The effects of surgicel and bone wax hemostatic agents on bone healing: An experimental study

Background:

The biological effects of hemostatic agends on the physiological healing process need to be tested. The aim of this study was to assess the effects of oxidized cellulose (surgicel) and bone wax on bone healing in goats’ feet.

Materials and Methods:

Three congruent circular bone defects were created on the lateral aspects of the right and left metacarpal bones of ten goats. One defect was left unfilled and acted as a control; the remaining two defects were filled with bone wax and surgicel respectively. The 10 animals were divided into two groups of 5 animals each, to be sacrificed at the 3^rd and 5^th week postoperatively. Histological analysis assessing quality of bone formed and micro-computed tomography (MCT) measuring the quantities of bone volume (BV) and bone density (BD) were performed. The results of MCT analysis pertaining to BV and BD were statistically analyzed using two-way analysis of variance (ANOVA) and posthoc least significant difference tests.

Results:

Histological analysis at 3 weeks showed granulation tissue with new bone formation in the control defects, active bone formation only at the borders for surgicel filled defects and fibrous encapsulation with foreign body reaction in the bone wax filled defects. At 5 weeks, the control and surgicel filled defects showed greater bone formation; however the control defects had the greatest amount of new bone. Bone wax filled defects showed very little bone formation. The two-way ANOVA for MCT results showed significant differences for BV and BD between the different hemostatic agents during the two examination periods.

Conclusion:

Surgicel has superiority over bone wax in terms of osseous healing. Bone wax significantly hinders osteogenesis and induces inflammation.     

Mechanisms of action of brain insulin against neurodegenerative diseases

Insulin, a pancreatic hormone, is best known for its peripheral effects on the metabolism of glucose, fats and proteins. There is a growing body of evidence linking insulin action in the brain to neurodegenerative diseases. Insulin present in central nervous system is a regulator of central glucose metabolism nevertheless this glucoregulation is not the main function of insulin in the brain. Brain is known to be specifically vulnerable to oxidative products relative to other organs and altered brain insulin signaling may cause or promote neurodegenerative diseases which invalidates and reduces the quality of life. Insulin located within the brain is mostly of pancreatic origin or is produced in the brain itself crosses the blood-brain barrier and enters the brain via a receptor-mediated active transport system. Brain Insulin, insulin receptor and insulin receptor substrate-mediated signaling pathways play important roles in the regulation of peripheral metabolism, feeding behavior, memory and maintenance of neural functions such as neuronal growth and differentiation, neuromodulation and neuroprotection. In the present review, we would like to summarize the novel biological and pathophysiological roles of neuronal insulin in neurodegenerative diseases and describe the main signaling pathways in use for therapeutic strategies in the use of insulin to the cerebral tissues and their biological applications to neurodegenerative diseases.     

"Triple Trouble" in A Case of Mass Lesion

Bronchogenic carcinoma, the commonest lung tumor occurs more frequently in the elderly with typical symptoms of cough, haemoptysis, weight loss, dyspnoea or chest pain. These symptoms mimic common respiratory infections in en-demic areas like pulmonary tuberculosis. Also, metastasis at presentation itself is common, the favoured sites being liver, contra-lateral lungs, bones, brain, etc., although unusual and rare sites like heart also are known. We herein report a rare association of both carcinoma with active pulmonary tuberculosis in the same lobe associated with intracardiac metastasis. Very few cases have been published describing lung carcinoma with intracardiac metastasis. We hope the documentation of this rare case will shed further light into the subject area and improve clinical education.     

Role of Helicobacter pylori infection in pathogenesis of atherosclerosis

Though a century old hypothesis, infection as a cause for atherosclerosis is still a debatable issue. Epidemiological and clinical studies had shown a possible association but inhomogeneity in the study population and study methods along with potential confounders have yielded conflicting results. Infection triggers a chronic inflammatory state which along with other mechanisms such as dyslipidemia, hyper-homocysteinemia, hypercoagulability, impaired glucose metabolism and endothelial dysfunction, contribute in pathogenesis of atherosclerosis. Studies have shown a positive relations between Cytotoxic associated gene-A positive strains of Helicobacter pylori and vascular diseases such as coronary artery disease and stroke. Infection mediated genetic modulation is a new emerging theory in this regard. Further large scale studies on infection and atherosclerosis focusing on multiple pathogenetic mechanisms may help in refining our knowledge in this aspect.     

Bisphosphonate‐associated osteonecrosis of the jaw: does it occur in children?

Background  Bisphosphonate use in adult patients has been linked to osteonecrosis of the jaw (ONJ). This complication has not been systematically assessed in a paediatric population receiving bisphosphonates.
Objective  To assess our cohort of paediatric patients treated with intravenous bisphosphonate for occurrence of ONJ.
Design  Observational study at a tertiary children's hospital.
Patients  A total of 42 paediatric patients with osteoporosis who received bisphosphonate infusions for a mean of 6·5 years (SD 2·7 years) were assessed clinically and radiographically for possible ONJ. Among 42, 37 patients had received disodium pamidronate 1 mg/kg/dose at a mean cumulative dose of 19·8 mg/kg and zoledronic acid (ZA) 0·05 mg/kg/dose at a mean cumulative dose of 0·49 mg/kg; four had received ZA and one received pamidronate alone. Invasive dental treatment during bisphosphonate treatment, a known risk factor for osteonecrosis, was specifically assessed.
Results  In all patients assessed, including 11 who had invasive dental treatment, there were no cases of osteonecrosis.
Conclusion  ONJ has so far not been demonstrated in this patient group.     

The IL-21 receptor augments Th2 effector function and alternative macrophage activation

The IL-21 receptor (IL-21R) shows significant homology with the IL-4R, and CD4+ Th2 cells are an important source of IL-21. Here we examined whether the IL-21R regulates the development of Th2 responses in vivo. To do this, we infected IL-21R-/- mice with the Th2-inducing pathogens Schistosoma mansoni and Nippostrongylus brasiliensis and examined the influence of IL-21R deficiency on the development of Th2-dependent pathology. We showed that granulomatous inflammation and liver fibrosis were significantly reduced in S. mansoni-infected IL-21R-/- mice and in IL-21R+/+ mice treated with soluble IL-21R-Fc (sIL-21R-Fc). The impaired granulomatous response was also associated with a marked reduction in Th2 cytokine expression and function, as evidenced by the attenuated IL-4, IL-13, AMCase, Ym1, and FIZZ1 (also referred to as RELMalpha) responses in the tissues. A similarly impaired Th2 response was observed following N. brasiliensis infection. In vitro, IL-21 significantly augmented IL-4Ralpha and IL-13Ralpha1 expression in macrophages, resulting in increased FIZZ1 mRNA and arginase-1 activity following stimulation with IL-4 and IL-13. As such, these data identify the IL-21R as an important amplifier of alternative macrophage activation. Collectively, these results illustrate an essential function for the IL-21R in the development of pathogen-induced Th2 responses, which may have relevance in therapies for both inflammatory and chronic fibrotic diseases.     

Prevention of murine antiphospholipid syndrome by BAFF blockade

OBJECTIVE: This study was undertaken to determine whether BAFF blockade can be used to prevent or treat antiphospholipid syndrome in a mouse model. METHODS: Eight- and 12-week-old (NZW x BXSB)F(1) mice were treated with BAFF-R-Ig or TACI-Ig alone or in addition to a short course of CTLA-4Ig. Mice were monitored for thrombocytopenia and proteinuria. Sera were tested for anticardiolipin antibodies (aCL), BAFF levels, and levels of soluble vascular cell adhesion molecule and E-selectin. Mice were killed at 17, 22, or 32 weeks of age, and kidneys and hearts were subjected to histologic examination. Spleen cells were phenotyped and enzyme-linked immunospot assays for autoantibody-producing B cells were performed. RESULTS: Both BAFF-R-Ig and TACI-Ig prevented disease onset and significantly prolonged survival. Treated mice had significantly smaller spleens than controls, with fewer B cells and fewer activated and memory T cells. BAFF blockade did not prevent the development of aCL, and there was only a modest delay in the development of thrombocytopenia. However, treated mice had significantly less nephritis and myocardial infarcts than did controls. CONCLUSION: Our findings suggest that aCL are generated in the germinal center, which is relatively independent of BAFF. Effector function of antiplatelet antibodies was only modestly affected by BAFF blockade. In contrast, myocardial infarctions were prevented, suggesting that triggering of thromboses requires both autoantibodies and mediators of inflammation. Similarly, renal damage requires both immune complexes and effector cells. The dissociation between autoantibody production and inflammation that may occur with B cell-depleting therapies underscores the role of B cells as effector cells in the autoimmune response.