In vitro osteogenic cell proliferation, mineralization, and in vivo osseointegration of injection molded high-density polyethylene-based hybrid composites in rabbit animal model

The present work reports the biocompatibility property of injection molded HDPE-HA-Al2O3 hybrid composites. In vitro cytocompatibility results reveal that osteogenic cell viability and bone mineralization are favorably supported in a statistically significant manner on HDPE-20% HA-20% Al2O3 composite, in comparison to HDPE-40 wt.% HA or HDPE-40 wt.% Al2O3. The difference in cytocompatibility property is explained in terms of difference in substrate wettability/surface energy and importantly, both the cell proliferation at 7 days or bone mineralization at 21 days on HDPE-20% HA-20% Al2O3 composite are either comparable or better than sintered HA. The progressive healing of cylindrical femoral bone defects in rabbit animal model was assessed by implantation experiments over 1, 4 and 12 weeks. Based on the histological analysis as well as histomorphometrical evaluation, a better efficacy of HDPE-20% HA-20% Al2O3 over high-density polyethylene (HDPE) for bone regeneration and neobone formation at host bone-implant interface was established. Taken together, the present study unequivocally establishes that despite the presence of 20% Al2O3, HDPE-based hybrid composites are as biocompatible as HA in vitro or better than HDPE in vivo.

Turing and animal coat patterns

The present article describes a beautiful contribution of Alan Turing to our understanding of how animal coat patterns form. The question that Turing posed was the following. A collection of identical cells (or processors for that matter), all running the exact same program, and all communicating with each other in the exact same way, should always be in the same state. Yet they produce nonhomogeneous periodic patterns, like those seen on animal coats. How does this happen? Turing gave an elegant explanation for this phenomenon, namely that differences between the cells due to small amounts of random noise can actually be amplified into structured periodic patterns. We attempt to describe his core conceptual contribution below.

Nutritional benefits from domatia inhabitants in an ant-plant interaction: interlopers do pay the rent

1. How a symbiosis originates and is maintained are important evolutionary questions. Symbioses in myrmecophytes (plants providing nesting for ants) are believed to be maintained by protection and nutrients provided by specialist plant-ants in exchange for nesting spaces (called domatia) and nourishment offered by ant-plants. However, besides the benefits accrued from housing protective ants, the mechanisms contributing to the fitness advantages of bearing domatia have rarely been examined, especially because the domatia trait is usually constitutively expressed, and many myrmecophytes have obligate mutualisms with single ant species resulting in invariant conditions. 2. In the unspecialized ant-plant Humboldtia brunonis (Fabaceae) that offers extrafloral nectar to ants, only some plants produce domatia in the form of hollow internodes. These domatia have a self-opening slit making them more prone to interlopers and are occupied mostly by non-protective ants and other invertebrates, especially arboreal earthworms. The protection mutualism with ants is restricted in geographical extent, occurring only at a few sites in the southernmost part of this plant's range in the Western Ghats of India. 3. We examined nutrient flux from domatia residents to the plant using stable isotopes. We found that between 9% (earthworms) and 17% (protective or non-protective ants) of nitrogen of plant tissues nearest the domatium came from domatia inhabitants. Therefore, interlopers such as earthworms and non-protective ants contributed positively to the nitrogen budget of localized plant modules of this understorey tree. N-15-enriched feeding experiments with protective ants demonstrated that nutrients flowed from domatia inhabitants to nearby plant modules. Fruit set did not differ between paired hand-pollinated inflorescences on domatia and non-domatia bearing branches. This was possibly due to the nutrient flux from domatia to adjacent branches without domatia within localized modules. 4. This study has demonstrated the nutritive role of non-protective ants and non-ant invertebrates, hitherto referred to as interlopers, in an unspecialized myrmecophyte. Our study suggests that even before the establishment of a specialized ant-plant protection mutualism, nutritional benefits conferred by domatia inhabitants can explain the fitness benefits of bearing domatia, and thus the maintenance of a trait that facilitates the establishment of a specialized ant-plant symbiosis.

Development, in vitro and in vivo characterization of zoledronic acid functionalized hydroxyapatite nanoparticle based formulation for treatment of osteoporosis in animal model

We investigated the potential of using novel zoledronic acid (ZOL)-hydroxyapatite (HA) nanoparticle based drug formulation in a rat model of postmenopausal osteoporosis. By a classical adsorption method, nanoparticles of HA loaded with ZOL (HNLZ) drug formulation with a size range of 100-130 nm were prepared. 56 female Wistar rats were ovariectomized (OVX) or sham-operated at 3 months of age. Twelve weeks post surgery, rats were randomized into seven groups and treated with various doses of HNLZ (100, 50 and 25 mu g/kg, intravenous single dose), ZOL (100 mu g/kg, intravenous single dose) and HA nanoparticle (100 mu g/kg, intravenous single dose). Untreated OVX and sham OVX served as controls. After three months treatment period, we evaluated the mechanical properties of the lumbar vertebra and femoral mid-shaft. Femurs were also tested for trabecular microarchitecture. Sensitive biochemical markers of bone formation and bone resorption in serum were also determined. With respect to improvement in the mechanical strength of the lumbar spine and the femoral mid-shaft, the therapy with HNLZ drug formulation was more effective than ZOL therapy in OVX rats. Moreover, HNLZ drug therapy preserved the trabecular microarchitecture better than ZOL therapy in OVX rats. Furthermore, the HNLZ drug formulation corrected increase in serum levels of bone-specific alkaline phosphatase, procollagen type I N-terminal propeptide, osteocalcin, tartrate-resistant acid phosphatase 5b and C-telopeptide of type 1 collagen better than ZOL therapy in OVX rats. The results strongly suggest that HNLZ novel drug formulation appears to be more effective approach for treating severe osteoporosis in humans. (C) 2014 Elsevier B.V. All rights reserved.

The Evolution of Animal Welfare and the 3Rs in Brazil, China, and India

Increasingly, scientific collaborations and contracts cross country borders. The need for assurance that the quality of animal welfare and the caliber of animal research conducted are equivalent among research partners around the globe is of concern to the scientific and laboratory animal medicine communities, the general public, and other key stakeholders. Therefore, global harmonization of animal care and use standards and practices, with the welfare of the animals as a cornerstone, is essential. In the evolving global landscape of enhanced attention to animal welfare, a widely accepted path to achieving this goal is the successful integration of the 3Rs in animal care and use programs. Currently, awareness of the 3Rs, their implementation, and the resulting animal care and use standards and practices vary across countries. This variability has direct effects on the animals used in research and potentially the data generated and may also have secondary effects on the country's ability to be viewed as a global research partner. Here we review the status of implementation of the 3Rs worldwide and focus on 3 countries-Brazil, China and India-with increasing economic influence and an increasing footprint in the biomedical research enterprise.

A novel DNA intercalator, 8-methoxy pyrimido4 `,5 `:4,5]thieno (2,3-b)quinoline-4(3H)-one induces apoptosis in cancer cells, inhibits the tumor progression and enhances lifespan in mice with tumor

Polycyclic aromatic molecules such as ellipticine intercalate into double-stranded DNA and interfere with physiological functions. In the present study, we evaluate the chemotherapeutic potential of MPTQ on animal models and its mode of action. In order to test the antitumor activity, monohydrochloride of MPTQ was orally administered in mice bearing tumor. Results showed a significant inhibition of tumor growth compared to that of untreated controls. More importantly, mean lifespan of tumor bearing animals treated with MPTQ was significantly higher as compared to that of untreated tumor bearing mice suggesting that the treatment affected viability of cancerous cells, but not of normal cells. Consistent with this, we find that administration of MPTQ to normal mice did not cause any major side effects as observed upon hematological and serum profiling. We also found that MPTQ induces cytotoxicity in cancer cell lines, by activating apoptosis both by intrinsic and extrinsic pathways. Thus, MPTQ could be used as a potential cancer therapeutic agent. (c) 2011 Wiley Periodicals, Inc.

Physiological role of FolD (methylenetetrahydrofolate dehydrogenase), FchA (methenyltetrahydrofolate cyclohydrolase) and Fhs (formyltetrahydrofolate synthetase) from Clostridium perfringens in a heterologous model of Escherichia coli

Most organisms possess bifunctional FolD 5,10-methylenetetrahydrofolate (5,10-CH2-THF) dehydrogenase-cyclohydrolase] to generate NADPH and 10-formyltetrandrofolate (10-CHO-THF) required in various metabolic steps. In addition, some organisms including Clostridium perfringens possess another protein, Fhs (formyltetrahydrofolate synthetase), to synthesize 10-CHO-THF. Here, we show that unlike the bifunctional FolD of Escherichia coli (Eco FolD), and contrary to its annotated bifunctional nature, C. perfringens FolD (Cpe FoID) is a monofunctional 5,10-CH2-THF dehydrogenase. The dehydrogenase activity of Cpe FoID is about five times more efficient than that of Eco FolD. The 5,10-methenyltetrahydrofolate (5,10-CH+-THF) cyclohydrolase activity in C. perfringens is provided by another protein, FchA (5,10-CH+-THF cyclohydrolase), whose cyclohydrolase activity is similar to 10 times more efficient than that of Eco FolD. Kinetic parameters for Cpe Fhs were also determined for utilization of all of its substrates. Both Cpe FoID and Cpe FchA are required to substitute for the single bifunctional FolD in E. coli. The simultaneous presence of Cpe FoID and Cpe FchA is also necessary to rescue an E coli folD deletion strain (harbouring Cpe Fhs support) for its formate and glycine auxotrophies, and to alleviate its susceptibility to trimethoprim (an antifolate drug) or UV light. The presence of the three clostridial proteins (FolD, FchA and Fhs) is required to maintain folate homeostasis in the cell.