Comparison of veterinary drugs and veterinary homeopathy: part 1

For many years after its invention around 1796, homeopathy was widely used in people and later in animals. Over the intervening period (1796-2016) pharmacology emerged as a science from Materia Medica (medicinal materials) to become the mainstay of veterinary therapeutics. There remains today a much smaller, but significant, use of homeopathy by veterinary surgeons. Homeopathic products are sometimes administered when conventional drug therapies have not succeeded, but are also used as alternatives to scientifically based therapies and licensed products. The principles underlying the veterinary use of drug-based and homeopathic products are polar opposites; this provides the basis for comparison between them. This two-part review compares and contrasts the two treatment forms in respect of history, constituents, methods of preparation, known or postulated mechanisms underlying responses, the legal basis for use and scientific credibility in the 21st century. Part 1 begins with a consideration of why therapeutic products actually work or appear to do so

Mercuration of apo-alpha-lactalbumin: binding of Hg2+ followed by protein-mediated nanoparticle formation

Nanoparticles and nanocrystals of mercury are formed when Hg2+ salt reacts with apo-alpha-lactalbumin (apoa-alpha-LA). Reduction followed by nanoparticle formation is further augmented by the protein, as it also acts as a coating agent. The initial interaction of Hg2+ with apo-alpha-LA was demonstrated by changes observed in absorption, emission, and CD spectroscopy, where the latter technique also detected structural changes in the protein. Such structural changes are expected when Hg2+ binds to the protein, and therefore, the binding was determined by isothermal titration calorimetry (ITC). The binding was further proven by MALDI, which showed mercurated species of protein with a Gaussian distribution exhibiting a weighted average of 6 and 9 Hg2+ ions bound to protein when apo-alpha-LA was treated with 10 and 100 equivalents, respectively. The molecular dynamics studies revealed the binding of Hg2+ ions followed by the structural changes that occurred in the protein. The reaction between Hg2+ and apo-alpha-LA yields noncrystalline nanoparticles at lower molar ratios of Hg2+ and crystalline ones at higher molar ratios. The existence of both of these nanoparticles was proven by extensive TEM studies, and the mercury nanocrystals were further studied using fluorescence microscopy. X-ray photoelectron spectroscopy demonstrated that the protein has the ability to convert Hg2+ to Hg-0, and the resultant Hg-0 cluster is known to be less harmful than Hg2+ to the organism. All of these studies support the use of apo-alpha-LA in the form of nanoparticles and nanocrystals to detoxify Hg2+

Evidence of Rapid Coaggregation of Globular Proteins during Amyloid Formation

The question of how an aggregating protein can influence aggregation of other proteins located in its vicinity is particularly significant because many proteins coexist in cells. We demonstrate <i>in vitro</i> coaggregation and cross-seeding of lysozyme, bovine serum albumin, insulin, and cytochrome <i>c</i> during their amyloid formation. The coaggregation process seems to be more dependent on the temperature-induced intermediate species of these proteins and less dependent on their sequence identities. Because amyloid-linked inclusions and plaques are recognized as multicomponent entities originating from aggregation of the associated protein, these findings may add new insights into the mechanistic understanding of amyloid-related pathologies

3D scaffold induces efficient bone repair: in vivo studies of ultra-structural architecture at the interface

The repair of critical bone loss remains a challenge to orthopaedic surgeons. Various artificial scaffolds have been intensively evaluated to provide an alternative solution for the repair and regeneration of bone defects; however, the inconsistent clinical performances of available materials have prompted the development of reactive 3D scaffolds for bone tissue engineering. We have studied the ability of a functionally designed 3D scaffold to bridge critical size defects and induce new bone formation in a New Zealand white rabbit tibial model, and have evaluated its ultra-structural properties using a combination of techniques, such as solid-state nuclear magnetic resonance (ssNMR), scanning electron microscopy (SEM), energy dispersive X-ray (EDX) and micro-computed tomography (mu-CT) with MIMICS (R) (Materialise's Interactive Medical Image Control System). ssNMR showed the structural similarity of the synthetic biomaterial to naturally occurring human bone. SEM studies showed an increase in Ca/P ratio with time, the progressively uniform distribution of elements in healed bones, and increased new bone formation, finally resembling native (intact) bone mu-CT and MIMICS (R) demonstrated the pattern and morphology of new bone formed, with a noticeable shift in the HU unit towards compact bone, from week 2 to 25. The results suggest that in the critical size bone defect, the scaffold enhanced the formation of new bone having biomaterial composition, ultra-structure and quality resembling that of native bone, thus suggesting significant improvement in guided bone regeneration. This research provides a promising new avenue for orthopaedic implant design that safely biodegrades while promoting new bone growth

Bioconductive 3D nano-composite constructs with tunable elasticity to initiate stem cell growth and induce bone mineralization

Bioactive 3D composites play an important role in advanced biomaterial design to provide molecular coupling and improve integrity with the cellular environment of the native bone. In the present study, a hybrid lyophilized polymer composite blend of anionic charged sodium salt of carboxymethyl chitin and gelatin (CMCh(Na)-GEL) reinforced with nano-rod agglomerated hydroxyapatite (nHA) has been developed with enhanced biocompatibility and tunable elasticity. The scaffolds have an open, uniform and interconnected porous structure with an average pore diameter of 157 +/- 30 mu M and 89.47 + 0.03% with four dimensional X-ray. The aspect ratio of ellipsoidal pores decrease from 4A to 1.2 with increase in gelatin concentration; and from 2.14 to 1.93 with decrease in gelling temperature. The samples were resilient with elastic stain at 1.2 MPa of stress also decreased from 0.33 to 0.23 with increase in gelatin concentration. The crosslinker HMDI (hexamethylene diisocyanate) yielded more resilient samples at 1.2 MPa in comparison to glutaraldehyde. Increased crosslinking time from 2 to 4 h in continuous compression cycle show no improvement in maximum elastic stain of 1.2 MPa stress. This surface elasticity of the scaffold enables the capacity of these materials for adherent self renewal and cultivation of the NTERA-2 cL.D1 (NT2/D1), pluripotent embryonal carcinoma cell with biomechanical surface, as is shown here. Proliferation with MG-63, ALP activity and Alizarin red mineralization assay on optimized scaffold demonstrated ***p < 0.001 between different time points thus showing its potential for bone healing. In pre-clinical study histological bone response of the scaffold construct displayed improved activity of bone regeneration in comparison to self healing of control groups (sham) up to week 07 after implantation in rabbit tibia critical-size defect. Therefore, this nHA-CMCh(Na)-GEL scaffold composite exhibits inherent and efficient physicochemical, mechanical and biological characteristics based on gel concentrations, gelatin mixing and gelling temperature thus points to creating bioactive 3D scaffolds with tunable elasticity for orthopedic applications. (C) 2016 Elsevier B.V. All rights reserved