Osteotomy Healing in Children With Osteogenesis Imperfecta Receiving Bisphosphonate Treatment

A decade ago our group had reported that osteotomy healing was commonly delayed in children with moderate to severe osteogenesis imperfecta (OI) who were treated with intravenous pamidronate infusions. We subsequently maintained a bisphosphonate infusion–free interval of 4 months after osteotomy and changed the surgical approach (use of an osteotome instead of a power saw). In addition, zoledronic acid has become the standard intravenous bisphosphonate for treatment of OI at our institution. In the present study, we compared osteotomy healing before and after these changes were instituted. We evaluated bone healing post‐osteotomy on standard radiographs after 261 intramedullary rodding procedures involving osteotomies (139 femur, 112 tibia) in 110 patients (age at surgery 1.2 to 20.4 years). Delayed healing was diagnosed when the osteotomy line was visible 12 months after the event. We observed delayed bone healing after 48 of the 114 osteotomies (42%) performed with the new approach, and in 106 of the 147 osteotomies (72%) using the previous approach (p = 0.001). The odds for delayed osteotomy healing were significantly lower with the new approach even after adjustment for age, sex, height Z‐score, weight Z‐score, OI type, and bone involved (odds ratio = 0.17; 95% confidence interval 0.16–0.47). Thus, delayed osteotomy healing occurred less frequently in the past 10 years than in the decade before that. It is likely that this improved result is attributable to the implemented changes in both medical and surgical management. © 2015 American Society for Bone and Mineral Research.     

Nanosensors for diagnosis with optical,electric and mechanical transducers

Nanosensors with high sensitivity utilize electrical, optical, and acoustic properties to improve the detection limits of analytes. The unique and exceptional properties of nanomaterials (large surface area to volume ratio, composition, charge, reactive sites, physical structure and potential) are exploited for sensing purposes. High-sensitivity in analyte recognition is achieved by preprocessing of samples, signal amplification and by applying different transduction approaches. In this review, types of signals produced and amplified by nanosensors (based on transducers) are presented, to sense exceptionally small concentrations of analytes present in a sample. The use of such nanosensors, sensitivity and selectivity can offer different advantages in biomedical applications like earlier detection of disease, toxins or biological threats and create significant improvements in clinical as well as environmental and industrial outcomes. The emerging discipline of nanotechnology at the boundary of life sciences and chemistry offers a wide range of prospects within a number of fields like fabrication and characterization of nanomaterials, supramolecular chemistry, targeted drug supply and early detection of disease related biomarkers.

Nanosensors with high sensitivity utilize electrical, optical, and acoustic properties to improve the detection limits of analytes.     

Polypharmacy and falls in older people: Balancing evidence-based medicine against falls risk

The term polypharmacy has negative connotations due to its association with adverse drug reactions and falls. This spectrum of adverse events widens when polypharmacy occurs among the already vulnerable geriatric population. To date, there is no consensus definition of polypharmacy, and diverse definitions have been used by various researchers, the most common being the consumption of multiple number of medications. Taking multiple medications is considered a risk factor for falls through the adverse effects of drug–drug or drug–disease interactions. Falls studies have determined that taking ≥ 4 drugs is associated with an increased incidence of falls, recurrent falls, and injurious falls. In light of existing evidence, careful and regular medication reviews are advised to reduce the effect of polypharmacy on falls. However, intervention studies on medication reviews and their effectiveness on falls reduction have been scarce. This article reviews and discusses the evidence behind polypharmacy and its association with falls among older individuals, and highlights important areas for future research.     

Clavanin A Improves Outcome of Complications from Different Bacterial Infections

The rapid increase in the incidence of multidrug-resistant infections today has led to enormous interest in antimicrobial peptides (AMPs) as suitable compounds for developing unusual antibiotics. In this study, clavanin A, an antimicrobial peptide previously isolated from the marine tunicate Styela clava, was selected as a purposeful molecule that could be used in controlling infection and further synthesized. Clavanin A was in vitro evaluated against Staphylococcus aureus and Escherichia coli as well as toward L929 mouse fibroblasts and skin primary cells (SPCs). Moreover, this peptide was challenged here in an in vivo wound and sepsis model, and the immune response was also analyzed. Despite displaying clear in vitro antimicrobial activity toward Gram-positive and -negative bacteria, clavanin A showed no cytotoxic activities against mammalian cells, and in acute toxicity tests, no adverse reaction was observed at any of the concentrations. Moreover, clavanin A significantly reduced the S. aureus CFU in an experimental wound model. This peptide also reduced the mortality of mice infected with E. coli and S. aureus by 80% compared with that of control animals (treated with phosphate-buffered saline [PBS]): these data suggest that clavanin A prevents the start of sepsis and thereby reduces mortality. These data suggest that clavanin A is an AMP that could improve the development of novel peptide-based strategies for the treatment of wound and sepsis infections.     

Alendronate PLGA microspheres with high loading efficiency for dental applications

Purpose: Alendronate sodium, used systemically as a bone protective agent, proved to also be effective locally in various dental bone applications. Development of alendronate-loaded microspheres with high loading efficiency for such applications would be greatly challenged by the hydrophilicity and low MW of the drug. The aim of this study was to incorporate alendronate sodium, into poly (lactide-co-glycolide) (PLGA) microspheres (MS) with high loading efficiency.

Methods: Three multiple emulsion methods: water-in-oil-in-water (W/O/W), water-in-oil-in-oil (W/O₁/O₂) and solid-in-oil-in-oil (S/O₁/O₂) were tested. In addition to entrapment efficiency, MS were characterized for surface morphology, particle size, in vitro drug release and in vitro degradation of the polymer matrix. Alendronate microspheres with maximum drug loading and good overall in vitro performance were obtained using the W/O₁/O₂ emulsion technique.

Results: Drug release from the microspheres exhibited a triphasic release pattern over a period of 13 days, the last fast release phase being associated with more rapid degradation of the PLGA matrix.

Conclusions: Biocompatible, biodegradable PLGA microspheres incorporating alendronate sodium with high loading efficiency obtained in this study may offer promise as a delivery system for bisphosphonates in dental and probably other clinical applications.     

Group-Based Differences in Anti-Aging Bias Among Medical Students

Medical students (MS) may develop ageist attitudes early in their training that may predict their future avoidance of caring for the elderly. This study sought to determine MS’ patterns of explicit and implicit anti-aging bias, intent to practice with older people and using the quad model, the role of gender, race, and motivation-based differences. One hundred and three MS completed an online survey that included explicit and implicit measures. Explicit measures revealed a moderately positive perception of older people. Female medical students and those high in internal motivation showed lower anti-aging bias, and both were more likely to intend to practice with older people. Although the implicit measure revealed more negativity toward the elderly than the explicit measures, there were no group differences. However, using the quad model the authors identified gender, race, and motivation-based differences in controlled and automatic processes involved in anti-aging bias.     

DNA histochemical analysis in oral squamous cell carcinoma

BACKGROUND: Recent years have witnessed an increasing emphasis on the role of nuclear DNA and its application in experimental pathological diagnosis to predict prognosis and management of certain neoplasm. AIMS: to establish objective criteria for the degree of differentiation and histochemical quantitative of nuclear DNA of oral squamous cell carcinoma (OSCC) using microspectrophotometric analysis. MATERIAL AND METHODS: The study was conducted on histologic materials from patient with OSCC. Two histological grading systems were used; Broder's and invasive front grading system were recorded. Microspectrophotometry was applied on Feulgen-stained sections to determine the quality of tumour nuclear DNA content in two different histological grading systems of OSCC. RESULTS: Nuclear DNA content increased significantly with decreasing tissue differentiation as well with increasing tumour size. CONCLUSION: The grading system and DNA content provides more objective and accurate criteria which relate the morphologic finding to biologic activity and growth patterns of oral cancer as compared to histologic differentiation alone.     

The pattern of immune cell infiltration in chromoblastomycosis: involvement of macrophage inflammatory protein-1 alpha/CCL3 and fungi persistence

Chromoblastomycosis (CR) is a subcutaneous chronic mycosis characterized by a granulomatous inflammatory response. However, little is known regarding the pattern of leukocyte subsets in CR and the pathways involved in their recruitment. The objective of this study was to assess the cellular subsets, chemokine, chemokine receptors and enzymes in CR. The inflammatory infiltrate was characterized by immunohistochemistry using antibodies against macrophages (CD68), Langerhans'cells (S100), lymphocytes (CD3, CD4, CD8, CD45RO, CD20 and CD56) and neutrophils (CD15). The expression of MIP-1alpha (Macrophage inflammatory protein-1alpha), chemokine receptors (CXCR3 and CCR1) and enzymes (superoxide dismutase-SOD and nitric oxide synthase-iNOS) was also evaluated by the same method. We observed an increase in all populations evaluated when compared with the controls. Numbers of CD15(+) and CD56(+) were significantly lower than CD3(+), CD4(+), CD20(+) and CD68(+) cells. Statistical analysis revealed an association of fungi numbers with CD3, CD45RO and iNOS-positive cells. Furthermore, MIP-1alpha expression was associated with CD45RO, CD68, iNOS and CXCR3. Our results suggest a possible role of MIP-1alpha and fungi persistence in the cell infiltration in CR sites.     

Hepatitis C therapy—the future looks bright

Hepatitis C virus (HCV) infections affect about 170 million individuals worldwide and can be life-threatening if left untreated. Over the past three decades, ribavirin and interferon-α have remained the only available medicines for treating hepatitis C sufferers. Given that this combination therapy is partially effective at best and is associated with severe side-effects, there is an unmet need for new molecular entities which inhibit HCV replication. By employing a combination of structure-based drug design together with high-throughput screening approaches, several pharmaceutical companies have been successful in identifying potentially useful compounds for treating HCV infections. This article provides an overview of some of the small-molecule inhibitors that have shown promise so far in clinical trials and which could reach the clinic within the next three years.     

Measurement of Serum N-Acetyl ß Glucosaminidase Activity in Patients with Breast Cancer

N-acetyl-β-glucosaminidase (NAG) activity measured in sera from 129 breast cancer patients was elevated (mean 18.2 units/l) compared with that in sera from 28 healthy women (11.6 units/l) (p=0.001). There was a weak correlation between NAG activity and carcinoembryonic antigen (CEA) and CA-153, but no relationship to age, menopausal status, node status, stage, histology of tumour or to steroid receptors. NAG, CEA and CA-153 were measured in periodic follow-up samples taken after surgery (up to 26 months) from 17 patients. NAG activity fluctuated within a narrow range, unlike CEA and CA-153. In 70% of cases the pattern was similar to at least one of the other markers, and was generally maintained at a higher level in patients who suffered relapse compared with those who remained disease-free up to the last follow-up, but was not significantly altered before relapse. The measurement of NAG activity is unlikely to be of value in predicting time or occurrence of relapse or of clinical utility in post-surgical therapy. Increased appearance in serum may aid metastasis by degrading the extracellular matrix and it may be better investigated as a predictor of progression from in situ to invasive and metastatic cancer.