results: 464 patients with onychomycosis were analyzed. The culture was positive in 83 % (385/464) of the cases. It was mainly observed in women 72 % (276/385), age group was between 31 and 65 years 70.1 % (270/385), of urban areas 76 % (292/385) their activities were house as and household chores activity 41 % (157 / 385). 23 % (87/385) presented one or more comorbidities associated with onychomycosis, with diabetes in 70 % (61/385) of these. The location was in toenails in 58.2 % (259/400), fingernail in 31.2 % (141/400) and in 10.1 % (45/400) of the cases onychomycosis were observed in Both locations. The most frequently isolated genera were Trichophyton and Candida, and the species were T. rubrum and Candida parapsilosis. In the onychomycosis of the toenails, dermatophytes were isolated in 63.7 % (165/259), while in the fingernails, Candida spp. in 77.3 % (107/141). Conclusion: onychomycosis produces an affectation that is mostly adult patients, usually women who are engaged in household activities, from urban areas, the main involvement were toenails, being the most frequent agent isolated were, T. rubrum and C. parapsilosis.

Passive Sampling for Indoor and Outdoor Exposures to Chlorpyrifos, Azinphos-Methyl, and Oxygen Analogs in a Rural Agricultural Community.

BACKGROUND: Recent studies have highlighted the increased potency of oxygen analogs of organophosphorus pesticides. These pesticides and oxygen analogs have previously been identified in the atmosphere following spray applications in the states of California and Washington. OBJECTIVES: We used two passive sampling methods to measure levels of the ollowing organophosphorus pesticides: chlorpyrifos, azinphos-methyl, and their oxygen analogs at 14 farmworker and 9 non-farmworker households in an agricultural region of central Washington State in 2011. METHODS: The passive methods included polyurethane foam passive air samplers deployed outdoors and indoors and polypropylene deposition plates deployed indoors. We collected cumulative monthly samples during the pesticide application seasons and during the winter season as a control. RESULTS: Monthly outdoor air concentrations ranged from 9.2 to 199 ng/m3 for chlorpyrifos, 0.03 to 20 ng/m3 for chlorpyrifos-oxon, < LOD (limit of detection) to 7.3 ng/m3 for azinphos-methyl, and < LOD to 0.8 ng/m3 for azinphos-methyl-oxon. Samples from proximal households (≤ 250 m) had significantly higher outdoor air concentrations of chlorpyrifos, chlorpyrifos-oxon, and azinphos-methyl than did samples from nonproximal households (p ≤ 0.02). Overall, indoor air concentrations were lower than outdoors. For example, all outdoor air samples for chlorpyrifos and 97% of samples for azinphos-methyl were > LOD. Indoors, only 78% of air samples for chlorpyrifos and 35% of samples for azinphos-methyl were > LOD. Samples from farmworker households had higher indoor air concentrations of both pesticides than did samples from non-farmworker households. Mean indoor and outdoor air concentration ratios for chlorpyrifos and azinphos-methyl were 0.17 and 0.44, respectively. CONCLUSIONS: We identified higher levels in air and on surfaces at both proximal and farmworker households. Our findings further confirm the presence of pesticides and their oxygen analogs in air and highlight their potential for infiltration of indoor living environments. Citation: Gibbs JL, Yost MG, Negrete M, Fenske RA. 2017. Passive sampling for indoor and outdoor exposures to chlorpyrifos, azinphos-methyl, and oxygen analogs in a rural agricultural community. Environ Health Perspect 125:333-341; http://dx.doi.org/10.1289/EHP425.

Consideraciones clínicas y endocrinológicas en mujeres con trastorno bipolar / Clinical and endocrine considerations in bipolar women

El trastorno bipolar es una de las enfermedades mentales más discapacitantes. Existen diferencias en cuanto al tipo de episodios más frecuentes, la polaridad predominante y la frecuencia de comorbilidad según el sexo. En la mujer es importante considerar la etapa de vida reproductiva en que se encuentra, pues se sabe que puede influir en el curso de la enfermedad. Se ha informado una elevada comorbilidad del trastorno bipolar con trastorno disfórico premenstrual y una exacerbación de los síntomas en el período premenstrual en el 44% al 65%, que puede conducir a un peor curso de la enfermedad. El embarazo no parece incrementar la presencia de episodios de la enfermedad; sin embargo, el tratamiento se complica de forma importante, mientras que la suspensión de la medicación puede llevar a recaídas, el mantenerlo puede llevar a resultados obstétricos negativos, malformaciones congénitas e incluso alteraciones del neurodesarrollo. De tal manera que la evaluación de riesgo-beneficio en estas pacientes tiene que ser muy cautelosa. En el posparto, claramente se relaciona con un incremento en el riesgo de presentar algún episodio afectivo. Al llegar a la transición a la menopausia parecieran incrementarse los episodios de tipo depresivo. La relación entre el ciclo reproductivo y la presencia de episodios de enfermedad, así como los estudios en otras entidades psiquiátricas, han llevado a considerar que una relación entre las hormonas gonadales y los neurotransmisores podrían subyacer a esta entidad. En el presente artículo describimos algunas de las observaciones relacionadas con estrógenos, progesterona y sus metabolitos, testosterona y deshidroepiandrosterona

Bipolar disorder is one of the most disabling psychiatric illnesses. Some characteristics of the disorder vary with sex, such as predominant polarity, frequency and type of comorbidity, and type of episodes presented. In the case of bipolar women, it is important to consider reproductive events, due to their influence in the course of the disorder. High comorbidity of bipolar disorder and premenstrual dysphoric disorder with an exacerbation of symptoms in the premenstrual period has been reported in 44% to 65% which may lead to a worse disease course. In general, women with premenstrual symptom exacerbation show more affective - particularly depressive - episodes, more frequent relapses, and more severe symptomatology. Pregnancy does not appear to increase presence of bipolar episodes, but significantly complicates treatment. On the one hand, stopping the treatment, particularly abruptly, increases the risk of relapse; while on the other, the use of mood stabilizers represents a risk for the newborn. Poor neonatal outcomes, congenital malformations and neurodevelopment alterations in children of mothers exposed to mood stabilizers during pregnancy have been reported. So, a meticulous benefit-risk assessment should be carried out in pregnant bipolar women. In the postpartum period, a clearer relation with increased risk of affective episode has been observed; while the perimenopause increases depressive episodes. The inter-relation between reproductive cycle and bipolar episodes suggests that gonadal hormones are involved in their physio-pathology. Here we discuss some of the observations related to testosterone, dehydroepiandrosterone, estrogens, and progesterone

Alucinaciones visuales en pacientes con privación sensorial: ¿síndrome de Charles Bonnet? / Visual hallucinations in sensory deprived patients: Charles Bonnet syndrome?

Introducción: Existen pacientes que, después de lesiones cerebrales o periféricas, pierden alguna función sensorial, como la vista o el oído. Paradójicamente, después de perder esta función, presentan alucinaciones complejas relacionadas con la función perdida. Se sabe que este fenómeno puede presentarse ante lesiones en cualquier nivel de la vía visual, especialmente en el nivel de la retina.Objetivo: Revisar la bibliografía existente acerca del síndrome de Charles Bonnet para conocer los últimos avances con respecto a este fenómeno.Método: Se revisaron las bases de datos de PubMed y PsychInfo con las siguientes palabras clave: síndrome de Charles Bonnet; alucinaciones visuales; alucinosis peduncular; Charles Bonnet; privación sensorial. Se incluyeron aquellos artículos que efectivamente trataran del tema. Asimismo, se revisaron los textos clásicos referentes a este síndrome y los artículos mencionados en la bibliografía encontrada.Resultados: En el presente artículo se describe la historia del síndrome, el fenómeno clínico, los factores de riesgo, los criterios diagnósticos, los tratamientos empleados, otros fenómenos similares y las teorías propuestas para explicarlo.Discusión y conclusión: A la fecha continúan siendo controvertidos los criterios diagnósticos del síndrome de Charles Bonnet, en especial en lo referente a la preservación absoluta del insight como condición sine qua non. Descrito desde el siglo XVIII, el síndrome de Charles Bonnet corresponde al prototipo de alucinaciones visuales en pacientes con privación visual, si bien, de acuerdo con la presente revisión, la fenomenología de éste es bastante variada, siendo cuestionable si resulta también el prototipo de las alucinaciones con insight preservado.

Introduction: Some patients, after brain or peripheral injuries, lose a sensory function, such as sight or hearing, but paradoxically experience complex hallucinations related to the function they have lost. It is known that this phenomenon may appear with injuries at any level in the visual pathway, especially in the retina.Objective:To review the existent bibliography on the Charles Bonnet syndrome to establish the state of the art with regards to this phenomenon.Method: The databases PubMed and PsychInfo were searched for articles containing the following keywords: Charles Bonnet syndrome; visual hallucinations; peduncular hallucinosis; Charles Bonnet; sensory deprivation. We included those related to the subject. We also included the classic texts referring to this phenomenon and the articles mentioned in the literature.Results: In the present study, we describe the history of Charles Bonnet syndrome, clinical presentation, risk factors, diagnostic criteria, treatment employed, similar conditions and the theories seeking to explain it.Discussion and conclusion: To date, the diagnostic criteria for Charles Bonnet syndrome remain controversial, especially those concerning the absolute preservation of insight as a sine qua non factor to establish the diagnosis. Conclusion: Described since the 18th century, the Charles Bonnet syndrome corresponds to the prototype of visual hallucinations in patients with visual deprivation, although, according to the present review, its phenomenology is vast, remaining unclear if it corresponds to the prototype of hallucinations with preserved insight.

Encuesta a madres de recién nacidos internados en unidades de cuidados intensivos / Survey with mothers of Newborns admitted to Intensive care Units

Con el fin de clarificar el desarrollo vincular de la madre y sus hijo prematuro,detectar qué tipo de acciones del Servicio impiden o facilitan este desarrollo y averiguar cúales conductas de los padres son las más recurrentes,se realizó un encuesta que consistió en 31 preguntas con respuestas múltiples,que fue completada por las mamás de recién nacidpos pretérminos de menos de 2.000 gramos,transcurridos los 10 días de internación en las unidades de terapia intensiva.En la encuesta se interrogó sobre la concurrencia precoz de la mamá a los sectores de internación,la información recibida de los profesionales y la requerida por los padres,la predisposición a la lactanciamel contacto con las mamás con sus bebés y la frecuencia de visitas a la Unidad de Terapia Intensiva(UTI)La concurrencia de las mamñas a los sectores de internación,tanto en cesáreas como en partos vaginales,se produjo pasadas las primeras 24 horas,la información dada fue mejor recibida por los padres de recién nacidos(RN)de menos de 1250 gramos de peso,asimismo fue significativa la predisposición a amamantar de las madres de RN de menor peso al nacimiento

Luxación congénita de cadera y estacionalidad / Luxation coxae congenita and the seasons

En el presente trabajo, se analizan los datos concernientes a la incidencia de luxación congénita de cadera en el Hospital de Gineco-Obstetricia de la Unidad Médica Oblatos del Instituto Mexicano del Seguro Social en la ciudad de Guadalajara, Jalismo, México, correspondientes a un año. De acuerdo con los resultados, se obtiene una correlación inversa entre la temperatura y el número de casos, ambos estadísticamente significativos, demostrándose la estacionalidad de la luxación congénita de cadera

On the origin of ring chromosomes about an apparently non-deleted r(18) (p11q23)

Un cromosoma 18 en anillo sin pérdida aparente de cromatina fue observado en una paciente de 13 años de edad discretamente afectada. A partir de esta observación y de casos previamente descritos de cromosomas anulares se concluye que en algunas instancias un anillo podría resultar de una fusión anormal de ambos telómeros de una cromátida o de un cromosoma sin rompimiento ni deleción

Sindrome de Holt: una malformacion acral heterogenea autosomica dominante. / Holt's syndrome : dominant autosomic heterogeneous acral malformation

Se describe una familia que presento en un progenitor braquidactilia tipo "E" y en una hija polidactilia postaxial tipo "A".Esta observacion confirma una disostosis autosomica dominante heterogenea caracterizada por braquidactilia polisindactilia, descrita por Holt, cuyo nombre se propone para designar el sindrome

Estudios bioquimicos en una paciente con enfermedad de orina de jarabe de arce. / Biochemical studies in a patient with maple syrup urine disease

Se presenta los resultados de los estudios bioquimicos cualitativos y cuantitativos realizados en una familia (padres y 2 ninas) en la que el caso indice presento caracteristicas clinicas sugestivas de la enfermedad de orina de jarabe de arce (EOJA). Dos pruebas cualitativas para la deteccion de errores congenitos del metabolismo -cloruro ferrico y 2,4-dinitrofenilhidrazina- fueron positivas en el caso indice. Mediante metodos cromatograficos se encontraron cantidades elevadas de leucina, valina y acido alfa-cetoisocaproico en el plasma y la orina de la proposita. Los leucocitos perifericos de la paciente incubados en presencia de 1,C14-leucina, no fueron capaces de formar 14CO2.Estos resultados confirmaron el diagnostico y sugirieron la forma clasica de la enfermedad. Con la metodologia utilizada no fue posible identificar el estado heterozigoto em ambos padres.En la hermana de la proposita los resultados fueron normales. Se enfatiza la importancia de la deteccion temprana de esta enfermedad con en objeto de establecer la terapia adecuada y ofrecer asesoriamiento genetico