Post-Mortem Immunohistochemical Evidence of β2-Adrenergic Receptor Expression in the Adrenal Gland

The evidence from post-mortem biochemical studies conducted on cortisol and catecholamines suggest that analysis of the adrenal gland could provide useful information about its role in human pathophysiology and the stress response. Authors designed an immunohistochemical study on the expression of the adrenal β2-adrenergic receptor (β2-AR), a receptor with high-affinity for catecholamines, with the aim to show which zones it is expressed in and how its expression differs in relation to the cause of death. The immunohistochemical study was performed on adrenal glands obtained from 48 forensic autopsies of subjects that died as a result of different pathogenic mechanisms using a mouse monoclonal β2-AR antibody. The results show that immunoreactivity for β2-AR was observed in all adrenal zones. Furthermore, immunoreactivity for β2-AR has shown variation in the localization and intensity of different patterns in relation to the original cause of death. To the best of our knowledge, this is the first study that demonstrates β2-AR expression in the human cortex and provides suggestions on the possible involvement of β2-AR in human cortex hormonal stimulation. In conclusion, the authors provide a possible explanation for the observed differences in expression in relation to the cause of death

Effects of Serenoa repens, selenium and lycopene (Profluss®) on chronic inflammation associated with benign prostatic hyperplasia: results of "FLOG" (Flogosis and Profluss in Prostatic and Genital Disease), a multicentre Italian study.

Objective To evaluate the efficacy of Profluss® on prostatic chronic inflammation (PCI). Materials and Methods We prospectively enrolled 168 subjects affected by LUTS due to bladder outlet obstruction submitted to 12 cores prostatic biopsy for suspected prostate cancer + 2 cores collected for PCI valuation. First group consisted of 108 subjects, with histological diagnosis of PCI associated with BPH and high grade PIN and/or ASAP, randomly assigned to 1:1 ratio to daily Profluss® (group I) for 6 months or to control group (group Ic). Second group consisted of 60 subjects, with histological diagnosis of BPH, randomly assigned to 1:1 ratio to daily Profluss® + α-blockers treatment (group II) for 3 months or to control group (group IIc). After 6 months first group underwent 24 cores prostatic re-biopsy + 2 cores for PCI while after 3 months second group underwent two-cores prostatic for PCI. Specimens were evaluated for changes in inflammation parameters and for density of T-cells (CD3, CD8), B-cells (CD20) and macrophages (CD68). Results At follow-up there were statistical significant reductions of extension and grading of flogosis, mean values of CD20, CD3, CD68 and mean PSA value in group I compared to Ic, while extension and grading of flogosis in group II were inferior to IIc but not statistical significant. A statistically significant reduction in the density of CD20, CD3, CD68, CD8 was demonstrated in group II in respect to control IIc. Conclusions Serenoa repens+Selenium+Lycopene may have an anti-inflammatory activity that could be of interest in the treatment of PCI in BPH and/or PIN/ASAP patients

Effects of Serenoa Repens, Selenium and Lycopene (Profluss®) on chronic inflammation associated with Benign Prostatic Hyperplasia: results of "FLOG" (Flogosis and Profluss in Prostatic and Genital Disease), a multicentre Italian study

Objective To evaluate the efficacy of Profluss® on prostatic chronic inflammation (PCI). Materials and Methods We prospectively enrolled 168 subjects affected by LUTS due to bladder outlet obstruction submitted to 12 cores prostatic biopsy for suspected prostate cancer + 2 cores collected for PCI valuation. First group consisted of 108 subjects, with histological diagnosis of PCI associated with BPH and high grade PIN and/or ASAP, randomly assigned to 1:1 ratio to daily Profluss® (group I) for 6 months or to control group (group Ic). Second group consisted of 60 subjects, with histological diagnosis of BPH, randomly assigned to 1:1 ratio to daily Profluss® + α-blockers treatment (group II) for 3 months or to control group (group IIc). After 6 months first group underwent 24 cores prostatic re-biopsy + 2 cores for PCI while after 3 months second group underwent two-cores prostatic for PCI. Specimens were evaluated for changes in inflammation parameters and for density of T-cells (CD3, CD8), B-cells (CD20) and macrophages (CD68). Results At follow-up there were statistical significant reductions of extension and grading of flogosis, mean values of CD20, CD3, CD68 and mean PSA value in group I compared to Ic, while extension and grading of flogosis in group II were inferior to IIc but not statistical significant. A statistically significant reduction in the density of CD20, CD3, CD68, CD8 was demonstrated in group II in respect to control IIc. Conclusions Serenoa repens+Selenium+Lycopene may have an anti-inflammatory activity that could be of interest in the treatment of PCI in BPH and/or PIN/ASAP patients

Caspase 9 and caspase 3 immunohistochemical pattern in skeletal and cardiac muscles at different times after death: An experimental study on pmi estimation

(1) Background: The estimation of the post mortem interval (PMI) is a challenge for forensic pathologists because data emerging from methods commonly applied are not always conclusive, since several conditions exist that may affect the reliability of these parameters. Thus, new approaches have been proposed to overcome such a limit. In recent years, several studies have been performed on proteins analyzing their expression/degradation patterns in relation to the progressing of the post mortem interval. (2) Methods: The immunoreactivity patterns of two apoptosis mediators— Caspase 9 and Caspase 3—have been tested in order to evaluate their potential role as markers of the post mortem interval. The immunohistochemical analysis was performed on samples of skeletal and cardiac muscles obtained from rats at 0, 4, 8, 12, 24 and 72 h after death. (3) Results: The observed immunoreactivity patterns of both Caspase 9 and Caspase 3 showed a significant correlation with increasing post mortem interval either in skeletal or cardiac muscles, while the comparison of the immunoreactivity patterns of the two apoptotic mediators within each tissue appeared consistent with a preliminary activation of the “initiator” Caspase 9, which, in turn, subsequently activates the “executioner” Caspase 3. (4) Conclusion: The different expressions and decrease immunohistochemically observed on both caspases with progressing PMI support the usefulness of the combined analysis for post mortem interval estimation

Use of drugs for attrv amyloidosis in the real world: How therapy is changing survival in a non-endemic area

Background: Over the past decade, three new drugs have been approved for the treatment of hereditary amyloid transthyretin (ATTRv) polyneuropathy. The aim of this work was to analyze whether current therapies prolong survival for patients affected by ATTRv amyloidosis. Methods: The study was conducted retrospectively, analyzing the medical records of 105 patients with genetic diagnoses of familial amyloidotic polyneuropathy followed at the two referral centers for the disease in Sicily, Italy. Of these, 71 received disease-modifying therapy, while 34 received only symptomatic treatment or no therapy. Results: The most used treatment in our patient cohort was tafamidis, followed by liver transplantation, patisiran, inotersen, and diflunisal. The median survival was significantly longer for treated vs. untreated patients (12 years vs. 8 years). In the 71 patients who received disease-modifying treatment, the presence of cardiac involvement, weight loss, or autonomic dysfunction at diagnosis was not related to survival. Conversely, patients diagnosed in the early stage of the disease (PND 1) had significantly longer survival than those diagnosed in the late stage (PND 2–4)

Beneficial Effects of Polydeoxyribonucleotide (PDRN) in an In Vitro Model of Fuchs Endothelial Corneal Dystrophy

Fuchs endothelial corneal dystrophy (FECD) is a bilateral, hereditary syndrome characterized by progressive irreversible injury in the corneal endothelium; it is the most frequent cause for corneal transplantation worldwide. Oxidative stress induces the apoptosis of corneal endothelial cells (CECs), and has a crucial function in FECD pathogenesis. The stimulation of the adenosine A2A receptor (A2Ar) inhibits oxidative stress, reduces inflammation and modulates apoptosis. Poly-deoxyribonucleotide (PDRN) is a registered drug that acts through adenosine A2Ar. Thus, the goal of this study was to assess the effect of PDRN in an in vitro FECD model. Human Corneal Endothelial Cells (IHCE) were challenged with H2O2 (200 µM) alone or in combination with PDRN (100 µg/mL), PDRN plus ZM241385 (1 µM) as an A2Ar antagonist, and CGS21680 (1 µM) as a well-known A2Ar agonist. H2O2 reduced the cells’ viability and increased the expression of the pro-inflammatory markers NF-κB, IL-6, IL-1β, and TNF-α; by contrast, it decreased the expression of the anti-inflammatory IL-10. Moreover, the pro-apoptotic genes Bax, Caspase-3 and Caspase-8 were concurrently upregulated with a decrease of Bcl-2 expression. PDRN and CGS21680 reverted the negative effects of H2O2. Co-incubation with ZM241385 abolished the effects of PDRN, indicating that A2Ar is involved in the mode of action of PDRN. These data suggest that PDRN defends IHCE cells against H2O2-induced damage, potentially as a result of its antioxidant, anti-inflammatory and antiapoptotic properties, suggesting that PDRN could be used as an FECD therapy

Effects of pesticides on Chelon labrosus (Risso, 1827) evaluated by enzymatic activities along the north eastern Sicilian coastlines (Italy)

Pesticides are frequently applied to agricultural activities to improve harvest, in terms of yield and product quality. Useful tools for ecotoxicological studies of marine ecosystems are based on biomarker application on bioindicator key fish species. The main aim of the present study was to detect the potential presence of pesticides in a polluted coastal marine environment, namely Milazzo Gulf, situated in the north eastern coast of Sicily (Italy), by measuring the enzymatic activities of the ecotoxicological biomarkers acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in brain and blood samples of Chelon labrosus. Also, Marinello Reserve was selected as a reference site. The data showed a significant inhibition in AChE (81%) and BChE (71%) activities in fish from Milazzo Gulf in respect to those from the reference site. The esterase inhibition is primarily due to the presence of organophosphorus insecticides and carbamates that resulted, in Milazzo Gulf, higher in concentration in respect to the reference quality standard decree (D.M. 260, 2010). The results obtained in this study confirm the suspected presence of insecticides in waters and fish from Milazzo Gulf, which may lead to a considerable hazard to humans. This study confirms the relevant advantages of the biomarker approach on fish species in the ecotoxicological evaluation of marine environments

Trend in potassium intake and Na/K ratio in the Italian adult population between the 2008 and 2018 CUORE project surveys

Background and aims: Low potassium intake, in addition to high sodium, has been associated with higher risk of hypertension and CVD. The Study assessed habitual potassium intake and sodium/potassium ratio of the Italian adult population from 2008 to 2012 to 2018–2019 based on 24-h urine collection, in the framework of the CUORE Project/MINISAL-GIRCSI/MENO SALE PIU’ SALUTE national surveys. Methods and results: Data were from cross-sectional surveys of randomly selected age-and-sex stratified samples of resident persons aged 35–74 years in 10 (out of 20) Italian regions. Urinary electrolyte and creatinine measurements were performed in a central laboratory. Analyses considered 942 men and 916 women, examined in 2008–2012, and 967 men and 1010 women, examined in 2018–2019. In 2008–2012, the age-standardized mean of potassium intake (urinary potassium accounts for 70% of potassium intake) was 3147 mg (95% CI 3086–3208) in men and 2784 mg (2727–2841) in women, whereas in 2018–2019, it was 3043 mg (2968–3118) and 2561 mg (2508–2614) respectively. In 2008–2012, age-adjusted prevalence of persons with an adequate potassium intake (i.e. ≥ 3510 mg/day) was 31% (95% CI 28–34%) for men and 18% (16–21%) for women; in 2018–2019, it was 26% (23–29%) and 12% (10–14%) respectively. The sodium/potassium ratio significantly decreased both in men and women. Conclusions: The average daily potassium intake of the Italian general adult population remains lower than the WHO and EFSA recommended level. These results suggest the need of a revision to strengthen initiatives for the promotion of an adequate potassium intake at the population level

Proton-proton elastic scattering at the LHC energy of {\surd} = 7 TeV

Proton-proton elastic scattering has been measured by the TOTEM experiment at the CERN Large Hadron Collider at {\surd}s = 7 TeV in dedicated runs with the Roman Pot detectors placed as close as seven times the transverse beam size (sbeam) from the outgoing beams. After careful study of the accelerator optics and the detector alignment, |t|, the square of four-momentum transferred in the elastic scattering process, has been determined with an uncertainty of d t = 0.1GeV p|t|. In this letter, first results of the differential cross section are presented covering a |t|-range from 0.36 to 2.5GeV2. The differential cross-section in the range 0.36 < |t| < 0.47 GeV2 is described by an exponential with a slope parameter B = (23.6{\pm}0.5stat {\pm}0.4syst)GeV-2, followed by a significant diffractive minimum at |t| = (0.53{\pm}0.01stat{\pm}0.01syst)GeV2. For |t|-values larger than ~ 1.5GeV2, the cross-section exhibits a power law behaviour with an exponent of -7.8_\pm} 0.3stat{\pm}0.1syst. When compared to predictions based on the different available models, the data show a strong discriminative power despite the small t-range covered.Comment: 12pages, 5 figures, CERN preprin

Trend of salt intake measured by 24-h urine collection in the Italian adult population between the 2008 and 2018 CUORE project surveys

Background and aims: The WHO Global Action Plan for the Prevention of non-communicable diseases (NCDs) recommends a 30% relative reduction in mean population salt/sodium intake. The study assessed the trend in the habitual salt intake of the Italian adult population from 2008 to 2012 to 2018–2019 based on 24-h urinary sodium excretion, in the framework of the CUORE Project/MINISAL-GIRCSI/MENO SALE PIU’ SALUTE national surveys. Methods and results: Data were from cross-sectional surveys of randomly selected age and sex–stratified samples of resident persons aged 35–74 years in 10 (out of 20) Italian Regions distributed in North, Centre and South of the Country. Urinary sodium and creatinine measurements were carried out in a central laboratory. The analyses included 942 men and 916 women examined in 2008–2012, and 967 men and 1010 women examined in 2018–2019. The age-standardized mean daily population salt (sodium chloride) intake was 10.8 g (95% CI 10.5–11.1) in men and 8.3 g (8.1–8.5) in women in 2008–2012 and respectively 9.5 g (9.3–9.8) and 7.2 g (7.0–7.4) in 2018–2019. A statistically significant (p<0.0001) salt intake reduction was thus observed over 10 years for both genders, and all age, body mass index (BMI) and educational classes. Conclusions: The average daily salt intake of the Italian general adult population remains higher than the WHO recommended level, but a significant reduction of 12% in men and 13% in women has occurred in the past ten years. These results encourage the initiatives undertaken by the Italian Ministry of Health aimed at the reduction of salt intake at the population level