Menstrual blood-derived stromal cells modulate functional properties of mouse and human macrophages.

Menstrual blood-derived stromal cells (MenSCs) are emerging as a strong candidate for cell-based therapies due to their immunomodulatory properties. However, their direct impact on innate immune populations remains elusive. Since macrophages play a key role in the onset and development of inflammation, understanding MenSCs implication in the functional properties of these cells is required to refine their clinical effects during the treatment of inflammatory disorders. In this study, we assessed the effects that MenSCs had on the recruitment of macrophages and other innate immune cells in two mouse models of acute inflammation, a thioglycollate (TGC)-elicited peritonitis model and a monobacterial sepsis model. We found that, in the TGC model, MenSCs injection reduced the percentage of macrophages recruited to the peritoneum and promoted the generation of peritoneal immune cell aggregates. In the sepsis model, MenSCs exacerbated infection by diminishing the recruitment of macrophages and neutrophils to the site of infection and inducing defective bacterial clearance. Additional in vitro studies confirmed that co-culture with MenSCs impaired macrophage bactericidal properties, affecting bacterial killing and the production of reactive oxygen intermediates. Our findings suggest that MenSCs modulate the macrophage population and that this modulation must be taken into consideration when it comes to future clinical applications.

BNCT research activities at the Granada group and the project NeMeSis: Neutrons for medicine and sciences, towards an accelerator-based facility for new BNCT therapies, medical isotope production and other scientific neutron applications.

The Granada group in BNCT research is currently performing studies on: nuclear and radiobiological data for BNCT, new boron compounds and a new design for a neutron source for BNCT and other applications, including the production of medical radioisotopes. All these activities are described in this report.

Radiobiology data of melanoma cells after low-energy neutron irradiation and boron compound administration.

The cold neutron beam at the PF1b line at the Institut Laue-Langevin (ILL), without fast neutrons and a low contribution of gamma rays, is a very suitable facility to measure cell damage following low-energy neutron irradiation. The biological damage associated with the thermal and the boron doses can be obtained in order to evaluate the relative biological effectiveness (RBE) for Boron Neutron Capture Therapy. Three different experiments were carried out on the A375 melanoma cell line: the first one in a hospital LINAC, to obtain the reference radiation data, and the other two at the ILL, in which the damage to cells with and without boron compounds added was measured.

The pleiotropic role of proteoglycans in extracellular vesicle mediated communication in the tumor microenvironment.

Compartmental exchange between cells through extracellular vesicles (EVs), including exosomes and microvesicles, has emerged as a central mechanism that coordinates the complex communication between malignant and stromal cells during tumor initiation and evolution. Some of the most critical processes of EV-mediated communication, including EV biogenesis and EV uptake, can be mediated by heparan sulfate proteoglycans (HSPGs) that reside on the surface of producer and recipient cells as well as on EVs. With interestingly similar, HSPG-dependent, pathways as the ones exploited by some viruses, EVs may, in an evolutionary perspective, be viewed as endogenous counterparts of viral particles. Cancer cell-derived EVs exert their protumorigenic effects by direct interactions of biologically active surface molecules, by transfer of proteins and nucleic acids into recipient cells or by transfer of metabolites that can be utilized as an energy source by the recipient cell. Here, we discuss the pleiotropic role of the HSPG family in these different contexts of EV communication with a specific focus on tumor development. We propose EV-associated PGs as dynamic reservoirs and chaperones of signaling molecules with potential implications in ligand exchange between EVs and tumor target cells. The protumorigenic consequences of EV mediated communication through HSPG should motivate the development of therapeutic approaches targeting EV-HSPG interactions as a novel strategy in cancer treatment.

Relación entre la presencia de anemia y el riesgo de osteoporosis en mujeres con artritis reumatoide / Relationship between the presence of anemia and the risk of osteoporosis in women with rheumatoid arthritis

Introducción: Los pacientes con artritis reumatoide presentan mayor prevalencia de osteoporosis, en parte por el uso de glucocorticoides; sin embargo, existen otros factores causales. Material y métodos: Se estudiaron 122 mujeres con el diagnóstico de artritis reumatoide. Se determinaron las concentraciones séricas de hemoglobina y se realizó densitometría ósea por medio de absorciometría de rayos X de energía dual. Se utilizó un modelo de regresión logística multivariante para determinar la asociación de las variables estudiadas. Resultados: El 32,8% de las mujeres estudiadas presentó hemoglobina <12 g/dL. La media de la T-score en columna lumbar fue -1,8±1,5; el 36,9% presentó una masa ósea baja, el 32,8% criterio de osteoporosis y el 30,3% T-score normal. La media de la T-score de fémur fue -0,6±1,4; el 63,9% fue con valor normal, el 23,8%, presentó masa ósea baja y el 12,3% criterio de osteoporosis. Se encontró relación entre hemoglobina ≥12 g/dL y una densidad mineral ósea (DMO) de fémur normal (p=0,003), y entre una hemoglobina <12 g/dL y DMO de fémur con osteoporosis (p<0,000). Existió una asociación independiente entre la osteoporosis y el índice de masa corporal <30 kg/m2 (OR=4,1; IC 95%: 1,4-11,4; p=0,009) y la presencia de anemia (OR=8,9; IC 95%: 3,7-22,4; p=0,001). Conclusiones: En nuestro trabajo se observa una asociación entre la anemia y la baja densidad mineral ósea en mujeres con AR principalmente en la región femoral, lo que hace importante el manejo adecuado y oportuno de la anemia en estas pacientes

Introduction: Patients with rheumatoid arthritis present a high prevalence of osteoporosis, partly due to the use of glucocorticoids. However, there are other causal factors. Material and methods: 122 women diagnosed with rheumatoid arthritis were studied. Serum hemoglobin concentrations were determined and bone densitometry carried out by dual energy X-ray absorptiometry. A multivariate logistic regression model was used to determine the association of the variables studied. Results: 32.8% of the women studied presented hemoglobin <12 g/dL. The mean T-score in the lumbar spine was -1.8±1.5; 36.9% had a low bone mass, 32.8% osteoporosis criteria and 30.3% normal T-score. The mean of the femur T-score was -0.6±1.4; 63.9% was normal value, 23.8% presented low bone mass and 12.3% criterion of osteoporosis. Hemoglobin ≥12 g/dL and a bone mineral density (BMD) of the normal femur (p=0.003), and between hemoglobin <12 g/dL and BMD of femur with osteoporosis (p<0.000). There was an independent association between osteoporosis and body mass index <30 kg/m2 (OR=4.1, 95% CI: 1.4-11.4, p=0.009) and the presence of anemia (OR=8.9, 95% CI: 3.7-22.4, p=0.001). Conclusions: In our study, we observed an association between anemia and low bone mineral density in women with RA mainly in the region femoral, which indicates that adequate and timely management of anemia is important in these patients

Síndrome metabólico y actividad de la enfermedad en pacientes con lupus eritematoso sistémico / Metabolic syndrome and disease activity in patients with systemic lupus erythematosus

Resumen: OBJETIVO: determinar la frecuencia del síndrome metabólico en una cohorte de pacientes con lupus eritematoso sistémico y su relación con la actividad de la enfermedad y los factores de riesgo cardiovascular. MATERIAL Y MÉTODO: estudio descriptivo, transversal y observacional en el que de junio de 2015 a junio de 206 se incluyeron pacientes con diagnóstico de lupus eritematoso sistémico según los criterios SLICC 2012, la actividad de la enfermedad se evaluó mediante el índice SLEDAI 2K. Se estableció la existencia de síndrome metabólico de acuerdo con los criterios NECP ATP III. Las variables categóricas se compararon con χ2 y las continuas con U de Mann-Whitney o t de Student. Finalmente se utilizó un modelo de regresión logística multivariante para determinar la asociación de las variables estudiadas y el síndrome metabólico. RESULTADOS: se incluyeron 102 pacientes de los que 41% tenía síndrome metabólico (60% de los hombres y 39% de las mujeres). Las principales alteraciones fueron hipoalfalipoproteinemia (75.5%), perímetro abdominal aumentado (63%) e hipertrigliceridemia (60%). Se observó que a mayor número de componentes del síndrome metabólico existía mayor actividad de la enfermedad. Un índice SLEDAI 2K ≥ 4 se asoció independientemente con síndrome metabólico (RR 2.89; IC 1.21-6.89; p=0.017). La administración de hidroxicloroquina se asoció de manera independiente con la ausencia de síndrome metabólico (RR 0.48; IC 0.19-0.39; p=0.14). Se encontró significación entre la actividad de la enfermedad y la hipoalfalipoproteinemia (p=0.007) y la hipertrigliceridemia (p=0.035). CONCLUSIONES: existe frecuencia alta de síndrome metabólico en las pacientes con lupus eritematoso sistémico, la cual se asocia con la actividad de la enfermedad.

Abstract: OBJECTIVE: To determine the frequency of metabolic syndrome in a cohort of patients with systemic lupus erythematous and its relationship with disease activity and cardiovascular risks factors. MATERIAL AND METHOD: A descriptive, cross-sectional and observational study including patients diagnosed with systemic lupus erythematous according to the SLICC 2012 criteria, disease activity was evaluated through SLEDAI 2K from June 2015 to June 2016. The presence of metabolic syndrome was established according to the NECP ATP III criteria. Categorical variables were compared with χ2 and the continuous ones with Mann-Withney U or Student t. Finally, a logistic regression multivariate model was used to determine the association of the studied variables and the metabolic syndrome. RESULTS: One hundred two patients were included; from which 41 % of the patients presented with metabolic syndrome (60% of men and 39% of women). The main alterations were hypoalphalipoproteinemia (75.5%), elevated abdominal circumference (63%) and hypertriglyceridemia (60%). It was observed that with a higher number of components of the metabolic syndrome a major disease activity existed. An SLEDAI 2K index ≥ 4 was associated independently with the presence of metabolic syndrome (RR 2.89; IC 1.21-6.89; p=0.017). Hydroxicloroquine use was associated in an independent manner with the absence of the metabolic syndrome (RR 0.48; IC 0.19-0.39; p=0.14). Statistic significance was found between disease activity and hypoalphalipoproteinemia (p=0.007) and hypertriglyceridemia (p=0.035). CONCLUSION: There is a high frequency of metabolic syndrome in patients with systemic lupus erythematous, which is associated with disease activity.

Hypoxia regulates global membrane protein endocytosis through caveolin-1 in cancer cells.

Hypoxia promotes tumour aggressiveness and resistance of cancers to oncological treatment. The identification of cancer cell internalizing antigens for drug targeting to the hypoxic tumour niche remains a challenge of high clinical relevance. Here we show that hypoxia down-regulates the surface proteome at the global level and, more specifically, membrane proteome internalization. We find that hypoxic down-regulation of constitutive endocytosis is HIF-independent, and involves caveolin-1-mediated inhibition of dynamin-dependent, membrane raft endocytosis. Caveolin-1 overexpression inhibits protein internalization, suggesting a general negative regulatory role of caveolin-1 in endocytosis. In contrast to this global inhibitory effect, we identify several proteins that can override caveolin-1 negative regulation, exhibiting increased internalization at hypoxia. We demonstrate antibody-mediated cytotoxin delivery and killing specifically of hypoxic cells through one of these proteins, carbonic anhydrase IX. Our data reveal that caveolin-1 modulates cell-surface proteome turnover at hypoxia with potential implications for specific targeting of the hypoxic tumour microenvironment.

Effect of ZNF217 gene polymorphisms on colorectal cancer development in a Mexican population.

The ZNF217 gene, a potential oncogene amplified and overexpressed in several cancers including colorectal cancer (CRC), acts as a transcription factor that activates or represses target genes. The polymorphisms rs16998248 (T>A) and rs35720349 (C>T) in coronary artery disease have been associated with reduced expression of ZNF217. In this study, we analyzed the 2 polymorphisms in Mexican patients with CRC. Genotyping of rs16998248 and rs35720349 sites was performed by polymerase chain reaction-restriction fragment length polymorphism in 203 Mexican Mestizos, 101 CRC patients, and 102 healthy blood donors. Although no statistical differences regarding genotype and allele frequencies of ZNF217 polymorphisms were observed (P > 0.05), linkage disequilibrium was significant in CRC patients (r(2) = 0.39, P < 0.0001), as a result of reduced AC haplotype frequency. Thus, the AC haplotype may protect against CRC.

Human decidual stromal cells secrete soluble pro-apoptotic factors during decidualization in a cAMP-dependent manner.

STUDY QUESTION: Is there a relationship between decidualization and apoptosis of decidual stromal cells (DSC)? SUMMARY ANSWER: Decidualization triggers the secretion of soluble factors that induce apoptosis in DSC. WHAT IS KNOWN ALREADY: The differentiation and apoptosis of DSC during decidualization of the receptive decidua are crucial processes for the controlled invasion of trophoblasts in normal pregnancy. Most DSC regress in a time-dependent manner, and their removal is important to provide space for the embryo to grow. However, the mechanism that controls DSC death is poorly understood. STUDY DESIGN, SIZE, DURATION: The apoptotic response of DSC was analyzed after exposure to different exogenous agents and during decidualization. The apoptotic potential of decidualized DSC supernatants and prolactin (PRL) was also evaluated. PARTICIPANTS/MATERIALS, SETTING, METHODS: DSC lines were established from samples of decidua from first trimester pregnancies. Apoptosis was assayed by flow cytometry. PRL production, as a marker of decidualization, was determined by enzyme-linked immunosorbent assay. MAIN RESULTS AND THE ROLE OF CHANCE: DSCs were resistant to a variety of apoptosis-inducing substances. Nevertheless, DSC underwent apoptosis during decidualization in culture, with cAMP being essential for both apoptosis and differentiation. In addition, culture supernatants from decidualized DSC induced apoptosis in undifferentiated DSC, although paradoxically these supernatants decreased the spontaneous apoptosis of decidual lymphocytes. Exogenously added PRL did not induce apoptosis in DSC and an antibody that neutralized the PRL receptor did not decrease the apoptosis induced by supernatants. LIMITATIONS, REASONS FOR CAUTIONS: Further studies are needed to examine the involvement of other soluble factors secreted by decidualized DSC in the induction of apoptosis. WIDER IMPLICATIONS OF THE FINDINGS: The present results indicate that apoptosis of DSC occurs in parallel to differentiation, in response to decidualization signals, with soluble factors secreted by decidualized DSC being responsible for triggering cell death. These studies are relevant in the understanding of how the regression of decidua, a crucial process for successful pregnancy, takes place. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the Consejería de Economía, Innovación y Ciencia, Junta de Andalucía (Grant CTS-6183, Proyectos de Investigación de Excelencia 2010 to C.R.-R.) and the Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Spain (Grants PS09/00339 and PI12/01085 to E.G.O.). E.L.-D. was supported by fellowships from the Ministerio de Educación y Ciencia, Spain and the University of Granada. The authors have no conflict of interest.

Influencia de la capacidad funcional sobre el perfil lipídico, daño muscular y perfil bioquímico en personas mayores no institucionalizadas / Influence of functional capacity on lipid profile, muscle damage and biochemical profile among community-dwelling elderly-people

Objetivo. Describir la influencia que la capacidad funcional tiene sobre el perfil bioquímico y daño muscular, así como analizar la relación existente entre estas variables en personas mayores no institucionalizadas. Método. Se utilizó un diseño de corte transversal-observacional en el que se incluyeron 43 sujetos (19 hombres y 24 mujeres). Se analizó la capacidad funcional (T6MW, TUG, CST y PM) y variables bioquímicas (colesterol total, HDL, LDL, triglicéridos, glucosa, GOT, GPT, creatinina y CK). Se establecieron diferencias en función del nivel de capacidad funcional de cada una de las pruebas, así como las relaciones entre cada una de las variables. Resultados. Los sujetos que obtuvieron mayores niveles en los test de capacidad funcional obtuvieron resultados más satisfactorios para las diferentes variables de estudio bioquímico (p < 0,05). Estas diferencias se mantuvieron también cuando los datos fueron analizados atendiendo al género. Además, se observó una correlación entre el daño muscular y las diferentes variables de capacidad funcional testadas. Conclusión. Este estudio muestra la influencia que la capacidad funcional en mayores presenta sobre parámetros bioquímicos asociados a enfermedades metabólicas o cardiovasculares, así como sobre el daño muscular y sugiere la necesidad de implementar actividades tanto aeróbicas como de fuerza en población mayor(AU)

Objective. To analyze the influence of functional capacity on the biochemical profile and muscle damage and to test the level of relationship between these variables among community-dwelling elderly people. Method. A cross-sectional, observational study with 43 participants (19 males and 24 women) was performed. Functional capacity (including 6MWT, TUG test, CST test and Hand grip strength test), and biochemical profile (including total cholesterol, HDL, LDL, triglycerides, glucose, GOT, GPT, creatine and CK) were assessed. Differences on biochemical profile-related variables regarding the functional capacity level were analyzed. The level of relationship between the variables comprising these two domains was also assessed. Results. Those participants with a better results in functional capacity variables also achieved the better results in regard of the biochemical parameters measured (p < 0,05). These differences were also maintained after a gender-based analysis. Moreover, relationships between muscle damage and functional capacity variables were also achieved. Conclusion. This study shows the influence of the functional capacity on the biochemical parameters (mostly associated to cardiovascular and metabolic diseases) along with the influence that such variables have on the muscle damage and suggest the needed on the implementation of both aerobic and strength training for elderly(AU)

Side effects of rodent control on non-target species: Rodenticides increase parasite and pathogen burden in great bustards.

For many years anticoagulant rodenticides have been used in vole control campaigns, in spite of the proven risk of secondary poisoning of non-target predators and scavengers. In this paper we analyse for the first time great bustard exposure and intoxication by anticoagulant rodenticides in Spain, based on residues found in the livers of 71 bustard carcasses collected during 1991-2010. Ten individuals contained chlorophacinone and one flocoumafen. Chlorophacinone level was significantly correlated with the pathogen and parasite burden of intoxicated birds. Moreover, through the last 12 years the annual number of great bustards that present chlorophacinone in liver collected in our study areas was correlated with vole peaks at a nearby area, suggesting that the ingestion of rodenticide was proportional to the amounts spread in the fields. We conclude that rodenticide consumption is a regular event among great bustards when baited cereal is spread on fields, and that this may cause chronic weakening of intoxicated individuals, possibly affecting their survival. Future rodent control actions should consider these negative side effects on non target granivorous steppe and farmland species, particularly when they are globally threatened.

HDAC inhibitors with different gene regulation activities depend on the mitochondrial pathway for the sensitization of leukemic T cells to TRAIL-induced apoptosis.

Epigenetic modifications commonly associated with tumor development, such as histone deacetylation, may influence the resistance of some tumor cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) by regulating gene transcription of components of the TRAIL signalling pathway. In the present study we have analyzed the effect of six different histone deacetylase inhibitors (HDACi), belonging to the four classic structural families, on TRAIL-induced apoptosis in leukemic T cell lines. Non-toxic and functional doses of all HDACi but apicidin, similarly sensitized different leukemic T cell lines to TRAIL-induced apoptosis, while they showed no effect on the resistance of normal T lymphocytes. Sensitizing doses of vorinostat, valproic acid, sodium butyrate and MS-275 regulated the expression of TRAIL-R2, c-FLIP and Apaf-1 in leukemic cells while TSA modulated only the expression of Apaf-1. The synergistic effect of all HDACi and TRAIL was inhibited in Bcl-2-overexpressing leukemic T cells. Thus, different HDACi may affect the expression of different TRAIL-related genes, but regulation of the mitochondrial pathway seems to be essential for the TRAIL sensitizing effect of HDACi in leukemic T cells. Overall, HDACi represent a promising and safe strategy in combination with TRAIL for treatment of T-cell leukaemia.

ATP-binding cassette transporter ABCB5 gene is expressed with variability in malignant melanoma.

BACKGROUND: Melanoma is a malignant neoplasm with high metastatic disease risk and elevated mortality. Incidence of melanoma varies according to geographic region and genetic BACKGROUND: Epidemiological studies indicate that acral melanoma (AM) is among the most common melanomas in the Mexican population. While extensive studies have identified genes associated with melanoma, little is known about the genes involved in the pathogenesis of AM. OBJECTIVE: To compare the gene expression patterns between primary melanoma and normal skin. METHODS: We used 10 samples of fresh acral melanomas and normal skin for the study of differential gene expression and 22 samples of melanoma for in situ hybridization. RESULTS: We first identified a gene that was present in a sample of AM and absent in normal skin. DNA sequencing of this differentially expressed gene revealed that it corresponded to ABCB5, a gene recently implicated in the regulation of progenitor cell fusion. Furthermore, we detected ABCB5 expression in other melanoma specimens by RT-PCR. We showed that nine out of ten melanomas were positive for ABCB5 while only one melanoma and normal skin samples were negative. All ABCB5 expressing melanomas had variable gene expression according to in situ hybridization studies, suggesting that the ABCB5 gene may be differentially regulated by individual melanomas. CONCLUSIONS: The ABCB5 gene may be related to the properties of chemoresistance and aggressiveness of melanoma. The high expression found in samples of acral melanoma may provide more insight on the pathogenesis of this common type of melanoma in the Mexican population, frequently associated with poor prognosis.

Expresión variable del gen ABCB5 de las transportadoras de casetes de unión a ATP en el melanoma maligno / ATP-binding Cassette Transporter ABCB5 Gene is Expressed with Variability in Malignant Melanoma

Background: Melanoma is a malignant neoplasm with high metastatic disease risk and elevated mortality. Incidence of melanoma varies according to geographic region and genetic background. Epidemiological studies indicate that acral melanoma (AM) is among the most common melanomas in the Mexican population. While extensive studies have identified genes associated with melanoma, little is known about the genes involved in the pathogenesis of AM. Objective: To compare the gene expression patterns between primary melanoma and normal skin. Methods: We used 10 samples of fresh acral melanomas and normal skin for the study of differential gene expression and 22 samples of melanoma for in situ hybridization. Results: We first identified a gene that was present in a sample of AM and absent in normal skin. DNA sequencing of this differentially expressed gene revealed that it corresponded to ABCB5, a gene recently implicated in the regulation of progenitor cell fusion. Furthermore, we detected ABCB5 expression in other melanoma specimens by RT-PCR. We showed that nine out of ten melanomas were positive for ABCB5 while only one melanoma and normal skin samples were negative. All ABCB5 expressing melanomas had variable gene expression according to in situ hybridization studies, suggesting that the ABCB5 gene may be differentially regulated by individual melanomas. Conclusions: The ABCB5 gene may be related to the properties of chemoresistance and aggressiveness of melanoma. The high expression found in samples of acral melanoma may provide more insight on the pathogenesis of this common type of melanoma in the Mexican population, frequently associated with poor prognosis (AU)

Introducción: El melanoma es una neoplasia maligna que presenta una elevada mortalidad y un alto riesgo de desarrollar metástasis. La incidencia de esta enfermedad varía en función de la región geográfica y el trasfondo genético. Estudios epidemiológicos indican que el melanoma acral es uno de los más comunes en la población mexicana. Hay una gran cantidad de estudios sobre genes asociados al melanoma, sin embargo, se sabe muy poco de los genes que se relacionan con el melanoma acral. Objetivo: Comparar el patrón de expresión génica entre melanomas acrales primarios y piel sana. Métodos: Se utilizaron muestras en fresco de 10 lesiones de melanoma acral y piel sana para el estudio de expresión diferencial de genes y 22 muestras de melanoma para la hibridación in situ. Resultados: Identificamos un gen que estaba presente en una muestra de melanoma acral y ausente en la piel normal. La secuenciación de este gen reveló que correspondía al gen ABCB5, recientemente implicado en la regulación de la fusión de células progenitoras. Al realizar RT-PCR de otros melanomas se detectó la expresión de este gen: 9 de 10 melanomas fueron positivos para ABCB5. Todos los melanomas tuvieron una expresión variable de ABCB5 detectado por hibridación in situ, lo cual sugiere que el gen puede ser regulado diferencialmente en melanomas individuales. Conclusiones: El gen ABCB5 podría estar relacionado con las propiedades de resistencia a la quimioterapia y la agresividad del melanoma. La elevada expresión encontrada en las muestras de melanoma acral podría ayudar a la mejor comprensión de la patogenia de esta forma frecuente de melanoma en la población mexicana, que se asocia generalmente con un peor pronóstico (AU)

Linkage disequilibrium between four MTTP gene polymorphisms in a Mexican population.

BACKGROUND: The microsomal triglyceride transfer protein plays an important role in the folding, assembling and secretion of lipoproteins that contain apoprotein B. Different polymorphisms in the MTTP gene have been associated with risk factors for coronary heart disease and diabetes, the first and fourth most common causes of death in Mexico, respectively. AIM: The objective of this study was to assess allele, genotype and haplotype frequencies of six MTTP polymorphisms in an unselected Mexican population. SUBJECTS AND METHODS: Six polymorphisms were analysed by DNA sequencing of polymerase chain reaction products in 155 Mexican individuals and Hardy-Weinberg equilibrium, genetic variability, linkage disequilibrium and neutrality test were evaluated. RESULTS: The rare alleles of the six polymorphisms analysed had frequencies greater than 1% and their genotype distributions were in accordance with Hardy-Weinberg equilibrium. All three promoter and I/T 128 polymorphisms were in linkage disequilibrium. Twelve different haplotypes were observed; GATGGT (70.44%) and TTCGGC (13.91%) were the most common. Diversity patterns in this Mexican population deviate significantly from expectations of the standard neutral model for infinite allele. CONCLUSION: The -493 G/T, -400 A/T, -164 T/C and I/T 128 polymorphisms can be useful for association studies in this population.

[Renal cell carcinoma presenting as paraneoplastic neurological dysfunction]. / Carcinoma renal que debuta como cuadro neurológico paraneoplásico.

INTRODUCTION: Malignant tumors sometimes initiate as paraneoplastic syndromes even years before the most common symptoms appear. These first manifestations could be the key for the diagnosis of "occult" malignancy. METHODS: We report the case of a 66 year old man with a renal cell carcinoma. The first symptom was a paraneoplastic cerebellar degeneration appeared 6 years before the first urologic manifestations. CONCLUSIONS: A progressive cerebellar syndrome could be the first manifestation of a renal cell carcinoma, even years before the first urologic symptoms. We must suspect an occult neoplasia in such patients.

Carcinoma renal que debuta como cuadro neurológico paraneoplásico / Renal cell carcinoma presenting as paraneoplastic neurological dysfunction

Introducción: Los procesos tumorales pueden de manera ocasional mostrar su primera manifestación con una sintomatología neurológica, no originada por metástasis, sino del denominado tipo paraneoplásico, que puede aparecer incluso años antes de los síntomas habituales del tumor. Este tipo de manifestaciones iniciales pueden ser la clave del descubrimiento de una neoplasia oculta. Métodos: Presentamos el caso de un varón de 66 años afecto de un carcinoma renal, cuya manifestación inicial consistió únicamente en un cuadro neurológico progresivo de tipo cerebeloso paraneoplásico, aparecido 6 años antes de la primera sintomatología urológica. Conclusiones: La aparición de una sintomatología neurológica cerebelosa progresiva puede ser la única y primera manifestación de un carcinoma renal, incluso años antes de las primeras manifestaciones urológicas. Debe sospecharse la existencia de una neoplasia oculta en los pacientes con esta sintomatología (AU)

Introduction: Malignant tumors sometimes initiate as paraneoplastic syndromes even years before the most common symptoms appear. These first manifestations could be the key for the diagnosis of 'occult' malignancy. Methods: We report the case of a 66 year old man with a renal cell carcinoma. The first symptom was a paraneoplastic cerebellar degeneration appeared 6 years before the first urologic manifestations. Conclusions: A progressive cerebellar syndrome could be the first manifestation of a renal cell carcinoma, even years before the first urologic symptoms. We must suspect an occult neoplasia in such patients (AU)

Genetic admixture, relatedness, and structure patterns among Mexican populations revealed by the Y-chromosome.

Y-linked markers are suitable loci to analyze genetic diversity of human populations, offering knowledge of medical, forensic, and anthropological interest. In a population sample of 206 Mestizo males from western Mexico, we analyzed two binary loci (M3 and YAP) and six Y-STRs, adding to the analysis data of Mexican Mestizos and Amerindians, and relevant worldwide populations. The paternal ancestry estimated in western Mexican-Mestizos was mainly European (60-64%), followed by Amerindian (25-21%), and African ( approximately 15%). Significant genetic heterogeneity was established between Mestizos from western (Jalisco State) and northern Mexico (Chihuahua State) compared with Mexicans from the center of the Mexican Republic (Mexico City), this attributable to higher European ancestry in western and northern than in central and southeast populations, where higher Amerindian ancestry was inferred. This genetic structure has important implications for medical and forensic purposes. Two different Pre-Hispanic evolutionary processes were evident. In Mesoamerican region, populations presented higher migration rate (N(m) = 24.76), promoting genetic homogeneity. Conversely, isolated groups from the mountains and canyons of the Western and Northern Sierra Madre (Huichols and Tarahumaras, respectively) presented a lower migration rate (N(m) = 10.27) and stronger genetic differentiation processes (founder effect and/or genetic drift), constituting a Pre-Hispanic population substructure. Additionally, Tarahumaras presented a higher frequency of Y-chromosomes without Q3 that was explained by paternal European admixture (15%) and, more interestingly, by a distinctive Native-American ancestry. In Purepechas, a special admixture process involving preferential integration of non-Purepecha women in their communities could explain contrary genetic evidences (autosomal vs. Y-chromosome) for this tribe.

[Anaphylaxis and anaphylactic shock]. / Anafilaxia y choque anafiláctico.

Term anaphylaxis means an immediate hypersensitivity reaction mediated by IgE that produces a clinical syndrome with systemic affection of variable severity. Its prevalence varies according to the habits of each region and of the studied population from 3.2 to 7.6 cases per 100,000 inhabitants per year. Anaphylaxis secondary to the food ingestion accounts for 30-50% of the cases. Some risk factors have been defined, among them the most important are asthma, food allergy and previous reactions to the same food. Biphasic anaphylactic reactions are those presenting a recurrence of anaphylactic symptoms, after the initial remission of them. Success of treatment is based on the early recognition of signs and symptoms and the instauration of treatment with adrenaline.

Cytotoxic effect of curcumin on Giardia lamblia trophozoites.

Giardia lamblia is one of the most important worldwide causes of intestinal infections produced by protozoa. Thus, the search for new alternative therapeutic approaches for this parasitic disease is very important. Common drugs used to control and eradicate this infection, frequently exhibit side effects that force patients to abandon treatment. The present work evaluates the anti-protozoan activity of curcumin, the main constituent of turmeric. Axenic G. lamblia (Portland 1 strain) cultures were exposed to different concentrations of curcumin. Its effects were evaluated on parasite growth, adhesion capacity and parasite morphology. We also evaluated the capacity of curcumin to induce an apoptosis-like effect. All curcumin concentrations inhibited trophozoite growth and adhesion in more than 50% in dose and time dependent manner. Morphological changes were described as protrusions formed under the cytoplasmic membrane, deformation due to swelling and cell agglutination. Curcumin induced apoptosis-like nuclear staining in dose and time dependent manner. In conclusion, curcumin exhibited a cytotoxic effect in G. lamblia inhibiting the parasite growth and adherent capacity, induced morphological alterations, provoked apoptosis-like changes. Future in vitro and in vivo experiments are endowed to elucidate the effect of curcumin in an experimental model of G. lamblia infection, analyze the involvement of ion channels in the swelling effect of curcumin during an apparent osmotic deregulation in G. lamblia trophozoites. This will lead to the proposal of the action mechanism of curcumin as well as the description of mechanism involved during the activation process for the apoptotic-like effect.