Resistance to deltamethrin in Triatoma infestans (Hemiptera: Reduviidae): Does it influence the phenotype of antennae, wings, and heads?

In vector control terms, insecticide resistance is the development of the capacity, of an insect population, to tolerate doses of an insecticide that are lethal to most individuals in a typical population of the same species. The genetic changes that determine resistance may have adaptive costs in the resistant phenotype or, conversely, may result in an adaptive advantage when compared to susceptible insects in the environment without insecticides. Triatoma infestans is one of the main vectors of Trypanosoma cruzi in the southern cone of South America. High insecticide resistance in T. infestans was detected in Argentina in Salta and Chaco provinces. The objective of this study was to determine the possible morphometric changes in wings, heads, and the antennal phenotype of deltamethrin-resistant T. infestans (RR) males and females compared to susceptible insects (SS), evaluating its implication in adaptive processes such as olfactory capacity, dispersion, and probability of colonizing new habitats, among others. Nine type I landmarks were marked on wings, 5 type II landmarks on heads, and 10 antennal sensilla were counted on 106 adults of both sexes (resistant and susceptible from first and second laboratory generations). Morphological divergence was observed between the two groups (RR and SS). The RR insects showed smaller sizes of wings and heads and shape compatible with lower dispersal potential and different active dispersal behaviors. Antennae also revealed sensory simplification in RR and divergence between RR and SS, although more marked in females. This study characterizes for the first time T. infestans RR and SS through wings, heads, and antennae. The results suggest a lower dispersive potential in resistant insects and the differences described lay the foundations for the identification of a resistance biomarker in triatomines.

Modelo multivariable para la planificación del entrenamiento en fútbol profesional / Multivariable Training Planning Model in Professional Soccer

El objetivo de este estudio fue describir un modelo multivariable de planificación del entrenamiento para la monitorización semanal y su periodización en relación con el perfil dinámico competitivo. Veintidós futbolistas profesionales participaron este estudio. Se analizaron 30 microciclos competitivos donde se registró individualmente todas las sesiones de entrenamiento y partidos de competición mediante GPS. Los resultados mostraron una fase de carga con valores cercanos a los alcanzados en competición, pero con estímulos diferenciados en días consecutivos, y otra fase de reducción de la carga en forma de tapering previa a la competición. La carga acumulada semanalmente mostró poca variabilidad entre los microciclos, observándose un promedio de 0.6%. La gestión dinámica de la carga presentó una ratio A:C que osciló entre 0.89-1.13. El modelo multivariable para la planificación del entrenamiento semanal es un método eficaz para monitorizar la carga del entrenamiento en relación con el perfil de rendimiento. (AU)

The aim of this study was to describe a multivariable training planning model for weekly monitoring and its periodization in relation to the dynamic competitive profile. Twenty-two professional soccer players participated in this study. Thirty competitive microcycles were analyzed. Thirty competitive microcycles were recorded individually in all training sessions and competition matches through a GPS device. The results showed a loading phase with values close to those achieved in competition, but with differentiated stimuli on consecutive days, and another phase of load reduction in the form of tapering prior to competition. The weekly accumulated load showed little variability between the microcycles; an average of 0.6% was observed. Dynamic load management presented an A: C ratio that ranged from 0.89-1.13. It can be concluded that the multivariate model for planning weekly training is an effective method to monitor training load in relation to performance profile. (AU)

Contaminating viral sequences in high-throughput sequencing viromics: a linkage study of 700 sequencing libraries.

OBJECTIVES: Sample preparation for high-throughput sequencing (HTS) includes treatment with various laboratory components, potentially carrying viral nucleic acids, the extent of which has not been thoroughly investigated. Our aim was to systematically examine a diverse repertoire of laboratory components used to prepare samples for HTS in order to identify contaminating viral sequences. METHODS: A total of 322 samples of mainly human origin were analysed using eight protocols, applying a wide variety of laboratory components. Several samples (60% of human specimens) were processed using different protocols. In total, 712 sequencing libraries were investigated for viral sequence contamination. RESULTS: Among sequences showing similarity to viruses, 493 were significantly associated with the use of laboratory components. Each of these viral sequences had sporadic appearance, only being identified in a subset of the samples treated with the linked laboratory component, and some were not identified in the non-template control samples. Remarkably, more than 65% of all viral sequences identified were within viral clusters linked to the use of laboratory components. CONCLUSIONS: We show that high prevalence of contaminating viral sequences can be expected in HTS-based virome data and provide an extensive list of novel contaminating viral sequences that can be used for evaluation of viral findings in future virome and metagenome studies. Moreover, we show that detection can be problematic due to stochastic appearance and limited non-template controls. Although the exact origin of these viral sequences requires further research, our results support laboratory-component-linked viral sequence contamination of both biological and synthetic origin.

'RA and the microbiome: do host genetic factors provide the link?

Rheumatoid arthritis (RA) is a chronic autoimmune disease, characterised by painful synovium inflammation, bony erosions, immune activation and the circulation of autoantibodies. Despite recent advances in therapeutics enabling disease suppression, there is a considerable demand for alternative therapeutic strategies as well as optimising those available at present. The relatively low concordance rate between monozygotic twins, 20-30% contrasts with heritability estimates of ∼65%, indicating a substantive role of other risk factors in RA pathogenesis. There is established evidence that RA has an infective component to its aetiology. More recently, differences in the commensal microbiota in RA compared to controls have been identified. Studies have shown that the gut, oral and lung microbiota is different in new onset treatment naïve, and established RA patients, compared to controls. Key taxonomic associations are an increase in abundance of Porphyromonas gingivalis and Prevotella copri in RA patients, compared to healthy controls. Host genetics may provide the link between disease and the microbiome. Genetic influence may be mediated by the host immune system; a differential response to RA associated taxa is suggested. The gut microbiome contains elements which are as much as 30% heritable. A better understanding of the influence of host genetics will shed light onto the role of the microbiome in RA. Here we review the role of the microbiome in RA through the lens of host genetics, and consider future research areas addressing microbiome study design and bioinformatics approaches.

Estatus funcional de adultos mayores de Tláhuac, Ciudad de México / Functional status of senior adults in Tlahuac, Mexico City / Status funcional de idosos de Tláhuac, Cidade do México

Resumen La identificación de la capacidad de funcionalidad en el adulto mayor es una valoración conveniente. Se concibe que la funcionalidad está relacionada con lograr satisfacer sus necesidades básicas, bienestar emocional y social, significa independencia y, por lo tanto, con calidad de vida. El objetivo de este estudio fue identificar el grado de funcionalidad que presentan los adultos mayores de 60 años y mayores que asisten a consulta en 4 centros de salud ubicados en la delegación Tláhuac, Ciudad de México durante el periodo de junio a diciembre de 2014. Fue una investigación exploratoria, en una muestra por conveniencia de 754 adultos mayores; se utilizaron 5 ítems del apartado A del instrumento "Evaluación Funcional del Adulto Mayor" el cual fue aplicado en los centros de salud. Para el procesamiento de la información se utilizó estadística descriptiva. Resultados: El 82% de los adultos mayores fueron independientes y el 18% están en riesgo de dependencia. Las actividades que presentaron menor porcentaje de dependencia fueron preparar sus alimentos y realizar tareas domésticas. Conclusión: Los resultados arrojados en el presente estudio implican sensibilizar a los profesionales de los centros de salud para que incorporen en sus programas propuestas para mantener la funcionalidad en este grupo etario como son ejercicio mental y físico, hábitos alimentarios, ocupación del tiempo y el manejo de situaciones estresantes.

Abstract It is important to address the functional status of senior adults because this is an indicator of their capacities to fulfill their basic needs, as well as to have emotional and social wellbeing, and thus to live a life with quality and independence. The objective of this study was to identify the degree of functionality in seniors 60 years and older who visit four health centers in Tlahuac, Mexico City. Data were collected from June to December 2014. This was an exploratory study on a convenience sample of 754 senior adults. Five items from the section A of the instrument Senior Adult Functional Status (Evaluación Funcional del Adulto Mayor (EFAM)) were used. The questions were asked in the health centers. Descriptive statistics were performed. Results: 82% of the seniors showed being independent while 18% were at risk of being dependent. The activities which demonstrated lower percentage of dependence were preparation of their food and performing their domestic tasks, Conclusion: The findings of this study suggest that health professionals should be sensitized to incorporate proposals in their programs to help maintain the functional status of this population. These activities should focus on: physical and mental exercise, good dietary habits, adequate use of time, and stress management.

Resumo A identificação da capacidade de funcionalidade em idosos é uma valorização conveniente. Concebendo que a funcionalidade está relacionada em conseguir satisfazer suas necessidades básicas, bem-estar emocional e social, significa independência, neste conceito a qualidade de vida está considerada. O objetivo deste estudo foi identificar o grau de funcionalidade que apresentam os idosos de 60 anos e mais velhos, que assistem a consulta em quatro centros de saúde localizados no município Tláhuac, Cidade de México, durante o período de junho a dezembro de 2014. Foi uma pesquisa exploratória, em uma amostra de conveniência de 754 idosos, utilizaram-se cinco itens do apartado A do instrumento "Avaliação Funcional do Idoso" (EFAM), o qual foi aplicado nos centros de saúde. Para o processamento da informação utilizou-se estatística descritiva. Resultados: O 82% dos idosos foram independentes e o 18% estão em risco de dependência. As atividades que apresentaram menor porcentagem de dependência foram preparar seus alimentos e realizar fazeres domésticos. Conclusão: Os resultados obtidos no presente estudo procuram sensibilizar aos professionais dos centros de saúde para que incorporem nos seus programas, propostas para manter a funcionalidade neste grupo etário como são o exercício físico e mental, hábitos alimentares, ocupação do tempo e o manejo de situações estressantes.

Economic analysis of the single-dose immunization strategy against hepatitis A in Argentina.

BACKGROUND: Vaccination against hepatitis A (HA) was carried out only as part of a limited outbreak control strategy in Argentina until June 2005, when universal immunization in infants was introduced into the national immunization calendar. A single-dose strategy was chosen instead of the standard two-dose schedule used elsewhere. This study aimed to estimate preventive, medical, and non-medical costs related to HA and to compare these costs in the periods before and after mass vaccination. METHODS: A retrospective analysis estimated treatment costs of HA and unspecified hepatitis cases reported to the National Health Surveillance System from 2000 to 2010. Costs related to immunization, fulminant hepatitis (FH), liver transplantation, and death were projected as well. Using a social perspective and a healthcare system perspective, costs in two 5-year periods were compared: 2000-2004 versus 2006-2010. Finally, we evaluated the impact of different discount rates, FH risk, and exclusion of unspecified hepatitis cases in the sensitivity analysis. RESULTS: Total HA and unspecified hepatitis cases decreased from 157,871 in 2000-2004 to 17,784 in 2006-2010. Medical and non-medical costs decreased from US$11,811,600 and US$30,118,222 to US$1,252,694 and US$4,995,895 in those periods, respectively. Immunization costs increased from US$6,506,711 to US$40,912,132. Total preventive, medical, and non-medical costs decreased from US$48,436,534 to US$47,160,721, representing a 2.6% reduction in total costs between the two periods. When a healthcare system perspective was considered or unspecified hepatitis cases were excluded, total costs were 130.2% and 30.8% higher in 2006-2010 than in the previous period, respectively. CONCLUSION: After implementation of the universal single-dose vaccination against HA in infants in Argentina, an impressive decline was observed in HA cases, with a decrease in medical and non-medical costs in the first 5 years. The single-dose strategy, which is simpler and less expensive than the standard two-dose scheme, can be a good alternative for future vaccination policies in other countries where HA is endemic.

Comparison of two wild rodent species as sentinels of environmental contamination by mine tailings.

BACKGROUND: Contamination with heavy metals is among the most hazardous environmental concerns caused by mining activity. A valuable tool for monitoring these effects is the use of sentinel organisms. Particularly, small mammals living inside mine tailings are an excellent study system because their analysis represents a realistic approach of mixtures and concentrations of metal exposure. PURPOSE: We analyzed metal tissue concentrations and DNA damage levels for comparison between genders of a sentinel (Peromyscus melanophrys) and a nonsentinel (Baiomys musculus) species. Also, the relationship between DNA damage and the distance from the contamination source was evaluated. METHODS: This study was conducted in an abandoned mine tailing at Morelos, Mexico. Thirty-six individuals from both species at the exposed and reference sites were sampled. Metal concentrations in bone and liver of both species were analyzed by atomic absorption spectrophotometry, and DNA damage levels were assayed using the alkaline comet assay. RESULTS: In general, concentrations of zinc, nickel, iron, and manganese were statistically higher in exposed individuals. A significant effect of the organ and the site on all metal tissue concentrations was detected. Significant DNA damage levels were registered in the exposed group, being higher in B. musculus. Females registered higher DNA damage levels than males. A negative relationship between distance from the mine tailing and DNA damage in B. musculus was observed. CONCLUSIONS: We consider that B. musculus is a suitable species to assess environmental quality, especially for bioaccumulable pollutants--such as metals--and recommend that it may be considered as a sentinel species.

Effect of inhaled dust mite allergen on regional particle deposition and mucociliary clearance in allergic asthmatics.

BACKGROUND: Acute exacerbations in allergic asthmatics may lead to impaired ability to clear mucus from the airways, a key factor in asthma morbidity. OBJECTIVE: The purpose of this study was to determine the effect of inhaled house dust mite challenge on the regional deposition of inhaled particles and mucociliary clearance (MCC) in allergic asthmatics. METHODS: We used gamma scintigraphy (inhalation of (99m) Tc -sulphur colloid particles) to measure the regional particle deposition and MCC in allergic asthmatics (n=12) 4 h following an inhaled dust mite allergen challenge (Dermatophagoides farinae extract; PD(max) =fall in forced expiratory volume in 1 s of 10%) for comparison with baseline non-challenge measures. RESULTS: In responders (n=9 PD(max) dose), lung function returned to pre-challenge values by 3 h but was significantly decreased at 6 and 24 h in three of the responders (i.e. late-phase response) and induced sputum eosinophils were increased at 24 h post-challenge (P<0.05). Responders showed enhanced bronchial airway deposition of inhaled particles (P<0.05) and slowed clearance from the central lung zone (P<0.01) at 4 h post-challenge compared with the baseline (no allergen challenge) that was predicted by the PD(max) allergen concentration (r=-0.70, P<0.05). The decline in lung function at 24 h post-challenge correlated with reduced MCC from the central lung zone (r=-0.78, P<0.02) and PD(max) . Non-responders (n=3) showed no change in lung function, regional deposition or MCC post-challenge vs. baseline. CONCLUSIONS AND CLINICAL RELEVANCE: These data suggest that regional deposition and clearance of inhaled particles may be sensitive for detecting mild airway obstruction associated with early- and late-phase allergen-induced effects on mucus secretions. The study was listed on clinicaltrials.gov (NCT00448851).

The dynamics of the O(1D) + HCl --> OH + Cl reaction at a 0.26 eV collision energy: a comparison between theory and experiment.

The dynamics of the O((1)D) + HCl(v = 0, j = 0) --> Cl + OH reaction at a 0.26 eV collision energy has been investigated by means of a quasiclassical trajectory (QCT) and statistical quantum and quasiclassical methods. State-resolved cross sections and Cl atom velocity distributions have been calculated on two different potential energy surfaces (PESs): the H2 surface (Martinez et al. Phys. Chem. Chem. Phys. 2000, 2, 589) and the latest surface by Peterson, Bowman, and co-workers (PSB2) (J. Chem. Phys. 2000, 113, 6186). The comparison with recent experimental results reveals that the PSB2 PES manages to describe correctly differential cross sections and the velocity distributions of the departing Cl atom. The calculations on the H2 PES seem to overestimate the OH scattering in the forward direction and the fraction of Cl at high recoil velocities. Although the comparison of the corresponding angular distributions is not bad, significant deviations with a statistical description are found, thus ruling out a complex-forming mechanism as the dominant reaction pathway. However, for the ClO + H product channel, the QCT and statistical predictions are found to be in good agreement.

Microbial fructosyltransferases and the role of fructans.

Microbial fructosyltransferases are polymerases that are involved in microbial fructan (levan, inulin and fructo-oligosaccharide) biosynthesis. Structurally, microbial fructosyltransferase proteins share the catalytic domain of glycoside hydrolases 68 family and are grouped in seven phylogenetically related clusters. Fructosyltransferase-encoding genes are organized in operons or in clusters associated with other genes related to carbohydrate metabolism or fructosyltransferase secretion. Fructosyltransferase gene expression is mainly regulated by two-component systems or phosphorelay mechanisms that respond to sucrose availability or other environmental signals. Microbial fructans are involved in conferring resistance to environmental stress such as water deprivation, nutrient assimilation, biofilm formation, and as virulence factors in colonization. As a result of the biological and industrial importance of fructans, fructosyltransferases have been the subject of extensive research, conducted to improve their enzymatic activity or to elucidate their biological role in nature.

Colocalization of CB1 receptors with L1 and GAP-43 in forebrain white matter regions during fetal rat brain development: evidence for a role of these receptors in axonal growth and guidance.

There is recent evidence supporting the notion that the cannabinoid signaling system plays a modulatory role in the regulation of cell proliferation and migration, survival of neural progenitors, neuritic elongation and guidance, and synaptogenesis. This assumption is based on the fact that cannabinoid 1-type receptors (CB(1) receptors) and their ligands emerge early in brain development and are abundantly expressed in certain brain regions that play key roles in these processes. We have recently presented in vivo evidence showing that this modulatory action might be exerted through regulating the synthesis of the cell adhesion molecule L1 that is also a key element for those processes. To further explore this issue, we conducted here immunohistochemical studies aimed at determining the cellular substrates of CB(1) receptor-L1 interactions in the rat brain during late fetal development. In this period, we previously found that the activation of CB(1) receptors increased L1 synthesis in several forebrain white matter regions but not in gray matter areas. Using double labeling studies, we observed here colocalization of both proteins in fiber tracts including the corpus callosum, the adjacent subcortical white matter, the internal capsule and the anterior commissure. Experiments conducted with cultures of fetal rat cortical nerve cells revealed that L1 is present mainly in neurons but not in glial cells. This fact, together with the results obtained in the double labeling studies, would indicate that L1 and CB(1) receptors should possibly be present in axons elongating through these white matter tracts, or, alternatively, in migrating neurons. Further experiments confirmed the presence of CB(1) receptors in elongating axons, since these receptors colocalized with growth-associated protein 43 (GAP-43), a marker of growth cones, but not with synaptophysin, a marker of active synaptic terminals, in the same forebrain white matter regions. Lastly, using cultured fetal rat cortical neurons, we also observed that the activation of cannabinoid receptors increased the levels of the full-length L1 and altered those of some active proteolytic fragments of this protein whose generation has been associated with specific steps in the process of neuritic elongation in cultured neurons. In summary, we have demonstrated that the effects caused by cannabinoid agonists on L1 are facilitated by the colocalization of this cell adhesion molecule with CB(1) receptors in several forebrain white matter regions during fetal brain development. We have provided strong evidence that this phenomenon occurs in axons elongating through these white matter tracts, and we have explored in vitro how cannabinoid receptors influence L1 levels. Considering the role played by L1 in different events related to neural development, our observations support the occurrence of a physiological mechanism by which the cannabinoid system might regulate the process of axonal growth and guidance through regulating the synthesis and function of L1.

[Characterization of neuronal ceroid lipofuscinosis in Venezuelan children]. / Caracterización de la ceroidolipofuscinosis en niños venezolanos.

INTRODUCTION: Neuronal ceroid lipofuscinosis (NCL), represents a group of inherited neurodegenerative disorders. Based on the age of the patient at onset, clinical course and ultrastructural morphology it has been identified three clinical types for the pediatric group: 1) Infantile NCL (INCL); 2) Late infantile NCL (LINCL); and 3) Juvenile NCL (JNCL). Other variants or atypical forms represent around 20% of the NCL in different populations. Genetic advances have made possible a better characterization, diagnostic and classification of these disorders. CASE REPORTS: We present the clinical, neurophysiological, neuroradiological, and morphological data from 6 patients with NCL, who were assessed at the pediatric neurology department of the Hospital Universitario de Maracaibo during a ten years period (1993 2003). All 6 cases corresponded with the late infantile form. Age of onset ranged form 2 to 5 years. For most of the patients initial symptoms included seizures, psychomotor delay, accompanied by macular degeneration and optic atrophy. The EEG was characterized by high voltage spikes elicited by low frequency photic stimulation, in 5 cases. Neuroimaging findings were characteristic of the late infantile form of the NCL. In three patients a decreased intensity of signal was seen in the thalami and putamen on T2-weighted images. The ultrastructural examination of the samples obtained through a biopsy showed curvilinear bodies in all patients. CONCLUSION: There is not epidemiological data of the NCL in Venezuela; it is presumed the presence of clinical forms and variants in the pediatric group. This first study could contribute to the knowledge and a better research of this group of disorders in our population.

Telomerase activity in well-differentiated papillary thyroid carcinoma correlates with advanced clinical stage of the disease.

Clinical relevance and stage correlation of telomerase activity in well-differentiated papillary thyroid carcinoma (WD PTC) has not been well determined, as its reported activity could be due to the analysis of tumors with lymphocytic infiltrates or aggressive variants of papillary carcinomas. We conducted a prospective study of telomerase activity in WD PTC without inflammatory infiltrates and correlated it with clinical stage. Fifty WD PTCs were analyzed for telomerase activity by PCR-based TRAP (telomeric repeat amplification protocol) assay. Results were correlated with stage and other clinicopathologic variables. Twenty-one (42%) WD PTCs demonstrated telomerase activity. The enzyme was detected more frequently in stage III/IVa WD PTCs (p = 0.02) and in tumors with extra thyroidal extension (p = 0.04). The risk of presenting advanced disease (stage III/IVa) and extrathyroidal growth was significantly increased in telomerase-positive tumors (p = 0.01; odds ratio [OR] 4.4 [95%CI 1.3-14.7]) and (p = 0.04; OR 3.6 [95%CI 1.1-11.7]), respectively. Also, a correlation was found between telomerase activity and age. There was no correlation of telomerase activity with gender, histologic variant, tumor size, or cervical lymph node metastasis. Telomerase activity was observed in 42% of WD PTC and was detected more frequently in AJCC TNM stage III/IVa cases. This finding suggests that telomerase deregulation could be involved in tumor progression.

Study of the mechanism of Flavobacterium sp. for hydrolyzing organophosphate pesticides.

The biotransformation by Flavobacterium sp. of the following organophosphate pesticides was experimentally and theoretically studied: phorate, tetrachlorvinphos, methyl-parathion, terbufos, trichloronate, ethoprophos, phosphamidon, fenitrothion, dimethoate and DEF. The Flavobacterium sp. ATCC 27551 strain bearing the organophosphate-degradation gene was used. Bacteria were incubated in the presence of each pesticide for a duration of 7 days. Parent pesticides were identified and quantified by means of a gas-chromatography mass spectrum system. Activity was considered as the amount (micromol) of each pesticide degraded by Flavobacterium sp. Also, structural parameters obtained by means of the CAChe program package for biomolecules, the reactivity index of phosphorus, of oxygen at the P = O function and of sulfur at the P = S function, and lipophilicity (log Poct) (ALOGPS v. 2.0) were obtained for each pesticide. Pesticides were hydrolyzed at the bond between phosphorous and the heteroatom, producing phosphoric acid and three metabolites. Enzymatic activity was significantly explained by the following multiple linear relationship: Enzymatic activity = 162.2 - 9.5(dihedral angle energy) - 25.0(Total energy) - 0.51(Molecular weight). Finally, a mechanism of Flavobacterium sp. to hydrolyze pesticides was proposed.

Interleukin-10 promotes B16-melanoma growth by inhibition of macrophage functions and induction of tumour and vascular cell proliferation.

The aim of this study was to investigate the mechanisms by which interleukin-10 (IL-10) induces tumour growth in a mouse-melanoma model. A B16-melanoma cell line (B16-0) was transfected with IL-10 cDNA and three clones that secreted high (B16-10), medium and low amounts of IL-10 were selected. Cell proliferation and IL-10 production were compared in vitro, and tumour growth, percentages of necrotic areas, tumour cells positive for proliferating cell nuclear antigen (PCNA), IL-10 receptor (IL-10R) and major histocompatibility complex type I (MHC-I) and II (MHC-II), as well as infiltration of macrophages, CD4+ and CD8+ lymphocytes and blood vessels were compared in vivo among IL-10-transfected and non-transfected tumours. Proliferation and tumour growth were greater for IL-10-transfected than for non-transfected cells (P < 0.001), and correlated with IL-10 concentration (r > or =0.79, P < 0.006). Percentages of tumour cells positive for PCNA and IL-10R were 4.4- and 16.7-fold higher, respectively, in B16-10 than in B16-0 tumours (P < 0.001). Macrophage distribution changed from a diffuse pattern in non-transfected (6.4 +/- 1.7%) to a peripheral pattern in IL-10-transfected (3.8 +/- 1.7%) tumours. The percentage of CD4+ lymphocytes was 7.6 times higher in B16-10 than in B16-0 tumours (P = 0.002). The expression of MHC-I molecules was present in all B16-0 tumour cells and completely negative in B16-10 tumour cells. In B16-0 tumours, 89 +/- 4% of the whole tumour area was necrotic, whereas tumours produced by B16-10 cells showed only 4.3 +/- 6% of necrotic areas. IL-10-transfected tumours had 17-fold more blood vessels than non-transfected tumours (61.8 +/- 8% versus 3.5 +/- 1.7% blood vessels/tumour; P < 0.001). All the effects induced by IL-10 were prevented in mice treated with a neutralizing anti-IL-10 monoclonal antibody. These data indicate that IL-10 could induce tumour growth in this B16-melanoma model by stimulation of tumour-cell proliferation, angiogenesis and immunosuppression.

Bioactive compounds from Iostephane heterophylla (Asteraceae).

The novel bisabolene sesquiterpenes 3-6, were isolated from Iostephane heterophylla, using bioguided fractionation. The new compounds were determined to be (12R/12S)-12,13-epoxy-xanthorrhizols (3,4) and (12R/12S)-12,13-dihydro-12,13-dihydroxy-xanthorrizols (5,6) and their structures were characterized by analysis of spectroscopic data and by chemical correlation from xanthorrhizol (2). The stereochemistry at C-12 of 5 was deduced using the modified Mosher experiment. Some of the isolated compounds elicited activity against gram positive and gram negative bacteria, levadura and dermatophytes.

Toluene alters mu-opioid receptor expression in the rat brainstem.

Toluene is an ototoxic organic solvent widely used in industry and could be a cause of sleep apnea. Acute toluene administration in rats induces an increase in the number of neural cells immunostained for mu-opioid receptors in several brainstem nuclei, such as the inferior colliculus, dorsal and lateral periaqueductal gray and dorsal raphe, without changes in the superior colliculus and the interpeduncular and lateral reticular nuclei. These data suggest that mu-opioid receptors could be involved in toluene-induced neurotoxic effects on the physiological regulation of breathing during sleep, and auditive function.