Streptococcus equi subsp. zooepidemicus: High molecular diversity of Argentinian strains isolated from mares with endometritis.

Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) is a mucosal commensal of the lower genital tract in horses and is the most isolated bacterium causing endometritis in mares. The aim of this study was to determine the molecular diversity of S. zooepidemicus obtained from endometritis in mares in Buenos Aires province, Argentina. Thirty isolates obtained from the uterus of mares in 2005 and 2017 were studied. The MLST scheme was applied to identify the Argentinian genotypes and the clonal relationships and patterns of evolutionary descent were identified using the eBURST algorithm - goeBURST. Twenty six different Sequence types (STs) were identified, being only 11 of them previously reported in horses and also, from several host species and tissues. The other 15 STs were reported in Argentinian reproductive strains of mares in our study for the first time. The genotypes obtained from uterus in Argentina were not evenly distributed when all the published S. zooepidemicus STs were analysed, thus, it was not possible to establish that the same lineage circulates in our equine population. The fact that the identified genotypes were also reported in other countries, diverse samples and host species suggest that there is not a host, and an anatomical niche adaptation. Finally, the isolation of the same genotype in the vagina/clitoris and the uterus of the same mare highlights the versatility of S. zooepidemicus and its role as an opportunistic pathogen.

L-theanine abates oxidative stress and mitochondrial dysfunction in myocardial ischemia-reperfusion injury by positively regulating the antioxidant response.

L-theanine (L-THE), a non-protein amino acid isolated from Camelia sinensis, has antioxidant properties that could prevent oxidative damage and mitochondrial dysfunction generated by myocardial ischemia and reperfusion (I/R) injury. The present study aimed to identify the effects of pretreatment with L-THE in rat hearts undergoing I/R. Wistar rats received vehicle or 250 mg/Kg L-THE intragastrically for 10 days. On day 11, hearts were removed under anesthesia and exposed to I/R injury in the Langendorff system. Measurement of left ventricular developed pressure and heart rate ex vivo demonstrates that L-THE prevents I/R-induced loss of cardiac function. Consequently, the infarct size of hearts subjected to I/R was significantly decreased when L-THE was administered. L-THE also mitigated I/R-induced oxidative injury in cardiac tissue by decreasing reactive oxygen species and malondialdehyde levels, while increasing the activity of antioxidant enzymes, SOD and CAT. Additionally, L-THE prevents oxidative phosphorylation breakdown and loss of inner mitochondrial membrane potential caused by I/R, restoring oxygen consumption levels, increasing respiratory control and phosphorylation efficiency, as well as buffering calcium overload. Finally, L-THE modifies the expression of genes involved in the antioxidant response through the overexpression of SOD1, SOD2 and CAT; as well as the transcriptional factors PPARα and Nrf2 in hearts undergoing I/R. In conclusion, L-THE confers cardioprotection against I/R injury by preventing oxidative stress, protecting mitochondrial function, and promoting overexpression of antioxidant genes. More studies are needed to place L-THE at the forefront of cardiovascular research and recommend its therapeutic use.

Safety of HelixComplex snail mucus (HSM) as a novel food pursuant to Regulation (EU) 2015/2283.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on HelixComplex Snail Mucus (HSM) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF consists of snail mucus collected from Helix aspersa maxima and is proposed to be used by adults as a food supplement. The data provided by the applicant about the composition and stability of the NF together with the report of the subchronic toxicity study were overall considered unsatisfactory. The Panel noted inconsistencies in the reporting of the certificates of analysis and of the data on the subchronic toxicity provided by the applicant. Owing to these deficiencies, the Panel cannot establish a safe intake level of the NF. The Panel concludes that the safety of the NF has not been established.

Conservation biological control of arthropod pests using native plants.

Habitat or vegetation manipulation is a strategy within conservation biological control, yet, its formal study is relatively recent and lacking in many parts of the world, particularly when using native plants. We found 56 studies dealing with native plants and conservation biological control, from 2002 to 2022. Most were carried out in developed countries, and studied the provision of flower resources to natural enemies' complexes in several crops. The main gaps in knowledge, similar to studies with non-native plants, were the lack of understanding mechanisms, unknown effects on pest populations, and absence of cost-benefit analyses. Breaching these gaps will allow this strategy to be more transferable among cropping systems and locations and will promote its use by farmers.

Distribution of potentially harmful elements in attic dust from the City of Coronel (Chile).

Attic dusts provide an indirect measure of airborne pollutants deposited in the urban environment. The objectives of this study are: (1) to determine the concentrations of As, Ba, Cd, Co, Cr, Cu, Mn, Ni, Pb, Sr, V and Zn in attic dust in the City of Coronel, (2) to evaluate the source apportionment of PHE and (3) to assess the risk of health effects from exposure in adults and children. In the City of Coronel, attic dust samples were collected in 19 houses. The concentrations of As, Ba, Cd, Co, Cr, Cu, Mn, Ni, Pb, Sr, V and Zn were measured in ICP-OES after Aqua Regia digestion of < 75 µm dust sample. The median (and the range) concentration (mg kg-1) of potentially harmful elements was: As 16 (7-72), Ba 154 (53-251), Cd 0.8 (0.25-14.5), Co 12, (8-22), Cr 38 (22-482), Cu 107 (44-1641), Mn 698 (364-1245), Ni 51 (24-1734), Pb 66 (18-393), Sr 131 (52-252), V 129 (57-376) and Zn 815 (107-9761). The exploratory data analysis shows that Ni, Cu, Cr, Zn, Pb and As distribution is dominated by anthropogenic sources and characterized by high extreme values. Principal component analysis shows four factors. One factor is geogenic, while the other three factors are associated with transport emissions and the industrial park. The resulting median of cumulative noncarcinogenic risk (HIs) value for attic dust was 3.49 for children. This is significant, as any value greater than one indicates an elevated risk.

Linking toxicity and predation in a venomous arthropod: the case of Tityus fuhrmanni (Scorpiones: Buthidae), a generalist predator scorpion.

BACKGROUND: Scorpions are arachnids that have a generalist diet, which use venom to subdue their prey. The study of their trophic ecology and capture behavior is still limited compared to other organisms, and aspects such as trophic specialization in this group have been little explored. METHODS: In order to determine the relationship between feeding behavior and venom toxicity in the scorpion species Tityus fuhrmanni, 33 specimens were offered prey with different morphologies and defense mechanisms: spiders, cockroaches and crickets. In each of the experiments we recorded the following aspects: acceptance rate, immobilization time and the number of capture attempts. The median lethal dose of T. fuhrmanni venom against the three different types of prey was also evaluated. RESULTS: We found that this species does not have a marked difference in acceptance for any of the evaluated prey, but the number of capture attempts of spiders is higher when compared to the other types of prey. The immobilization time is shorter in spiders compared to other prey and the LD50 was higher for cockroaches. CONCLUSIONS: These results indicate that T. fuhrmanni is a scorpion with a generalist diet, has a venom with a different potency among prey and is capable of discriminating between prey types and employing distinct strategies to subdue them.

Novel seM-types of Streptococcus equi subsp. equi identified in isolates circulating in Argentina.

BACKGROUND: Strangles is a worldwide infectious disease caused by Streptococcus equi subsp. equi that affects the upper respiratory tract of horses. Streptococcus equi subsp. equi characterisation by seM-typing is internationally used for epidemiological studies and comparison of isolates. OBJECTIVES: To identify and to compare the seM-types of Argentinian isolates of Streptococcus equi subsp. equi. STUDY DESIGN: Investigation of bacterial isolates using molecular and phylogenetic approaches. METHODS: A total of 59 Argentinian isolates of Streptococcus equi subsp. equi obtained between 2007 and 2019 were studied by seM-typing. The sequence similarity of Argentinian seM-types and the other alleles available on the seM database was determined using BLAST and phylogenetic analysis was performed using the Neighbour-Joining algorithm. The amino acid sequences were predicted and compared with the predicted amino acid sequence of the reference strain 4047 using the MEGA 7 software and PROVEAN tool. RESULTS: Eight seM-types were found among the isolates. Only one of them (seM-61) has been previously reported and the other seven alleles (seM-129, seM-130, seM-131, seM-132, seM-133, seM-134 and seM-135) were novel seM sequences. High genetic similarity was observed among the Argentinian seM-types, with the exception of seM-130. No functional effects of amino acid differences were predicted. MAIN LIMITATIONS: The number of related and unrelated isolates per year. CONCLUSIONS: Seven novel seM-types and seM-61 that were previously reported in Brazil were circulating in Argentina which were identified as circulating in Argentinian horses between 2007 and 2019. The high genetic similarity among the Argentinian and Brazilian seM-types suggests that there is a geographical distribution of strain types. The geographical restriction of strains is likely to reflect the movement of horses between different equine disciplines and neighbouring countries.

Linking toxicity and predation in a venomous arthropod: the case of Tityus fuhrmanni (Scorpiones: Buthidae), a generalist predator scorpion

Background: Scorpions are arachnids that have a generalist diet, which use venom to subdue their prey. The study of their trophic ecology and capture behavior is still limited compared to other organisms, and aspects such as trophic specialization in this group have been little explored. Methods: In order to determine the relationship between feeding behavior and venom toxicity in the scorpion species Tityus fuhrmanni, 33 specimens were offered prey with different morphologies and defense mechanisms: spiders, cockroaches and crickets. In each of the experiments we recorded the following aspects: acceptance rate, immobilization time and the number of capture attempts. The median lethal dose of T. fuhrmanni venom against the three different types of prey was also evaluated. Results: We found that this species does not have a marked difference in acceptance for any of the evaluated prey, but the number of capture attempts of spiders is higher when compared to the other types of prey. The immobilization time is shorter in spiders compared to other prey and the LD50 was higher for cockroaches. Conclusions: These results indicate that T. fuhrmanni is a scorpion with a generalist diet, has a venom with a different potency among prey and is capable of discriminating between prey types and employing distinct strategies to subdue them.(AU)

Linking toxicity and predation in a venomous arthropod: the case of Tityus fuhrmanni (Scorpiones: Buthidae), a generalist predator scorpion

Abstract Background: Scorpions are arachnids that have a generalist diet, which use venom to subdue their prey. The study of their trophic ecology and capture behavior is still limited compared to other organisms, and aspects such as trophic specialization in this group have been little explored. Methods: In order to determine the relationship between feeding behavior and venom toxicity in the scorpion species Tityus fuhrmanni, 33 specimens were offered prey with different morphologies and defense mechanisms: spiders, cockroaches and crickets. In each of the experiments we recorded the following aspects: acceptance rate, immobilization time and the number of capture attempts. The median lethal dose of T. fuhrmanni venom against the three different types of prey was also evaluated. Results: We found that this species does not have a marked difference in acceptance for any of the evaluated prey, but the number of capture attempts of spiders is higher when compared to the other types of prey. The immobilization time is shorter in spiders compared to other prey and the LD50 was higher for cockroaches. Conclusions: These results indicate that T. fuhrmanni is a scorpion with a generalist diet, has a venom with a different potency among prey and is capable of discriminating between prey types and employing distinct strategies to subdue them.

Exposure to Anthropogenic Areas May Influence Colonization by Zoonotic Microorganisms in Scavenging Birds.

Wild bird species have commonly been implicated as potential vectors of pathogens to other species, humans included. However, the habitat where birds live could influence the probability to acquire these pathogens. Here, we evaluated if the characteristics of the environment used by obligate scavenging birds (vultures) influence their colonization by zoonotic pathogens. For this, we particularly focused on Salmonella spp., a zoonotic pathogen commonly present in bird species. The occurrence of this bacteria was evaluated in free ranging Andean condors (Vultur gryphus) using natural environments from Argentina and compared with those obtained from condors under human care. In addition, we compared our results with those reported for other wild vultures using natural and anthropized environments at a global scale. We did not find Salmonella spp. in samples of wild condors. Captive condor samples presented Salmonella spp. with an occurrence of 2.8%, and one isolate of Meticilin Resistant Staphylococcus aureus, among other potential pathogenic microorganisms. Moreover, some species of free ranging vultures from diverse geographical areas using anthropized environments tend to present higher occurrences of Salmonella spp. These results highlight the importance of pristine ecosystems to protect vultures' health toward pathogenic microorganisms that can produce disease in these birds, but also in other species. We call for more studies evaluating differences in occurrence of zoonotic pathogens in vultures according to the quality of the environment they use. Even when vultures have not been implicated in zoonotic pathogen spread, our results add information to evaluate potential events of pathogen spillover between vultures and from these birds to other species.

Factores relacionados con el resultado de los tratamientos endodónticos realizados en una institución universitaria con odontólogos en formación / Factors related to the result of endodontic treatments performed in a university institution with dentists in training / Fatores relacionados ao resultado de tratamentos endodônticos realizados em instituição universitária com dentistas em treinamento

Resumen Introducción y objetivo: el tratamiento endodóntico se realiza para tratar la enfermedad pulpoperiapical y puede tener un porcentaje de éxito de más del 90% en condiciones ideales para su realización. Dentro de los factores que condicionan la práctica clínica, se encuentran la anatomía interna del diente, las habilidades del operador, el conocimiento de la técnica, los instrumentos empleados y el tiempo operatorio. El éxito lo determina la supervivencia y la ausencia de signos clínicos y radiográficos en el seguimiento. Determinar los factores asociados al resultado del tratamiento de endodoncia, realizado por estudiantes de pregrado en odontología de una universidad colombiana. Materiales y métodos: estudio de cohorte retrospectivo con una cohorte expuesta y una no expuesta a la periodontitis apical. Se evaluaron clínica y radiográficamente todos los pacientes cuyo motivo de consulta fue endodoncia durante los años 2013-2014. Resultados: la media de edad de los pacientes fue 51,23 (DE = 14,23) con un mayor porcentaje de participación de mujeres (71,1%). En el diagnóstico inicial se encontró un 26% de dientes con Periodontitis apical. Se encontró asociación entre una mediana mayor de consultas y no presentar Periodontitis apical al final del tratamiento. En los análisis bivariados y multivariados se encontró asociación de la presencia de accidentes y endodoncia suboturada con la presencia de Periodontitis apical al final del tratamiento. Conclusión: seguir protocolos y guía de atención que permitan evitar los accidentes y conservar la adecuada longitud en la conformación y obturación pueden incrementar la frecuencia de éxito en los tratamientos.

Abstract Introduction and objetive: an endodontic treatment is performed to treat pulp-periapical disorders and may have a success rate of over 90% under ideal conditions. Among the factors that need to be considered, knowledge of the internal anatomy of the root, operator skills, selected technique, instruments involved and surgical time are the most important to determine the success of such treatment. Success implies the survival of the tooth in the oral cavity as well as the absence of clinical and radiographic signs and symptoms. The purpose of this work was to determine the factors associated to the success of an endodontic treatment performed by undergraduate dental students in a Colombian university. Materials and methods: a retrospective study with cohorts exposed and unexposed to apical periodontitis was carried out. Patients who consulted for endodontic treatment in 2013-2014 were invited to participate and were assessed both clinically and radiographically. Results: mean age was 51.23 (SD 14.23) years and higher percentage of female participation (71.1%) was observed. At initial diagnosis, 26% of teeth were diagnosed with apical periodontitis. An association between a high consultation mean and absence of apical periodontitis at the end of treatment was found. Bivariate and multivariate analyses showed an association between the presence of procedure accidents and under-filled root canal obturation with the presence of apical periodontitis at the end of treatment. Conclusion: success rate of endodontic treatments may be increased by carefully following protocols and attention guidelines to reduce the possibility of accidents and to keep an adequate length of the canal filling.

Resumo Introdução e objetivo: um tratamento endodôntico é realizado para tratar distúrbios pulpar-periapicais e pode ter uma taxa de sucesso superior a 90% em condições ideais. Entre os fatores que precisam ser considerados, o conhecimento da anatomia interna da raiz, as habilidades do operador, a técnica selecionada, os instrumentos envolvidos e o tempo cirúrgico são os mais importantes para determinar o sucesso desse tratamento. O sucesso implica a sobrevivência do dente na cavidade oral, bem como a ausência de sinais e sintomas clínicos e radiográficos. O objetivo deste trabalho foi determinar os fatores associados ao sucesso de um tratamento endodôntico realizado por estudantes de graduação em odontologia de uma universidade colombiana. Materiais e métodos: estudo retrospectivo com coortes expostas e não expostas à periodontite apical. Os pacientes que consultaram para tratamento endodôntico em 2013-2014 foram convidados a participar e foram avaliados clinicamente e radiograficamente. Resultados: a média de idade foi de 51,23 (DP 14,23) anos e maior percentual de participação feminina (71,1%). No diagnóstico inicial, 26% dos dentes foram diagnosticados com periodontite apical. Foi encontrada associação entre alta média de consulta e ausência de periodontite apical ao final do tratamento. As análises bivariadas e multivariadas mostraram associação entre a presença de acidentes do procedimento e a obturação do canal radicular com preenchimento insuficiente com a presença de periodontite apical ao final do tratamento. Conclusão: a taxa de sucesso dos tratamentos endodônticos pode ser aumentada seguindo-se cuidadosamente os protocolos e diretrizes de atenção para reduzir a possibilidade de acidentes e manter um comprimento adequado do preenchimento do canal.

The regulation of protein acetylation influences the redox homeostasis to protect the heart.

The cellular damage caused by redox imbalance is involved in the pathogenesis of many cardiovascular diseases. Besides, redox imbalance is related to the alteration of protein acetylation processes, causing not only chromatin remodeling but also disturbances in so many processes where protein acetylation is involved, such as metabolism and signal transduction. The modulation of acetylases and deacetylases enzymes aids in maintaining the redox homeostasis, avoiding the deleterious cellular effects associated with the dysregulation of protein acetylation. Of note, regulation of protein acetylation has shown protective effects to ameliorate cardiovascular diseases. For instance, HDAC inhibition has been related to inducing cardiac protective effects and it is an interesting approach to the management of cardiovascular diseases. On the other hand, the upregulation of SIRT protein activity has also been implicated in the relief of cardiovascular diseases. This review focuses on the major protein acetylation modulators described, involving pharmacological and bioactive compounds targeting deacetylase and acetylase enzymes contributing to heart protection through redox homeostasis.

Correlation of the need for orthodontic treatment between the self-perception of chilean adolescents aged 14 to 18 years and the dentist's diagnosis / Correlación de la necesidad de tratamiento ortodóncico entre la autopercepción de adolescentes chilenos de 14 a 18 años con la observación del odontólogo

Background: To correlate the need for orthodontic treatment between the self-perception of Chilean adolescents from 14 to 18 years old with the observation of a dentist using the same assessment scale, as well as to determine if covariates such as gender, age and type of school influence the self-perception of the adolescent and the examiner. Material and Methods: Cross-sectional descriptive study of adolescents aged 14 to 18 years from public, subsidized and private schools in Temuco, Chile. The probability sample is stratified by course, from first to fourth year, a total of 414 students participated, according to the eligibility criteria. The photographic score of the aesthetic component (AC) of the Index of Orthodontic Treatment Need (IOTN) was used. The statistical analysis of the data was performed with the SPSS Statistics program v.23. Results: 94.9% of the adolescents perceived themselves as having good aesthetics. The examiner considered that 77% presented this condition, p<0.00. Males perceived themselves better than females. At age 15, 1.7% of students considered themselves to have poor aesthetics, p<0.01. From the examiner's perspective, aesthetics are related to type of school, p<0.00. Conclusion: Adolescents perceive themselves better aesthetically than do the evaluators. The school type factor, according to the IOTN-AC examiner, shows a higher proportion of students with no need for orthodontic treatment in private schools, and a threshold need in municipal and subsidized institutions.

Correlacionar la necesidad de tratamiento ortodóncico, entre la autopercepción de adolescentes con el diagnóstico de un evaluador odontólogo, utilizando la misma escala de valoración, así también determinar si las variables como el género, la edad y la dependencia educacional influyen en la autopercepción del adolescente y la observación del examinador. Material y Métodos: Estudio descriptivo de corte transversal, en adolescentes de 14 a 18 años de escuelas públicas, subvencionadas y privadas de Temuco-Chile. Muestreo probabilístico estratificado por cursos, de primero a cuarto medio con una muestra de 414 estudiantes, según los criterios de elegibilidad. Se utilizó el score fotográfico del componente estético (AC) del Índice de Necesidad de Tratamiento de Ortodoncia (INTO). El análisis estadístico de los datos fue realizado con el programa SPSS Statistics v.23. Resultados: El 94,9% de los adolescentes se autoperciben con una buena estética, el examinador considera que un 77% presenta esta condición, p<0,00. Los varones se perciben mejor que las damas. Los adolescentes de 15 años un 1,7% considera tener mala estética, p<0,01. Desde la perspectiva del examinador la estética se relaciona con la dependencia educacional, <0,01. Conclusión: Los adolescentes se autoperciben mejor estéticamente que lo diagnosticado por evaluadores odontólogos. El factor dependencia educacional según INTO-AC examinador, muestra mayor proporción de estudiantes sin necesidad de tratamiento ortodóncico en los establecimientos privados, y necesidad límite en los públicos y subvencionados.

Complete Genome Sequence of a Colombian Zika Virus Strain Obtained from BALB/c Mouse Brain after Intraperitoneal Inoculation.

A Zika virus (ZIKV) strain was isolated from an acute febrile patient during the Zika epidemics in Colombia. The strain was intraperitoneally inoculated into BALB/c mice, and 7 days postinoculation, neurological manifestations and ZIKV infection in the brain were demonstrated. The reported genome sequence is highly related to strains circulating in the Americas.

Redox signaling in ischemic postconditioning protection involves PKCε and Erk1/2 pathways and converges indirectly in Nrf2 activation.

Ischemic-postconditioning (iPostC) exerts cardioprotection by preserving redox homeostasis in the reperfused heart. This protective effect has been associated with the activation of endogenous antioxidant response driven by transcription factor Nrf2 and with the activation of 'reperfusion injury salvage kinases' (RISK) as PI3K, PKC and Erk1/2. Redox homeostasis is essential for normal cell physiology since reactive oxygen species (ROS) are crucial for processes that involve protein signaling. Thus, it has become clear that not only the perturbation of redox balance to oxidative state is deleterious but also towards a reductive state contributing to pathogenesis of diseases. However, there is still a scarce knowledge about the role of ROS in the cardioprotective signals mediated by RISK in postconditioned hearts. Therefore, we studied the role of ROS as initiator of RISK signaling molecules in iPostC-conferred cardioprotection. With the aim to study the relationship between redox-dependent RISK activation and the downstream activation of the transcription factor Nrf2, we evaluated the effect of redox signaling disruption by the effect of ascorbic acid in iPostC hearts. Our results showed that PKCε and Erk1/2 activation is redox-dependent and that concurs downstream with Nrf2 deficient activation. Besides, using inhibitors we found that neither PI3K nor Erk1/2 are directly related with Nrf2 activation, indicating that these kinases have other targets. We conclude that redox signaling participates in cardioprotection triggered by iPostC through the action of kinase-dependent and -independent mechanisms and concurred with the downstream regulation of Nrf2-mediated antioxidant response to prolonged redox balance during long reperfusion.

Vicisitudes de los proyectos institucionales de atención psicosocial a víctimas del conflicto armado colombiano / Vicissitudes of the Psychosocial Attention Institutional Projects to Victims of the Colombian Armed Conflict

Comprender las experiencias subjetivas de los profesionales vinculados a proyectos de intervención con víctimas de violencia política en el ámbito psicosocial en la ciudad de Medellín y otros municipios del departamento de Antioquia, en relación con sus vivencias de malestar ético y desgaste emocional por su participación en estos proyectos, nos ha permitido identificar la forma como los proyectos están construidos, sus lógicas tecnocráticas y burocráticas, los problemas en los tiempos de ejecución y contratación, además de su escasa contextualización y sensibilidad a la realidad de las comunidades afectadas, realidad que termina convirtiéndose en generador de daño y revictimización, además de lesionar la integridad psíquica y ética de estos profesionales.

Understanding the subjective experiences of the professionals connected with intervention projects with victims of political violence in the psychosocial environment in the city of Medellín and other municipalities of the State of Antioquia, in terms of their experiences of ethical discomfort and emotional drain, for their participation in these projects, has helped us to identify the manner how these projects are built, their technocratic and bureaucratic common-sense, the problems in the execution and hiring times, as well as their limited contextualization and sensitivity to the reality of the affected communities, such a reality becomes a creator of harm and revictimization, which also damages the psychic and ethical integrity of those professionals.

Sustained blockade of ascorbic acid transport associated with marked SVCT1 loss in rat hepatocytes containing increased ascorbic acid levels after partial hepatectomy.

The liver has an extraordinary regenerative capacity in response to partial hepatectomy (PHx), which develops with neither tissue inflammation response nor alterations in the whole organism. This process is highly coordinated and it has been associated with changes in glutathione (GSH) metabolism. However, there are no reports indicating ascorbic acid (AA) levels after partial hepatectomy. AA and GSH act integrally as an antioxidant system that protects cells and tissues from oxidative damage and imbalance observed in a variety of diseases that affect the liver. Although rat hepatocytes are able to synthesize AA and GSH, which are the providers of AA for the whole organism, they also acquire AA from extracellular sources through the sodium-coupled ascorbic acid transporter-1 (SVCT1). Here, we show that hepatocytes from rat livers subjected to PHx increase their GSH and AA levels from 1 to 7 days post hepatectomy, whose peaks precede the peak in cell proliferation observed at 3 days post-hepatectomy. The increase in both antioxidants was associated with higher expression of the enzymes involved in their synthesis, such as the modifier subunit of enzyme glutamine cysteine ligase (GCLM), glutathione synthetase (GS), gulonolactonase (GLN) and gulonolactone oxidase (GULO). Importantly, rat hepatocytes, that normally exhibit kinetic evidence indicating only SVCT1-mediated transport of AA, lost more than 90% of their capacity to transport it at day 1 after PHx without evidence of recovery at day 7. This observation was in agreement with loss of SVCT1 protein expression, which was undetectable in hepatocytes as early as 2h after PHx, with partial recovery at day 7, when the regenerated liver weight returns to normal. We conclude that after PHx, rat hepatocytes enhance their antioxidant capacity by increasing GSH and AA levels prior to the proliferative peak. GSH and AA are increased by de novo synthesis, however paradoxically hepatocytes from rat subjected to PHx also suppress their capacity to acquire AA from extracellular sources through SVCT1.

Maternal serum cytokine levels in pregnancies complicated with threatened preterm labour.

OBJECTIVE: To investigate serum inflammatory markers in singleton gestations complicated with threatened preterm labour (TPL). METHODS: Pregnant women complicated with TPL (n = 61) were recruited to measure maternal serum levels of a panel of cytokines and C-reactive protein and then compared to controls without TPL, matched for gestational age (n = 64) and term pregnancies in the prodromal phase of labour (PPL) (n = 31). In addition, baseline cytokine levels were compared among cases and controls according to the outcome. RESULTS: Women with TPL displayed higher CRP and white blood counts levels together with lower granulocyte macrophage colony-stimulating factor (GMC-SF) compared to both controls without TPL and to term gestations in the PPL. Also, interleukin 10 (IL-10), IL-6, IL-7, IL-8 and tumour necrosis alpha (TNF-α) levels were found significantly higher in TPL cases as compared to controls without TPL and term women in the PLL. Baseline cytokine levels (except IL-10) were higher among TPL cases who later delivered preterm. TPL cases delivering preterm displayed lower GMC-SF levels as compared to those delivering at term. Multivariate analysis found that gestational age at birth positively correlated with cervical length and inversely with CRP, IL-6 and TNF-α levels (p < 0.0001). CONCLUSIONS: TPL and preterm birth were related to inflammatory changes in the maternal side that correlate with cervical shortening and the initiation of uterine contractions.

Glutathione system participation in thoracic aneurysms from patients with Marfan syndrome.

BACKGROUND: Aortic dilatation in Marfan syndrome (MFS) is progressive. It is associated with oxidative stress and endothelial dysfunction that contribute to the early acute dissection of the vessel and can result in rupture of the aorta and sudden death. We evaluated the participation of the glutathione (GSH) system, which could be involved in the mechanisms that promote the formation and progression of the aortic aneurysms in MFS patients. PATIENTS AND METHODS: Aortic aneurysm tissue was obtained during chest surgery from eight control subjects and 14 MFS patients. Spectrophotometrical determination of activity of glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR), lipid peroxidation (LPO) index, carbonylation, total antioxidant capacity (TAC), and concentration of reduced and oxidized glutathione (GSH and GSSG respectively), was performed in the homogenate from aortic aneurysm tissue. RESULTS: LPO index, carbonylation, TGF-ß1, and GR activity were increased in MFS patients (p < 0.04), while TAC, GSH/GSSG ratio, GPx, and GST activity were significantly decreased (p < 0.04). CONCLUSIONS: The depletion of GSH, in spite of the elevated activity of GR, not only diminished the activity of GSH-depend GST and GPx, but increased LPO, carbonylation and decreased TAC. These changes could promote the structural and functional alterations in the thoracic aorta of MFS patients.

The chaperonin CCT inhibits assembly of α-synuclein amyloid fibrils by a specific, conformation-dependent interaction.

The eukaryotic chaperonin CCT (chaperonin containing TCP-1) uses cavities built into its double-ring structure to encapsulate and to assist folding of a large subset of proteins. CCT can inhibit amyloid fibre assembly and toxicity of the polyQ extended mutant of huntingtin, the protein responsible for Huntington's disease. This raises the possibility that CCT modulates other amyloidopathies, a still-unaddressed question. We show here that CCT inhibits amyloid fibre assembly of α-synuclein A53T, one of the mutants responsible for Parkinson's disease. We evaluated fibrillation blockade in α-synuclein A53T deletion mutants and CCT interactions of full-length A53T in distinct oligomeric states to define an inhibition mechanism specific for α-synuclein. CCT interferes with fibre assembly by interaction of its CCTζ and CCTγ subunits with the A53T central hydrophobic region (NAC). This interaction is specific to NAC conformation, as it is produced once soluble α-synuclein A53T oligomers form and blocks the reaction before fibres begin to grow. Finally, we show that this association inhibits α-synuclein A53T oligomer toxicity in neuroblastoma cells. In summary, our results and those for huntingtin suggest that CCT is a general modulator of amyloidogenesis via a specific mechanism.