Inhibitory effects of agmatine on monoamine oxidase (MAO) activity: Reconciling the discrepancies

Abstract Agmatine has been functionally characterized as an important hormone and co-neurotransmitter in mammals. Given its ability in binding Imidazoline sites, a regolatory site of monoaminoxydase, it has been suggested to be involved in many neurological aspects. However, its inhibitory effect on this enzyme still remains an unanswered question. This present study is aimed to asses whether different experimental conditions could affect the agmatine action on monoaminoxydase activity. We demonstrate that the monoaminoxydase inhibition by agmatine is obtained under alkaline conditions and a long time of incubation. No inhibitiory action was found for shorter times of reaction at elevated pH, or at neutral condition and long time of incubation. No inhibition was also detected by substituting the monoamineoxydase substrate tyramine with kynuramine, however, while in these conditions a remarkable inhibition was shown by two aminoxydase inhibitors tranylcypromine and idazoxan. Herein, we discuss a mechanism model and the functional consequences of agmatine action on monoaminoxydase

Sex-related differences in risk factors, type of treatment received and outcomes in patients with atrial fibrillation and acute stroke: Results from the RAF-study (Early Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation)

Introduction: Atrial fibrillation is an independent risk factor of thromboembolism. Women with atrial fibrillation are at a higher overall risk for stroke compared to men with atrial fibrillation. The aim of this study was to evaluate for sex differences in patients with acute stroke and atrial fibrillation, regarding risk factors, treatments received and outcomes. Methods Data were analyzed from the “Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation” (RAF-study), a prospective, multicenter, international study including only patients with acute stroke and atrial fibrillation. Patients were followed up for 90 days. Disability was measured by the modified Rankin Scale (0–2 favorable outcome, 3–6 unfavorable outcome). Results: Of the 1029 patients enrolled, 561 were women (54.5%) (p < 0.001) and younger (p < 0.001) compared to men. In patients with known atrial fibrillation, women were less likely to receive oral anticoagulants before index stroke (p = 0.026) and were less likely to receive anticoagulants after stroke (71.3% versus 78.4%, p = 0.01). There was no observed sex difference regarding the time of starting anticoagulant therapy between the two groups (6.4 ± 11.7 days for men versus 6.5 ± 12.4 days for women, p = 0.902). Men presented with more severe strokes at onset (mean NIHSS 9.2 ± 6.9 versus 8.1 ± 7.5, p < 0.001). Within 90 days, 46 (8.2%) recurrent ischemic events (stroke/TIA/systemic embolism) and 19 (3.4%) symptomatic cerebral bleedings were found in women compared to 30 (6.4%) and 18 (3.8%) in men (p = 0.28 and p = 0.74). At 90 days, 57.7% of women were disabled or deceased, compared to 41.1% of the men (p < 0.001). Multivariate analysis did not confirm this significance. Conclusions: Women with atrial fibrillation were less likely to receive oral anticoagulants prior to and after stroke compared to men with atrial fibrillation, and when stroke occurred, regardless of the fact that in our study women were younger and with less severe stroke, outcomes did not differ between the sexes

Microclimate monitoring in the Carcer Tullianum: temporal and spatial correlation and gradients evidenced by multivariate analysis; first campaign

Too often microclimate studies in the field of cultural heritage are published without any or scarce information on sampling design, sensors (type, number, position) and instrument validation. Lacking of this fundamental information does not allow an open discussion in the scientific community. This work aims to be an invitation for a different approach

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Broncalt®, class ii medical device, in patients with chronic relapsed upper airways disease: A survey in clinical practice

Chronic respiratory otorhinolaryngological (ORL) diseases may exacerbate. Broncalt® is a class II Medical Device containing: thermal water (Medesano, PR, Italy), hyaluronic acid, and grapefruit seed extract. It could exert a safe and effective anti-inflammatory, washing, and antimicrobial activity. The current survey, conducted in clinical practice of 84 Italian ORL centers, evaluated its safety and efficacy in the treatment of patients with exacerbated chronic upper airways disease. The 459 (254 males, mean age 44.7 years) patients were evaluated at baseline (T0) and after a 2-week treatment (T1), treated or not-treated with Broncalt®. Signs and symptoms severity were measured by visual analogue scale. Broncalt® significantly, quickly, and safely diminished the clinical features in all sub-groups (p<0.001 for all). In conclusion, Broncalt® is a class II Medical Device able to exert a safe, quick, and effective activity in patients with relapsed chronic ORL disorders. (www.actabiomedica.it)

Broncalt®, class II medical device, in patients with acute upper airways disease: A survey in clinical practice

Inflammation is a common pathogenic mechanism involved in many otorhinolaryngological (ORL) disorders. Broncalt® is a class II Medical Device containing: Thermal water (Medesano, PR, Italy), hyaluronic acid, and grapefruit seed extract. It has been reported that it exerted a safe and effective anti-inflammatory, washing, and antimicrobial activity by virtue of these components. Therefore, the aim of the current survey, conducted in clinical practice of 84 Italian ORL centers, was to evaluate its safety and efficacy in the treatment of patients with acute upper airways disease. The 3,533 (1,797 males, mean age 43.5 years) patients were evaluated at baseline (T0) and after a 2-week treatment (T1) with or without Broncalt®. Signs and symptoms severity were measured by visual analogue scale. Broncalt® significantly and safely diminished the clinical features in all sub-groups (p<0.001 for all). Interestingly, Broncalt® significantly induced a faster symptom relief already within 3 days after the start of the treatment. In conclusion, Broncalt® is a class II Medical Device able to exert a safe and effective activity in patients with acute ORL disorders. (www.actabiomedica.it)

The oral selective oestrogen receptor degrader (SERD) AZD9496 is comparable to fulvestrant in antagonising ER and circumventing endocrine resistance.

BACKGROUND: The oestrogen receptor (ER) is an important therapeutic target in ER-positive (ER+) breast cancer. The selective ER degrader (SERD), fulvestrant, is effective in patients with metastatic breast cancer, but its intramuscular route of administration and low bioavailability are major clinical limitations. METHODS: Here, we studied the pharmacology of a new oral SERD, AZD9496, in a panel of in vitro and in vivo endocrine-sensitive and -resistant breast cancer models. RESULTS: In endocrine-sensitive models, AZD9496 inhibited cell growth and blocked ER activity in the presence or absence of oestrogen. In vivo, in the presence of oestrogen, short-term AZD9496 treatment, like fulvestrant, resulted in tumour growth inhibition and reduced expression of ER-dependent genes. AZD9496 inhibited cell growth in oestrogen deprivation-resistant and tamoxifen-resistant cell lines and xenograft models that retain ER expression. AZD9496 effectively reduced ER levels and ER-induced transcription. Expression analysis of short-term treated tumours showed that AZD9496 potently inhibited classic oestrogen-induced gene transcription, while simultaneously increasing expression of genes negatively regulated by ER, including genes potentially involved in escape pathways of endocrine resistance. CONCLUSIONS: These data suggest that AZD9496 is a potent anti-oestrogen that antagonises and degrades ER with anti-tumour activity in both endocrine-sensitive and endocrine-resistant models