a-facile-efficient-approach-for-production-reversible-disulfide-cross

A Facile and Efficient Approach for the Production of Reversible Disulfide Cross-linked Micelles

Nanomedicine is an emerging form of therapy that harnesses the unique properties of particles that are nanometers in scale for biomedical application. ...

University of California, Davis

Intertrochanteric fractures are a significant orthopaedic burden. The aim of this study was to assess how the Percutaneous Compression Plate (PCCP) technique performs compared to the traditional dynamic hip screw (DHS). A meta-analysis of all head to head trials (1995-2006) comparing the two techniques was performed. Early mortality (< or = 1 year) was the major outcome of interest. Secondary outcomes of interest included operation time (minutes), blood transfusion requirements, post-operative infection and length of stay in hospital (days). There was a decreased trend in overall mortality in the PCCP group [CI 0.84, (0.48 to 1.47), Chi-square = 1.36, p = 0.51]. Similar trends favouring the PCCP technique were seen with the other outcomes. PCCP being a relatively new technique has the potential to become the gold standard in the repair of intertrochanteric hip fractures. However, owing to the limitations of this meta-analysis, a large randomised controlled trial is required.

The percutaneous compression plate versus the dynamic hip screw: a meta-analysis.

Spindle cell lipomas (SCLs) are a group of benign lipogenic tumours, typically arising in the posterior neck, upper back and shoulder of elderly male patients. Approximately 80% of these tumours arise in characteristic location, but 20% arise in unusual locations, thereby making these cases more difficult to diagnose. We present a case of SCL occurring in the right periorbital region of a 14-year-old boy. The MRI was suggestive of possible malignancy. Diagnosis of neurofibroma was made on incisional biopsy. However, the histopathological and immunohistochemical analyses of the excised lesion confirmed the diagnosis of SCL.

Spindle cell lipoma.

Structural modifications of nonsteroidal anti-inflammatory drugs (NSAIDs) have successfully reduced the side effect of gastrointestinal ulceration without affecting anti-inflammatory activity, but they may increase the risk of myocardial infarction with chronic use. The fact that nitroxyl (HNO) reduces platelet aggregation, preconditions against myocardial infarction, and enhances contractility led us to synthesize a diazeniumdiolate-based HNO-releasing aspirin and to compare it to an NO-releasing analogue. Here, the decomposition mechanisms are described for these compounds. In addition to protection against stomach ulceration, these prodrugs exhibited significantly enhanced cytotoxcity compared to either aspirin or the parent diazeniumdiolate toward nonsmall cell lung carcinoma cells (A549), but they were not appreciably toxic toward endothelial cells (HUVECs). The HNO-NSAID prodrug inhibited cylcooxgenase-2 and glyceraldehyde 3-phosphate dehydrogenase activity and triggered significant sarcomere shortening on murine ventricular myocytes compared to control. Together, these anti-inflammatory, antineoplasic, and contractile properties suggest the potential of HNO-NSAIDs in the treatment of inflammation, cancer, or heart failure.

Synthesis and chemical and biological comparison of nitroxyl- and nitric oxide-releasing diazeniumdiolate-based aspirin derivatives.

Aneurysmal bone cysts are rare benign lesions of bone tissue. They are composed of vascular spaces blood-filled and surrounded by fibrous tissue septa. They are considered as pseudo cysts because of lack of epithelial lining. Here, we describe a giant case of ABC in 12-year-old female child having a massive swelling over the right side of the mandible treated with segmental resection and reconstruction with a reconstruction plate. Case is also discussed with the review of literature.

Giant aneurysmal bone cyst of the mandible: A case report and review of literature.

Nitroxyl (HNO) donors have been shown to elicit a variety of pharmacological responses, ranging from tumoricidal effects to treatment of heart failure. Isopropylamine-based diazeniumdiolates have been shown to produce HNO on decomposition under physiological conditions. Herein, we report the synthesis and HNO release profiles of primary alicyclic amine-based diazeniumdiolates. These compounds extend the range of known diazeniumdiolate-based HNO donors. Acetoxymethyl ester-protected diazeniumdiolates were also synthesized to improve purification and cellular uptake. The acetoxymethyl derivative of cyclopentylamine diazeniumdiolate not only showed higher cytotoxicity toward cancer cells as compared to the parent anion but was also effective in combination with tamoxifen for targeting estrogen receptor α-negative breast cancer cells.

Analysis of the HNO and NO donating properties of alicyclic amine diazeniumdiolates.

Diazeniumdiolate-based aspirin prodrugs have previously been shown to retain the anti-inflammatory properties of aspirin while protecting against the common side effect of stomach ulceration. Initial analysis of two new prodrugs of aspirin that also release either nitroxyl (HNO) or nitric oxide (NO) demonstrated increased cytotoxicity toward human lung carcinoma cells compared to either aspirin or the parent nitrogen oxide donor. In addition, cytotoxicity was significantly lower in endothelial cells, suggesting cancer-specific sensitivity. To assess the chemotherapeutic potential of these new prodrugs in treatment of breast cancer, we studied their effect both in cultured cells and in a nude mouse model. Both prodrugs reduced growth of breast adenocarcinoma cells more effectively than the parent compounds while not being appreciably cytotoxic in a related nontumorigenic cell line (MCF-10A). The HNO donor also was more cytotoxic than the related NO donor. The basis for the observed specificity was investigated in terms of impact on metabolism, DNA damage and repair, apoptosis, angiogenesis and metastasis. The results suggest a significant pharmacological potential for treatment of breast cancer.

Gaurav Bharadwaj

Department of Biochemistry & Molecular Medicine

University of California, Davis

A Facile and Efficient Approach for the Production of Reversible Disulfide Cross-linked Micelles