Effects of Dietary Copper and Escherichia coli Challenge on the Immune Response and Gill Oxidative Balance in the Freshwater Mussel Diplodon chilensis.

Copper is a water and sediment pollutant that can be biomagnified by phytoplankton, and it often co-occurs with fecal bacteria. We addressed the combined effects of copper and Escherichia coli on the immune response and gill oxidative balance of the freshwater mussel Diplodon chilensis. Bivalves were sorted into four groups fed with 1) control algae, 2) bacteria (E. coli), 3) copper-enriched algae (Cu2+ ) algae, and 4) copper-enriched algae followed by bacteria (Cu2+ + E. coli). Cellular and humoral immune and cytotoxic variables were analyzed in hemolymph, and detoxifying/antioxidant enzyme activities (glutathione S-transferase [GST] and catalase [CAT]) and lipid peroxidation (thiobarbituric acid reactive substances [TBARS]) were studied in gill tissue. The total hemocyte number increased after Cu2+ exposure, independently of the E. coli challenge. The proportion of hyalinocytes significantly diminished in the E. coli and Cu2+ groups but not in Cu2+ + E. coli groups; granulocytes significantly increased with E. coli but not with Cu2+ + E. coli treatments. Phagocytic activity was higher in all treatments than in control mussels. Acid phosphatase activity was increased by E. coli and inhibited by Cu2+ and Cu2+ + E. coli. Both E. coli and Cu2+ but not Cu2+ + E. coli augmented alkaline phosphatase activity. The Cu2+ and Cu2+ + E. coli treatments reduced the lysosomal membrane stability and cell viability. Humoral bacteriolytic and phenol oxidase activities were not affected by any treatment. The Cu2+ treatment induced gill CAT and GST activities and increased TBARS levels. The Cu2+ + E. coli treatment reversed this CAT and GST stimulation and increased the Cu2+ effect on TBARS. Dietary Cu2+ affects bivalves' immunological and oxidative status and impairs defensive responses against bacteria. In turn, E. coli potentiates the gill oxidative effects of Cu2+ . Environ Toxicol Chem 2023;42:154-165. © 2022 SETAC.

HCV eradication with DAAs differently affects HIV males and females: A whole miRNA sequencing characterization.

Gender-specific consequences after HCV eradication are unexplored. MicroRNAs (miRNAs) play a crucial role in the immune response against viral infections. However, few have highlighted miRNA role in sex-biased disease or therapy response. We aim to assess gender differences reflected in the miRNA expression of HIV/HCV-coinfected patients who achieve sustained virological response (SVR) with direct acting antivirals (DAAs). We conducted a prospective study of miRNA expression in PBMCs from 28 chronic HIV/HCV-coinfected patients (HIV/HCV) at baseline and after achieving SVR with DAAs. Sixteen HIV-monoinfected patients (HIV) and 36 healthy controls (HC) were used as controls. Identification of significant differentially expressed (SDE) miRNAs was performed with generalized linear model and mixed GLMs. We also explored putative dysregulated biological pathways. At baseline, the HIV/HCV patients showed differences in the miRNA profile concerning the HIV group (165 and 102 SDE miRNAs for males and females, respectively). Gender-stratified analysis of HIV/HCV group at baseline versus at SVR achievement showed higher differences in males (80 SDE miRNAs) than in females (55 SDE miRNAs). After SVR, HIV/HCV group showed similar values to HIV individuals, especially in females (1 SDE miRNA). However, ten miRNAs in males remained dysregulated, which were mainly involved in cancer, fatty acid, and inflammatory pathways. Taken together, our results show gender-biased dysregulation in the miRNA expression profile of PBMCs after HCV eradication with DAAs. These differences were normalized in females, while miRNA profile and their target-related pathways in males lack of normalization, which may be related to a high-risk of developing liver-related complications.

Different HCV Exposure Drives Specific miRNA Profile in PBMCs of HIV Patients.

Micro RNAs (miRNAs) are essential players in HIV and HCV infections, as both viruses modulate cellular miRNAs and interact with the miRNA-mediated host response. We aim to analyze the miRNA profile of HIV patients with different exposure to HCV to explore specific signatures in the miRNA profile of PBMCs for each type of infection. We massively sequenced small RNAs of PBMCs from 117 HIV+ infected patients: 45 HIV+ patients chronically infected with HCV (HIV/HCV+), 36 HIV+ that spontaneously clarified HCV after acute infection (HIV/HCV-) and 36 HIV+ patients without previous HCV infection (HIV). Thirty-two healthy patients were used as healthy controls (HC). Differential expression analysis showed significantly differentially expressed (SDE) miRNAs in HIV/HCV+ (n = 153), HIV/HCV- (n = 169) and HIV (n = 153) patients. We found putative dysregulated pathways, such as infectious-related and PI3K signaling pathways, common in all contrasts. Specifically, putatively targeted genes involved in antifolate resistance (HIV/HV+), cancer-related pathways (HIV/HCV-) and HIF-signaling (HIV) were identified, among others. Our findings revealed that HCV strongly influences the expression profile of PBMCs from HIV patients through the disruption of its miRNome. Thus, different HCV exposure can be identified by specific miRNA signatures in PBMCs.

Dronabinol en manejo de apetito y pérdida de peso en pacientes con cáncer terminal, VIH, cuidados paliativos y vejez. Revisión de la literatura / Dronabinol in appetite management and weight loss in patients with terminal cancer, HIV, palliative care and old age. Literature review

Resumen: Introducción: La caquexia es un síndrome asociado al cáncer avanzado, VIH, pacientes en quimioterapia y quienes tienen seguimiento en cuidados paliativos. La prevalencia es de 25% de los pacientes con diagnóstico de cáncer, 26% en quienes reciben quimioterapia y de 14 a 38% de pacientes con VIH. Un pilar para el manejo es el cannabis debido al efecto del delta-9-tetrahidrocanabinol (THC), del cual se derivó el dronabinol, un fármaco desarrollado para estimular apetito y ganancia de peso. El objetivo de esta revisión bibliográfica es obtener la información sobre los cannabinoides y la evidencia más sólida existente con respecto al uso del dronabinol en pacientes que han presentado pérdida de peso y apetito. Material y métodos: Revisión de la bibliografía con buscador PubMed con las palabras clave Palliative care (cuidados paliativos), Cannabinoids (cannabinoides), cachexia (caquexia), Dronabinol (dronabinol), Appetite (apetito), de 1990 a 2018, limitado a humanos, obteniendo 259 artículos, eliminando 222 por repetirse o tener poca relevancia, dejando 37 artículos para análisis. Resultados: De 37 artículos revisados, nueve fueron estudios experimentales, 10 revisiones sistematizadas, un metaanálisis y 16 artículos de recomendaciones y sugerencias de manejo. Conclusión: El manejo del apetito y pérdida de peso en pacientes en cuidados paliativos, VIH, ancianos o en quimioterapia debe ser multidisciplinario, involucrando nutriólogos, psicólogos y médicos, ajustando el manejo a las características individuales que manifiesten. El dronabinol es un fármaco de primera elección para el manejo de dichos síntomas cuando la historia natural de la enfermedad se acompaña de náusea, vómito o dolor.

Abstract: Introduction: Cachexia is a syndrome associated with advanced cancer, HIV, patients on chemotherapy and those who are followed in palliative care. The prevalence is 25% of patients diagnosed with cancer, 26% in those receiving chemotherapy and 14 to 38% of patients with HIV. A mainstay for management is cannabis, due to the effect of delta-9-tetrahydrocannabinol (THC) from which dronabinol, a drug developed to stimulate appetite and weight gain, was derived. The aim of this literature review is to obtain information on cannabinoids and the strongest existing evidence regarding the use of dronabinol in patients who have presented weight and appetite loss. Material and methods: Literature review with PubMed search engine with the keywords Palliative care, Cannabinoids, cachexia, Dronabinol, Appetite, from 1990 to 2018, limited to humans, obtaining 259 articles, eliminating 222 for repetition or low relevance, leaving 37 articles for analysis. Results: Out of 37 articles reviewed 9 were experimental studies, 10 systematized reviews, 1 meta-analysis and 16 articles of recommendations and management suggestions. Conclusion: The management of appetite and weight loss in palliative care, HIV, elderly or chemotherapy patients should be multidisciplinary, involving nutritionists, psychologists and physicians, adjusting the management to the individual characteristics manifested. Dronabinol is a drug of first choice for the management of these symptoms when the natural history of the disease is accompanied by nausea, vomiting or pain.

Changes in Body Size during Early Growth Are Independently Associated with Arterial Properties in Early Childhood.

Nutritional status in early life stages has been associated with arterial parameters in childhood. However, it is still controversial whether changes in standardized body weight (z-BW), height (z-BH), BW for height (z-BWH) and/or body mass index (z-BMI) in the first three years of life are independently associated with variations in arterial structure, stiffness and hemodynamics in early childhood. In addition, it is unknown if the strength of the associations vary depending on the growth period, nutritional characteristics and/or arterial parameters analyzed. AIMS: First, to compare the strength of association between body size changes (Δz-BW, Δz-BH, Δz-BWH, Δz-BMI) in different time intervals (growth periods: 0-6, 0-12, 0-24, 0-36, 12-24, 12-36, 24-36 months (m)) and variations in arterial structure, stiffness and hemodynamics at age 6 years. Second, to determine whether the associations depend on exposure to cardiovascular risk factors, body size at birth and/or on body size at the time of the evaluation (cofactors). Anthropometric (at birth, 6, 12, 24, 36 m and at age 6 years), hemodynamic (peripheral and central (aortic)) and arterial (elastic (carotid) and muscular (femoral) arteries; both hemi-bodies) parameters were assessed in a child cohort (6 years; n =632). The association between arterial parameters and body size changes (Δz-BW, Δz-BH, Δz-BWH, Δz-BMI) in the different growth periods was compared, before and after adjustment by cofactors. RESULTS: Δz-BW 0-24 m and Δz-BWH 0-24 m allowed us to explain inter-individual variations in structural arterial properties at age 6 years, with independence of cofactors. When the third year of life was included in the analysis (0-36, 12-36, 24-36 m), Δz-BW explained hemodynamic (peripheral and central) variations at age 6 years. Δz-BH and Δz-BMI showed limited associations with arterial properties. CONCLUSION: Δz-BW and Δz-BWH are the anthropometric variables with the greatest association with arterial structure and hemodynamics in early childhood, with independence of cofactors.

Stroke volume and cardiac output non-invasive monitoring based on brachial oscillometry-derived pulse contour analysis: Explanatory variables and reference intervals throughout life (3-88 years).

BACKGROUND: Non-invasive assessment of stroke volume (SV), cardiac output (CO) and cardiac index (CI) has shown to be useful for the evaluation, diagnosis and/or management of different clinical conditions. Through pulse contour analysis (PCA) cuff­based oscillometric devices would enable obtaining ambulatory operator-independent non-invasive hemodynamic monitoring. There are no reference intervals (RIs), when considered as a continuum in childhood, adolescence and adult life, for PCA-derived SV [SV(PCA)], CO [CO(PCA)] and CI [CI(PCA)]. The aim of the study were to analyze the associations of SV(PCA), CO(PCA) and CI(PCA) with demographic, anthropometric, cardiovascular risk factors (CVRFs) and hemodynamic parameters, and to define RIs and percentile curves for SV(PCA), CO(PCA) and CI(PCA), considering the variables that should be considered when expressing them. METHODS: In 1449 healthy subjects (3-88 years) SV(PCA), CO(PCA) and CI(PCA) were non-invasively obtained (Mobil-O-Graph; Germany). ANALYSIS: associations between subject characteristics and SV(PCA), CO(PCA) and CI(PCA) levels (correlations; regression models); RIs and percentiles for SV(PCA), CO(PCA) and CI(PCA) (parametric methods; fractional polynomials). RESULTS: Sex, age, and heart rate would be explanatory variables for SV, CO, and CI levels. SV levels were also examined by body height, while body surface area (BSA) contributing to evaluation of CO and CI. CVRFs exposure did not contribute to independently explain the values of the dependent variables. SV, CO and CI levels were partially explained by the oscillometric-derived signal quality. RIs and percentiles were defined. CONCLUSIONS: Reference intervals and percentile for SV(PCA), CO(PCA) and CI(PCA), were defined for subjects from 3-88 years of age, results are expressed according to sex, age, heart rate, body height and/or BSA.

Exposure to hydrocarbons and chlorpyrifos alters the expression of nuclear receptors and antioxidant, detoxifying, and immune response proteins in the liver of the rainbow trout, Oncorhynchus mykiss.

The development of oil and gas production together with the fruit production in nearby areas of North Patagonia, Argentina, suggests aquatic pollution scenarios which include permanent oil pollution combined with short events of pesticides application. It has been reported that oil hydrocarbons activate the aryl hydrocarbon receptor (AhR) pathway in the rainbow trout, Oncorhynchus mykiss, and that the insecticide Chlorpyrifos (CPF) interacts with these effects. Thus, it is interesting to investigate whether hydrocarbons and insecticides, applied by separate or combined, can affect fish health and reproductive signaling by acting on different nuclear receptors' regulatory pathways. To study this kind of interactions, we exposed juvenile rainbow trout to water accommodated fraction (WAF) of crude oil (62 µg L-1 TPH) for 48 h and subsequently exposed the livers ex vivo to the insecticide Chlorpyrifos (CPF) (20 µg L-1) for 1 h. We analyzed the mRNA expression of nuclear receptors and proteins involved in detoxifying, antioxidant, immune and apoptosis responses by qRT-PCR. We also performed histopathological analysis. WAF induced the expression of the androgen (AR) and the Liver X receptor (LXR) by 8- and 3-fold, respectively. AR induction was reversed by subsequent exposure to CPF. The progesterone receptor (PR) and glucocorticoid receptor (GR) were increased 2-fold and 3-fold by WAF respectively, while estrogen and mineralocorticoid receptors were not affected. GR was also induced by CPF with an additive effect in the WAF-CPF treatment. The antioxidant genes, gamma glutamyl transferase (GGT), superoxide dismutase (SOD1) were induced by WAF (2-3-fold). WAF upregulated the ATP Binding Cassette Subfamily C Member 2 (ABCC2, MRP2) (4-fold) and downregulated alkaline phosphatase. WAF also induced the inflammatory interleukins (IL) IL-8, and IL-6 and the anti-inflammatory IL-10, while CPF induced the inflammatory tumor necrosis factor (-α) and IL-6, and activated the intrinsic apoptotic pathway through the induction of caspases 3 and 9. Both, WAF and CPF downregulated the expression of the extrinsic apoptosis initiator caspase 8 and the inflammatory caspase 1. In conclusion, WAF hydrocarbons alter O. mykiss endocrine regulation by inducing AR, PR and GR. The subsequent exposure to CPF reverses AR, suggesting a complex interaction of different pollutants in contaminated environments, WAF hydrocarbons alter liver metabolism by inducing the expression of LXR, GR, antioxidant and detoxifying enzymes, and both inflammatory and anti-inflammatory cytokines, and causing mild hepatic steatosis. CPF activates inflammatory and stress responses associated with the induction of inflammatory cytokines together with apoptosis initiator and executioner caspases.

Aortic pressure and forward and backward wave components in children, adolescents and young-adults: Agreement between brachial oscillometry, radial and carotid tonometry data and analysis of factors associated with their differences.

Non-invasive devices used to estimate central (aortic) systolic pressure (cSBP), pulse pressure (cPP) and forward (Pf) and backward (Pb) wave components from blood pressure (BP) or surrogate signals differ in arteries studied, techniques, data-analysis algorithms and/or calibration schemes (e.g. calibrating to calculated [MBPc] or measured [MBPosc] mean pressure). The aims were to analyze, in children, adolescents and young-adults (1) the agreement between cSBP, cPP, Pf and Pb obtained using carotid (CT) and radial tonometry (RT) and brachial-oscillometry (BOSC); and (2) explanatory factors for the differences between approaches-data and between MBPosc and MBPc.1685 subjects (mean/range age: 14/3-35 y.o.) assigned to three age-related groups (3-12; 12-18; 18-35 y.o.) were included. cSBP, cPP, Pf and Pb were assessed with BOSC (Mobil-O-Graph), CT and RT (SphygmoCor) records. Two calibration schemes were considered: MBPc and MBPosc for calibrations to similar BP levels. Correlation, Bland-Altman tests and multiple regression models were applied. Systematic and proportional errors were observed; errors´ statistical significance and values varied depending on the parameter analyzed, methods compared and group considered. The explanatory factors for the differences between data obtained from the different approaches varied depending on the methods compared. The highest cSBP and cPP were obtained from CT; the lowest from RT. Independently of the technique, parameter or age-group, higher values were obtained calibrating to MBPosc. Age, sex, heart rate, diastolic BP, body weight or height were explanatory factors for the differences in cSBP, cPP, Pf or Pb. Brachial BP levels were explanatory factors for the differences between MBPosc and MBPc.

Arterial Structural and Functional Characteristics at End of Early Childhood and Beginning of Adulthood: Impact of Body Size Gain during Early, Intermediate, Late and Global Growth.

An association between nutritional characteristics in theearlylife stages and the state of the cardiovascular (CV) system in early childhood itself and/or at the beginning of adulthood has been postulated. It is still controversial whether changes in weight, height and/or body mass index (BMI) during childhood or adolescence are independently associated with hemodynamics and/or arterial properties in early childhood and adulthood. AIMS: First, to evaluate and compare the strength of association between CVproperties (at 6 and 18 years (y)) and (a) anthropometric data at specific growth stages (e.g., birth, 6 y, 18 y) and (b) anthropometric changes during early (0-2 y), intermediate (0-6 y), late (6-18 y) and global (0-18 y) growth. Second, to determine whether the associations between CVproperties and growth-related body changes depend on size at birth and/or at the time of CVstudy. Third, to analyze the capacity of growth-related body size changes to explain hemodynamic and arterial properties in early childhood and adulthood before and after adjusting for exposure to CV risk factors. Anthropometric, hemodynamic (central, peripheral) and arterial parameters (structural, functional; elastic, transitional and muscular arteries) were assessed in two cohorts (children, n = 682; adolescents, n = 340). Data wereobtained and analyzed following identical protocols. RESULTS: Body-size changes in infancy (0-2 y) and childhood (0-6 y) showed similar strength of association with CV properties at 6 y. Conversely, 0-6, 6-18 or 0-18 ychanges were not associated with CV parameters at 18 y. The association between CV properties at 6 yand body-size changes during growth showed: equal or greater strength than the observed for body-size at birth, and lower strength compared to that obtained for current z-BMI. Conversely, only z-BMI at 18 y showed associations with CV z-scores at 18 y. Body size at birth showed almost no association with CVproperties at 6 or 18 y. CONCLUSION: current z-BMI showed the greatest capacity to explain variations in CV properties at 6 and 18 y. Variations in some CV parameters were mainly explained by growth-related anthropometric changes and/or by their interaction with current z-BMI. Body size at birth showed almost no association with arterial properties at 6 or 18 y.

Budding and Division of Giant Vesicles Linked to Phospholipid Production.

The self-reproduction of supramolecular assemblies based on the synthesis and self-assembly of building blocks is a critical step towards the construction of chemical systems with autonomous, adaptive, and propagation properties. In this report, we demonstrate that giant vesicles can grow and produce daughter vesicles by synthesizing and incorporating phospholipids in situ from ad-hoc precursors. Our model involves acyl chain elongation via copper(I)-catalyzed azide-alkyne [3 + 2] cycloaddition reaction and the ensuing production of synthetic phospholipids to induce budding and division. In addition, the growth and budding of giant vesicles were compatible with the encapsulation and transfer of macromolecules as large as lambda phage DNA to the buds. This chemical system provides a useful model towards the implementation of cell-like compartments capable of propagation and transport of biological materials.

Forward and Backward Aortic Components and Reflection Indexes in Children and Adolescents: Determinants and Role in High Pressure States.

BACKGROUND: High blood pressure states (HBP) would differ in wave components and reflections indexes, which could associate clinical and prognostic implications. The study aims: 1) to characterize the association of aortic wave components and reflection parameters (backward [Pb], forward [Pf], Pb/Pf ratio and augmentation index [AIx]) with demographic, anthropometric, hemodynamic and arterial parameters in healthy children and adolescents; 2) to generate multivariate prediction models for the associations, to contribute to understand the main determinants of Pf, Pb, Pb/Pf and AIx; 3) to identify if differences in wave reflection indexes observed in HBP could be explained by differences in the analyzed parameters. METHODS: Healthy children and adolescents (n=816, females: 386; Age: 3-20 years) were studied. EVALUATIONS: central aortic pressure and wave components (Pb, Pf, Pb/Pf and AIx determination with SphygmoCor [SCOR] and Mobil-o-Graph [MOG]); anthropometric assessment; regional arterial stiffness (carotid-femoral, carotid-radial pulse wave velocity [PWV] and PWV ratio); carotid intima-media thickness; carotid and femoral distensbility; cardiac output; systemic vascular resistances (SVR). Simple and multiple regression models were constructed to determine aortic wave parameters; the main explanatory variables. Normotensive and HBP groups were compared. Differences in wave reflection indexes were analyzed before and after controlling for explanatory variables. Equivalences between SphygmoCor and Mobil-O-Graph data were assessed (correlation and Bland-Altman analyses). RESULTS AND CONCLUSION: There were systematic and proportional differences between the data obtained with SphygmoCor and Mobil-O-Graph devices. Heart rate (HR), peripheral pulse pressure, height and weight were the variables that isolated (simple associations) or combined (multiple associations), showed the major capability to explain interindividual differences in Pf, Pb, Pb/Pf and AIx. Arterial stiffness also showed explanatory capacity, being the carotid the artery with the major contribution. HBP associated higher Pf, Pb, AIx and lower Pb/Pf ratio. Those findings were observed together with higher weight, arterial stiffness and HR. After adjusting for anthropometric characteristics, HR, cardiac output and SVR, the HBP group showed greater Pf and Pb. Then, Pf and Pb characteristics associated with HBP would not be explained by anthropometric or hemodynamic factors. Evaluating wave components and reflection parameters could contribute to improve the comprehension and management of HBP states.

Alterations in the intestine of Patagonian silverside (Odontesthes hatcheri) exposed to microcystin-LR: Changes in the glycosylation pattern of the intestinal wall and inhibition of multidrug resistance proteins efflux activity.

Accumulation and toxicity of cyanobacterial toxins, particularly microcystin-LR (MCLR) have been extensively studied in fish and aquatic invertebrates. However, MCLR excretion mechanisms, which could reduce this toxin's effects, have received little attention. The Patagonian silverside, Odontesthes hatcheri, is an omnivorous-planktivorous edible fish, which has been shown to digest cyanobacterial cells absorbing MCLR and eliminating the toxin within 48h without suffering significant toxic effects. We studied the effects of MCLR on glycoconjugate composition and the possible role of multidrug resistance associated proteins (Abcc) in MCLR export from the cells in O. hatcheri intestine. We treated O. hatcheri with 5µg MCLRg(-1) body mass administered with the food. Twenty four hours later, the intestines of treated and control fish were processed for lectin-histochemistry using concanavalin A (ConA), Triticum vulgaris agglutinin (WGA), and Dolichos biflorus agglutinin (DBA). MCLR affected the distribution of glycoconjugates by augmenting the proportion of ConA-positive at the expense of WGA-positive cells. We studied MCLR effects on the transport of the Abcc-like substrates 2,4-dinitrophenyl-S-glutathione (DNP-SG) and calcein in ex vivo intestine preparations (everted and no-everted sacs and strips). In treated preparations, CDNB together with MCLR (113µg MCLRg(-1) intestine, equivalent to 1.14µmolL(-1) when applied in the bath) or the Abcc inhibitor, MK571 was applied for one hour, during which DNP-SG was measured in the bath every 10min in order to calculate mass-specific DNP-SG transport rate. MCLR significantly inhibited DNP-SG transport (p<0.05), especially in middle intestine (47 and 24%, for luminal and serosal transport, respectively). In middle intestine strips, MCLR and MK571inhibited DNP-SG transport in a concentration dependent fashion (IC50 3.3 and 0.6µmolL(-1), respectively). In middle intestine strips incubated with calcein-AM (0.25µmolL(-1)), calcein efflux was inhibited by MCLR (2.3µmolL(-1)) and MK571 (3µmolL(-1)) by 38 and 27%, respectively (p<0.05). Finally, middle intestine segments were incubated with different concentrations of MCLR applied alone or together with 3µM MK571. After one hour, protein phosphatase 1 (PP1) activity, the main target of MCLR, was measured. 2.5µM MCLR did not produce any significant effect, while the same amount plus MK571 inhibited PP1 activity (p<0.05). This effect was similar to that of 5µM MCLR. Our results suggest that in O. hatcheri enterocytes MCLR is conjugated with GSH via GST and then exported to the intestinal lumen through Abcc-like transporters. This mechanism would protect the cell from MCLR toxicity, limiting toxin transport into the blood, which is probably mediated by basolateral Abccs. From an ecotoxicological point of view, elimination of MCLR through this mechanism would reduce the amount of toxin available for trophic transference.

Changes in Central Aortic Pressure Levels, Wave Components and Determinants Associated with High Peripheral Blood Pressure States in Childhood: Analysis of Hypertensive Phenotype.

The aims were to determine whether children's high peripheral blood pressure states (HBP) are associated with increased central aortic blood pressure (BP) and to characterize hemodynamic and vascular changes associated with HBP in terms of changes in cardiac output (stroke volume, SV), arterial stiffness (aortic pulse wave velocity, PWV), peripheral vascular resistances (PVR) and net and relative contributions of reflected waves to the aortic pulse amplitude. We included 154 subjects (mean age 11; range 4-16 years) assigned to one of two groups: normal peripheral BP (NBP, n = 101), defined as systolic and diastolic BP < 90th percentile, or high BP (HBP, n = 53), defined as average systolic and/or diastolic BP levels ≥90th percentile (curves for sex, age and body height). The HBP group included children with hypertensive and pre-hypertensive BP levels. After a first analysis, groups were compared excluding obese and dyslipidemic children. Peripheral and central aortic BP, PWV and pulse wave-derived parameters (augmentation index, forward and backward wave components' amplitude) were measured using gold-standard techniques, applanation tonometry (SphygmoCor) and oscillometry (Mobil-O-Graph). Independent of the presence of dyslipidemia and/or obesity, aortic systolic and pulse BP were higher in HBP than in NBP children. The increase in central BP could not be explained by an increase in the relative contribution of reflections to the aortic pressure wave, higher PVR or by an augmented peripheral reflection coefficient. Instead, the rise in central BP would be explained by an increase in the amplitude of both incident and reflected wave components.

Childhood Obesity Associates Haemodynamic and Vascular Changes That Result in Increased Central Aortic Pressure with Augmented Incident and Reflected Wave Components, without Changes in Peripheral Amplification.

The aims were to determine if childhood obesity is associated with increased central aortic blood pressure (BP) and to characterize haemodynamic and vascular changes associated with BP changes in obese children and adolescents by means of analyzing changes in cardiac output (stroke volume, SV), arterial stiffness (aortic pulse wave velocity, PWV), peripheral vascular resistances (PVR), and net and relative contributions of reflected waves to the aortic pulse wave amplitude. We included 117 subjects (mean/range age: 10 (5-15) years, 49 females), who were obese (OB) or had normal weight (NW). Peripheral and central aortic BP, PWV, and pulse wave-derived parameters (augmentation index, amplitude of forward and backward components) were measured with tonometry (SphygmoCor) and oscillometry (Mobil-O-Graph). With independence of the presence of dyslipidemia, hypertension, or sedentarism, the aortic systolic and pulse BP were higher in OB than in NW subjects. The increase in central BP could not be explained by the elevation in the relative contribution of reflections to the aortic pressure wave and higher PVR or by an augmented peripheral reflection coefficient. Instead, the rise in central BP could be explained by an increase in the amplitude of both incident and reflect wave components associated to augmented SV and/or PWV.

Modulating effects of orally supplied Euglena gracilis on the physiological responses of the freshwater mussel Diplodon chilensis, exposed to sewage water pollution in a Patagonian river (Argentina).

In order to test if orally supplied Euglena sp. cells modulate the physiological status of bivalves during bioremediation procedures, we evaluated the effect of Euglena gracilis diet on the immune response, oxidative balance and metabolic condition of Diplodon chilensis exposed to sewage water pollution. Mussels were fed for 90 days with E. gracilis (EG) or Scenedesmus vacuolatus (SV, control diet), and then exposed for 10 days at three sites along the Pocahullo river basin: 1) an unpolluted site, upstream of the city (control, C); 2) upstream (UpS) and 3) downstream (DoS) from the main tertiary-treated sewage discharge, in the city of San Martín de los Andes, Northwest Patagonia, Argentina. Our results show that the total hemocyte number decreases while pollution load increases along the river course for both, EG and SV mussels. Phagocytic activity is higher in EG mussels than in SV ones under all conditions. Reactive oxygen species (ROS) production in hemocytes increases with the increase in the pollution load, being significantly higher for EG mussels than for SV ones at DoS; no changes are observed for total oxyradical scavenging capacity (TOSC). Hemocytes' viability is increased for E. gracilis diet at C and remains unchanged in this group of mussels when exposed at the polluted sites. Lysosomal membrane stability is higher in EG mussels than in SV ones for all conditions, although it is decreased at polluted sites compared with that at C. Antioxidant (catalase) and detoxifying (gluthatione S-transferase) defenses are generally lower in gills and digestive gland of EG mussels than in SV ones. Lipid peroxidation (TBARS) is evident in gills of EG mussels at C, and in digestive gland of the same group, at all the sites. Gill mass factor (GF) is affected by the E. gracilis diet; it is increased at C and decreased at polluted sites when compared with that of SV ones. Digestive gland mass factor (DGF) is higher in EG mussels than in SV ones. In D. chilensis, continuous and long term feeding with E. gracilis cells favors immune response and reduces the damage caused by sewage pollution exposure on hemocytes. Nevertheless, diet and transplantation procedures may produce negative effects on the oxidative balance of gills and digestive gland and should be taken into account for bioremediation strategies.

Long-term feeding with Euglena gracilis cells modulates immune responses, oxidative balance and metabolic condition in Diplodon chilensis (Mollusca, Bivalvia, Hyriidae) exposed to living Escherichia coli.

We evaluated the modulating effect of long-term feeding with lyophilized Euglena gracilis cells on immune response, oxidative balance and metabolic condition of the freshwater mussel Diplodon chilensis. Mussels, previously fed with Scenedesmus vacuolatus (SV) or E. gracilis (EG) for 90 days, were challenged with an environmentally relevant concentration of Escherichia coli in water for 5 days, under feeding or starvation conditions. EG diet increased overall phagocytic activity and tissue hemocyte accumulation (gill and mantle), and favored hemocyte viability upon E. coli challenge. Tissular hemocyte accumulation, and humoral bacteriolytic activity and protein content were similarly stimulated by EG and E. coli, with no further effect when both stimuli were combined. Both, E. coli challenge and EG diet reduced gill bacteriolytic activity with respect to nonchallenged SV mussels, while no effect was observed in challenged EG mussels. Gill and digestive gland protein contents, along with digestive gland bacteriolytic activity were higher in EG than in SV mussels. Both SV and EG mussels showed increased gill mass upon E. coli challenge, while digestive gland mass was increased by bacterial challenge only in SV mussels. Bacterial challenge produced no effect on humoral reactive oxygen species levels of both groups. Total oxyradical scavenging capacity levels was reduced in challenged SV mussels but remained unaffected in EG ones. In general, EG diet decreased glutathione S-transferase and catalase activities in gill and digestive gland, compared with SV diet; but increased enzyme activity was evident in challenged mussels of both groups. Gill and digestive gland lipid peroxidation levels were higher in EG than in SV mussels but E. coli challenge had stronger effect on SV mussels. Adductor muscle RNA:DNA ratio was higher in EG mussels than in SV ones, and increased upon E. coli challenge in mussels of both groups. E. gracilis can be suggested as a nutritional and protective diet complement suitable for filtering bivalves. However, our results obtained from starved mussels show that starvation periods after supplying this diet should be avoided, since these could revert part of the acquired benefits and/or exacerbate detrimental effects.

Health status and bioremediation capacity of wild freshwater mussels (Diplodon chilensis) exposed to sewage water pollution in a glacial Patagonian lake.

Deleterious effects on health and fitness are expected in mussels chronically exposed to sewage water pollution. Diplodon chilensis inhabiting SMA, an area affected by untreated and treated sewage water, shows increased hemocyte number and phagocytic activity, while bacteriolytic and phenoloxidase activities in plasma and reactive oxygen species production in hemocytes are lower compared to mussels from an unpolluted area (Yuco). There are not differences in cell viability, lysosomal membrane stability, lipid peroxidation and total oxygen scavenging capacity between SMA and Yuco mussels' hemocytes. Energetic reserves and digestive gland mass do not show differences between groups; although the condition factor is higher in SMA than in Yuco mussels. Gills of SMA mussels show an increase in mass and micronuclei frequency compared to those of Yuco. Mussels from both sites reduce bacterial loads in polluted water and sediments, improving their quality with similar feeding performance. These findings suggest that mussels exposed to sewage pollution modulate physiological responses by long-term exposure; although, gills are sensitive to these conditions and suffer chronic damage. Bioremediation potential found in D. chilensis widens the field of work for remediation of sewage bacterial pollution in water and sediments by filtering bivalves.

Transient elastography to rule out esophageal varices and portal hypertensive gastropathy in HIV-infected individuals with liver cirrhosis.

BACKGROUND/AIMS: It is recommended that patients with cirrhosis undergo endoscopic screening to rule out the presence of gastroesophageal varices: a noninvasive predictive method to identify cirrhotic patients with a very low risk of esophageal varices could potentially avoid unnecessary endoscopies. METHODS: We studied in 85 HIV-infected patients with cirrhosis the association between the absence of esophageal varices and portal hypertensive gastropathy, assessed by endoscopy, and liver stiffness measurement by transient elastography. We analyzed other parameters related to portal hypertension and hepatic function. RESULTS: Values of transient elastography and platelet count were significantly associated with absence of esophageal varices/portal hypertensive gastropathy. The area under the receiver operating characteristics curve [95% confidence interval (CI)] of transient elastography for the prediction of the absence of esophageal varices/portal hypertensive gastropathy was 0.7 (0.58-0.81). A liver stiffness measurement value less than 20 kPa was highly predictive of the absence of esophageal varices and portal hypertensive gastropathy. The combination of transient elastography (<20 kPa) and platelet count (>120 × 10 cells/l) had the highest negative predictive value (100%, CI 95% 77.2-100) for absence of esophageal varices and portal hypertensive gastropathy. CONCLUSION: Transient elastography combined with platelet count is useful for predicting the absence of esophageal varices and portal hypertensive gastropathy and, therefore, avoid unnecessary diagnostic endoscopies in HIV-infected patients with liver cirrhosis.

Morbidity and mortality of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: national cancer institute, Mexico city, Mexico.

Peritoneal carcinomatosis (PC) is generally considered a lethal disease, with a poor prognosis. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as a new approach for peritoneal surface disease. This study investigated the early experience with this combined modality treatment at a single institute. From January 2007 to March 2010, 24 patients were treated After aggressive CS, with HIPEC (cisplatin 25 mg/m(2)/L and mitomycin C 3.3 mg/m(2)/L was administered for 90-minutes at 40.5° C). These data suggest that aggressive CRS with HIPEC for the treatment of PC may result in low mortality and acceptable morbidity. Rigorous patient selection, appropriate and prudent operative procedures were associated with encouraging results in our experience.

A domino-based approach toward stereodefined heavily functionalized cyclohexanes: synthesis of iridal's core structure.

A stereoselective synthesis of heavily functionalized six-membered ring subunits, which possess functionality at sites appropriate for further elaboration, is described. The cyclopentanone moiety of hydrindenediol is required to achieve total facial selectivity during the pre-domino installation of the second quaternary center, while oxidative cleavage is responsible for the ring-expanding rearrangement. A microwave-assisted version of the key domino transformation and a test of concept approach toward the iridal core structure are also presented.