Impact of child obesity on adipose tissue physiology: assessment of adipocytokines and inflammatory cytokines as biomarkers of obesity

Obesity could be interpreted as a low grade inflammatory state. The role of cytokines for innate and acquired immune response and adipocytokines in pathogenesis of obesity is not completely understood. The aim of the study was to evaluate anthropometric parameters, adipocytokines and inflammatory cytokine levels as biomarkers of childhood obesity. This investigation was designed as a longitudinal observational study. Forty-seven obese children (19 males and 28 females) were enrolled by Pediatric Clinic of the Foundation IRCCS Policlinico San Matteo, Pavia, Italy. For each patients a blood sample, used for other biochemical evaluations, was collected. Cytokines and adipocytokines plasmatic levels were determined using an ELISA method. Plasma leptin levels are in correlation with age (r=0.5; P<0.001) and BMI-z score (r=0.36; P<0.001), particularly in girls; plasma resistin levels are in inverse correlation with age, particularly in boys (r=-0.67; P<0.001) and in correlation with BMI-z score (r=0.52; P=0.002). Plasma leptin and resistin levels show a good correlation with antrophometric parameters of child obesity (sex and BMI z score). This study suggests that leptin and resistin can be considered as biomarker of childhood obesity and its comorbility. We observed a statistically significant correlation between plasma leptin and resistin levels and antrophometric parameters of child obesity (sex and BMI z score). This study suggests that adipocytokines, such as leptin and resistin, can be considered as biomarkers of childhood obesity

Changes in physiological activities and root exudation profile of two grapevine rootstocks reveal common and specific strategies for Fe acquisition

In several cultivation areas, grapevine can suffer from Fe chlorosis due to the calcareous and alkaline nature of soils. This plant species has been described to cope with Fe deficiency by activating Strategy I mechanisms, hence increasing root H+ extrusion and ferric-chelate reductase activity. The degree of tolerance exhibited by the rootstocks has been reported to depend on both reactions, but to date, little emphasis has been given to the role played by root exudate extrusion. We studied the behaviour of two hydroponically-grown, tolerant grapevine rootstocks (Ramsey and 140R) in response to Fe deficiency. Under these experimental conditions, the two varieties displayed differences in their ability to modulate morpho-physiological parameters, root acidification and ferric chelate reductase activity. The metabolic profiling of root exudates revealed common strategies for Fe acquisition, including ones targeted at reducing microbial competition for this micronutrient by limiting the exudation of amino acids and sugars and increasing instead that of Fe(III)-reducing compounds. Other modifications in exudate composition hint that the two rootstocks cope with Fe shortage via specific adjustments of their exudation patterns. Furthermore, the presence of 3-hydroxymugenic acid in these compounds suggests that the responses of grapevine to Fe availability are rather diverse and much more complex than those usually described for Strategy I plants

Promoción educativa a extensionistas e investigadores en la evaluación del impacto económico y ambiental de tecnologías críticas en producciones seleccionadas del sector agropecuario

Ponencia presentada en las VIII Jornadas Interdisciplinarias de Estudios Agrarios y Agroindustriales. Buenos Aires, Argentina, 31 de octubre al 1 de noviembre de 2013Entre los determinantes de la adopción, es posible que existan diferencias entre la visión de los técnicos y los productores. El conocimiento o disponibilidad de la tecnología no es condición suficiente de adopción. Trabajar con distintas estrategias para los productores grandes, medianos y chicos, facilita el diseño de alternativas de intervención, considerando calidad, sostenibilidad social y ambiental. Se pretende contribuir a mejorar las oportunidades de acceso a la tecnología de los productores familiares del sector agropecuario. El proyecto articula con los Centros Regionales de INTA de las provincias de San Luis, Buenos Aires, Corrientes y Tucumán, donde actualmente se ejecuta el Proyecto Específico de INTA AEES 303532. En los Encuentros se trabajo con técnicos extensionistas e investigadores de INTA, UNC y otras instituciones. Se realizo un trabajo grupal activo, participativo y reflexivo, utilizando una metodología gradual, intencional y continua, en cincos Encuentros durante la ejecución del proyecto. Cada una de las estrategias diseñadas fue sometida a una evaluación de impacto económico y ambiental. Se espera que los extensionista del INTA y extra INTA, puedan manejar estas herramientas metodológicas que les permitan evaluar el impacto económico y ambiental de la adopción de las tecnologías críticas.Fil: Meyer Paz, Roberto Oscar. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias. Departamento de Desarrollo Rural; Argentina.Fil: Giancola, Silvana Inés. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Economía y Sociología; Argentina.Fil: Morandi, Jorge Luis. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Famaillá, Tucumán; Argentina.Fil: Roberi, Ariel Arturo. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias. Departamento de Desarrollo Rural; Argentina.Fil: Andreu, Edgardo Mario. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias. Departamento de Producción Animal; Argentina.Fil: Carranza, Alejandro. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias. Departamento de Producción Animal; Argentina.Fil: Serena, Jorge Alberto. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias. Departamento de Desarrollo Rural; Argentina.Fil: Némoz, Juan Pablo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Cuenca del Salado. Agencia de Extensión Rural Azul; Argentina.Fil: Marastoni, Ariel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Mercedes, Corrientes; Argentina.Fil: Uguet Vaquer, Jaime Pablo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Mercedes, Corrientes; Argentina.Fil: Dutto, Jorge Omar. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias. Departamento de Recursos Naturales; Argentina.Fil: Salvador, María Laura. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias. Departamento de Desarrollo Rural; Argentina

Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (&lt;1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses. Interpretation: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists

COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Background and objectives: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. Methods: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score &gt; 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). Results: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p &lt; 0.001), RR = 2.19 for ICU admission (p &lt; 0.001), and RR = 2.43 for death (p &lt; 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). Discussion: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR&nbsp;=&nbsp;2.05, 95%CI&nbsp;=&nbsp;1.39–3.02, p&nbsp;&lt;&nbsp;0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR&nbsp;=&nbsp;0.42, 95%CI&nbsp;=&nbsp;0.18–0.99, p&nbsp;=&nbsp;0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

[D-Ala2]-Deltorphin I Peptoid and Retropeptoid Analogues: Synthesis, Biological Activity and Conformational Investigations.

The synthesis is described of a [D-Ala(2)]-deltorphin I peptoid analogue in which all amino acid residues have been substituted by the corresponding N-alkylglycine residues. The [D-Ala(2)]-deltorphin I retropeptoid was also prepared as well as [AlaI,D-Ala(2)]-deltorphin 1 and the corresponding peptoid. Structural investigations by FT-IR and fluorescence measurements were carried out on the synthetic analogues and on some [D-Ala(2)]-deltorphin 1 peptide-peptoid hybrids previously prepared. According to the fluorescence measurements the distance between the aromatic residues in the deltorphin I peptoid and retropeptoid is similar to that suggested for the delta- and mu-opioids, respectively. Measurements of CD in the presence of beta-cyclodextrin, and some preliminary pharmacological experiments were also performed. No dichroic bands are present in the spectrum of the [Ntyr(1),D-Ala(2)]-deltorphin 1, but an increasing dichroic effect appears in the spectra of both the deltorphin I peptoid and retropeptoid. Activity tests on isolated organ preparations showed that the modifications made produced a dramatic decrease in the agonistic activity of the synthetic derivatives

SYNTHESIS, CONFORMATION AND BIOLOGICAL ACTIVITY OF DERMORPHIN AND DELTORPHIN I ANALOGUES CONTAINING N-ALKYLGLYCINE IN PLACE OF RESIDUES IN POSITION 1,3,5 AND 6

Syntheses are described of new dermorphin and [D-Ala(2)]deltorphin I analogues in which the phenylalanine, the tyrosine or the valine residues have been substituted by the corresponding N-alkylglycine residues. Structural investigations by CD measurements in different solvents and preliminary pharmacological experiments were carried out on the resulting peptide-peptoid hybrids. The contribution from aromatic side chain residues is prominent in the CID spectra of dermorphin analogues and the assignment of a prevailing secondary structure could be questionable. In the CD spectra of deltorphin analogues the aromatic contribution is lower and the dichroic curves indicate the predominance of random conformer populations. The disappearance of the aromatic contribution in the [Ntyr(1), D-Ala(2)]-deltorphin spectrum could be explained in terms of high conformational freedom of the N-terminal residue. The kinetics of degradation of the synthetic peptoids digestion by rat and human plasma enzymes were compared with that of [Leu(5)]-enkephalin. The binding to opioid receptors was tested on crude membrane preparations from CHO cells stably transfected with the mu- and delta-opioid receptors. The biological potency of peptoids was compared with that of dermorphin in GPI preparations and with that of deltorphin I in MVD preparations. All the substitutions produced a dramatic decrease in the affinity of the peptide-peptoid hybrids for both the mu- and delta-opioid receptors. Nval(5) and/or Nval(6) containing hybrids behaved as mu-opioid receptor agonists and elicit a dose-dependent analgesia (tail-flick test) when injected i.c.v. in rats