Effect of Transforming Growth Factor-ß upon Taenia solium and Taenia crassiceps Cysticerci.

Taeniids exhibit a great adaptive plasticity, which facilitates their establishment, growth, and reproduction in a hostile inflammatory microenvironment. Transforming Growth Factor-ß (TGFß), a highly pleiotropic cytokine, plays a critical role in vertebrate morphogenesis, cell differentiation, reproduction, and immune suppression. TGFß is secreted by host cells in sites lodging parasites. The role of TGFß in the outcome of T. solium and T. crassiceps cysticercosis is herein explored. Homologues of the TGFß family receptors (TsRI and TsRII) and several members of the TGFß downstream signal transduction pathway were found in T. solium genome, and the expression of Type-I and -II TGFß receptors was confirmed by RT-PCR. Antibodies against TGFß family receptors recognized cysticercal proteins of the expected molecular weight as determined by Western blot, and different structures in the parasite external tegument. In vitro, TGFß promoted the growth and reproduction of T. crassiceps cysticerci and the survival of T. solium cysticerci. High TGFß levels were found in cerebrospinal fluid from untreated neurocysticercotic patients who eventually failed to respond to the treatment (P = 0.03) pointing to the involvement of TGFß in parasite survival. These results indicate the relevance of TGFß in the infection outcome by promoting cysticercus growth and treatment resistance.

The network of antigen-antibody reactions in adult women with breast cancer or benign breast pathology or without breast pathology.

The Immunoglobulin G (IgG) antibody response to different protein antigens of the mammary ductal carcinoma by adult women affected by Breast Cancer (BC) distinguishes at least 103 proteins that differ in their molecular weights (MW). The IgG producing cell clones (nodes) coexist with each other in each individual organism and share energy resources among themselves, as well as factors that control the level of expression and Specificity of their IgG antibodies. So, it can be proposed that among them there is a Network of interconnections (links) unveiled by the antigens, which specifically react with the IgG antibodies produced by the clones. This Network possibly regulates IgG antibodies' activity and effectiveness. We describe the Network of nodes and links that exists between the different antigens and their respective IgG producing cell clones against the extracted protein antigens from the cells of the T47D Cell-Line, in 50 women with BC, 50 women with Benign Breast Pathology (BBP) and 50 women without breast pathology (H). We have found that women with BBP have the highest number of Links, followed by the H group and, lastly, the women with BC, a finding which suggests that cancer interferes with the Connectivity between the IgG producing cell clones and blocks the expression of 322 links in women with BBP and 32 links in women with H. It is also plausible that the largest number of links in the women with BBP indicates the Network's state of arousal that provides protection against BC. On the other hand, there were many missing links in the BC group of women; the clone which lost more links in the BC group was the hub 24, which point to some of the antigens of T47D as potentially useful as vaccines, as the immune system of women with BBP is well aware of them.

Validación en México del inventario de ajuste de Weinberger (WAI) / Validation of the Mexican version of the Weinberger Adjustment Inventory (WAI)

Introducción La incapacidad para aprender a regular los arranques emocionales y la inhibición excesiva de emociones se asocian con una gran variedad de problemáticas personales e interpersonales, así como con alteraciones psicológicas y de salud. Weinberger desarrolló un inventario que evalúa dos aspectos centrales del ajuste socioemocional: la experiencia subjetiva de distrés y la contención emocional. El inventario sólo existía en inglés, por lo que resolvimos traducirlo al español y validarlo en una población de hispanoparlantes mexicanos. Método El cuestionario traducido y revisado se aplicó a 452 participantes, respetando la escala Likert del cuestionario original de cinco puntos. Los participantes fueron personas adultas (mayores de 18 años) sin distinción de sexo que tenían un nivel de escolaridad mínimo de secundaria. Resultados Tras el análisis de la capacidad discriminatoria de los reactivos por el método de grupos extremos y el análisis factorial por el método de componentes principales, el cuestionario quedó conformado por 44 reactivos, agrupados en cuatro factores: 1. Dominio de sí mismo con un total de 19 preguntas que explicaron 18.68% de la varianza, 2. Experiencia subjetiva de distrés, compuesto por 12 preguntas que explicaron 10.84% de la varianza, 3. Defensividad, el cual constó de siete preguntas que explicaron 7.10% de la varianza y 4. Consideración hacia los demás, que agrupó seis preguntas que explicaron 6.54% de la varianza. Finalmente, se evaluó la confiabilidad del cuestionario utilizando el alpha de Cronbach, y quedó como sigue: Dominio de sí mismo 0.89, Experiencia subjetiva de distrés 0.84, Defensividad 0.69 y Consideración hacia los demás 0.74. Conclusiones El Inventario de Weinberger es una herramienta útil para evaluar el ajuste socioemocional, así como para determinar la magnitud de la inhibición emocional en una población, abordar su prevención e instrumentar acciones para la atención de los casos que lo ameriten.

Introduction The inability to control emotional outbursts and the excessive inhibition of emotions are associated with a variety of personal and interpersonal problems, psychological disorders and health status. Weinberger developed an inventory to assesses two central aspects of socio-emotional adjustment: the subjective experience of distress and restraint. As the inventory was in English, we decided to translate it into Spanish and validated it in a population of Spanish-speaking Mexicans. Method The revised Spanish WAI was applied to 452 participants using the same Likert scale used in the English WAI, in which each answer was given a score of five points. The participants were adults (over 18 years) of either sex with a minimum educational level of high school. Results After analyzing the discriminatory power of the questions by the method of extreme groups and factor analysis by principal components analysis, the Spanish WAI was composed of 44 items, which were divided into four factors: 1. Restraint, which grouped together a total of 19 questions, which explained 18.68% of the variance, 2. Subjective experience of distress, consisting of 12 questions, which accounted for 10.84% of the variance, 3. Defensiveness, consisting of seven questions that explained 7.10% of the variance, and 4. Consideration for Others, which grouped six questions that explained 6.54% of the variance. Finally, we assessed the reliability of the questionnaire using Cronbach's alpha as follows: Restraint 0.89, Subjective experience of distress 0.84, Defensiveness 0.69, and Consideration for others 0.74. Conclusions Weinberger's Inventory is a useful instrument to assess restraint as an important aspect of emotional distress of individuals, and to measure the magnitude of restraint in a population, and thus allowing preventive and therapeutic actions in cases that deserve it.

Evolution, molecular epidemiology and perspectives on the research of taeniid parasites with special emphasis on Taenia solium.

Human cysticercosis is known since old historical times in Greece and China; however, human infections by tapeworms have accompanied human beings for more that hundred thousand years. The disease is tightly bound to poverty and lack of hygiene, and has been eradicated in developed countries, but continues being a public health problem in developing countries of Latin-American, Sub-Saharan Africa and Asia, and is also remerging in a number of non endemic countries. It is considered a neglected disease. Here we revise a number of key scientific contributions on taeniid biology that open new avenues for more effective approaches to the control of cysticercosis. The evolution of flatworms and class Cestoda is analyzed, with special emphasis on the emergence of taeniid parasites and the colonization of the human species by tapeworms. The complex molecular host-parasite interplay in this relationship as result of co-evolution between two distantly related organisms. The relevant host and parasite's factors, in the prospect of identifying species-specific molecular markers useful in epidemiological studies carried out in endemic countries. The new possibilities arising with the characterization of the genomes for several species of tapeworms, including a deeper understanding of these organisms, as well as improved tools for diagnosis, vaccination and drug treatment. The need to revise the current control and management strategies for this tropical neglected disease.

Flow cytometry analysis of cell population dynamics and cell cycle during HIV-1 envelope-mediated formation of syncytia in vitro.

Cell fusion occurs in physiological and pathological conditions and plays a role in regulation of cell fate. The analysis of cell population dynamics and cell cycle in cell-cell fusion experiments is necessary to determine changes in the quantitative equilibrium of cell populations and to identify potential bystander effects. Here, using cocultures of Jurkat HIV-1 envelope expressing cells and CD4(+) cells as a model system and flow cytometry for the analysis, the number, viability, and cell cycle status of the populations participating in fusion were determined. In 3-day cocultures, a sustained reduction of the number of CD4(+) cells was observed while they showed high viability and normal cell cycle progression; fusion, but not inhibition of proliferation or death, accounted for their decrease. In contrast, the number of Env(+) cells decreased in cocultures due to fusion, death, and an inherent arrest at G1. Most of syncytia formed in the first 6 h of coculture showed DNA synthesis activity, indicating that the efficient recruitment of proliferating cells contributed to amplify the removal of CD4(+) cells by syncytia formation. Late in cocultures, approximately 50% of syncytia were viable and a subpopulation still underwent DNA synthesis, even when the recruitment of additional cells was prevented by the addition of the fusion inhibitor T-20, indicating that a population of syncytia may progress into the cell cycle. These results show that the quantitative analysis of cellular outcomes of cell-cell fusion can be performed by flow cytometry.

Immunological variation in Taenia solium porcine cysticercosis: measurement on the variation of the antibody immune response of naturally infected pigs against antigens extracted from their own cysticerci and from those of different pigs.

Although it is widely assumed that both antigen and host immunological variability are involved in the variable intensity of natural porcine infections by Taenia solium (T. solium) cysticercis and success of immunodiagnostic tests vaccines, the magnitude of such combined variability has not been studied or measured at all. In this paper we report statistical data on the variability of the antibody response of naturally infected pigs against the antigens extracted from the vesicular fluids of their own infecting cysts (variance within pigs) and against antigen samples extracted from cysts of other cysticercotic pigs (variance among pigs). The variation between pigs was greater than the inter-pigs variations, which suggests that a concomitant immunity process prevents the establishment of cysts coming from a subsequent challenge. In so doing, we found that there is not a single antigenic band that was recognized by all hosts and that antigens varied among the cysts within the same pigs as well as among pigs. Our results may be valuable for the improvement of immunodiagnostic tests and of effective vaccines against naturally acquired porcine T. solium cysticercosis.

Human neurocysticercosis: immunological features involved in the host's susceptibility to become infected and to develop disease.

Human neurocysticercosis (NC) is a clinically and radiologically heterogeneous disease caused by the establishment of Taenia solium larvae in the central nervous system. Herein, the immunological and endocrinological features involved in resistance to infection and severe forms of the disease are reviewed, and their clinical relevance is discussed.

Development of the S3Pvac vaccine against porcine Taenia solium cysticercosis: a historical review.

Herein we present a review of our research dealing with vaccination against experimental and naturally acquired porcine Taenia solium cysticercosis using Taenia crassiceps-derived antigens. Results strongly support that the different versions of S3Pvac vaccine are indeed effective against porcine T. solium cysticercosis. Immunological results related to vaccination prove that protection is at least partially mediated by specific immunity. The data also support the validity of T. crassiceps murine cysticercosis as an effective tool to identify vaccine candidates against some metacestode infections.

Development of the S3Pvac vaccine against murine Taenia crassiceps cysticercosis: a historical review.

Our work of the last 25 yr was concerned with the development of a vaccine aimed to prevent porcine Taenia solium cysticercosis and was based on cross-reacting Taenia crassiceps antigens that had proved protective against experimental intraperitoneal murine T. crassiceps cysticercosis (EIMTcC). In recent times the efficacy of the vaccine has been considered in need of confirmation, and the use of EIMTcC has been questioned as a valid tool in screening for vaccine candidates among the many antigens possibly involved. A review of our work divided in 2 parts is presented at this point, the first dealing with EIMTcC and the second with porcine T. solium cysticercosis (presented in this issue). Herein, we revise our results using EIMTcC as a measure of the protective capacity of T. crassiceps complex antigen mixtures, of purified native antigens, and of S3Pvac anti-cysticercosis vaccine composed by 3 protective peptides: GK-1, KETc1, and KETc12 either synthetic or recombinantly expressed and collectively or separately, by diverse delivery systems when administered at different doses and by different routes. Statistical analyses of the data lead confidently to the strong inference that S3Pvac is indeed an effective vaccine against EIMTcC via specific and non-specific mechanisms of protection.

Cuáles y qué tan graves son los daños a la salud individual y a la sociedad causados por el consumo de drogas lícitas e ilícitas / What and how severe is the damage inflicted by the consumption of licit and illicit drugs upon the health of human individuals and upon society

Resumen En vista del amplio consumo de drogas lícitas e ilícitas en casi todo el mundo occidental, nosotros sospechamos que no eran tantos ni tan graves los daños que causan, como se afirma, y decidimos evaluar la solidez de tal sospecha. La sospecha resultó correcta en términos de la salud física individual de los usuarios, pues las drogas no aparecen entre las primeras quince causas de Morbilidad ni de Mortalidad en los habitantes de México, EUA, Canadá, España, el Reino Unido y Holanda. En cambio, las drogas sí causan daño psicológico y social al individuo por propiciar indolencia motivacional, cuadros psicóticos serios, potencialmente irreversibles, e inducir la comisión de conductas riesgosas (accidentes de tránsito) y hasta criminales (robos, asaltos, violaciones). El consumo de drogas también lesiona la integridad y economía de las familias de los usuarios y daña a la comunidad, pues se eleva la tasa de desempleo, disminuyen los ingresos fiscales, incrementan los costos de los programas de desarrollo, de seguridad y de beneficencia, así como propician la exclusión de los usuarios en el trabajo, escuelas, clubes y servicios públicos diversos. Nuestros resultados son de interés para el diseño de las acciones destinadas al control del consumo de drogas para que sean congruentes con el tipo, gravedad y extensión del daño individual y social que las drogas causen.

Abstract In view of the widespread use of licit and illicit in most of the Western world, we suspect that there were not so many and so serious the damages that they cause, as stated, and we decided to assess the strength of such suspicion. The suspicion was correct in terms of physical health of individual users, as drugs do not appear among the top fifteen causes of morbidity or mortality in the population of Mexico, USA, Canada, Spain, the United Kingdom and the Netherlands. However, drugs do cause psychological and social harm to the individual by promoting motivational indolence, serious psychotic symptoms potentially irreversible, and induce the commission of risky behaviors (traffic accidents) and even criminals (robbery, assault, rape). Drug use also damages the integrity and economy of the families of users and harms to the community, since it raises the rate of unemployment, lower tax revenues, increase costs of development programs, safety and welfare, and favor the exclusion of users in the workplace, schools, clubs and various utilities. Our results are of interest for the design of actions to control drug use to be consistent with the type, severity and extent of the individual and social harm that drugs cause.

Neurocysticercosis is still prevalent in Mexico / La neurocisticercosis es aún prevalente en México

In this work, we report the published cases of human and porcine cysticercosis, as well as Taenia solium taeniasis diagnosed in Mexico during the last 10 years. Numerical data allow us to state that this disease remains as a public health problem in our country. Whereas efficient tools have been developed for the diagnosis and prevention of cysticercosis, we strongly recommend further measures allowing the control and eventual eradication of this parasite in Mexico.

En este trabajo reportamos los casos publicados de cisticercosis humana y porcina, así como de teniosis por Taenia solium diagnosticados en México en los últimos 10 años. Los datos numéricos nos permiten sostener que esta parasitosis continúa siendo un problema de salud pública en nuestro país. Considerando que se han desarrollado herramientas eficientes para el diagnóstico y la prevención de la cisticercosis, recomendamos enfáticamente seguir promoviendo las medidas que permitan el control y posterior erradicación de esta parasitosis en México.

Neurocysticercosis is still prevalent in Mexico.

In this work, we report the published cases of human and porcine cysticercosis, as well as Taenia solium taeniasis diagnosed in Mexico during the last 10 years. Numerical data allow us to state that this disease remains as a public health problem in our country. Whereas efficient tools have been developed for the diagnosis and prevention of cysticercosis, we strongly recommend further measures allowing the control and eventual eradication of this parasite in Mexico.

Protein and antigen diversity in the vesicular fluid of Taenia solium cysticerci dissected from naturally infected pigs.

Cysticercosis caused by Taenia solium is a health threat for humans and pigs living in developing countries, for which there is neither a flawless immunodiagnostic test nor a totally effective vaccine. Suspecting of individual diversity of hosts and parasites as possible sources of the variations of the parasite loads among cysticercotic animals and of the limited success of such immunological applications as well as, we explored and measured both in nine cases of naturally acquired porcine cysticercosis. For this purpose, 2-Dimensional IgG immunoblots were performed by reacting the sera of each cysticercotic pig with the antigens contained in the vesicular fluid (VF) of their own cysticerci. We found an unexpectedly large diversity among the proteins and antigens contained in each of the nine VFs. Also diverse were the serum IgG antibody responses of the nine pigs, as none of their 2D- immunoblot images exhibited the same number of spots and resembled each other in only 6.3% to 65.3% of their features. So large an individual immunological diversity of the cysticercal antigens and of the infected pigs´ IgG antibody response should be taken into account in the design of immunological tools for diagnosis and prevention of cysticercosis and should also be considered as a possibly significant source of diversity in Taenia solium´s infectiveness and pathogenicity.

Recombinant S3Pvac-phage anticysticercosis vaccine: Simultaneous protection against cysticercosis and hydatid disease in rural pigs.

This paper provides macroscopic and histological evidence on the statistically significant protective effects of S3Pvac-phage vaccination against porcine cysticercosis and hydatidosis. The study included 391 rustically bred pigs (187 vaccinated and 204 controls). Vaccination significantly reduced the prevalence of cysticercosis by 61.7%. Vaccination also significantly reduced by 56.1% the prevalence of hydatidosis caused by Echinococcus granulosus in pigs. The presence of the vaccine epitopes in both cestodes is probably involved in the cross-protection observed. Increased inflammation was found in 5% of cysticerci recovered from controls, versus 24% from vaccinated pigs (P<0.01). Hydatid cysts were non-inflammatory in either group. Vaccination was effective to prevent one single disease, but it failed to prevent the simultaneous infections with both parasites in a same pig. The widening of the S3Pvac-phage vaccine protective repertoire to include hydatidosis is a convenient feature that should reduce the prevalence of two frequent zoonoses that affect rustic porcine breading with a single action. Thus, the costs of two different vaccination programs would be reduced to a single one with significant reduction in both zoonoses.

Quantitative and phenotypic analyses of lymphocyte-monocyte heterokaryons induced by the HIV envelope proteins: Significant loss of lymphoid markers.

Cells infected with the human immunodeficiency virus (HIV) can fuse with CD4(+) cells leading to the formation of multinucleated cells. The presence of multinucleated cells infected with HIV in tissues of patients has been documented, although their cellular composition and role in AIDS pathogenesis is still under study. Here, we present evidence of in vitro heterotypic lymphocyte-monocyte fusion in cocultures of lymphocytic Jurkat T cells expressing the HIV-1 gp120/gp41 glycoproteins (Env) and CD4(+) monocytic THP-1 cells. Using a previously characterized method that involves differential labeling of fusion partners with fluorescent probes and flow cytometry analysis after coculture, up to 20% of double fluorescent cells were detected in 48h. This double fluorescent cell population was produced by heterotypic lymphocyte-monocyte fusion as it was not observed when Jurkat T cells expressing a mutant non-fusogenic Env protein were used. Heterokaryon formation was inhibited by an anti-CD4 monoclonal antibody and the HIV-fusion inhibitor peptide T-20. About 68% of heterokaryons remained alive and non-apoptotic after 2days of coculture. In heterokaryons, CD4 was barely detectable and the expression of the CD3 and CD28 lymphoid markers was greatly reduced, whereas the expression of CD32 and the intracellular antigen CD68, both markers of monocytic cells, remained unchanged. In contrast with unfused T cells, heterokaryons only expressed very low levels of the lymphoid activation marker CD25 following treatment with PMA plus ionomycin. These studies point to the possible generation of lymphocyte-monocyte heterokaryons with a myeloid phenotype during HIV infection, with unknown consequences for AIDS pathogenesis.

Neurocysticercosis, a persisting health problem in Mexico.

BACKGROUND: The ongoing epidemiological transition in Mexico minimizes the relative impact of neurocysticercosis (NC) on public health. However, hard data on the disease frequency are not available. METHODOLOGY: All clinical records from patients admitted in the Instituto Nacional de Neurologia y Neurocirugia (INNN) at Mexico City in 1994 and 2004 were revised. The frequencies of hospitalized NC patients in neurology, neurosurgery and psychiatry services, as well as NC mortality from 1995 through 2009, were retrieved. Statistical analyses were made to evaluate possible significant differences in frequencies of NC patients' admission between 1994 and 2004, and in yearly frequencies of NC patients' hospitalization and death between 1995 and 2009. PRINCIPAL FINDINGS: NC frequency in INNN is not significantly different in 1994 and 2004. Between these two years, clinical severity of the cases diminished and the proportion of patients living in Mexico City increased. Yearly frequencies of hospitalization in neurology and psychiatry services were stable, while frequencies of hospitalization in neurosurgery service and mortality significantly decreased between 1995 and 2009. CONCLUSIONS: Our findings show a stable tendency of hospital cases during the last decade that should encourage to redouble efforts to control this ancient disease.

Decreased CD4 and wide-ranging expression of other immune receptors after HIV-envelope-mediated formation of syncytia in vitro.

In human HIV infection, multinucleated cells (syncytia) are formed by fusion of HIV-infected cells with CD4+ cells. In order to examine possible functional implications of syncytia formation for the immune response, the expression of important surface molecules by T-cell syncytia and surrounding cells that remain unfused (bystander cells) was analyzed in cocultures of HIV-Env- and CD4-expressing E6 Jurkat T cells. Fusion partners were differentially labeled with lipophilic probes, and syncytia and bystander cells were identified by flow cytometry. The cellular phenotype and response to activation stimulus after fusion were analyzed with antibodies coupled to third-party fluorochromes. Cocultured unfused E6 cells showed a marked decrease in CD4 expression, suggesting the selective recruitment of cells strongly expressing CD4 into syncytia. However, the incorporated CD4 was not detected in the syncytia, whereas the range of expression of CD28, ICAM-1, CXCR4 and CD3 was wider than that of unfused cells. Limited expression of CD4 in the bystander unfused population, as well as in the newly formed syncytia, would result in limitation of further viral entry and a failure to identify these cells, and it could partially contribute to functional impairment and a decrease in the number of CD4+ T cells in AIDS. Most of the syncytia were viable and expressed CD25 and IL-2 in response to activation by phorbol myristate acetate (PMA) and ionomicyn. Thus, syncytia populations harboring widely heterogeneous levels of receptors would constitute a potential source of anomalous immune function.

Clinical heterogeneity of human neurocysticercosis results from complex interactions among parasite, host and environmental factors.

Human neurocysticercosis (NC) is endemic in most countries of Latin America, Asia and Africa and is re-emerging in some industrialized nations. Both within and among endemic countries, NC is very variable in its clinical and radiological features, as well as in the intensity of the immuno-inflammatory reactions of the hosts. This review, focusing on the Mexican experience, describes and interprets the heterogeneity of NC as the result of different combinations among factors associated with the parasite, host and environment. The review may serve to foster similar descriptive efforts in other endemic areas of the world in order to facilitate the identification of the distinct factors that participate in the complex pathogenesis and diverse clinical outcomes of NC. In particular, it is necessary to understand the precise physiopathology of the inflammatory reaction associated with NC, as inflammation is one of the characteristics of those NC cases that are clinically more severe and less responsive to current treatments. Devising new medical interventions through the use of molecular regulators of the innate and adaptive immune responses of the host is a largely unexplored approach that could improve the existing forms of treatment.

Budding of Taenia crassiceps cysticerci in vitro is promoted by crowding in addition to hormonal, stress, and energy-related signals.

Taenia crassiceps cysticerci (cysts) reproduce by budding. The cysts' production of buds was measured in vitro to explore parasite and environmental-related factors involved in the extreme individual variation in parasite loads of inbred mice. Cysts were placed in in vitro culture for 10 days at initial parasite densities of 1, 5, 10 cysts/well in 1 ml of RPMI Medium 1640 without serum. Results showed that there is considerable intrinsic initial variation among inoculated cysts in their production of buds and that increasing parasite density (crowding) stimulates the overall production of buds and recruit into budding most of the cysts. Identical cultures were then subjected to various treatments such as heating and exposure to peroxide to induce stress, or to 17beta-estradiol, insulin, glucose, or insulin+glucose to supplement putatively limiting hormonal and energy resources. All treatments increased budding but the parasites' strong budding response to crowding alone overshadows the other treatments.