Chronic treatment with long-acting nifedipine reduces vasoconstriction to endothelin-1 in essential hypertension

Essential hypertension is associated with enhanced biological activity of endothelin-1 (ET-1) and impaired endothelium-dependent vasodilatation. Dihydropyridine calcium antagonists have antioxidant activity in vitro, and they improve endothelial function in vivo. We tested whether calcium antagonists also influence the biological activity of ET-1 in essential hypertensive (EH) patients in the presence and absence of hypercholesterolemia. In 9 healthy subjects (normotensive [NT] subjects, age: 48.3+/-7.6 years; blood pressure: 118+/-8.6/69+/-5.4 mm Hg) and 21 EH subjects (age: 50.0+/-7.8 years; blood pressure: 164.4+/-5.4/103.8+/-4.4 mm Hg), we studied forearm blood flow and its modification induced by intrabrachial administration of ET-1, phenylephrine, acetylcholine, and sodium nitroprusside at baseline and after 24 weeks of treatment with a nifedipine gastrointestinal therapeutic system (30 to 60 mg per day). At baseline, the first dose of ET-1 (0.5 microg/100 mL of forearm tissue per minute) caused a slight vasodilatation in NT but not in EH subjects, whereas the following higher doses caused a comparable dose-dependent vasoconstriction in EH and NT subjects. The effect of acetylcholine was significantly reduced in EH as compared with NT subjects. In contrast, sodium nitroprusside and phenylephrine had similar effects in NT and EH subjects. After chronic treatment with the nifedipine gastrointestinal therapeutic system, the vasoconstrictor effect induced by both ET-1 and phenylephrine was significantly blunted, whereas the response to acetylcholine was significantly increased and the vasodilation to sodium nitroprusside unchanged. Hypercholesterolemic EH subjects showed a further reduced response to acetylcholine compared with normocholesterolemic EH subjects, and the nifedipine gastrointestinal therapeutic system restored the vasodilation to acetylcholine in this subgroup. In conclusion, in EH subjects, chronic treatment with a long-acting dihydropyridine calcium antagonist not only exhibits a blood pressure-lowering effect but also reduces ET-1-induced vasoconstriction and improves endothelium-dependent vasodilation. Those vasculoprotective effects may importantly contribute to a reduction in major clinical events seen during treatment with these compound

Prognostic role of KRAS mutations in Sardinian patients with colorectal carcinoma

The presence of mutations in the KRAS gene is a predictor of a poor clinical response to EGFR-targeted agents in patients affected by colorectal cancer (CRC), but its significance as a global prognostic factor remains unclear. The aim of the present study was to evaluate the impact of the KRAS mutational status on time to first metastasis (TTM) and overall survival (OS) in a cohort of Sardinian CRC patients. A total of 551 patients with metastatic CRC at the time of enrolment were included. Clinical and pathological features of the disease, including follow-up information, were obtained from medical records and cancer registry data. For mutational analysis formalin-fixed paraffin-embedded tissue samples were processed using a standard protocol. The coding sequence and splice junctions of exons 2 and 3 of the KRAS gene were screened for mutations by direct automated sequencing. Overall, 186 KRAS mutations were detected in 183/551 (33%) patients: 125 (67%) were located in codon 12, 36 (19%) in codon 13, and 18 (10%) in codon 61. The remaining mutations (7; 4%) were detected in uncommonly-affected codons. No significant correlation between KRAS mutations and gender, age, anatomical location and stage of the disease at the time of diagnosis was identified. Furthermore, no prognostic value of KRAS mutations was found considering either TTM or OS. When patients were stratified by KRAS mutational status and gender, males were significantly associated with a longer TTM. The results of the present study indicate that KRAS mutation correlated with a slower metastatic progression in males with CRC from Sardinia, irrespective of the age at diagnosis and the codon of the mutatio

DETECTION OF AFLATOXIN M1 IN BULK-TANK MILK AND SHEEP CHEESE

The Aflatoxin M1 (AFM1) content in 118 bulk-tank sheep milk samples was evaluated using an ELISA commercial kit. During a lactation, three bulk-tank milk samples were collected from each of 40 semi-extensive farms, selected on the basis of high level of concentrate supplementation as risk factor for exposure to Aflatoxin B1 (AFB1). The AFM1 content was also determined in 38 sheep cheese samples collected from a dairy plant where the farms enrolled in the survey shipped the milk. In the three sampling the concentrate supplementation recorded in the farms ranged between (mean±sd) 492.2±257.7 and 397.7±214.3. AFM1 was detected in 1 bulk-tank sheep milk sample (0.8%) at concentrations as little as 5.2 ng/L while in 117 it was not detectable (<5 ng/L). AFM1 was also detected in 5 (13.2%) out of 38 samples of ripened sheep cheese at levels (mean±sd) of 58.1±7.8 ng/Kg. A very low AFM1 content in bulk mik and cheese was observed, as the result of the implementation of good agricultural and good farming practices

Compliance with evidence-based clinical guidelines in the management of acute biliary pancreatitis: the MANCTRA-1 study protocol

Despite existing evidence-based practice guidelines for the management of biliary acute pancreatitis (AP), the clinical compliance with recommendations is overall poor. Studies in this field have identified significant discrepancies between evidence-based recommendations and daily clinical practice. The most commonly reported gaps between clinical practice and AP guidelines include the indications for CT scan, need and timing of artificial nutritional support, indications for antibiotics, and surgical/endoscopic management of biliary AP. The MANCTRA-1 (coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis) study is aiming to identify the areas for quality improvement that will require new implementation strategies. The study primary objective is to evaluate which items of the current AP guidelines are commonly disregarded and if they correlate with negative clinical outcomes according to the different clinical presentations of the disease. We attempt to summarize the main areas of sub-optimal care due to the lack of compliance with current guidelines to provide the basis for introducing a number of bundles in AP patients' management to be implemented during the next years. The MANCTRA-1 study is an international multicenter, retrospective cohort study with the purpose to assess the outcomes of patients admitted to hospital with a diagnosis of biliary AP and the compliance of surgeons worldwide to the most up-to-dated international guidelines on biliary AP. ClinicalTrials.Gov ID Number: NCT04747990, Date: February 23, 2021. Protocol Version V2.2

Business development in renewable energy

This paper discusses how to foster development of renewable energy business. Factors that impede or enhance renewable energy in the EU 27 member states in the period 1998–2008 are analyzed. Nine factors are considered: population density, production output and energy sector output to indicate market conditions, public total expenditures, subsidies and environmental protection expenditures to indicate institutional conditions, R&D, share of students in population and venture capital to indicate firm’s resources. Scarce space for business development and vested energy interests are the main impediments. R&D and venture capital are main drivers. The US and EU support for R&D and venture capital in renewable energy are compared. The US support is larger and mainly based on R&D grants. It has generated large, innovative enterprises. The EU support is mainly based on price guarantees for renewable energy delivery to grid. It has generated many enterprises. Building capabilities through stakeholders’ networks in early phase of business development and clusters in the later phase is recommended

CHARACTERIZATION OF LACTIC ACID BACTERIA ISOLATED FROM A TRADITIONAL PASTA FILATA CHEESE

In this paper are reported the results of the characterization of the lactic acid microflora isolated from Sardinian &ldquo;provoletta&rdquo;, a traditional pasta filata cheese obtained from cow&rsquo;s milk. Cheese samples from two batches were taken in triplicate from three dairy plants after 7 and 21 days of ripening. Each sample was analyzed for mesophilic and thermophilic lactic acid bacteria (LAB). From plates, 118 isolates were identified by Rep- PCR GTG5, species-specific PCR and DNA sequencing. The identified LAB belonged to 7 different species: Lb. paracasei, Lb. rhamnosus, Lb. delbrueckii, Lb. fermentum, E. faecalis, E. faecium e Lc. Lactis. Enterococci were the most common isolates, they were recovered from all the dairy plants and from all the products analysed at 7 and at 20 days of ripening. Although with some differences within the various producers, the technology used aids mesophilic LAB growth, guaranteeing a large biodiversity protection