Acute Hepatitis E Virus infection with coincident reactivation of Epstein-Barr virus infection in an immunosuppressed patient with rheumatoid arthritis: a case report.

BACKGROUND: Hepatitis E virus (HEV) is the most recently discovered of the hepatotropic viruses, and is considered an emerging pathogen in developed countries with the possibility of fulminant hepatitis in immunocompromised patients. Especially in the latter elevated transaminases should be taken as a clue to consider HEV infection, as it can be treated by discontinuation of immunosuppression and/or ribavirin therapy. To our best knowledge, this is a unique case of autochthonous HEV infection with coincident reactivation of Epstein-Barr virus (EBV) infection in an immunosuppressed patient with rheumatoid arthritis (RA). CASE PRESENTATION: A 68-year-old Swiss woman with RA developed hepatitis initially diagnosed as methotrexate-induced liver injury, but later diagnosed as autochthonous HEV infection accompanied by reactivation of her latent EBV infection. She showed confounding serological results pointing to three hepatotropic viruses (HEV, Hepatitis B virus (HBV) and EBV) that could be resolved by detection of HEV and EBV viraemia. The patient recovered by temporary discontinuation of immunosuppressive therapy. CONCLUSIONS: In immunosuppressed patients with RA and signs of liver injury, HEV infection should be considered, as infection can be treated by discontinuation of immunosuppression. Although anti-HEV-IgM antibody assays can be used as first line virological tools, nucleic acid amplification tests (NAAT) for detection of HEV RNA are recommended--as in our case--if confounding serological results from other hepatotropic viruses are obtained. After discontinuation of immunosuppressive therapy, our patient recovered from both HEV infection and reactivation of latent EBV infection without sequelae.

Environmental factors in multiple sclerosis [Environmental factors in multiple sclerosis]

Although multiple sclerosis (MS) is recognized as a disorder involving the immune system, the interplay of environmental factors and individual genetic susceptibility seems to influence MS onset and clinical expression, as well as therapeutic responsiveness. Multiple human epidemiological and animal model studies have evaluated the effect of different environmental factors, such as viral infections, vitamin intake, sun exposure, or still dietary and life habits on MS prevalence. Previous Epstein-Barr virus infection, especially if this infection occurs in late childhood, and lack of vitamin D (VitD) currently appear to be the most robust environmental factors for the risk of MS, at least from an epidemiological standpoint. Ultraviolet radiation (UVR) activates VitD production but there are also some elements supporting the fact that insufficient UVR exposure during childhood may represent a VitD-independent risk factor of MS development, as well as negative effect on the clinical and radiological course of MS. Recently, there has been a growing interest in the gut-brain axis, a bidirectional neuro-hormonal communication system between the intestinal microbiota and the central nervous system (CNS). Indeed, components of the intestinal microbiota may be pro-inflammatory, promote the migration of immune cells into the CNS, and thus be a key parameter for the development of autoimmune disorders such as MS. Interestingly most environmental factors seem to play a role during childhood. Thus, if childhood is the most fragile period to develop MS later in life, preventive measures should be applied early in life. For example, adopting a diet enriched in VitD, playing outdoor and avoiding passive smoking would be extremely simple measures of primary prevention for public health strategies. However, these hypotheses need to be confirmed by prospective evaluations, which are obviously difficult to conduct. In addition, it remains to be determined whether and how VitD supplementation in adult life would be useful in alleviating the course of MS, once this disease has already started. A better knowledge of the influence of various environmental stimuli on MS risk and course would certainly allow the development of add-on therapies or measures in parallel to the immunotherapies currently used in MS.

Importance of amoebae as a tool to isolate amoeba-resisting microorganisms and for their ecology and evolution: the Chlamydia paradigm.

Free-living amoebae are distributed worldwide and are frequently in contact with humans and animals. As cysts, they can survive in very harsh conditions and resist biocides and most disinfection procedures. Several microorganisms, called amoeba-resisting microorganisms (ARMs), have evolved to survive and multiply within these protozoa. Among them are many important pathogens, such as Legionella and Mycobacteria, and also several newly discovered Chlamydia-related bacteria, such as Parachlamydia acanthamoebae, Estrella lausannensis, Simkania negevensis or Waddlia chondrophila whose pathogenic role towards human or animal is strongly suspected. Amoebae represent an evolutionary crib for their resistant microorganisms since they can exchange genetic material with other ARMs and develop virulence traits that will be further used to infect other professional phagocytes. Moreover, amoebae constitute an ideal tool to isolate strict intracellular microorganisms from complex microbiota, since they will feed on other fast-growing bacteria, such as coliforms potentially present in the investigated samples. The paradigm that ARMs are likely resistant to macrophages, another phagocytic cell, and that they are likely virulent towards humans and animals is only partially true. Indeed, we provide examples of the Chlamydiales order that challenge this assumption and suggest that the ability to multiply in protozoa does not strictly correlate with pathogenicity and that we should rather use the ability to replicate in multiple and diverse eukaryotic cells as an indirect marker of virulence towards mammals. Thus, cell-culture-based microbial culturomics should be used in the future to try to discover new pathogenic bacterial species.

Complications following an accidental sodium hypochlorite extrusion: A report of two cases

Sodium hypochlorite (NaOCl) is the most commonly used solution in root canal treatments, as it is a low-cost method that displays a very effective antimicrobial activity against microbiota of infected root canals. However, this solution can cause complications especially due to its cytotoxic features. When this solution is injected into the adjacent tissues, the patient usually experiences intense pain, and an urgent treatment should be implemented in order to prevent a long-term sequelae. This paper describes the clinical features of two patients that experienced an accidental extrusion of NaOCl after endodontic treatment of varying severity and with different treatments. Furthermore, it shows the long-term neurologic injuries that this type of accidents may cause and a treatment protocol for these situations will be suggested.

Hydrology, light and the use of organic and inorganic materials as structuring factors of biological communities in Mediterranean streams

Hydrological disturbances, light availability and nutrients are the most relevant factors determining the structure of the biological communities in Mediterranean rivers. While some hydrological disturbances are able to induce catastrophic effects, which may cause a complete reset in physical and biological conditions, continued enrichment or changes in light availability are factors leading to the progressive shift in the communities of autotrophs and heterotrophs in the systems. Primary production in Mediterranean streams shows relevant seasonal changes which mainly follows the variations in light availability. In most forested streams, the algal community is shade-adapted. Nutrient enrichment (especially phosphorus) leads to marked increases in primary production, but this increase is not lineal and there is a saturation of algal biomass even in the most enriched systems. The heterotrophs (bacteria, fungi) are related to the pattern of DOC availability (which most depends on the seasonal discharge and leaf fall dynamics) and to the available substrata in the stream. It has been repeatedly observed that shorttime increases of extracellular enzyme activities are related to the accumulation of autochthonous (algal) and/or allochthonous (leaves) organic matter on the streambed during spring and summer, this being more remarkable in dry than in wetter years. Flow reduction favours detritus concentration in pools, and the subsequent increase in the density and biomass of the macroinvertebrate community. In Mediterranean streams collectors are accounting for the highest density and biomass, this being more remarkable in the least permanent systems, in accordance with the effect of floods on the organic matter availability. Nutrients, through the effect on the primary producers, also affect the trophic food web in the streams by favouring the predominance of grazers

Probiotic lactobacilli and bifidobacteria in the mouth – in vitro studies on saliva-mediated functions and acid production

Probiotic lactobacilli and bifidobacteria in the mouth – in vitro studies on saliva-mediated functions and acid production Probiotics are viable bacteria which, when used in adequate amounts, are beneficial to the health of the host. Although most often related to intestinal health, probiotic bacteria can be found also in the mouth after consumption of products that contain them. This study aimed at evaluating the oral effects of probiotic bacteria already in commercial use. In a series of in vitro studies, the oral colonisation potential of different probiotic bacteria, their acid production and potential saliva-mediated effects on oral microbial ecology were investigated. The latter included effects on the salivary pellicle, the adhesion of other bacteria, and the activation of the peroxidase system. Streptococcus mutans, Streptococcus gordonii, Aggregatibacter actinomycetemcomitans and Helicobacter pylori were used as bacterial indicators of the studied phenomena. There were significant differences between the probiotic strains in their colonisation potential. They all were acidogenic, although using different sugars and sugar alcohols. However, their acid production could be inhibited by the peroxidase system. Based on the results, it can be suggested that probiotic bacteria might influence the oral microbiota by different, partly species or strain-specific means. These include the inhibition of bacterial adhesion, modification of the enamel pellicle, antimicrobial activity, and activation of the peroxidase system. To conclude, probiotic strains differed from each other in their colonisation potential and other oral effects as evaluated in vitro. Both positive and potentially harmful effects were observed, but the significance of the perceived results needs to be further evaluated in vivo.

Nutrimetabolomics fingerprinting to identify biomarkers of bread exposure in a free-living population from the PREDIMED study cohort

Bread is one of the most widely consumed foods. Its impact on human health is currently of special interest for researchers. We aimed to identify biomarkers of bread consumption by applying a nutrimetabolomic approach to a free-living population. An untargeted HPLC q-TOF-MS and multivariate analysis was applied to human urine from 155 subjects stratified by habitual bread consumption in three groups: non-consumers of bread (n = 56), white-bread consumers (n = 48) and whole-grain bread consumers (n = 51). The most differential metabolites (variable importance for projection ≥1.5) included compounds originating from cereal plant phytochemicals such as benzoxazinoids and alkylresorcinol metabolites, and compounds produced by gut microbiota (such as enterolactones, hydroxybenzoic and dihydroferulic acid metabolites). Pyrraline, riboflavin, 3-indolecarboxylic acid glucuronide, 2,8-dihydroxyquinoline glucuronide and N-α-acetylcitrulline were also tentatively identified. In order to combine multiple metabolites in a model to predict bread consumption, a stepwise logistic regression analysis was used. Receiver operating curves were constructed to evaluate the global performance of individual metabolites and their combination. The area under the curve values [AUC (95 % CI)] of combined models ranged from 77.8 % (69.1 86.4 %) to 93.7 % (89.4 98.1 %), whereas the AUC for the metabolites included in the models had weak values when they were evaluated individually: from 58.1 % (46.6 69.7 %) to 78.4 % (69.8 87.1 %). Our study showed that a daily bread intake significantly impacted on the urinary metabolome, despite being examined under uncontrolled free-living conditions. We further concluded that a combination of several biomarkers of exposure is better than a single biomarker for the predictive ability of discriminative analysis.

Nutrimetabolomics fingerprinting to identify biomarkers of bread exposure in a free-living population from the PREDIMED study cohort

Bread is one of the most widely consumed foods. Its impact on human health is currently of special interest for researchers. We aimed to identify biomarkers of bread consumption by applying a nutrimetabolomic approach to a free-living population. An untargeted HPLC q-TOF-MS and multivariate analysis was applied to human urine from 155 subjects stratified by habitual bread consumption in three groups: non-consumers of bread (n = 56), white-bread consumers (n = 48) and whole-grain bread consumers (n = 51). The most differential metabolites (variable importance for projection ≥1.5) included compounds originating from cereal plant phytochemicals such as benzoxazinoids and alkylresorcinol metabolites, and compounds produced by gut microbiota (such as enterolactones, hydroxybenzoic and dihydroferulic acid metabolites). Pyrraline, riboflavin, 3-indolecarboxylic acid glucuronide, 2,8-dihydroxyquinoline glucuronide and N-α-acetylcitrulline were also tentatively identified. In order to combine multiple metabolites in a model to predict bread consumption, a stepwise logistic regression analysis was used. Receiver operating curves were constructed to evaluate the global performance of individual metabolites and their combination. The area under the curve values [AUC (95 % CI)] of combined models ranged from 77.8 % (69.1 86.4 %) to 93.7 % (89.4 98.1 %), whereas the AUC for the metabolites included in the models had weak values when they were evaluated individually: from 58.1 % (46.6 69.7 %) to 78.4 % (69.8 87.1 %). Our study showed that a daily bread intake significantly impacted on the urinary metabolome, despite being examined under uncontrolled free-living conditions. We further concluded that a combination of several biomarkers of exposure is better than a single biomarker for the predictive ability of discriminative analysis.

Hidrocarbonetos e esterois como indicadores de fontes e destino de matéria orgânica em sedimentos da Baía de Sepetiba, Rio de Janeiro

The inputs of organic matter derived from natural and anthropogenic sources to Sepetiba Bay were investigated by using aliphatic hydrocarbons and sterols in superficial sediments. Concentrations ranged from 0.26 to 2.65 μg g-1, <0.01 to 17.41 μg g-1 and 0.77 and 9.24 μg g-1 for n-alkanes, UCM (unresolved complex mixture) and total sterols, respectively. The selected markers and ratios among individual compounds showed the major contribution of terrestrial sources to the total pool of sedimentary organic matter in the bay, but the accumulation of autochthonous organic matter increased with distance from the shoreline. The input of petroleum hydrocarbons and sewage (coprostanol in the range 0.01 to 0.43 μg g-1) were also detected, especially in the more urbanized regions of the bay, but at lower levels of contamination when compared to estuaries in other Brazilian coastal regions.

Poluição por mercúrio em aterros urbanos do período colonial no extremo sul do Brasil

Land reclamation fills in the city of Rio Grande (RS) are polluted by mercury with concentrations ranging from 0.3 to 18.7 mg kg-1. The level of Hg pollution decreases from the oldest landfills of 18th century to recent ones. Mercury distribution along vertical profiles resembles the same for copper, lead, and zinc, what allow supposing that mercury distribution has an autochthonous character. It is suggested that the principal source of mercury pollution was the activities related to animal skin and fair hair treatment, using ancient technology known as "carroting". Similar scenario of environmental risk could be met in other Brazilian cities with similar colonization history.

Lipídios como indicadores de fontes e distribuição de matéria orgânica particulada em um complexo estuarino-lagunar tropical (Mundaú-Manguaba, AL)

Fatty acids, alcohols and sterols were considered as markers of the source and distribution of particulate organic matter during the dry season in the Mundaú-Manguaba estuarine-lagoon system, NE Brazil. Lipid composition showed an overwhelming influence of autochthonous sources of organic matter in all system´s compartments, including the probable occurrence of algal blooms in specific areas. On the other hand, contamination by sewage was restricted to Mundaú lagoon. This scenario differed from known conditions observed in the wet season, illustrating the usefulness of the lipid biomarker approach for the characterization of other complex and dynamic systems in the Brazilian coastal zone.

Fontes e distribuição de matéria orgânica sedimentar no complexo estuarino-lagunar de Mundaú-Manguaba/AL, utilizando esterois e alcoóis como indicadores

The origin of the sedimentary organic matter in the Mundaú-Manguaba estuarine system was evaluated through the distribution and composition of sterols, alcohols and ancillary data. The muddy sediments of the lagoons are enriched in organic matter, derived from a mixture of autochthonous and allochthonous inputs. Mundaú exhibited moderate contamination by sewage, with coprostanol concentration as high as 4.4 µg g-1. The channels are characterized by sand and organic matter-poor sediments. The sediments from some rivers in the drainage basin accumulated organic matter derived only from terrestrial vegetation. Stanol/sterol ratios evidenced the preferential diagenesis of the autochthonous fraction of organic matter.

Probiotic interventions in infancy: Benefit and Safety Assessment of Extended Applications

Immaturity of the gut barrier system in the newborn has been seen to underlie a number of chronic diseases originating in infancy and manifesting later in life. The gut microbiota and breast milk provide the most important maturing signals for the gut-related immune system and reinforcement of the gut mucosal barrier function. Recently, the composition of the gut microbiota has been proposed to be instrumental in control of host body weight and metabolism as well as the inflammatory state characterizing overweight and obesity. On this basis, inflammatory Western lifestyle diseases, including overweight development, may represent a potential target for probiotic interventions beyond the well documented clinical applications. The purpose of the present undertaking was to study the efficacy and safety of perinatal probiotic intervention. The material comprised two ongoing, prospective, double-blind NAMI (Nutrition, Allergy, Mucosal immunology and Intestinal microbiota) probiotic interventions. In the mother-infant nutrition and probiotic study altogether 256 women were randomized at their first trimester of pregnancy into a dietary intervention and a control group. The intervention group received intensive dietary counselling provided by a nutritionist, and were further randomized at baseline, double-blind, to receive probiotics (Lactobacillus rhamnosus GG and Bifidobacterium lactis) or placebo. The intervention period extended from the first trimester of pregnancy to the end of exclusive breastfeeding. In the allergy prevention study altogether 159 women were randomized, double-blind, to receive probiotics (Lactobacillus rhamnosus GG) or placebo 4 weeks before expected delivery, the intervention extending for 6 months postnatally. Additionally, patient data on all premature infants with very low birth weight (VLBW) treated in the Department of Paediatrics, Turku University Hospital, during the years 1997 - 2008 were utilized. The perinatal probiotic intervention reduced the risk of gestational diabetes mellitus (GDM) in the mothers and perinatal dietary counselling reduced that of fetal overgrowth in GDM-affected pregnancies. Early gut microbiota modulation with probiotics modified the growth pattern of the child by restraining excessive weight gain during the first years of life. The colostrum adiponectin concentration was demonstrated to be dependent on maternal diet and nutritional status during pregnancy. It was also higher in the colostrum received by normal-weight compared to overweight children at the age of 10 years. The early perinatal probiotic intervention and the postnatal probiotic intervention in VLBW infants were shown to be safe. To conclude, the findings in this study provided clinical evidence supporting the involvement of the initial microbial and nutritional environment in metabolic programming of the child. The manipulation of early gut microbial communities with probiotics might offer an applicable strategy to impact individual energy homeostasis and thus to prevent excessive body-weight gain. The results add weight to the hypothesis that interventions aiming to prevent obesity and its metabolic consequences later in life should be initiated as early as during the perinatal period.

Efeito da solarização e do brometo de metila sobre a comunidade de fungos do solo

A microbiota do solo é de grande importância no desenvolvimento de culturas. Os métodos de controle, químico (brometo de metila) e físico (solarização), alteram essa microbiota. O presente trabalho objetivou estudar o comportamento da comunidade de fungos em solo solarizado e fumigado (brometo de metila). O delineamento experimental foi de blocos ao acaso, com três tratamentos (solarização, brometo de metila e testemunha) e sete repetições. A comunidade de fungos do solo foi avaliada de forma quantitativa e qualitativa, em três momentos (antes, durante e após a solarização) com amostras coletadas de três profundidades (0-5; 10-15 e 20-25 cm). Durante a solarização ocorreu uma redução na comunidade de fungos do solo, em termos quantitativos, em todas as camadas amostradas. No entanto, essa diminuição foi mais significativa na camada superficial (0-5cm). Em termos qualitativos, a solarização reduziu também o número de diferentes espécies de fungos do solo, mas na camada de 20-25 cm, essa diminuição foi a zero aos 56 dias de avaliação. A recolonização da microbiota do solo, em termos quantitativos, foi maior no tratamento com brometo de metila do que nos demais. Entretanto, esse aumento não foi o mesmo em termos qualitativos. Nos tratamentos solarizado e testemunha, o aumento na comunidade de fungos do solo foi acompanhado pela diversificação de espécies fúngicas.

Interactions between Polyunsaturated Fatty Acids and Probiotics

The prevalence of inflammatory based diseases has increased in industrialized countries over the last decades. For allergic diseases, two primary hypotheses have been proposed to explain this phenomenon, namely the hygiene and dietary evolution based hypothesis. Particularly, the reduced early exposure to microbes and an increase in the amount of polyunsaturated fatty acids (especially n-6 PUFA) in the diet have been discussed. Often, these two factors have been studied independently, even though both factors have been shown to possess potential health benefits and their mode of action to share similar mechanisms. The hypothesis of the present study was that demonstrate that PUFA and probiotics are not separate entities as such but do interact with each other. In the present study, we investigated whether maternal diet and atopic status influence the PUFA composition of breast milk and serum fatty acids of infants, and whether the fatty acid absorption and utilization of infant formula fatty acids is affected by supplementation of infant formula with probiotic bacteria (Lactobacillus GG and Bifidobacterium lactis Bb-12). Moreover, we investigated the mechanisms by which different PUFA influence the physicochemical and functional properties of probiotics as well as functionality of epithelial cells in vitro. We demonstrated a carry-over effect of dietary fatty acids from maternal diet via breast milk into infants’ serum lipid fatty acids. Our data confirmed the previously shown allergy –related PUFA level imbalances, though it did not fully support the impaired desaturation and elongation capacity hypothesis. We also showed that PUFA incorporation into phospholipids of infants was influenced by probiotics in infant formula in a strain dependent manner. Especially,Bifidobacterium lactis Bb-12 in infant formula promoted the utilization of n-3 PUFA. Mechanistically, we demonstrated that probiotics (Lactobacillus GG, Lactobacillus casei Shirota and Lactobacillus bulgaricus) did incorporate and interconvert exogenous free PUFA in the growth medium into bacterial fatty acids strain and PUFA dependently. In general, high concentrations of free PUFA inhibited the growth and mucus adhesion of probiotics, whereas low concentrations of specific long chain PUFA were found to promote the growth and mucus adhesion of Lactobacillus casei Shirota. These effects were paralleled with only minor alterations in hydrophobicity and electron donor – electron acceptor properties of lactobacilli. Furthermore, free PUFA were also demonstrated to alter the adhesion capacity of the intestinal epithelial cells; n-6 PUFA tended to inhibit the Caco-2 adhesion of probiotics, whereas n-3 PUFA had either no or minor effects or even promote the bacterial adhesion (especially Lactobacillus casei Shirota) to PUFA treated Caco-2 cells. The results of this study demonstrate the close and bilateral interactions between dietary PUFA and probiotics. Probiotics were shown to influence the absorption and utilization of dietary PUFA, whereas PUFA were shown to alter the functional properties of both probiotics and mucosal epithelia. These findings suggest that a more thorough understanding of interactions between PUFA and intestinal microbiota is a prerequisite, when the beneficial effects of new functional foods containing probiotics are designed and planned for human intervention studies.