Ventilatory efficiency in long-term dyspnoeic patients following COVID-19 pneumonia.

BACKGROUND: Long COVID is defined as persistency of symptoms, such as exertional dyspnea, twelve weeks after recovery from SARS-CoV-2 infection. OBJECTIVES: To investigate ventilatory efficiency by the use of cardiopulmonary exercise testing (CPET) in patients with exertional dyspnea despite normal basal spirometry after 18 (T18) and 36 months (T36) from COVID-19 pneumonia. METHODS: One hundred patients with moderate-critical COVID-19 were prospectively enrolled in our Long COVID program. Medical history, physical examination and lung high-resolution computed tomography (HRCT) were obtained at hospitalization (T0), 3 (T3) and 15 months (T15). All HRCTs were revised using a semi-quantitative CT severity score (CSS). Pulmonary function tests were obtained at T3 and T15. CPET was performed in a subset of patients with residual dyspnea (mMRC ≥ 1), at T18 and at T36. RESULTS: Remarkably, at CPET, ventilatory efficiency was reduced both at T18 (V'E/V'CO2 slope = 31.4±3.9 SD) and T36 (V'E/V'CO2 slope = 31.28±3.70 SD). Furthermore, we identified positive correlations between V'E/V'CO2 slope at T18 and T36 and both percentage of involvement and CSS at HRCT at T0, T3 and T15. Also, negative linear correlations were found between V'E/V'CO2 slope at T18 and T36 and DLCO at T3 and T15. CONCLUSIONS: At eighteen months from COVID-19 pneumonia, 20 % of subjects still complains of exertional dyspnea. At CPET this may be explained by persistently reduced ventilatory efficiency, possibly related to the degree of lung parenchymal involvement in the acute phase of infection, likely reflecting a damage in the pulmonary circulation.

Gender differences in obstructive sleep apnea syndrome: a pilot study.

PURPOSE: OSAS is a syndrome that often presents clinically differently between men and women. The aim of this study was to assess the clinical presentation, nocturnal home sleep cardiorespiratory monitoring and therapeutic adherence to CPAP in both sexes to identify the most frequent patterns. METHODS: Data from the first visit, the nocturnal home sleep cardiorespiratory monitoring and follow-up visit of 74 OSA patients were collected. Exclusion criteria included other respiratory and/or neuromuscular diseases (including Obesity hypoventilation syndrome) and other non-respiratory sleep disorders. RESULTS: Men were older and had a higher supine AHI and ODI compared to women. In addition, BMI and age correlated positively with AHI in males. Women had a higher hypopneas frequency and better therapeutic adherence to CPAP. CONCLUSIONS: Men were associated with a higher AHI when sleeping in the supine position and this may be useful to look for new therapeutic options in combination with or as an alternative to CPAP. BMI correlated positively with AHI in men and this should be considered to stimulate weight loss as the main treatment to reduce the number of apneas/hypopneas, as men also had less therapeutic adherence to CPAP in our study. Females presented a significantly higher frequency of hypopneas than men, as well as a lower number of desaturation events per hour (ODI): these differences in the nocturnal home sleep cardiorespiratory monitoring could reflect different pathophysiological mechanisms of OSAS onset between the two sexes, which should be investigated in future scientific studies.

The Effects of Caloric Restriction on Inflammatory Targets in the Prostates of Aged Rats.

Numerous animal models have demonstrated that caloric restriction (CR) is an excellent tool to delay aging and increase the quality of life, likely because it counteracts age-induced oxidative stress and inflammation. The aging process can affect the prostate in three ways: the onset of benign prostatic hyperplasia, prostatitis, and prostate cancer. In this study, we used 14 aged male Sprague Dawley rats, which were allocated into two groups, at the age of 18 months old. One group was fed ad libitum (a normal diet (ND)), and the other group followed a caloric restriction diet with a 60% decrease in intake. The rats were sacrificed at the age of 24 months. By immunohistochemical (IHC) and Western blot (WB) analyses, we studied the variations between the two groups in immune inflammation and fibrosis-related markers in aged prostate tissues. Morphological examinations showed lower levels of prostatic hyperplasia and fibrosis in the CR rats vs. the ND rats. The IHC results revealed that the prostates of the CR rats exhibited a lower immune proinflammatory infiltrate level and a reduced expression of the NLRP3 inflammasome pathway, together with significantly reduced expressions of mesenchymal markers and the profibrotic factor TGFß1. Finally, by WB analysis, we observed a reduced expression of ERα, which is notoriously implicated in prostate stromal proliferation, and increased expressions of SOD1 and Hsp70, both exerting protective effects against oxidative stress. Overall, these data suggest that CR brings potential benefits to prostatic tissues as it reduces the physiological immune-inflammatory processes and the tissue remodeling caused by aging.

Forensic Proteomics for the Discovery of New post mortem Interval Biomarkers: A Preliminary Study.

Estimating the time since death (post mortem interval, PMI) represents one of the most important tasks in daily forensic casework. For decades, forensic scientists have investigated changes in post mortem body composition, focusing on different physical, chemical, or biological aspects, to discover a reliable method for estimating PMI; nevertheless, all of these attempts remain unsuccessful considering the currently available methodical spectrum characterized by great inaccuracies and limitations. However, recent promising approaches focus on the post mortem decomposition of biomolecules. In particular, significant advances have been made in research on the post mortem degradation of proteins. In the present study, we investigated early post mortem changes (during the first 24 h) in the proteome profile of the pig skeletal muscle looking for new PMI specific biomarkers. By mass spectrometry (MS)-based proteomics, we were able to identify a total of nine potential PMI biomarkers, whose quantity changed constantly and progressively over time, directly or inversely proportional to the advancement of post mortem hours. Our preliminary study underlines the importance of the proteomic approach in the search for a reliable method for PMI determination and highlights the need to characterize a large number of reliable marker proteins useful in forensic practice for PMI estimation.

Caloric Restriction Mitigates Kidney Fibrosis in an Aged and Obese Rat Model.

Caloric restriction is an effective intervention to protract healthspan and lifespan in several animal models from yeast to primates, including humans. Caloric restriction has been found to induce cardiometabolic adaptations associated with improved health and to delay the onset and progression of kidney disease in different species, particularly in rodent models. In both aging and obesity, fibrosis is a hallmark of kidney disease, and epithelial-mesenchymal transition is a key process that leads to fibrosis and renal dysfunction during aging. In this study, we used an aged and obese rat model to evaluate the effect of long-term (6 months) caloric restriction (-40%) on renal damage both from a structural and functional point of view. Renal interstitial fibrosis was analyzed by histological techniques, whereas effects on mesenchymal (N-cadherin, Vimentin, Desmin and α-SMA), antioxidant (SOD1, SOD2, Catalase and GSTP1) inflammatory (YM1 and iNOS) markers and apoptotic/cell cycle (BAX, BCL2, pJNK, Caspase 3 and p27) pathways were investigated using Western blot analysis. Our results clearly showed that caloric restriction promotes cell cycle division and reduces apoptotic injury and fibrosis phenotype through inflammation attenuation and leukocyte infiltration. In conclusion, we highlight the beneficial effects of caloric restriction to preserve elderly kidney function.

Conservative oxygen supplementation during helmet continuous positive airway pressure therapy in patients with COVID-19 and respiratory failure: a pilot study.

Background: Respiratory failure is a severe complication in coronavirus disease 2019 (COVID-19) pneumonia that, in addition to oxygen therapy, may require continuous positive airway pressure (CPAP) support. It has been postulated that COVID-19 lung injury may share some features with those observed in hyperoxic acute lung injury. Thus, a correct target arterial oxygen tension (P aO2 ) during oxygen supplementation may be crucial to protect the lung from further tissue damage. The aims of this study were: 1) to evaluate the effects of conservative oxygen supplementation during helmet CPAP therapy on mortality and intensive care unit (ICU) admission in patients with COVID-19 and respiratory failure, and 2) to evaluate the effect of conservative oxygen supplementation on new-onset organ failure and secondary pulmonary infections. Methods: This was a single-centre, historically controlled study of patients with severe respiratory failure due to COVID-19 pneumonia, receiving either conservative or nonconservative oxygen supplementation during helmet CPAP. A cohort receiving conservative oxygen supplementation was studied prospectively in which oxygen supplementation was administered with a target P aO2 <100 mmHg. Results of this cohort were compared with those of a cohort who had received liberal oxygen supplementation. Results: 71 patients were included in the conservative cohort and 75 in the nonconservative cohort. Mortality rate was lower in the conservative cohort (22.5% versus 62.7%; p<0.001). Rates of ICU admission and new-onset organ failure were lower in the conservative cohort (14.1% versus 37.3%; p=0.001 and 9.9% versus 45.3%; p<0.001, respectively). Conclusions: In patients with COVID-19 and severe respiratory failure, conservative oxygen supplementation during helmet CPAP was associated with improved survival, lower ICU admission rate and less new-onset organ failure.

An Experimental Study on Antioxidant Enzyme Gene Expression in Trematomus newnesi (Boulenger, 1902) Experimentally Exposed to Perfluoro-Octanoic Acid.

Antarctica is the continent with the lowest local human impact; however, it is susceptible to pollution from external sources. Emerging pollutants such as perfluoroalkyl substances pose an increasing threat to this environment and therefore require more in-depth investigations to understand their environmental fate and biological impacts. The present study focuses on expression analysis at the transcriptional level of genes coding for four antioxidant enzymes (sod1, sod2, gpx1, and gpx4) in the liver and kidney of an Antarctic fish species, Trematomus newnesi (Boulenger, 1902). mRNA levels were also assessed in fish exposed to 1.5 µg/L of perfluoro-octanoic acid for 10 days. The kidney showed a higher level of expression than the liver in wildlife specimens. In the liver, the treatment induced an increase in gene expression for all the considered enzymes, whereas in the kidney, it induced a general decrease. The obtained results advance the scientific community's understanding of how the potential future presence of anthropogenic contaminants in the Southern Ocean can affect the antioxidant system of Antarctic fishes. The presence of pollutants belonging to the perfluoroalkyl substances in the Southern Ocean needs to be continuously monitored in parallel with this type of research.

The Role of Pulmonary Function Testing and Lung Imaging in the Long-Term Follow-Up of Patients with COVID-19 Pneumonia.

BACKGROUND: Post-COVID-19 Interstitial Lung Disease (PC-ILD) is characterized by fibrotic-like signs at high-resolution computed tomography (HRCT) and pulmonary function tests (PFTs) abnormalities after SARS-CoV-2 infection. It is still not clear how frequent these tests should be performed to rule out long-term consequences of COVID-19 pneumonia. OBJECTIVES: The aims of our study were to evaluate the incidence and risk factors of PC-ILD and possibly to propose a long-term follow-up program. METHOD: One-hundred patients, hospitalized in our ward for moderate to critical COVID-19, underwent two follow-up visits at three and 15 months in which PFTs and HRCT were performed. RESULTS: At the 15-month follow-up, 8% of patients showed residual radiological and functional signs consistent with PC-ILD. All but one of these patients had already demonstrated PFTs and HRCT alterations at first follow-up visit, and the last 1 patient showed worsening of lung function during follow-up. These findings highlight the negative predictive value of PFTs at 3-month follow-up for the development of PC-ILD. Aging, severity of COVID-19, and degree of pulmonary involvement during acute infection proved to be significant risk factors for developing PC-ILD. CONCLUSIONS: Our study highlights the importance of PFTs in the long-term follow-up of patients affected by moderate to critical COVID-19 pneumonia. Further studies are needed to confirm our hypothesis that HRCT should be performed only in patients with PFTs abnormalities.

Risk factors and effect on mortality of superinfections in a newly established COVID-19 respiratory sub-intensive care unit at University Hospital in Rome.

BACKGROUND: Little is known on the burden of co-infections and superinfections in a specific setting such as the respiratory COVID-19 sub-intensive care unit. This study aims to (i) assess the prevalence of concurrent and superinfections in a respiratory sub-intensive care unit, (ii) evaluate the risk factors for superinfections development and (iii) assess the impact of superinfections on in-hospital mortality. METHODS: Single-center retrospective analysis of prospectively collected data including COVID-19 patients hospitalized in a newly established respiratory sub-intensive care unit managed by pneumologists which has been set up from September 2020 at a large (1200 beds) University Hospital in Rome. Inclusion criteria were: (i) COVID-19 respiratory failure and/or ARDS; (ii) hospitalization in respiratory sub-intensive care unit and (iii) age > 18 years. Survival was analyzed by Kaplan-Meier curves and the statistical significance of the differences between the two groups was assessed using the log-rank test. Multivariable logistic regression and Cox regression model were performed to tease out the independent predictors for superinfections' development and for mortality, respectively. RESULTS: A total of 201 patients were included. The majority (106, 52%) presented severe COVID-19. Co-infections were 4 (1.9%), whereas 46 patients (22%) developed superinfections, mostly primary bloodstream infections and pneumonia. In 40.6% of cases, multi-drug resistant pathogens were detected, with carbapenem-resistant Acinetobacter baumannii (CR-Ab) isolated in 47%. Overall mortality rate was 30%. Prior (30-d) infection and exposure to antibiotic therapy were independent risk factors for superinfection development whereas the development of superinfections was an independent risk factors for in-hospital mortality. CR-Ab resulted independently associated with 14-d mortality. CONCLUSION: In a COVID-19 respiratory sub-intensive care unit, superinfections were common and represented an independent predictor of mortality. CR-Ab infections occurred in almost half of patients and were associated with high mortality. Infection control rules and antimicrobial stewardship are crucial in this specific setting to limit the spread of multi-drug resistant organisms.

Analysis of Biologics Molecular Descriptors towards Predictive Modelling for Protein Drug Development Using Time-Gated Raman Spectroscopy.

Pharmaceutical proteins, compared to small molecular weight drugs, are relatively fragile molecules, thus necessitating monitoring protein unfolding and aggregation during production and post-marketing. Currently, many analytical techniques take offline measurements, which cannot directly assess protein folding during production and unfolding during processing and storage. In addition, several orthogonal techniques are needed during production and market surveillance. In this study, we introduce the use of time-gated Raman spectroscopy to identify molecular descriptors of protein unfolding. Raman spectroscopy can measure the unfolding of proteins in-line and in real-time without labels. Using K-means clustering and PCA analysis, we could correlate local unfolding events with traditional analytical methods. This is the first step toward predictive modeling of unfolding events of proteins during production and storage.

Risk of Seven-Day Worsening and Death: A New Clinically Derived COVID-19 Score.

This monocentric, retrospective, two-stage observational study aimed to recognize the risk factors for a poor outcome in patients hospitalized with SARS-CoV-2 infection, and to develop and validate a risk score that identifies subjects at risk of worsening, death, or both. The data of patients with SARS-CoV-2 infection during the first wave of the pandemic were collected and analyzed as a derivation cohort. Variables with predictive properties were used to construct a prognostic score, which was tried out on a validation cohort enrolled during the second wave. The derivation cohort included 494 patients; the median age was 62 and the overall fatality rate was 22.3%. In a multivariable analysis, age, oxygen saturation, neutrophil-to-lymphocyte ratio, C-reactive protein and lactate dehydrogenase were independent predictors of death and composed the score. A cutoff value of 3 demonstrated a sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of 93.5%, 68.5%, 47.4% and 97.2% for death, and 84.9%, 84.5%, 79.6% and 87.9% for worsening, respectively. The validation cohort included 415 subjects. The score application showed a Se, Sp, PPV and NPV of 93.4%, 61.6%, 29.5% and 98.1% for death, and 81%, 76.3%, 72.1% and 84.1% for worsening, respectively. We propose a new clinical, easy and reliable score to predict the outcome in hospitalized SARS-CoV-2 patients.

Systemic administration of sunflower oil exerts neuroprotection in a mouse model of transient focal cerebral ischaemia.

OBJECTIVES: Natural products are valuable sources of nutraceuticals for the prevention or treatment of ischemic stroke, a major cause of death and severe disability worldwide. Among the mechanisms implicated in cerebral ischemia-reperfusion damage, oxidative stress exerts a pivotal role in disease progression. Given the high antioxidant potential of most components of sunflower oil, we have explored its effects on ischemic brain injury produced in the mouse by transient occlusion of the middle cerebral artery (MCAo). KEY FINDINGS: Intraperitoneal (i.p.) administration of sunflower oil at doses of 3 ml/kg (48 h, 24 h and 1 h before MCAo) significantly reduced brain infarct volume and oedema assessed 24 h after the insult. This neuroprotective treatment schedule also prevented the elevation of brain lipid peroxidation produced by MCAo-reperfusion injury. By contrast, doses of 0.03 ml/kg of sunflower oil resulted ineffective on both cerebral damage and lipid peroxidation. Although sunflower oil did not affect serum levels of Diacron-reactive oxygen metabolites (d-ROMs), both 0.03 and 3 ml/kg dosing regimens resulted in the preservation of serum biological antioxidant potential (BAP) that was otherwise dramatically reduced 24 h after MCAo. CONCLUSIONS: Sunflower oil represents a promising source of neuroprotective extracts/compounds that can be exploited for the prevention and/or treatment of cerebral ischemia.

Antarctic Fish as a Global Pollution Sensor: Metals Biomonitoring in a Twelve-Year Period.

Antarctica represents a unique natural laboratory for ecotoxicological studies as it is characterized by low internal pollutants emissions but high external contamination levels. Indeed, warm temperatures promote pollutant evaporation (low latitudes), while cool temperatures (high latitudes) promote its deposition from the atmosphere on land/water. Metals are the most important pollutants in ecosystems and represent a serious and global threat to aquatic and terrestrial organisms. Since 2000, the risks posed by metals have led many States to ratify protocols aimed at reducing their emissions. Endemic Antarctic organisms represent excellent bioindicators in order to evaluate the efficacy of global measures adopted to mitigate pollutants release into the environment. In this study (supported by PNRA18-00133), we estimated the metals contamination levels and the metallothionein-1 expression in liver samples of two Antarctic fish species, the icefish Chionodraco hamatus and the red-blooded Trematomus bernacchii, collected in the same area during 2002 and 2014. The chosen area is located in the Ross Sea, a unique area as it is also isolated from the rest of the Southern Ocean. The analysis of contamination trends throughout this period showed, in both species, a significant increase over time of metals bioaccumulation and metallothionein-1 expression. In addition, our result clearly indicated that the detoxifying ability of the two organisms analyzed greatly differs, probably due to haemoglobin presence/absence. Our work represents an important early step to obtain valuable information in conservation strategies for both Antarctic and non-Antarctic ecosystems.

Microplastics in the Center of Mediterranean: Comparison of the Two Calabrian Coasts and Distribution from Coastal Areas to the Open Sea.

Plastic is everywhere-increasing evidence suggests that plastic pollution is ubiquitous and persistent in ecosystems worldwide. Microplastic pollution in marine environments is particularly insidious, as small fragmentation can increase interaction with biota and food chain access. Of particular concern is the Mediterranean Sea, which has become a large area of accumulation of plastic debris, including microplastics, whose polymeric composition is still largely unknown. In this study, we analyzed the polymeric composition, particle size distribution, shape, and color of small plastic particles (ranging from 50 to 5000 µm) collected from the sea surface in six stations at the center of the Mediterranean Sea. We also described, for the first time, the different distribution of microplastics from coastal areas up to 12 nautical miles offshore. The microplastic density was 0.13 ± 0.19 particles/m2, with a marked prevalence of smaller particles (73% < 3 mm) and a peak between 1 and 2 mm (34.74%). Microplastics composition analysis showed that the most abundant material was polyethylene (69%), followed by polypropylene (24%). Moreover, we reported a comparison of the two Calabrian coasts providing the first characterization of a great difference in microplastic concentration between the Tyrrhenian and Ionian sides (87% vs. 13%, respectively), probably due to the complex marine and atmospheric circulation, which make the Tyrrhenian side an area of accumulation of materials originating even from faraway places. We demonstrate, for the first time, a great difference in microplastic concentration between Tyrrhenian and Ionian Calabrian coasts, providing a full characterization and highlighting that microplastic pollution is affected by both local release and hydrography of the areas.

Short and Long Time Bloodstains Age Determination by Colorimetric Analysis: A Pilot Study.

Bloodstains found at crime scenes represent a crucial source of information for investigative purposes. However, in forensic practice, no technique is currently used to estimate the time from deposition of bloodstains. This preliminary study focuses on the age estimation of bloodstains by exploiting the color variations over time due to the oxidation of the blood. For this purpose, we used a colorimetric methodology in order to easily obtain objective, univocal and reproducible results. We developed two bloodstain age prediction algorithms: a short-term and a long-term useful model for the first 24h and 60 days, respectively. Both models showed high levels of classification accuracy, particularly for the long-term model. Although a small-scale study, these results improve the potential application of colorimetric analysis in the time-line reconstruction of violent criminal events.

Proinflammatory profile of visceral adipose tissue and oxidative stress in severe obese patients carrying the variant rs4612666 C of NLRP3 gene.

BACKGROUND: The activation of NLRP3 inflammasome machinery has a central role in obesity-induced inflammation. Genetic studies well support the involvement of functional variants of NLRP3 and its negative regulator, CARD8, in the pathogenesis of complex diseases with an inflammatory background. We have investigated the influence of NLRP3 (rs4612666; rs10754558) and CARD8 (rs204321) genetic variants in both the inflammatory status of visceral adipose tissue (VAT) from patients with severe obesity and in the systemic oxidative stress before and after sleeve-gastrectomy (SLG). METHODS: Twenty-three consecutive severe obese patients candidate to SLG were enrolled in the study. Visceral adipose tissue (VAT) biopsies, obtained during SLG, were used to evaluate the expression of NLRP3, IL-1ß, IL-6, and MCP-1 by real-time RT-PCR. DNA was extracted from peripheral blood lymphocytes and genotyped by RFLP analysis. Before and 3 months after SLG, all patients underwent the assessment of oxidative stress, biochemical parameters, and body composition as measured by bioelectrical impedance analysis (BIA). RESULTS: Increased expression of NLRP3, IL-6, IL-1ß, and MCP-1 mRNA was observed in VAT of rs4612666 C variant carriers, in which higher oxidative stress was also detected as compared to non-carrier individuals. In all patients, oxidative stress, biochemical and BIA parameters improved after SLG, regardless of genotype. No significant correlations were found with the other genetic variants. CONCLUSIONS: Our results suggest that the NLRP3 rs4612666 C variant may promote a worse pro-inflammatory milieu and higher oxidative stress, thus leading patients to a more severe obesity phenotype. A larger study is needed to confirm this assumption and to investigate the impact of the NLRP3 rs4612666 C variant on severe obesity.

A New Wearable System for Home Sleep Apnea Testing, Screening, and Classification.

We propose an unobtrusive, wearable, and wireless system for the pre-screening and follow-up in the domestic environment of specific sleep-related breathing disorders. This group of diseases manifests with episodes of apnea and hypopnea of central or obstructive origin, and it can be disabling, with several drawbacks that interfere in the daily patient life. The gold standard for their diagnosis and grading is polysomnography, which is a time-consuming, scarcely available test with many wired electrodes disseminated on the body, requiring hospitalization and long waiting times. It is limited by the night-by-night variability of sleep disorders, while inevitably causing sleep alteration and fragmentation itself. For these reasons, only a small percentage of patients achieve a definitive diagnosis and are followed-up. Our device integrates photoplethysmography, an accelerometer, a microcontroller, and a bluetooth transmission unit. It acquires data during the whole night and transmits to a PC for off-line processing. It is positioned on the nasal septum and detects apnea episodes using the modulation of the photoplethysmography signal during the breath. In those time intervals where the photoplethysmography is detecting an apnea, the accelerometer discriminates obstructive from central type thanks to its excellent sensitivity to thoraco-abdominal movements. Tests were performed on a hospitalized patient wearing our integrated system and the type III home sleep apnea testing recommended by The American Academy of Sleep Medicine. Results are encouraging: sensitivity and precision around 90% were achieved in detecting more than 500 apnea episodes. Least thoraco-abdominal movements and body position were successfully classified in lying down control subjects, paving the way toward apnea type classification.

Antioxidant/Anti-Inflammatory Effects of Caloric Restriction in an Aged and Obese Rat Model: The Role of Adiponectin.

Caloric restriction (CR) represents a powerful intervention for extending healthspan and lifespan in several animal models, from yeast to primates. Additionally, in humans, CR has been found to induce cardiometabolic adaptations associated with improved health. In this study, we evaluated in an aged and obese rat model the effect of long-term (6 months) caloric restriction (-40%) on the oxidative/inflammatory balance in order to investigate the underlining mechanisms. In plasma, we analyzed the oxidative balance by photometric tests and the adiponectin/tumor necrosis factor-α-induced gene/protein 6 (TSG-6) levels by Western blot analysis. In the white adipose tissue, we examined the protein levels of AdipoR1, pAMPK, NFκB, NRF-2, and glutathione S-tranferase P1 by Western blot analysis. Our results clearly showed that caloric restriction significantly improves the plasmatic oxidative/inflammatory balance in parallel with a major increase in circulating adiponectin levels. Additionally, at the level of adipose tissue, we found a positive modulation of both anti-inflammatory and antioxidant pathways. These adaptations, induced by caloric restriction, with the achievement of normal weight, suggest that inflammatory and redox imbalance in obese aged rats appear to be more linked to obesity than to aging.

Oxidative Imbalance and Kidney Damage: New Study Perspectives from Animal Models to Hospitalized Patients.

Chronic kidney disease (CKD) is a major public health problem worldwide and affects both elderly and young subjects. Its main consequences include the loss of renal function, leading to end-stage renal disease, an increased risk of cardiovascular disease, a significant increase in morbidity and mortality, and a decrease in health-related quality of life. This review arose in significant part from work in the authors' laboratory, complemented by literature data, and was based on a translational approach: we studied the role of many CKD risk factors, such as hypertension, obesity, and oxidative stress/inflammation. The aim was to identify new molecular mechanisms of kidney damage to prevent it through successful behavior modifications. For this purpose, in our studies, both human and animal models were used. In the animal models, we analyzed the mechanisms of renal damage induced by hypertension (spontaneously hypertensive rats) and obesity (cafeteria diet-fed rats), showing that redox disequilibrium in plasma and tissue is extremely important in renal alteration in terms of both oxidative damage (lipid peroxidation, altered expression antioxidant enzymes) and apoptotic pathway (intrinsic/extrinsic) activation. In hemodialysis patients, we explored the correlation between the global oxidative balance and both inflammatory markers and cardiovascular risk, showing a strong correlation between the oxidative index and the blood levels of C-reactive protein and previous cardiovascular events. This multilevel approach allowed us to individually and synergistically analyze some aspects of the complex pathogenic mechanisms of CKD in order to clarify the role of the new amplified risk factors for CKD and to prepare an effective personalized prevention plan by acting on both modifiable and nonmodifiable risk factors.