56 research outputs found
Efficacy and Safety of Novel Aspirin Formulations: A Randomized, Double-Blind, Placebo-Controlled Study.
Low-dose aspirin represents the best option in the secondary prevention of coronary artery disease, but its extensive use in primary prevention is limited by the occurrence of gastric mucosal lesions and increased risk of bleeding. We investigated the safety profile of a novel sublingual aspirin formulation in 200 healthy volunteers, randomly assigned to ten (n = 20 each) different 7-day once-daily treatment regimens. Gastric mucosal injury based on the modified Lanza score (MLS), the histopathology of gastric mucosa and the serum determination of thromboxane B2 (TXB2) and urinary 11-dehydro-TXB2 levels were evaluated at basal as well as after 7 days of each placebo or aspirin treatment regimen. In Groups A and B (placebo-oral and sublingual, respectively), no changes in MLS and in gastric mucosal micro-vessel diameter were found at day 7. In contrast, in Groups C and D (oral standard aspirin-100 and 50 mg daily, respectively), the median MLS was significantly increased. Very few changes were found in Groups E and F (standard sublingual aspirin-100 and 50 mg, respectively). Groups G and H (oral administration of micronized collagen-cogrinded aspirin) showed gastric protection compared to Groups C and D. Moreover, Groups I and L (sublingual collagen-cogrinded aspirin-100 and 50 mg, respectively) showed a significant reduction (Group I) or total abolition (Group L) of gastric mucosal lesions and no difference compared to the standard one in serum TXB2 and urinary 11-dehydro-TXB2 levels. In conclusion, our data show that the new formulation leads to a better safety profile compared to standard aspirin, representing a better therapeutic option for extended use in primary and secondary prevention of cardiovascular diseases
Pathophysiological Basis for Nutraceutical Supplementation in Heart Failure: A Comprehensive Review.
There is evidence demonstrating that heart failure (HF) occurs in 1-2% of the global population and is often accompanied by comorbidities which contribute to increasing the prevalence of the disease, the rate of hospitalization and the mortality. Although recent advances in both pharmacological and non-pharmacological approaches have led to a significant improvement in clinical outcomes in patients affected by HF, residual unmet needs remain, mostly related to the occurrence of poorly defined strategies in the early stages of myocardial dysfunction. Nutritional support in patients developing HF and nutraceutical supplementation have recently been shown to possibly contribute to protection of the failing myocardium, although their place in the treatment of HF requires further assessment, in order to find better therapeutic solutions. In this context, the Optimal Nutraceutical Supplementation in Heart Failure (ONUS-HF) working group aimed to assess the optimal nutraceutical approach to HF in the early phases of the disease, in order to counteract selected pathways that are imbalanced in the failing myocardium. In particular, we reviewed several of the most relevant pathophysiological and molecular changes occurring during the early stages of myocardial dysfunction. These include mitochondrial and sarcoplasmic reticulum stress, insufficient nitric oxide (NO) release, impaired cardiac stem cell mobilization and an imbalanced regulation of metalloproteinases. Moreover, we reviewed the potential of the nutraceutical supplementation of several natural products, such as coenzyme Q10 (CoQ10), a grape seed extract, Olea Europea L.-related antioxidants, a sodium-glucose cotransporter (SGLT2) inhibitor-rich apple extract and a bergamot polyphenolic fraction, in addition to their support in cardiomyocyte protection, in HF. Such an approach should contribute to optimising the use of nutraceuticals in HF, and the effect needs to be confirmed by means of more targeted clinical trials exploring the efficacy and safety of these compounds
Is the expression of the gene coding for cerato-platanin modulated by biotic and abiotic factors?
Ceratocystis platani is the causal agent of canker stain, the most dangerous disease affecting the plane trees. The fungus produces cerato-platanin (CP), a protein of about 12.4 kDa acting as a PAMP in host and non-host plants. On plane leaves CP elicits the transcription of defence-related genes earlier than C. platani does. The amino acid sequence 1-119 of CP is a new protein domain, called "cerato-platanin domain”; thus, CP is the founding member of the cerato-platanin family (pfam PF07249). To date, a number of highly conserved proteins produced by Ascomycetes and Basidiomycetes have been identified with this domain. They have been reported to interact with plants and humans, but very little is known about the regulation of the genes coding for these proteins and about their primary role in the lifestyle of producing fungi.
In the present work we demonstrated that CP is released by the fungus during the interaction with the host plant, and the expression of the cp gene is highly modulated. The gene was expressed more rapidly when the fungus was inoculated on the plane leaves than when it was grown in axenic culture. Potential abiotic and biotic stressors have been investigated: temperature, H2O2, umbelliferone (the reference plane phytoalexin), matric water stress, light (presence/absence), growth on sawdust of susceptible and resistant plane or elm trees, and co-culture with Trichoderma atroviride P1 and T. harzianum T22. The gene expression has been evaluated by qRT-PCR using TaqMan probes. The promoter region has been isolated and studied
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