From ancient leech to direct thrombin inhibitors and beyond: New from old

Medicinal leeches have been used in health care since before written history, with widely varying popularity over the centuries. Nowadays, medicinal leech therapy is mainly used in plastic and reconstructive microsurgery, with new interesting potential therapeutic applications in many other diseases. The leech's best-known salivary product, hirudin — one of the most powerful natural anticoagulants — was the only remedy to prevent blood clotting until the discovery of heparin. Starting from hirudin, pharmacological research succeeded in developing new anticoagulants, which represent a cornerstone of prevention and treatment of thromboembolic disease. While we are perhaps on the threshold of a new era of anticoagulation, with the development of FXI and XII inhibitors and direct reversible covalent thrombin inhibitors, which promise to achieve effective anticoagulation without bleeding risk. This review retraces the intriguing journey of these drugs in cardiovascular disease, highlighting the fil rouge that links the ancient leech to the current and oncoming antithrombotic therapy. We think that knowledge of the past is key to understanding and appreciating the present and to seize future opportunities

The first 3500 years of aspirin history from its roots - A concise summary

none3Aspirin is currently the most widely used drug worldwide, and has been clearly one of the most important pharmacological achievements of the twentieth century. Historians of medicine have traced its birth in 1897, but the fascinating history of aspirin actually dates back >3500 years, when willow bark was used as a painkiller and antipyretic by Sumerians and Egyptians, and then by great physicians from ancient Greece and Rome. The modern history of aspirin precursors, salicylates, began in 1763 with Reverend Stone - who first described their antipyretic effects - and continued in the 19th century with many researchers involved in their extraction and chemical synthesis. Bayer chemist Felix Hoffmann synthesized aspirin in 1897, and 70 years later the pharmacologist John Vane elucidated its mechanism of action in inhibiting prostaglandin production. Originally used as an antipyretic and anti-inflammatory drug, aspirin then became, for its antiplatelet properties, a milestone in preventing cardiovascular and cerebrovascular diseases. The aspirin story continues today with the growing evidence of its chemopreventive effect against colorectal and other types of cancer, now awaiting the results of ongoing primary prevention trials in this setting. This concise review revisits the history of aspirin with a focus on its most remote origins.Montinari, Maria Rosa; Minelli, Sergio; De Caterina, RaffaeleMontinari, Maria Rosa; Minelli, Sergio; De Caterina, Raffael

Morphology, Plasticity, and Transformation between Philosophy and Biology

In biology, interest in form was the prerogative of developmental biology, while it was practically neglected by evolutionary biology. This situation has changed a lot in recent decades and has led to a reinterpretation of the concept of evolution and evolutionism focusing more on the problem of form and morphology. In Italy, especially Alessandro Minelli, one of the editors of this issue, has dedicated his studies to the need to communicate form to structure, to reconnect morphology and evolution. This theme is a highly relevant one for philosophy, inasmuch as the question of form and morphology, since the days of Goethe and Bergson, has always been considered as the starting point for a philosophy of the living being endowed with its own categories that cannot be reduced to those of physics

Retrofitting unreinforced masonry by steel fiber reinforced mortar coating: uniaxial and diagonal compression tests

AbstractThin layers of mortar reinforced with steel fibers can be applied on one or both sides of bearing walls as an effective seismic strengthening of existing masonry buildings. To assess the effectiveness of this technique, an experimental study on masonry sub-assemblages was carried out at the University of Brescia. This paper summarizes and discusses the main results of the investigation, which included mechanical characterization tests on masonry and its components as well as on the Steel Fiber Reinforced Mortar (SFRM) used to retrofit the masonry samples. Uniaxial and diagonal compression tests were carried out on both unstrengthened wallets and masonry samples retrofitted with 25 mm thick SFRM coating. Both single-sided and double-sided retrofitting configurations for application on wall surfaces were considered. The results highlighted the ability of the technique to improve the compressive and the shear behavior of masonry, even in case of single-sided strengthening. Moreover, no premature debonding of coating was observed. Lastly, the manuscript presents the results of a numerical investigation that was performed both to simulate the diagonal compression tests described in the first part of the paper and to predict the response of panels with different strengthening configurations

Formulation and Characterization of Phytostanol Ester Solid Lipid Nanoparticles for the Management of Hypercholesterolemia: An ex vivo Study.

Background: Phytostanols are naturally occurring compounds that reduce blood cholesterol levels significantly. However, their aqueous insolubility poses formulation challenges. Aim: To formulate and characterize solid lipid nanoparticle carriers for phytostanol esters to enhance the bioavailability of phytostanols. Methods: Phytostanol ester solid lipid nanoparticles were formulated by the microemulsion method. They were characterized for particle size distribution, polydispersity index, shape, surface charge, entrapment efficiency, stability, chemical structure, and thermal properties. The uptake of the formulation by cell lines, HepG2 and HT-29, and its effect on cell viability were evaluated. Results: The formulation of solid lipid nanoparticles was successfully optimised by varying the type of lipids and their concentration relative to that of surfactants in the present study. The optimised formulation had an average diameter of (171 ± 9) nm, a negative surface charge of (− 23.0 ± 0.8) mV and was generally spherical in shape. We report high levels of drug entrapment at (89 ± 5)% in amorphous form, drug loading of (9.1 ± 0.5)%, nanoparticle yield of (67 ± 4)% and drug excipient compatibility. The biological safety and uptake of the formulations were demonstrated on hepatic and intestinal cell lines. Conclusion: Phytostanol ester solid lipid nanoparticles were successfully formulated and characterized. The formulation has the potential to provide an innovative drug delivery system for phytostanols which reduce cholesterol and have a potentially ideal safety profile. This can contribute to better management of one of the main risk factors of cardiovascular disease

Quantum Zeno effect in a multilevel molecule

We study the dynamics of the populations of a model molecule endowed with two sets of rotational levels of different parity, whose ground levels are energy degenerate and coupled by a constant interaction. The relaxation rate from one set of levels to the other one has an interesting dependence on the average collision frequency of the molecules in the gas. This is interpreted as a quantum Zeno effect due to the decoherence effects provoked by the molecular collisions.Comment: 42 pages, 10 figure

Foot dermatitis and productive traits in broiler chickens kept with different stocking densities, litter types and light regimen

The purpose of the research was to study the effects of high and low stocking density of broiler chickens, different types of litter and the adoption of short and long lighting regimen on broiler welfare through the evaluation of their productivity and incidence of foot pad dermatitis. 2,400 male Ross 508 were divided into 8 groups of four replicates each and reared in 32 pens according to a 3 factors experimental design of two levels each: low (LD) or high (HD) stocking density (11 and 14 birds/m2 for LD and HD respectively), chopped straw (CS) or wood shaving (WS) litters and short (SL) or long (LL) light regimens (16 h light and 8 h dark or 23 h light and 1 h dark respectively for SL and LL). Broiler growth rate and feed efficiency were positively influenced by a stocking density lower than 30 kg of live weight per m2. The adoption of a short light regimen reduced feed intake and improved feed conversion rate without modifying body live weight. Chickens reared on wood shaving litter showed a lower incidence of foot pad dermatitis

Robotic versus laparoscopic approach in colonic resections for cancer and Benign diseases. Systematic review and meta-analysis

Objectives The aim of this systematic review and meta-Analysis is to compare robotic colectomy (RC) with laparoscopic colectomy (LC) in terms of intraoperative and postoperative outcomes. Materials and Methods A systematic literature search was performed to retrieve comparative studies of robotic and laparoscopic colectomy. The databases searched were PubMed, Embase and the Cochrane Central Register of Controlled Trials from January 2000 to October 2014. The Odds ratio, Risk difference and Mean difference were used as the summary statistics. Results A total of 12 studies, which included a total of 4,148 patients who had undergone robotic or laparoscopic colectomy, were included and analyzed. RC demonstrated a longer operative time (MD 41.52, P<0.00001) and higher cost (MD 2.42, P<0.00001) than did LC. The time to first flatus passage (MD-0.51, P = 0.003) and the length of hospital stay (MD-0.68, P = 0.01) were significantly shorter after RC. Additionally, the intraoperative blood loss (MD-16.82, P<0.00001) was significantly less in RC. There was also a significantly lower incidence of overall postoperative complications (OR 0.74, P = 0.02) and wound infections (RD-0.02, P = 0.03) after RC. No differences in the postoperative ileus, in the anastomotic leak, or in the conversion to open surgery rate and in the number of harvested lymph nodes outcomes were found between the approaches. Conclusions The present meta-Analysis, mainly based on observational studies, suggests that RC is more time-consuming and expensive than laparoscopy but that it results in faster recovery of bowel function, a shorter hospital stay, less blood loss and lower rates of both overall postoperative complications and wound infections. Copyright: © 2015 Trastulli et al.OBJECTIVES: The aim of this systematic review and meta-analysis is to compare robotic colectomy (RC) with laparoscopic colectomy (LC) in terms of intraoperative and postoperative outcomes. MATERIALS AND METHODS: A systematic literature search was performed to retrieve comparative studies of robotic and laparoscopic colectomy. The databases searched were PubMed, Embase and the Cochrane Central Register of Controlled Trials from January 2000 to October 2014. The Odds ratio, Risk difference and Mean difference were used as the summary statistics. RESULTS: A total of 12 studies, which included a total of 4,148 patients who had undergone robotic or laparoscopic colectomy, were included and analyzed. RC demonstrated a longer operative time (MD 41.52, P<0.00001) and higher cost (MD 2.42, P<0.00001) than did LC. The time to first flatus passage (MD -0.51, P = 0.003) and the length of hospital stay (MD -0.68, P = 0.01) were significantly shorter after RC. Additionally, the intraoperative blood loss (MD -16.82, P<0.00001) was significantly less in RC. There was also a significantly lower incidence of overall postoperative complications (OR 0.74, P = 0.02) and wound infections (RD -0.02, P = 0.03) after RC. No differences in the postoperative ileus, in the anastomotic leak, or in the conversion to open surgery rate and in the number of harvested lymph nodes outcomes were found between the approaches. CONCLUSIONS: The present meta-analysis, mainly based on observational studies, suggests that RC is more time-consuming and expensive than laparoscopy but that it results in faster recovery of bowel function, a shorter hospital stay, less blood loss and lower rates of both overall postoperative complications and wound infections