Prolactin levels correlate with abnormal B cell maturation in MRL and MRL/lpr mouse models of systemic lupus erythematosus-like disease.

Prolactin (PRL) plays an important role in modulating the immune response. In B cells, PRL enhances antibody production, including antibodies with self-specificity. In this study, our aims were to determine the level of PRL receptor expression during bone-marrow B-cell development and to assess whether the presence of high PRL serum concentrations influences absolute numbers of developing populations and disease outcome in lupus-prone murine models. We observed that the PRL-receptor is expressed in early bone-marrow B-cell; the expression in lupus-prone mice, which had the highest level of expression in pro-B cells and immature cells, differed from that in wild-type mice. These expression levels did not significantly change in response to hyperprolactinemia; however, populations of pro-B and immature cells from lupus-prone strains showed a decrease in the absolute numbers of cells with high PRL-receptor expression in response to PRL. Because immature self-reactive B cells are constantly being eliminated, we assessed the expression of survival factor BIRC5, which is more highly expressed in both pro-B and immature B-cells in response to PRL and correlates with the onset of disease. These results identify an important role of PRL in the early stages of the B-cell maturation process: PRL may promote the survival of self-reactive clones.

Increased levels of prolactin receptor expression correlate with the early onset of lupus symptoms and increased numbers of transitional-1 B cells after prolactin treatment.

BACKGROUND: Prolactin is secreted from the pituitary gland and other organs, as well as by cells such as lymphocytes. Prolactin has an immunostimulatory effect and is associated with autoimmune diseases that are characterised by abnormal B cell activation, such as systemic lupus erythematosus (SLE). Our aim was to determine if different splenic B cell subsets express the prolactin receptor and if the presence of prolactin influences these B cell subsets and correlates with development of lupus. RESULTS: Using real-time PCR and flow cytometry, we found that different subsets of immature (transitional) and mature (follicular, marginal zone) B cells express different levels of the prolactin receptor and are differentially affected by hyperprolactinaemia. We found that transitional B cells express the prolactin receptor at higher levels compared to mature B cells in C57BL/6 mice and the lupus-prone MRL/lpr and MRL mouse strains. Transitional-1 (T1) B cells showed a higher level of prolactin receptor expression in both MRL/lpr and MRL mice compared to C57BL/6 mice. Hyperprolactinaemia was induced using metoclopramide, which resulted in the development of early symptoms of SLE. We found that T1 B cells are the main targets of prolactin and that prolactin augments the absolute number of T1 B cells, which reflects the finding that this B cell subpopulation expresses the highest level of the prolactin receptor. CONCLUSIONS: We found that all B cell subsets express the prolactin receptor but that transitional B cells showed the highest prolactin receptor expression levels. Hyperprolactinaemia in mice susceptible to lupus accelerated the disease and increased the absolute numbers of T1 and T3 B cells but not of mature B cells, suggesting a primary effect of prolactin on the early stages of B cell maturation in the spleen and a role of prolactin in B cell differentiation, contributing to SLE onset.

Intranasal anti-rabies DNA immunization promotes a Th1-related cytokine stimulation associated with plasmid survival time.

BACKGROUND AND AIMS: DNA vaccination has a great potential to decrease infectious diseases worldwide, such as rabies. Here we showed the effects of a single anti-rabies DNA vaccination applied intranasally (IN) on plasmid survival time, neutralizing antibody (NA) titers, G-protein expression and Th1/Th2-related cytokines. METHODS: Only one 50-µg dose of an anti-rabies DNA vaccine was IN administered to 160 Balb/c mice. Twenty mice were used for the neutralizing antibody study, 35 for the proliferation assay, 35 for Th1/Th2-related cytokines, 35 for glycoprotein expression by immunocytochemistry, and 35 for pGQH detection and G-protein mRNA expression. RESULTS: Th1-type related cytokines from spleen cells (IFN-γ, TNF-α, and IL-2) were detected. Rabies NA titers were ≥0.6 IUs from day 30 onward in the IN DNA-vaccinated group. The plasmid was identified in brains and lungs from days 3-15. The mRNA transcript was amplified in brains and lungs from days 3-30, and G-protein expression was observed in spleens, brains and lungs on days 3, 8, and 15. In all cases, a gradual decrease was observed on days 30 and 45 and absent on day 60. CONCLUSIONS: We found that Th1-type related cytokines (IL-2, IFN-γ, and TNF-α) were stimulated during the first month after DNA vaccination, correlating with the proliferation assays. Also, it was associated with the plasmid survival time remaining in lungs and brains prior to its degradation.

Effects of administration of caffeine on metabolic variables in neonatal pigs with peripartum asphyxia.

OBJECTIVE: To determine effects of 2 doses of caffeine on metabolic variables in neonatal pigs with peripartum asphyxia. ANIMALS: 180 neonatal pigs. PROCEDURES: Neonatal pigs were assigned to 2 groups (groups P and F) on the basis of results for a vitality scale (passed or failed, respectively). Within each group, there were 3 subgroups of 30 pigs each. Within each group, the 3 subgroups received a placebo that consisted of an empty gelatin capsule, a gelatin capsule that contained 20 mg of caffeine, and a gelatin capsule that contained 35 mg of caffeine, respectively; all capsules were administered orally (0 hours). Blood samples were collected immediately before and 24 hours after capsule administration. RESULTS: Pigs in groups P and F that received 20 or 35 mg of caffeine had significant increases in triglyceride concentrations. All pigs in groups P and F had a significant decrease in lactate concentrations, although the placebo-treated pigs in group F had larger decreases than did the group F pigs treated with 20 or 35 mg of caffeine. Glucose concentrations increased significantly in group F pigs treated with 20 or 35 mg of caffeine (30% and 50%, respectively), whereas glucose concentrations remained unchanged in group P pigs. In pigs treated with 35 mg of caffeine, the final weight obtained for group F was approximately 8% lower than that obtained for group P. CONCLUSIONS AND CLINICAL RELEVANCE: Administering caffeine immediately after birth to neonatal pigs with severe oxygen restriction resulted in significant improvements in metabolic variables.

Efecto de la aplicación de oxitocina en variables críticas sanguíneas de cerdas distócicas / Effects of oxytocin on critical blood variables from dystocic sows

The aim of the study was to monitor the sow maternal response to a low oxitocin dose in an advanced parturition stage in eutocic and maternal-foetal dystocia. Sixty York x Landrace sows, 30 with eutocic farrowing and 30 with maternal-foetal dystocia were assigned into two different groups: 15 received 0.083 IU/kg of oxytocin after the expulsion of the fifth piglet, and 15 received no treatment at all. Blood samples from every sow in trial were taken from the ear vein at three different times: immediately after membrane rupture, after the fifth piglet was born, and at the end of the farrowing. A third generation blood gas analyzer was used. Results show that when parturition was resumed, sows with maternal-foetal dystocia had significantly greater lactate, pCO2 and ear temperature (P < 0.001), compared with the eutocic sow group. Results from physiological variables and neonatal traits monitored in this experiment show evidence that oxytocin should not be used in normal parturition without stillbirths, since oxytocin in this case had adverse effects on sow performance. Oxytocin administered at the beginning of the second half of parturition decreased 50% the number of born alive with asphyxia in eutocic and dystocic sows, and on the other hand, decreased 50% the number of intra-partum stillbirths in the dystocic group. This is the first study describing the critical blood variables in dystocic sows (pH, pCO2, pO2, glucose, lactate and HCO3), using a third generation gasometry device.

Con el propósito de evaluar las respuestas maternas a dosis baja de oxitocina en estado avanzado del parto en cerdas con eutocia y distocia materno-fetal, se seleccionaron 60 cerdas de la cruza Yorkshire x Landrace, 30 eutócicas y 30 con distocia materno-fetal. Las cerdas de cada grupo fueron divididas en subgrupos: 15 recibieron 0.083 UI/kg de oxitocina después de la expulsión del quinto lechón, las otras 15 no fueron tratadas. Se obtuvieron muestras sanguíneas en cada una de las cerdas mediante punción de vena auricular después de la rotura de la fuente, al quinto lechón y al finalizar el parto; las muestras fueron evaluadas con un analizador de gases sanguíneos. Al finalizar el parto, las cerdas que presentaron partos con distocia materno-fetal incrementaron significativamente (P < 0.001) los niveles de lactato, pCO2 y temperatura, respecto de las hembras que presentaron partos eutócicos. Los resultados de las variables fisiológicas y los indicadores neonatales evaluados en este experimento son evidencia de que la oxitocina no debe aplicarse en partos con evolución normal sin nacidos muertos, ya que posee efectos adversos sobre el desempeño de la cerda. La oxitocina en cerdas, administrada al inicio de la segunda mitad del parto, disminuyó en 50% los nacidos con asfixia en cerdas eutócicas y distócicas; asimismo, redujo en 50% el número de muertes intraparto en las hembras distócicas. Los resultados del presente experimento determinan por primera vez la evolución de los parámetros críticos sanguíneos de la cerda con partos distócicos (pH, pCO2, pO2, glucosa, lactato y HCO3) utilizando equipo de gasometría de tercera generación.

Frequency of the serological reactivity against the caprine arthritis encephalitis lentivirus gp135 in children who consume goat milk.

BACKGROUND: Caprine arthritis encephalitis virus (CAEV) is a retrovirus belonging to the lentivirus genus that also includes the human immunodeficiency virus (HIV). CAEV may be transmitted to humans by goat milk consumption. It has been suggested that CAEV may also be involved in the immunological protection process against HIV, but this has not been demonstrated. Here we identified serological reactivity against CAEV gp135 in children who consumed goat milk. METHODS: Thirty sera samples from children (males between 6 and 16 years of age) who regularly consumed goat milk and a negative control of 30 serum samples from children (males between 6 and 12 years) with no previous contact with goats or goat dairy products were used. All sera were tested by Western blot against CAEV antigens. RESULTS: There were 18/30 serum samples from goat milk consumers that were reactive to CAEV gp135, and one reacted against gp50 simultaneously; none of the 30 serum samples from nonconsumers of goat dairy products reacted to viral proteins. CONCLUSIONS: These results showed that the positive response to gp135 may be the result of a repetitive stimulation without viral replication or the result of CAEV replication in humans. CAEV gp135 is codified by the env gene located on the viral particle surface as well as gp50. Moreover, there are similarities between CAEV gp135 and HIV-1 gp120, so there is a possibility that CAEV replicates in humans and may participate in immunological cross-phenomena, but this should be further studied.

Obstetric and fetal outcomes in dystocic and eutocic sows to an injection of exogenous oxytocin during farrowing.

Sixty hybrid Yorkshire-Landrace penned sows, 30 with eutocic farrowing and 30 experiencing a dystocic parturition, were studied to evaluate the obstetric and neonatal outcomes to low doses of oxytocin administered at advanced stages of parturition. Animals in each group were randomly subdivided into 2 subgroups: 15 eutocic and 15 dystocic sows received oxytocin 0.083 IU/kg (equivalent to 1 IU/12 kg body weight), administered intramuscularly after the delivery of the 5th piglet; the other 15 eutocic and 15 dystocic sows received saline solution intramuscularly at the same time. Oxytocin decreased the number of intrapartum deaths by approximately 50% (P = 0.002). No piglet was born dead from the saline- and oxytocin-treated eutocic sows. The highest viability score was observed among piglets born to eutocic sows treated with oxytocin. In summary, this dose schedule would help to decrease the number of stillbirths in both eutocic and dystocic farrowing sows.

Efficient post-exposure prophylaxis against rabies by applying a four-dose DNA vaccine intranasally.

We tested two post-exposure prophylaxes (PEPs) for rabies in laboratory animals; one was a traditional antirabies vaccine for humans via intramuscular route (IM), and the other was a DNA vaccine administered by intranasal route (IN). In contrast to The World Health Organization's recommended five-dose PEP, we gave only four doses without hyper-immune antirabies sera, making the PEP more rigorous. All animals were challenged with challenge virus strain (CVS); 16h later, PEP was applied. All animals that received the PEP with DNA/IN survived, and 87% of the rabbits and 80% of the mice that received the PEP with traditional antirabies vaccine/IM survived. Negative controls succumbed to infection. The expression of G protein was detected in the NALT, cerebellum, cerebral cortex (neocortex), cerebellum and hippocampus, mainly in the glial cells (microglia) and microvessels. On the other hand, plasmid construct was detected in brain and its mRNA expression in medium and posterior encephalon. The efficiency of this DNA/IN PEP is probably due to the early expression of the antigen in the brain stimulating the immune system locally.

Intradermal DNA vaccination in ear pinnae is an efficient route to protect cats against rabies virus.

A DNA vaccine against rabies (pGQH) was administrated to cats in order to examine different administration routes. Four groups of three cats each were inoculated with pGQH as follows: group A, intramuscularly (IM), 100 microg; group B, intranasally (IN), 100 microg; group C, intradermally into ear pinnae (ID-EP), 100 microg, and group D, IM, 200 microL of phosphate buffer solution (PBS) alone (control group). Blood was drawn on days 0, 30, 60, 90, 120, 150, and 180. Groups A, B, and C received a booster on day 30. At day 200 all animals were challenged. A passive transfer of cat sera, as well as a viral challenge, was performed in mice. The results displayed that neutralizing antibody titers were higher in cats of group C (ID-EP) showing high early titers (> 2 IU) and the highest titer was on day 120 (> 14 IU). In group B (IN), two out of three cats seroconverted on day 30 (> 0.5 IU), the third cat seroconverted until day 60 (> 0.5 IU). In contrast, the lowest levels of neutralizing antibodies were detected in group A (IM). The control group showed no anti-rabies antibodies. Groups A (IM) and D (control) succumbed after lethal challenge. All animals from the ID-EP group (C) survived, only one individual from the IN (B) group died. Mice that received cat sera from ID-EP, IM, and IN groups survived and were protected (30/30 survivors). Mice groups that received pre-immunization sera from cats were not protected (0/30 survivors). This study demonstrates that pGQH immunization was successful when it was administrated ID-EP, and acceptable through the IN route. The IM route, however, was not effective in cats. For vaccination, the IN route seems attractive due to its accessibility for application, but it seems to activate seroconversion slowly. The best route to promote anti-rabies antibody titers was the ID-EP route. This practical and efficient route should be further studied.

Obstetric and neonatal outcomes to recombinant porcine somatotropin administered in the last third of pregnancy to primiparous sows.

This study aimed to investigate whether the administration of recombinant porcine somatotropin (rpST) late in gestation is associated with increased rates of obstetric and neonatal complications in primiparous sows. From days 80 to 114 of gestational age, 20 primiparous sows were randomly assigned to receive an intramuscular injection of either saline or 6 mg rpST/day. Throughout pregnancy, sows were fed 2.5 to 3 kg/day of a corn-soybean diet (14 MJ ME/kg). Of 111 piglets born to control sows and 109 piglets born to treated sows, 8.1% and 17.4% piglets respectively died intrapartum (P=0.04). Glucose blood levels in sows and live-born piglets in the rpST-treated group were significantly higher than in their corresponding controls. Birth weight of live-born piglets in the treated group was 1.4 +/- 0.1 kg versus 1.3 +/- 0.1 kg in the control group (P<0.0001). Birth weight of piglets born dead was also higher in the former than in the latter group (P<0.0001). No evidence of teratogenicity was observed in either of the groups. In conclusion, rpST administration in late pregnancy to primparous sows increased the rate of neonatal deaths and was associated with higher blood glucose levels in both sows and piglets.

Cross-reactivity between caprine arthritis-encephalitis virus and type 1 human immunodeficiency virus.

BACKGROUND: Caprine arthritis encephalitis (CAE) is caused by the lentivirus caprine arthritis-encephalitis virus (CAEV), a member of the Retroviridae family that also includes the human immunodeficiency virus (HIV). Serum of CAEV-infected goats cross-reacts with HIV-1 antigens in enzyme-linked immunosorbent assay (ELISA) tests. We attempted to identify the proteins responsible for this cross-reactivity. METHODS: Fifty selected human sera (30 positive, 10 negative, and 10 indeterminate to HIV-1 by Western blot) and 50 selected goat sera (33 positive and 17 negative to CAEV by ELISA) were evaluated. Human and goat sera were tested by Western blot against HIV-1 and CAEV antigens. RESULTS: Cross-reactivity between surface glycoproteins gp120 (HIV-1) and gp135 (CAEV) was specific. Positive reaction of human sera to CAEV gp135 was more intense than that of goat sera to HIV-1 gp120. Surface glycoprotein sequences of the two viruses were compared by Lasergene software (Dynex Technologies, Inc., Chantilly, VA, USA). Three homologous regions were identified: the first in the internal domain of gp120; the second in the beta3 loop, and still another-with the greatest homology-in a short sequence of the proximal region of the external domain of gp120 between loops beta4 and beta8. CONCLUSIONS: Surface glycoproteins of HIV-1 and CAEV share structural regions essential for viral adsorption and for induction of neutralizing antibodies. Thus, human contact with CAEV eventually could be a possible source of HIV-1 false positive reactions and must be considered in the interpretation of HIV serologic results.

Efecto de ondas ultrasónicas de 25 a 50 Khz sobre el rendimiento reproductivo y el peso corporal de ratas Wistar / Effect of 22-50 KHz ultrasonic waves on reproductive performance and weight gain in Wistar rats

El presente trabajo se realizó con el propósito de conocer el efecto de las ondas ultrasónicas generadas por un dispositivo diseñado para ahuyentar roedores y disminuir su reproducción. El efecto de este equipo fue estudiado en ratas Wistar mantenidas en condiciones de bioterio. Con ese propósito se formaron dos grupos de ratas Wistar, uno testigo y el otro experimental, en donde se determinó si la acción constante de un dispositivo productor de ondas ultrasónicas, durante 12 semanas, interfiere con la capacidad reproductiva de ratas Wistar, evaluada por el número de días a parto, número de crías nacidas y destetadas. También se determinó la influencia de las ondas ultrasónicas en el crecimiento y desarrollo de las crías, utilizando como indicador la ganancia de peso semanal desde el destete hasta la doceava semana experimental. Los resultados obtenidos indican que las ondas ultrasónicas no afectan el peso corporal, ya que mediante la prueba de mediciones repetidas se comprobó que si bien existe diferencia aritmética, no hay diferencia estadística entre ambos grupos (P>0.05). En lo que respecta a las crías, el grupo tratado obtuvo 20 crías más que el grupo testigo; sin embargo, no existe diferencia estadística entre ambos grupos (P>0.05). La presencia continua de ondas ultrasónicas tampoco interfirió con la ganancia de peso de las crías, en comparación con el grupo testigo (P>0.05). Se concluye que las ondas ultrasónicas generadas por el aparato no afectan el tamaño y curva de crecimiento posterior al destete de la camada. Como consecuencia de lo anterior no parece recomendable utilizar este tipo de aparatos como un método para el control de roedores.

Cambios histoquímicos en la mucosa gástrica de ratas por el consumo de dietas hipersódicas durante el desarrollo / Histochemical changes in rats' gastric mucosa induced by the intake of high salt diets during postnatal development

La barrera de la mucosa gástrica es el principal mecanismo de protección para el estómago; sin embargo, existen elementos dietéticos irritantes consumidos a diario que pueden llegar a dañar dicha barrera, tal es el caso del cloruro de sodio o sal común. El presente estudio muestra que el consumo crónico de dietas hipersódicas durante el desarrollo posnatal de la rata Wistar, altera el tipo y distribución de mucopolisacáridos de la mucosa gástrica, presentando mucinas predominantemente de tipo intestinal (ácida), este cambio se puede considerar como una variable importante para el diagnóstico de diversas alteraciones gástricas

Ultrasonido Doppler color y terapia endovascular de displasias vasculares superficiales / Color Doppler ultrasound and endovascular approach of superficial vascular displasias

La escleroterapia de las displasias vasculares superficiales se ha monitorizado tradicionalmente con angiografía convencional o con sustracción digital. En este trabajo se evalúa la utilidad del ultrasonido (US) para este propósito. Metodología: Utilizamos ultrasonido bidimensional y Doppler color, para evaluación pre, trans y posesclerosis en 18 pacientes con edades de 24 días a 44 años y polvo de Gelfoam en alcohol absoluto, con contraste yodado, como agente esclerosante. El ultrasoniso (US) fue la guía fundamental y la angiografía digital sólo de apoyo secundario y por "seguridad", un anestesiólogo estuvo a cargo de la sedación y monitoreo de funciones vitales

Análisis bibliométrico de las características de los roedores y lagomorfos utilizados en investigaciones publicas en México, 1980-1989 / Use of terms describing the characteristics of rodents and rabbits in research published in Mexico from 1980 to 1989

Se realizó un estudio bibliométrico para conocer la información proporcionada sobre las características de los roedores y conejos de laboratorio en investigaciones publicadas en México de 1980 a 1989. De la sección de material y métodos, de cada artículo, se extrajeron las caracteristicas biológicas y ambientales que los comités editoriales de revistas internacionales recomiendan se incluyan, para asegurar la reproducibilidad y confiabilidad de los resultados. Estas fueron: 1. Especie y Número de animales utilizados, 2. cepa, 3. características biológicas (sexo, edad, peso, genotipo), 4. condición microbiológica o salud, 5. condiciones ambientales y tipo de alimentación y 6. periodo de aclimatación. Las especies y cepas más iutilizadas fueron la rata (57.74 por ciento) cepa Wistar (83 por ciento) y el ratón (15.49 por ciento) cepa BALB/C (70 por ciento). Sin embargo, la cepa sólo mencionó en el 50 por ciento de los trabajos. La edad y peso de los animales empleados mostró tendencia al uso de animales adultos jóvenes; sin embargo, esta información se omitió tambien en el 24 por ciento de los artículos publicados. Respecto a las condiciones de alojamiento, alimentación, condición microbiológica y periodo de cuarentena, éstas se mencionaron sólo en 2 a 16 por ciento de los trabajos. La condición microbiológica convencional fue la más utilizada. La ausencia de los descriptores antes mencionados dificulta la reproducibilidad de las investigaciones; por ello, se sugiere que los comités editoriales soliciten a los autores la inclusión en su trabajo de estos descriptores

Derivación bilioentérica convergente con mecanismo antireflujo: estudio experimental / Biliary-enteric derivation with antirefluz technic: an experimental study

Con el objeto de evitar reflujo en las derivaciones bilio-entéricas y las complicaciones que se derivan de este fenómeno: se puso a prueba una nueva técnica de derivación, denominada convergente con plicatura entero-entérica. Dicho procedimiento se llevó a cabo en un grupo de perros mestizos recién destetados. Los resultados mostraron que la nueva técnica presentó un menor número de complicaciones, comparada con las que se observaron en sujetos con la derivación "habitual en Y de Roux. No obstante, no suprime los efectos iniciales de la contaminación bilio-hepática