The carbonation kinetics of calcium hydroxide nanoparticles: A Boundary Nucleation and Growth description.

HYPOTHESIS: The reaction of Ca(OH)2 with CO2 to form CaCO3 (carbonation process) is of high interest for construction materials, environmental applications and art preservation. Here, the "Boundary Nucleation and Growth" model (BNGM) was adopted for the first time to consider the effect of the surface area of Ca(OH)2 nanoparticles on the carbonation kinetics. EXPERIMENTS: The carbonation of commercial and laboratory-prepared particles' dispersions was monitored by Fourier Transform Infrared Spectroscopy, and the BNGM was used to analyze the data. The contributions of nucleation and growth of CaCO3 were evaluated separately. FINDINGS: During carbonation the boundary regions of the Ca(OH)2 particles are densely populated with CaCO3 nuclei, and transform early with subsequent thickening of slab-like regions centered on the original boundaries. A BNGM limiting case equation was thus used to fit the kinetics, where the transformation rate decreases exponentially with time. The carbonation rate constants, activation energies, and linear growth rate were calculated. Particles with larger size and lower surface area show a decrease of the rate at which the non-nucleated grains between the boundaries transform, and an increase of the ending time of Ca(OH)2 transformation. The effect of temperature on the carbonation kinetics and on the CaCO3 polymorphs formation was evaluated.

Thymosin alpha-1 with peginterferon alfa-2a/ribavirin for chronic hepatitis C not responsive to IFN/ribavirin: an adjuvant role?

This study was conducted to determine whether the adding thymosin alpha-1 to standard of care for re-treatment of nonresponding hepatitis C infections can improve sustained viral response (SVR) rates. Patients (n = 552) with hepatitis C infections not responding to the combination of Peginterferon alfa-2a or 2b with ribavirin (RBV)were randomized to receive peginterferon alfa-2a 180 mg/week with RBV 800-1200 mg/daily plus either thymosin alpha-1 1.6 mg SC twice weekly (n = 275) or placebo (n = 277) for 48 weeks. Eighty-eight per cent of patients had HCV genotype 1, 6.6% type 4, 2.2% type 2 and 3.6% type 3. SVR rates in the intention to treat population were similar between thymosin alpha-1 and placebo (12.7%vs 10.5%; P = 0.407). Among patients who completed all 48 weeks of therapy, the SVR rate was significantly higher in the thymosin alpha-1 group at 41.0% (34/83) compared with 26.3% (26/99) in the placebo group (P = 0.048). No significant difference was observed between treatment groups in the incidence of adverse events. The addition of thymosin alpha-1 to the standard of care did not increase the on-treatment HCV viral response. Thymosin alpha-1 seems to play no role in the primary therapy of the disease. This study raises the hypothesis that thymosin alpha-1 may have a secondary therapeutic role as an adjuvant in the prevention of relapses in patients achieving a virologic response during therapy.

Thymosin-alpha 1 (Zadaxin) enhances the immunogenicity of an adjuvated pandemic H1N1v influenza vaccine (Focetria) in hemodialyzed patients: a pilot study.

BACKGROUND: Although influenza vaccination is widely recommended for immunosuppressed people, the same immune dysfunction that can increase the risk of contracting influenza might also compromise vaccine effectiveness, especially during pandemics. Clinical data have highlighted the role of adjuvants in improving vaccine efficacy. As uremic patients are especially vulnerable to infections, it is recommended that they should be vaccinated yearly against influenza. This paper presents the results of a pilot clinical trial, conducted in hemodialyzed patients with an adjuvated pandemic H1N1v influenza vaccine alone and combined with Thymosin-alpha 1. METHODS: Subjects were subdivided into 3 treatment groups receiving: the adjuvated pandemic influenza vaccine (Focetria) only (first treatment group), and the Vaccine+Thymosin alpha 1 (Zadaxin) at a dose of 3.2 and 6.4 mg (second and third treatment groups respectively). The immunoresponse was assessed on days 0, 21, 42, 84 and 168 after vaccine administration by means of Hemagglutination Inhibition (HI), Microneutralization (MN) and Single Radial Hemolysis (SRH) assays. The CHMP regards HI as the gold standard test to evaluate the immune response to influenza vaccines before influenza vaccines are licensed. The CHMP criteria are slightly different in adults (18-60-year-old subjects) and the elderly (>60 years old). Indeed, 40% of seroconversion, 70% of subjects seroprotected 21 days after vaccination, and a 2.5-fold increase in GMR (Geometric Mean Ratio) are required in adults, while in the elderly, the corresponding threshold values are: 30%, 60% and a 2-fold increase. All these criteria must be met for the licensing of a pandemic influenza vaccine. Safety evaluation was performed by means of Adverse Event (AE) recording, laboratory assays (hematology and chemistry), electrocardiogram, and assessment of vital signs. RESULTS: Three populations were considered: Intention-To-Treat (ITT) (94 patients), Per Protocol (PP) (82 patients), and Safety population (99 patients). With regard to the Geometric Mean Titer (GMT) and the Geometric Mean Ratio (GMR) of HI on Day 21 in the ITT population, both "Vaccine+Thymosin alpha 1" groups presented better results than the "Vaccine only" group. A large proportion of ITT patients in the two Vaccine+Thymosin alpha 1 groups achieved seroconversion by Day 21. On Day 42, the decrease in the GMT of HI was greater in the Vaccine+Thymosin alpha 1 groups than in the vaccine only group. Similar results were obtained in the PP population. The CHMP criteria were fully met in the groups treated with Vaccine+Thymosin alpha 1. No AE was found to be related to Thymosin alpha 1 nor to the Focetria vaccine. CONCLUSIONS: Although further studies in larger hemodialyzed populations are necessary, it can be concluded that Thymosin alpha 1 enhanced the immunogenicity of the pandemic influenza vaccine used. Moreover, it proved safe and well tolerated, and did not affect hematology or blood-chemistry values.

Utility of thymosin alpha-1 (Zadaxin) as a co-adjuvant in influenza vaccines: a review.

Influenza constitutes a serious problem for healthcare and social services worldwide, owing to its pattern and the severity of its complications in some categories of subjects at risk, such as the elderly and immunocompromised individuals. The only really effective means of combating influenza is vaccination. The elderly and immunocompromised subjects are refractory or low responders to vaccination. The need for ever more immunogenic and efficacious influenza vaccines, especially for subjects at risk, has prompted the development of adjuvated vaccines. With a view to enhancing the immune response in the elderly and in subjects at risk, the possibility of co-administering immunostimulants as Thymosin alpha-1 (Talpha1) with influenza vaccines has been investigated. Talpha1 is a biologically active peptide made up of 28 amino acids that can enhance T-cells, dendritic cell and antibody responses, modulate cytokines and chemokines production. Several studies were conducted and showed that Talpha1 ameliorate the performanc of influenza vaccination in elderly and subjects at risk. Although further studies on co-adjuvants are necessary, the future prospects of producing ever more efficacious influenza vaccines appear very promising.

Randomised clinical trial: the efficacy and safety of propionyl-L-carnitine therapy in patients with ulcerative colitis receiving stable oral treatment.

BACKGROUND: Ulcerative colitis (UC) is characterised by impaired fatty-acid oxidation; l-carnitine has a key role in fatty-acid metabolism and short-chain fatty acids such as butyrate and propionate are important energy source for intestinal epithelial cells. AIM: To evaluate efficacy and safety of colon-release propionyl-L-carnitine (PLC) in patients with mild-to-moderate UC receiving stable oral aminosalicylate or thiopurine therapy. METHODS: In a multicentre, phase II, double-blind, parallel-group trial, patients were randomised to receive PLC 1 g/day, PLC 2 g/day or placebo. Main inclusion criteria were as follows: age 18-75; disease activity index (DAI) score 3-10 inclusive, be under oral stable treatment with aminosalicylate or thiopurine. The primary endpoint was clinical/endoscopic response, defined as a decrease in DAI score ≥ 3 points or remission, defined as a DAI score ≤ 2 with no individual sub-score > 1. RESULTS: Of 121 patients who were randomised, 57 of 79 (72%) patients receiving PLC (combined 1 g and 2 g cohort) had a clinical/endoscopic response vs. 20 of 40 (50%) receiving placebo (P = 0.02). Specifically, in PLC 1 g/day group, 30 of 40 (75%) patients had clinical/endoscopic response (P = 0.02 vs. placebo) and 27 of 39 (69%) in the PLC 2 g/day group (P = 0.08 vs. placebo). Rates of remission were 22/40 (55%), 19/39 (49%), 14/40 (35%) in the PLC 1 g, PLC 2 g, and placebo groups, respectively. PLC had a similar safety profile to placebo; the most common adverse events were gastrointestinal. CONCLUSION: Propionyl-L-carnitine 1 g/day should be investigated further as a co-treatment for mild-to-moderate ulcerative colitis (NCT-01026857).

The effect of thymosin treatment of venous ulcers.

Venous ulcers are responsible for about 70% of the chronic ulcers of the lower limbs. Standard of care includes compression, dressings, debridement of devitalized tissue, and infection control. Thymosin beta 4 (Tbeta4), a synthetic copy of the naturally occurring 43 amino-acid peptide, has been found to have wound healing and anti-inflammatory properties, and is thought to exert its therapeutic effect through promotion of keratinocyte and endothelial cell migration, increased collagen deposition, and stimulation of angiogenesis. To assess the safety, tolerability, and efficacy of topically administered Tbeta4 in patients with venous stasis ulcers, a double-blind, placebo-controlled, dose-escalation study was conducted in eight European sites (five in Italy and three in Poland) that enrolled and randomized 73 patients. The safety profile of all doses of administered Tbeta4 was deemed acceptable and comparable to placebo. Efficacy findings from this Phase 2 study suggest that a Tbeta4 dose of 0.03% may have the potential to accelerate wound healing and that complete wound healing can be achieved within 3 months in about 25% of the patients, especially among those whose wounds are small to moderate in size or mild to moderate in severity.

Effects of zileuton, a new 5-lipoxygenase inhibitor, in experimentally induced colitis in rats.

The efficacy of zileuton, a new 5-lipoxygenase inhibitor, was investigated in comparison with sulphasalazine in an experimental model of rat colitis. Under light anaesthesia with ether, male rats were subjected to intracolonic administration of trinitrobenzene sulfonic acid (TNB) in 50% ethanol and were then sacrificed 2, 4 and 7 days after colitis induction. Untreated rats exhibited elevated colonic levels of leukotriene B4 (LTB4) and 6-keto-PGF1 alpha, and an increase in colonic myeloperoxidase (MPO) activity (investigated as an index of leukocyte adhesion and accumulation). Moreover, ulceration and inflammation of the distal colon with formation of granuloma and pathologic connections were observed. Treated rats received zileuton or sulphasalazine (50 mg/kg per os twice a day) 24 h before the induction of colitis until they were sacrificed. Treatment with the specific 5-lipoxygenase inhibitor, zileuton, resulted in significant reductions of colonic leukotriene B4 and 6-keto-PGF1 alpha synthesis, macroscopic and histological colonic damage and colonic inflammation as assessed by the measurement of MPO activity. In contrast, sulphasalazine had a lower effect than zileuton on LTB4 and MPO levels (p < 0.05), while it was able to reduce colonic damage and 6-keto-PGF1 alpha levels as well as zileuton. This study shows, therefore, that zileuton is effective in attenuating the lesions in an experimental model of colitis. Furthermore, the results are consistent with the hypothesis that leukotrienes play an important role in the pathogenesis of intestinal bowel diseases (IBD).