New advances in targeted gastric cancer treatment

Despite a decrease in incidence over past decades,gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic techniques, surgical and chemotherapeutic approaches, the development of novel therapeutic agents and treatment by multidisciplinary teams. Because multiple genetic mutations, epigenetic alterations, and aberrant molecular signalling pathways are involved in the development of gastric cancers, recent research has attempted to determine the molecular heterogeneity responsible for the processes of carcinogenesis, spread and metastasis. Currently, some novel agents targeting a part of these dysfunctional molecular signalling pathways have already been integrated into the standard treatment of gastric cancer, whereas others remain in phases of investigation within clinical trials. It is essential to identify the unique molecular patterns of tumours and specific biomarkers to develop treatments targeted to the individual tumour behaviour. This review analyses the global impact of gastric cancer, as well as the role of Helicobacter pylori infection and the efficacy of bacterial eradication in preventing gastric cancer development. Furthermore, the paper discusses the currently available targeted treatments and future directions of research using promising novel classes of molecular agents for advanced tumours.     

Idazoxan effects upon contractile activity in the rat aorta are related to alpha adrenoceptors and L-type channels

Idazoxan is an alpha(2) adrenoceptor antagonist and alpha(1)/alpha(2) partial agonist which also blocks imidazoline receptors. Although idazoxan is widely used in pharmacological studies, its intrinsic vasoactive properties could bring about some limitations. Others have shown that in rat aorta contracted by phenylephrine idazoxan induces relaxation and that in rat small arteries it preferentially antagonizes the alpha(1)-mediated response. We further investigated this matter, using the rat aorta and focusing on the endothelium-independent effects and on L-type channels. In our study, idazoxan inhibited the contraction induced by phenylephrine, an effect which was stronger in the presence of endothelium, but did not affect the contractions induced by various other agents (high potassium, angiotensin II, prostaglandin F(2alpha)). This preferential inhibition was attenuated by 10(-4) m, but not by 10(-5) m yohimbine, and also reduced by 10(-2) m tetraethylammonium and blunted by 10(-4) m methoxyverapamil. In concentrations above 10(-5) m idazoxan induced weak contractions of the de-endothelized rings, which were prazosin- and methoxyverapamil-sensitive. Others have suggested that cyclic guanosine monophospate mediates the idazoxan-induced endothelium-dependent relaxation, but this is difficult to reconcile with our findings. Potassium efflux could play some role in the direct relaxing effect of idazoxan. The observed idazoxan effects appear as based on action upon alpha(1) receptors, but a direct interaction with L-type calcium channels could also be taken into consideration.     

Interactions between magnesium and psychotropic drugs

Psychotropic drugs (antidepressants, antimanic drugs, antipsychotics, analgesic opioids, and others) are among the most frequently used medicines. Between these drugs and magnesium there are pharmacokinetic and pharmacodynamic interactions. Erythrocyte magnesium is decreased in patients with severe major depression (MD) vs normal subjects (44 +/- 2.7 mg/L in MD group vs 59.1 +/- 3.2 mg/L in control group, p < 0.01). Therapy with sertraline, 150 mg/day p.o. -21 days or with amitryptiline 3 x 25 mg/day p.o. 28 days increases significantly erythrocyte concentration of magnesium (56.9 +/- 5.22 mg/L after sertraline vs 44 +/- 2.7 mg/L before sertraline, p < 0.01). In patients with acute paranoid schizophrenia, erythrocyte magnesium concentration is decreased vs healthy subjects. Haloperidol, 8 mg/day, p.o. for 21 days or risperidone, 6 mg/day p.o. for 21 days have increased significantly erythrocyte magnesium concentration (46.21 +/- 3.1 mg/L before haloperidol and 54.6 +/- 2.7 mg/L after haloperidol, p < 0.05). Antimanic drugs (mood stabilizers) as carbamazepine, 600 mg/day, p.o., 4 weeks and sodium valproate, 900 mg/day p.o., 4 weeks, increased significantly magnesium in patients with bipolar disorder type I. Increased magnesium status positively correlated with enhancement of the clinical state. The existent data sustain the idea that an increase of erythrocyte magnesium is involved in the mechanism of action of some psychotropic drugs. Magnesium supply decreased the intensity of morphine-induced physical drug dependence. In heroin addicts, the plasma magnesium concentration is decreased.     

Synthesis of poly(alkenoic acid) with L-leucine residue and methacrylate photopolymerizable groups useful in formulating dental restorative materials

To develop resin-modified glass ionomer materials, we synthesized methacrylate-functionalized acrylic copolymer (PAlk-LeuM) derived from acrylic acid, itaconic acid and N-acryloyl-L-leucine using (N-methacryloyloxyethylcarbamoyl-N′-4-hydroxybutyl) urea as the modifying agent. The spectroscopic (proton/carbon nuclear magnetic resonance, Fourier transform infrared spectroscopy) characteristics, and the gel permeation chromatography/Brookfield viscosity measurements were analysed and compared with those of the non-modified copolymer (PAlk-Leu). The photocurable copolymer (PAlk-LeuM, ~14?mol% methacrylate groups) and its precursor (PAlk-Leu) were incorporated in dental ionomer compositions besides diglycidyl methacrylate of bisphenol A (Bis-GMA) or an analogue of Bis-GMA (Bis-GMA-1), triethylene glycol dimethacrylate and 2-hydroxyethyl methacrylate. The kinetic data obtained by photo-differential scanning calorimetry showed that both the degree of conversion (60.50–75.62%) and the polymerization rate (0.07–0.14?s^?1) depend mainly on the amount of copolymer (40–50 wt.%), and conversions over 70% were attained in the formulations with 40 wt.% PAlk-LeuM. To formulate light-curable cements, each organic composition was mixed with filler (90 wt.% fluoroaluminosilicate/10 wt.% hydroxyapatite) into a 2.7:1 ratio (powder/liquid ratio). The light-cured specimens exhibited flexural strength (FS), compressive strength (CS) and diametral tensile strength (DTS) varying between 28.08 and 64.79?MPa (FS), 103.68–147.13?MPa (CS) and 16.89–31.87?MPa (DTS). The best values for FS, CS and DTS were found for the materials with the lowest amount of PAlk-LeuM. Other properties such as the surface hardness, water sorption/water solubility, surface morphology and fluorescence caused by adding the fluorescein monomer were also evaluated.     

The Influence of Enzymatic Hydrolysis of Whey Proteins on the Properties of Gelatin-Whey Composite Hydrogels

Amino-acids, peptides, and protein hydrolysates, together with their coordinating compounds, have various applications as fertilizers, nutritional supplements, additives, fillers, or active principles to produce hydrogels with therapeutic properties. Hydrogel-based patches can be adapted for drug, protein, or peptide delivery, and tissue healing and regeneration. These materials have the advantage of copying the contour of the wound surface, ensuring oxygenation, hydration, and at the same time protecting the surface from bacterial invasion. The aim of this paper is to describe the production of a new type of hydrogel based on whey protein isolates (WPI), whey protein hydrolysates (WPH), and gelatin. The hydrogels were obtained by utilizing a microwave-assisted method using gelatin, glycerol, WPI or WPH, copper sulfate, and water. WPH was obtained by enzymatic hydrolysis of whey protein isolates in the presence of bromelain. The hydrogel films obtained have been characterized by FT-IR and UV-VIS spectroscopy. The swelling degree and swelling kinetics have also been determined.     

Surface Characteristics,Fluoride Release and Bond Strength Evaluation of Four Orthodontic Adhesives

Orthodontic adhesives have similar properties in terms of fluoride release, roughness, shear bond strength or cement debris for specific clinical conditions. Three commercial consecrated orthodontic adhesives (Opal Seal^®, Blugloo^®, Light Bond^®) were compared with an experimental orthodontic material (C1). Brackets were bonded to enamel using a self-etch technique followed by adhesive application and then de-bonded 60 days later. Share bond strength evaluation, scanning electron microscopy, atomic force microscopy and fluoride release analysis were performed. The highest amount of daily and cumulative fluoride release was obtained for the experimental material, while the lowest value was observed for Opal Seal^®. The materials evaluated in the current study presented adequate shear bond strength, with the experimental material having a mean value higher than Opal Seal and Blugloo. The atomic force microscopy measurements indicated that the smoothest initial sample is Opal Seal^® followed by Light Bond^®. Scanning electron microscopy evaluation indicated different aspects of cement debris on the enamel and/or bracket surface, according to the type of adhesive. The experimental material C1 presented adequate properties in terms of shear bond strength, fluoride release, roughness and enamel characteristics after de-bonding, compared to the commercial materials. Under these circumstances, it can be considered for clinical testing.