Serum testosterone levels in bipolar and unipolar depressed female patients and the role of medication status.

Objective: to compare testosterone levels between female depressed patients and female bipolar patients.Methods: Sixty-one female patients with major depressive disorder (MDD) (n = 23) or bipolar disorder (BD) (n = 38) between 18 and 45 years old were included in the study. Participants were evaluated during a depressive or manic episode with the Hamilton depression rating scale (HDRS) or Young mania rating scale (YMRS), respectively. No patients in the MDD group were taken valproate while in the BD group 14 (36.84%) were taken valproate. Total testosterone (TT) and free testosterone (FT) levels were quantified during the early follicular phase of the cycle, with radioimmunoassay or solid phase enzyme-linked immunoassay. Data were collected from May 2016 to February 2017.Results: Mean TT serum levels were significantly higher in BD patients in comparison to MDD patients. Although age and diagnosis were related to TT levels, however when we added valproate use in the analysis, only the relation between TT and valproate use remained significant.Conclusions: In this sample, TT levels were related to valproate use in patients with BD. More studies regarding the role of testosterone in affective symptoms should be conducted to clarify the relation between testosterone, affective disorders, and medication.KeypointsWe observed that testosterone levels were significant higher in bipolar women compared to women with MDD.The use of valproate could be associated with the testosterone levels in female patients with BD.Evaluation of women suffering BD should include a testosterone levels determination, particularly when they are taking valproate.

Overexpression of KIR inhibitory ligands (HLA-I) determines that immunosurveillance of myeloma depends on diverse and strong NK cell licensing.

Missing self recognition makes cancer sensitive to natural killer cell (NKc) reactivity. However, this model disregards the NKc licensing effect, which highly increases NKc reactivity through interactions of inhibitory killer cell immunoglobulin-like receptors (iKIR) with their cognate HLA-I ligands. The influence of iKIR/HLA-ligand (HLA-C1/C2) licensing interactions on the susceptibility to and progression of plasma cell (PC) dyscrasias was evaluated in 164 Caucasian patients and 286 controls. Compared to controls, myeloma accumulates KIR2DL1-L2+L3- genotypes (2.8% vs. 13.2%, p < 0.01, OR = 5.29) and less diverse peripheral repertoires of NKc clones. Less diverse and weaker-affinity repertoires of iKIR2D/HLA-C licensing interactions increased myeloma susceptibility. Thus, the complete absence of conventional iKIR2D/HLA-C licensing interactions (KIR2DL1-L2+L3-/C2C2, 2.56% vs. 0.35%; p < 0.05; OR = 15.014), single-KIR2DL3+/C1+ (20.51% vs. 10.84%; p < 0.05; OR = 2.795) and single-KIR2DL2+/C1+ (12.82% vs. 4.9%; p < 0.01; OR = 5.18) interactions were over-represented in myeloma, compared to controls. Additionally, KIR2DL1-L2+L3- (20% vs. 83%, p < 0.00001) as well as KIR3DL1- (23% vs. 82%, p < 0.00001) genotypes had a dramatic negative impact on the 3-y progression-free survival (PFS), particularly in patients with low-tumor burden. Remarkably, myeloma-PCs, compared to K562 and other hematological cancers, showed substantial over-expression of HLA-I ("increasing-self" instead of missing-self), including HLA-C, and mild expression of ligands for NKc activating receptors (aRec) CD112, CD155, ULBP-1 and MICA/B, which apparently renders myeloma-PCs susceptible to lysis mainly by licensed NKc. KIR2DL1-L2+L3-/C2C2 patients (with no conventional iKIR2D/HLA-C licensing interactions) lyse K562 but barely lyse myeloma-PCs (4% vs. 15%; p < 0.05, compared to controls). These results support a model where immunosurveillance of no-missing-self cancers, e.g., myeloma, mainly depends on NKc licensing.

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

Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Angiogenesis: Potencial Clinical Application.

Mesenchymal stem cells (MSCs) are adult multipotent stem cells that are able to differentiate into multiple specialized cell types including osteocytes, adipocytes, and chondrocytes. MSCs exert different functions in the body and have recently been predicted to have a major clinical/therapeutic potential. However, the mechanisms of self-renewal and tissue regeneration are not completely understood. It has been shown that the biological effect depends mainly on its paracrine action. Furthermore, it has been reported that the secretion of soluble factors and the release of extracellular vesicles, such as exosomes, could mediate the cellular communication to induce cell-differentiation/self-renewal. This review provides an overview of MSC-derived exosomes in promoting angiogenicity and of the clinical relevance in a therapeutic approach.

Hematological, biochemical, respiratory, cardiovascular and electroneurophysiological parameters in African green monkeys (Cercopithecus aethiops sabaeus). Its use in non-clinical toxicological studies.

BACKGROUND: The purpose of this study is to better characterize the hematological, biochemical, respiratory, cardiovascular and electroneurophysiological parameters in young adult Cercopithecus aethiops sabaeus of both sexes. The rhesus and cynomolgus monkeys are widely used as experimental primate models. However, only few articles have been published testing toxicological effects of pharmaceuticals on African green monkey. METHODS: The present study was carried out with the recompilation of all parameters recorded before the first drug administration in five sub-chronic or chronic toxicological studies performed on 66 Cercopithecus aethiops sabaeus, born in Cuba. RESULTS: This study provides hematological, biochemical, respiratory, cardiovascular and electroneurophysiological data for both choosing animals to be included into experiments and monitoring these parameters during the study. CONCLUSIONS: We conclude that this study provides valuable integrated data for determining the health status, including electroneurophysiological parameters, data not previously reported for this species, of the African green monkey.

Libre comercio y autonomía universitaria, un dilema actual: el caso colombiano / Livre-comercio e autonomia universitária, um dilema atual: o caso colombiano / Free trade and university autonomy, a present day dilemma: the Colombian case

En el presente ensayo se analizan las consecuencias que para la educación superior puede implicar la globalización y, en particular, el libre comercio. Para caracterizar con mayor especificidad el fenómeno, luego de indagar por la naturaleza de la universidad – institución emblemática de la educación superior– a través de un recorrido por la historia de ésta y del planteamiento de sus misiones y funciones sustantivas, se examinan los términos en que el Acuerdo General de Comercialización de Servicios –GATS– incluye la educación dentro de su ordenamiento, planteando las posibles consecuencias que tal inclusión puede tener para la educación superior. Luego se exponen los potenciales escenarios de la educación superior colombiana relacionados con la posición política que podría asumir el país con respecto a las directrices del GATS en los tratados que sobre el tema de Educación Superior pudiese llegar a suscribir.

No presente ensaio analiso as possíveis conseqüências produzidas pela globalização, particularmente o livre - comercio, no ensino superior. Para caracterizar com maior especificidade o fenômeno, logo após indagar pela natureza da universidade — instituição emblemática de ensino superior —, através de um recorrido pela história desta e da exposição da sua missão e funções substantivas, são examinados os termos pelos quais o Acordo Geral de Comercialização de Serviços (GATS) inclui o ensino dentro do seu ordenamento, expondo as possíveis conseqüências que tal inclusão pode ter para o ensino superior. Logo exponho os potenciais cenários do ensino superior colombiano, relacionados com a posição política que poderia assumir o país em relação às diretrizes do GATS nos tratados que sobre o tema de Ensino Superior pudesse chegar a subscrever.

This paper analyzes the consequences of globalization, and particularly of free trade, on higher education. Starting with a consideration of the nature and mission of the university, through a brief survey of its history, the paper examines the terms in which the General Agreement on Trade and Services–GATS–treats education, and reflects on the consequences of this treatment for higher education. Finally, it proposes the possible scenarios for Colombian higher education in terms of the position which the country might take regarding the orientations of GATS in terms of the treaties on higher education that might eventually be subscribed.

Systemic and skin toxicity in Cercopithecus aethiops sabaeus monkeys treated during 26 weeks with a high intravenous dose of the anti- epidermal growth factor receptor monoclonal antibody Nimotuzumab.

Nimotuzumab (h-R3) is a humanized anti-epidermal growth factor receptor monoclonal antibody (mAb) registered for treating head and neck tumours. The present study was designed to evaluate the systemic and skin toxicity of chronic intravenous administration of the h-R3 in a relevant species demonstrated by comparing the h-R3 binding affinity constants (Kd) in microsomal placental fractions from Homo sapiens and Cercopithecus aethiops monkeys using an EGF-Receptor radioligand competition assay. The Kd obtained for Nimotuzumab were 9.1 x 10(-8) M for monkeys and 4.5 x 10(-8) M for humans. Monkeys (n = 18) were distributed into 3 groups with 3 animals of each sex in each group. Group I received saline; group II received 2.85 mg/kg of h-R3; and group III received 28.57 mg/kg of the h-R3, which represent 1 and 10 times the human dose, and they were weekly intravenously treated during 26 weeks. During the study there were no deaths. Electroneurophysiological, sanguine chemistry and haematological results did not evidence alterations. Areas of haematomas, probably related with the administration procedure, were observed at the administration zones of all animals. The electrocardiography study showed at the end of the study a slight increase in the cardiac frequency of four treated animals without other signs. Unexpectedly, skin biopsies and a detailed clinical inspection of the animals did not detect the presence of cutaneous rash or any other skin toxicity sign reported for the majority of the anti-EGF-R monoclonal antibodies. It is concluded that doses up to 28.5 mg/kg of h-R3, intravenously administered during 26 weeks to Cercopithecus aethiops monkeys, do not produce considerable toxic effects.

Human leucocyte antigen-C in B chronic lymphocytic leukaemia.

This study aimed at characterising the distribution of human leucocyte antigen (HLA)-C alleles in a large group of patients with B chronic lymphocytic leukaemia from Southeastern Spain. Ninety-eight adult patients and 194 geographically and ethnically matched controls were studied. HLA-C was determined by polymerase chain reaction sequence-specific primers (PCR-SSP) and PCR-sequence-specific oligonucleotides (SSO) methods. The HLA-Cw*16 allele frequency was found to be significantly increased amongst patients compared with controls in our population (27.6% vs. 12.4%, P = 0.0012, Pc = 0.016). HLA-C dimorphism was also analysed but no association was found.

Terapéutica con imanes en afecciones del aparato locomotor / Magnetotherapy in affections of the locomotor system

Se informa sobre la utilización de imanes de alta potencia en las afecciones dolorosas e inflamatorias del aparato locomotor. Se analizan los resultados obtenidos en 200 pacientes tratados en la Clínica de Medicina Natural y Tradicional del ISCM de Camagüey. Sólo 6 pacientes mantuvieron igual sintomatología en las 5 sesiones de tratamiento; el resto, obtuvo franca mejoría o ausencia total de la sintomatología inicial. Los imanes provienen de generadores eléctricos en desuso, computadoras soviéticas desechadas, bocinas grandes, etc. No se observó intolerancia ni complicaciones con la utilización de este método

Candidiasis orofaringea en pacientes con SIDA o con neoplasias experiencia interinstitucional con fluconazol en Colombia / Oropharyngeal candidiasis in patients with AIDS or malignancies institutional experience with fluconazole in Colombia

Para evaluarla eficacia y seguridad de fluconazol en el tratamiento de la candidiasis orofaringea se efectuó un estudio prospectivo, abierto, no comparativo, en la consulta externa de las diversas Instituciones participantes. Se estudiaron 52 pacientes ambulatorios con candidiasis orofaringea comprobada por microbiología, distribuidos en dos grupos. El grupo I conformado por 42 pacientes con SIDA y el grupo II por 10 pacientes con otras causas de Inmunodeficiencia. Se les suministró un tratamiento con fluconazol oral (jarabe o cápsulas), 50 a 100mg en dosis única diaria durante 5 a 14 días. No se permitió tratamiento antimicótico tópico ni sistémico asociado. Se evaluó la curación o mejoría de la Infección micótica por negativización de los cultivos y desaparición del cuadro clínico. La mayoría de los pacientes, sin Importar la causa de la Inmunodeficiencia, mejoró en los primeros dos días de la terapia. Hubo curación clínica en 95% de los pacientes del grupo I y 100% del II. Los dos pacientes restantes del grupo I mejoraron. El estudio micológico en el grupo I, demostró curación en el 85%, mejoría en 10% y fracaso en 5%; para el grupo II, las cifras respectivas fueron 80%. 10% Y 10%. Un mes después de la última dosis. 50% de los pacientes que volvieron del grupo I (18/36) continuaban curados y él otro 50% había recaído. Para el grupo II, ocho de nueve que retomaron permanecían curados; el otro recayó. Se presentaron dos pacientes con eventos adversos atribuibles a fluconazol. Uno con náusea y otro con vértigo, que cedieron espontáneamente. Concluimos que el tratamiento de la candidiasis orofaringea con 50 a 100 mg de fluconazol, en dosis única diaria, durante 5 a 14 días es una terapia eficaz, de fácil cumplimiento por el paciente y muy bien tolerada.