Angiotensin type-2 (AT-2)-receptor activation reduces renal fibrosis in cyclosporine nephropathy: evidence for blood-pressure independent effect

Compound 21 (C21), selective agonist of AT2 receptors, shows antinflammatory effects in hypertension and nephroprotection in diabetes. The aim of this study was to evaluate the effects of C21 in cyclosporine nephropathy, which is characterized mainly by tubulo-interstitial fibrosis. Ten days before and during the experimental periods, low-salt diet was administered to Sprague Dawley rats. Cyclosporine-A (15mg/kg/day, i.p.) and cyclosporine-A plus C21 (0.3 mg/kg /day, i.p) were administered for 1 and 4 weeks. Control groups was left without any treatment. Blood pressure (plethysmographic method) and 24 hour albuminuria were measured once a week. At the end of the experiments, the kidneys were excised for histomorphometric analysis of renal fibrosis and for immunohistochemical evaluation of inflammatory infiltrates and type I and IV collagen expression.After 1 and 4 weeks, the rats treated with cyclosporine showed a significant increase (p <0.01) in blood pressure, no significant changes in albuminuria, a significant increase (p <0.01) in glomerular and tubulo-interstitial fibrosis and inflammatory infiltrates as compared to the control rats. Treatment with C21 did not modify the cyclosporine dependent increase of blood pressure, which was higher than in control rats, but after 4 weeks of treatment significantly reduced (p <0.01) glomerular and tubulo-interstitial fibrosis, type 1 collagen expression and macrophage infiltration, as compared to rats treated with cyclosporine.The administration of C21 showed a protective effect on cyclosporine nephropathy, decreasing renal fibrosis and macrophage infiltration. These data suggest that C21 may counteract tubulo-interstitial fibrosis, the most potent predictor of the progression of renal diseases

Clinical significance of epithelial-to-mesenchymal transition in laryngeal carcinoma: Its role in the different subsites

Background: During epithelial-to-mesenchymal transition, cancer cells lose adhesion capacity gaining migratory properties. The role of the process on prognosis has been evaluated in 50 cases of laryngeal carcinoma. Methods: E-cadherin, N-cadherin, β-catenin, α-catenin, γ-catenin, caveolin-1, and vimentin immunohistochemical expression were evaluated using a double score based on staining intensity and cellular localization. Results: Cytoplasmic E-cadherin and α/γ catenin staining were associated with a decrease in survival, cytoplasmic β-catenin was associated with advanced stage, and N-cadherin and vimentin expression were associated with poor differentiation and tumor relapse. On the basis of cancer cells, epithelial or mesenchymal morphological and immunophenotypic similarity we identified 4 main subgroups correlated with a transition to a more undifferentiated phenotype, which have a different pattern of relapse and survival. Conclusion: The negative prognostic role of epithelial-to-mesenchymal transition has been confirmed and a predictive role in glottic tumors has been suggested, leading us to propose epithelial-to-mesenchymal transition as an additional adverse feature in laryngeal carcinoma

On the environmental impacts of voluntary animal-based policies in the EU: Technical and political considerations

The livestock sector has a large influence on direct and indirect (via land use change) greenhouse gas emissions, with potential negative impacts on climate change. We quantify the environmental impacts related to the introduction of a voluntary animal-based policy supported by the European Union (EU), the Measure 14 of Rural Development Programmes 2014–2020 on animal welfare. In particular, we focus on methane and nitrous oxide emissions (direct impacts), and on carbon-based and nitrous oxide emissions from land use change (indirect impacts). Our case study is the dairy sector of the EU Member States. We found that the animal-based measures have (on average) limited environmental impacts, although marked differences exist across Member States

OP0086 GENDER INFLUENCE ON CLINICAL MANIFESTATIONS, DEPRESSIVE SYMPTOMS AND BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) SERUM LEVELS IN PATIENTS AFFECTED BY FIBROMYALGIA

Background:Fibromyalgia (FM) is a common rheumatic disease characterized by chronic widespread pain, sleep and mood disorders. A higher prevalence of FM in women compared with men is well known, although the specific differences in clinical manifestations related to gender are still poorly defined. Brain-Derived Neurotrophic Factor (BDNF) is an endogenous growth factor that gained attention for its potential as biomarker of several diseases, including FM and depression.Objectives:The aims of this study were to investigate gender-related difference among males and females affected by FM in clinical manifestations, depressive features and BDNF serum level, evaluating also the diagnostic potential of the latter.Methods:We consecutively enrolled adult patients affected by FM (ACR 2016) referring to our out-patient clinic. Each subject underwent clinical and answered to questionnaires for the severity of FM symptoms (Revised Fibromyalgia Impact Questionnaire, R-FIQ) and depressive symptoms (Beck Depression Inventory-II, BDI-II). We collected blood samples from a subgroup of patients of both sexes, matched for age, for BDNF serum level dosage through ELISA. BDNF levels were assessed also in a control group, matched for sex and age.Results:The cohort was composed by 201 FM patients (172 F, 29 M), mean age 49.13. Females showed higher values of R-FIQ total score (p=0,0005) as well the specific items of the R-FIQ for pain (p=0,013), fatigue (p=0,014), memory problems (p=0,007), tenderness to touch (p<0,0001), balance problems (p<0,0001) and sensitivity to environmental stimuli (p=0,012) when compared with males (fig. 1). There was no difference in BDI-II between males and females, but notably male patients reported a significantly higher frequency of coexisting depressive disorder (p=0,038) (fig. 2). Serum BDNF levels were evaluated in 40 FM patients and 40 healthy controls (HC) (F:M 1:1). BDNF levels were significantly lower in FM patients compared with HC (p<0,0001). Among FM patients, BDNF levels were lower in males compared with females (p<0,0001) (fig.3). BDNF did not correlate with any clinical and clinimetric parameter. BDNF showed a good diagnostic performance (AUC=0,89, CI95%=0,82-0,9630, p<0,0001) (fig. 4). At a cut-off value <6,47 ng/dl, BDNF showed a specificity of 75% and a sensibility of 92,31%,(CI 95%=79,68-97.35) for FM identification (LR=3,692).Conclusion:FM clinical manifestations are strongly dependant from gender. While females present a more severe disease and a higher burden of symptoms, mood disorders tend to be a major characteristic of males with FM. Reduced BDNF serum levels have been reported as typical of depressive disorders. Our findings of lower BDNF levels in male FM patients compared to females support this hypothesis. BDNF have potential as biomarker of the disease and should be validated in larger cohorts.References:[1]Sarzi-Puttini et al. Nature Reviews 2020[2]Colucci-D'Amato et al. Int J Molecular Sciences 2020[3]Nugraha et al. Rheumatol Int 2012[4]Schmitt et al. Ann Med 2016[5]Melchior et al. Neuroscience 2016[6]Stefani et al. Neuroscience Letters 2012Disclosure of Interests:None declare

L-lysine production at 65°C by auxotrophic-regulatory mutants of Bacillus stearothermophilus

The amino acid L-lysine was produced from auxotrophic-regulatory mutants ofBacillus stearothermophilus at a temperature of 60–65°C. One of the mutants (AEC 12 A5, S-(2-aminoethyl)-cysteiner, homoserine−), produced L-lysine at the concentration of 7.5 g/l in shaken flasks in minimal medium containing 5% glucose. Culture conditions for optimizing L-lysine production were not investigated. The aspartokinase activity of the wild strainB. stearothermophilus Zu 183 was inhibited by lysine alone and by threonine plus lysine. AEC resistant mutants showed an aspartokinase activity genetically desensitized to the feedback inhibition. Optimal temperature and pH of aspartokinase were 45°C and 9.5, respectively. The data provide significant evidence that mutants of the speciesB. stearothermophilus have a potential value for amino acid production

Dietary habits and nutrition in rheumatoid arthritis: can diet influence disease development and clinical manifestations?

Rheumatoid arthritis (RA) is a systemic, autoimmune disease characterized by joint involvement, with progressive cartilage and bone destruction. Genetic and environmental factors determine RA susceptibility. In recent years, an increasing number of studies suggested that diet has a central role in disease risk and progression. Several nutrients, such as polyunsaturated fatty acids, present anti-inflammatory and antioxidant properties, featuring a protective role for RA development, while others such as red meat and salt have a harmful effect. Gut microbiota alteration and body composition modifications are indirect mechanisms of how diet influences RA onset and progression. Possible protective effects of some dietary patterns and supplements, such as the Mediterranean Diet (MD), vitamin D and probiotics, could be a possible future adjunctive therapy to standard RA treatment. Therefore, a healthy lifestyle and nutrition have to be encouraged in patients with RA

Long term evaluation of mental fatigue by Maastricht Questionnaire in patients with OSAS treated with CPAP

Background. Patients with obstructive sleep apnoea syndrome (OSAS) suffer from disrupted sleep. Impaired nightly sleep leads to increase physical and mental fatigue. The effect of long term continuous positive airway pressure (CPAP) on mental fatigue in OSAS patients, assessed by Maastricht Questionnaire (MQ), has not been investigated yet. Methods. In order to evaluate the role of CPAP in improving mental fatigue of patients with OSAS, we studied 35 patients (26 males, age &lt;65 years at the time of the diagnosis) affected by OSAS, established by polysomnography (PSG). Patients were divided into two groups; 19 subjects (15 males), who refused CPAP therapy, and 16 patients (11 males) well matched for sex, age, body mass index (BMI), neck circumference, duration of follow up, and severity of disease, who had been treated with CPAP for at least two years. Results. All patients had severe OSAS with Respiratory Disturbance Index (RDI), of 48±20.9 (range 22-90) and 61.48±18.6 (range 34-101) respectively, for group one (untreated patients) and group two (CPAP treatment). In addition, all patients had severe impairment of mental fatigue and of daytime sleepiness, demonstrated by high values of MQ score (32.17±15.33 and 37.36±12.4, respectively) and Epworth Sleepiness Scale (ESS) (14.21±4.77 and 15.06±6.07 respectively). There was no statistical significant difference in the group one at baseline and after follow- up, in terms of BMI, MQ score, ESS, and RDI. In the CPAP group (group two), the patients reported a significant improvement of the quality of their mental health (MQ 37.36±12.4 vs. 16.41±9.02; p&lt;0.0001) and sleepiness (ESS 15.06±6.07 vs. 4.13±3.93; p&lt;0.0001) with a stable BMI. There was significant correlation between the severity of sleep apnoea, expressed as RDI, and MQ at admission compared to at the end of follow-up (r=0.4, p&lt;0.05). Conclusions. This study demonstrates an evident deterioration of mental fatigue in patients with OSAS, directly correlated to the severity of nocturnal disorder breathing; however supports the hypothesis that long term CPAP therapy significantly improves sleepiness and mental fatigue

Exhaled Interleukine-6 and 8-isoprostane in chronic obstructive pulmonary disease: effect of carbocysteine lysine salt monohydrate (SCMC-Lys).

Chronic obstructive pulmonary disease (COPD) is characterized by an airways inflammation and by an enhanced generation of reactive oxygen species. The aim of our study was to assess the inflammation and the oxidative stress in airways of COPD patients with acute exacerbation of disease and in stability. Furthermore, we investigated the anti-inflammatory and antioxidant effects of 6 months treatment with carbocysteine lysine salt monohydrate (SCMC-Lys) in COPD. We studied 30 mild acute COPD, 10 mild stable COPD and 15 healthy subjects. 8-isoprostane and Interleukine-6 were measured in their breath condensate through immunoassay. Significantly higher concentrations of exhaled 8-isoprostane and Interleukine-6 were found in acute COPD patients compared to stable COPD and healthy controls (21.8+/-5.1 vs. 13.2+/-2.0 vs. 4.7+/-1.8 pg/ml and 7.4+/-0.9 vs. 5.8+/-0.2 vs. 2.7+/-0.6 pg/ml, p<0.0001). COPD patients treated with SCMC-Lys showed a marked reduction of exhaled 8-isoprostane and Interleukine-6 (8.9+/-1.5 and 4.6+/-0.8 pg/ml, p<0.0001). These findings suggest that there is an increase of 8-isoprostane and Interleukine-6 concentrations in the breath condensate of COPD patients compared to healthy controls especially during acute exacerbations of the disease. Moreover, we showed an anti-inflammatory and antioxidant effect of short-term administration of SCMC-Lys in COPD, suggesting the importance of a further placebo-controlled study that should evaluate the effects of this drug

From food waste to eco-friendly functionalized polymer composites: Investigation of orange peels as active filler

: The development of eco-friendly polymer composites with multifunctional properties aligns with the goals of the circular economy agenda, which aims to minimize waste and promote the sustainable use of resources by closing the loop of product life cycles. Eco-friendly polymer composites play a crucial role in achieving these objectives. The present work focuses on the preparation of fully biobased blends obtained by melt mixing a bio-polyester, poly(butylene succinate-co-adipate) (PBSA), with orange peels up to 20&nbsp;wt%, to yield active polymer composites. Orange peels, employed here as natural filler, are largely available from food wastes, they are rich in phenolic compounds and possess antioxidant activity as shown by the experimental tests carried out. The thermal stability of the formulated composites is almost unchanged by the filler addition, showing only a slight decrease of the crystallization temperatures and crystalline fraction within the composites. The mechanical properties of the compounds evidence an increase in the elastic modulus together with a decrease in the tensile strength, while the elongation at break remains almost constant. The incorporation of the natural filler enabled the integration of antioxidant and antibacterial properties, which were absent in the original pristine polymer