Solomon Praveen Samuel

Atorvastatin activates heme oxygenase‐1 at the stress response elements

Statins are known to inhibit growth of a number of cancer cells, but their mechanism of action is not well established. In this study, human prostate adenocarcinoma PC‐3 and breast adenocarcinoma MCF‐7 cell lines were used as models to investigate the mechanism of action of atorvastatin, one of the statins. Atorvastatin was found to induce apoptosis in PC‐3 cells at a concentration of 1 μM, and in MCF‐7 cells at 50 μM. Initial survey of possible pathway using various pathway‐specific luciferase reporter assays showed that atorvastatin‐activated antioxidant response element (ARE), suggesting oxidative stress pathway may play a role in atorvastatin‐induced apoptosis in both cell lines. Among the antioxidant response genes, heme oxygenase‐1 (HO‐1) was significantly up‐regulated by atorvastatin. Pre‐incubation of the cells with geranylgeranyl pyrophosphate blocked atorvastatin‐induced apoptosis, but not up‐regulation of HO‐1, suggesting that atorvastatin‐induced apoptosis is dependent on GTPase activity and up‐regulation of HO‐1 gene is not. Six ARE‐like elements (designated StRE1 [stress response element] through StRE6) are present in the HO‐1 promoter. Atorvastatin was able to activate all of the elements. Because these StRE sites are present in clusters in HO‐1 promoter, up‐regulation of HO‐1 by atorvastatin may involve multiple StRE sites. The role of HO‐1 in atorvastatin‐induced apoptosis in PC‐3 and MCF‐7 remains to be studied.

Effect of atorvastatin on the cortical bones of corticosteroid treated rabbits

Osteoporosis (“secondary” osteoporosis) and avascular necrosis (AVN) of the femoral head are well‐known adverse effects of corticosteroid therapy. Statins have been reputed to increase bone strength and bone density. In this study, we evaluated the effect of atorvastatin calcium on the flexural properties (3‐point bending strength and modulus) of corticosteroid (methylprednisolone acetate) treated rabbit femurs and tibias. Our study hypothesis was that the use of statins would counteract the loss of bone strength caused by corticosteroid treatment. The 40 rabbits were divided into 5 groups: control, corticosteroid alone and corticosteroid combined with oral doses of atorvastatin calcium (2, 10, or 20 mg/day). A daily oral dose of atorvastatin calcium treatment for 70 days weakened the long bones of methylprednisolone acetate treated rabbits irrespective of the dosage (2, 10, or 20 mg). Cortical bone strength was assessed using the 3‐point bending test at the end of the study period. A daily oral dose of atorvastatin calcium did not attenuate the loss of cortical bone strength caused by corticosteroid treatment in rabbits. It appeared to decrease that bone strength. If these results hold true in humans, they would have wide applicability given the frequent combined use of corticosteroids and statins in many patients.

Biomechanics - Part II

Bone is a self-repairing structural material, which adapts its material properties and shape in response to a number of factors. Healthy bones do not develop spontaneous fractures during voluntary physical activities of life. However, an imbalance between bone strength and the mechanical loads placed on the bones can lead to bone fractures. Bone health is affected by a number of factors including age, gender, physical activity, systemic diseases, and drug treatment for various diseases. This chapter will discuss bone design as it relates to fracture resistance and locomotion, fracture prediction techniques, and fracture prevention.

Polyethylene glycol improves elution properties of polymethyl methacrylate bone cements

BACKGROUND Bone cements are used as adjuncts to fracture fixation methods and can also function as a local drug delivery system. The ability to elute drugs makes bone cement a promising and powerful chemotherapy treatment modality for osseous tumors. However, because of poor elution rates, the clinical application of this drug delivery mode remains challenging. Soluble fillers, such as sugars, salts, or biocompatible polymers, offer a solution to improve elution rates. This study quantified the effect of polyethylene glycol (PEG) on the elution properties of three commercially available bone cements. METHODS Two grams of Vertebroplastic, Palacos, and Confidence bone cement powder containing three concentrations (0%, 20%, or 50%) of PEG filler were hand mixed with 10 mg of methotrexate. This powder mixture was then polymerized with 1.0 mL of the cement specific liquid monomer. The cylindrical elution samples were placed in saline solution and methotrexate elution was recorded for 720 h. RESULTS The cumulative and daily elution rate increased as the concentration of PEG increased for each bone cement. However, the percent of increase depended on the bone cement used. Cumulative methotrexate elution increased by 40%-54% in case of the highest PEG filler concentration when compared with controls. CONCLUSIONS PEG soluble filler offers a promising method for improving methotrexate drug elution in bone cement. Future studies need to optimize the PEG and bone cement ratio that produces the greatest drug elution profile without sacrificing the biomechanical properties of bone cement.

A Comparison of Three C-Arm Draping Techniques to Minimize Contamination of the Surgical Field.

Summary: The use of intraoperative fluoroscopy has become a routine and useful adjunct within orthopaedic surgery. However, the fluoroscopy machine may become an additional source of contamination in the operating room, particularly when maneuvering from the anterior–posterior position to the lateral position. Consequently, draping techniques were developed to maintain sterility of the operative field and surgeon. Despite a variety of methods, no studies exist to compare the sterility of these techniques specifically when the fluoroscopy machine is in the lateral imaging position. We evaluated the sterility of 3 c-arm draping techniques in a simulated operative environment. The 3 techniques consisted of a traditional 3-quarter sterile sheet attached to the side of the operative table, a modified clip-drape method, and a commercially available sterile pouch. Our study demonstrated that the traditional method poses a high risk for sterile field contamination, whereas the modified clip-drape method and commercially available sterile pouch kept floor contamination furthest from the surgical field. With the current data, we urge surgeons to use modified techniques rather than the traditional draping method.

A Trip to the Dentist

The fluoridation of water in many US communities is estimated to have saved between

Science, Pseudoscience, and Not Science: How Do They Differ?

16 and

Tissue Engineering: Growing Replacement Human Tissue in the Lab

19 per person per year [1]. The cumulative effects of these savings, measured against an average per person annual cost of

Stockinette Application Over a Non-Prepped Foot Risks Proximal Contamination

0.50 per person, are enormous. And yet, in the past few years, several communities are discontinuing water fluoridation, with some politicians arguing that the introduction of fluoride should be a personal and individual decision, not one made by government [2]. Now, fluoridation has joined other hot-button topics in the debate about government’s role in healthcare policy.

The impact of enoxaparin administration in relationship to hemorrhage in mild traumatic brain injury

Many news stories related to health and the environment introduce and describe scientific concepts which may be unfamiliar to the reader. Often, the stories draw conclusions based on the scientific or technical concepts that were presented, with the result that the reader is left to rely on a correct interpretation of the concept by the writer. Similarly, many marketing and advertising claims for health-related products rely on anecdotal evidence, rather than on the outcomes of controlled research.