Cardioprotection with phosphodiesterase-5 inhibition--a novel preconditioning strategy

Phosphodiesterase type-5 (PDE-5) inhibitors including sildenafil, vardenafil and tadalafil are a new class of vasoactive drugs that have been developed for treatment of erectile dysfunction in patients. A growing number of studies in recent years suggest that sildenafil may be used clinically for treatment of pulmonary hypertension and endothelial dysfunction. In addition, recent studies primarily from our laboratory suggested that sildenafil has preconditioning-like powerful cardioprotective effect in the animal models of ischemia-reperfusion injury. Sildenafil has been found to exert cardioprotection through nitric oxide generated from endothelial and/or inducible nitric oxide synthases and opening of mitochondrial ATP-sensitive potassium channels. Future demonstration of the cardioprotective effect in patients with the relatively safe and effective FDA-approved PDE-5 inhibitors, such as sildenafil, could have an enormous impact on bringing the long-studied phenomena of ischemic and pharmacologic preconditioning to the clinical forefront.     

Dual release kinetics in a single dosage from core–shell hydrogel scaffolds

The development of drug delivery systems with microencapsulated therapeutic agents is a promising approach to the sustained and controlled delivery of various drug molecules. The incorporation of dual release kinetics to such delivery devices further adds to their applicability. Herein, novel core–shell scaffolds composed of sodium deoxycholate and trishydroxymethylaminomethane (NaDC–Tris) have been developed with the aim of delivering two different drugs with variable release rates using the same delivery vehicle. Data obtained from XRD studies, sol–gel transition temperature measurement, rheology and fluorescence studies of the core–shell systems indicate a significant alteration in the core and the shell microstructural properties in a given system as compared to the pure hydrogels of identical compositions. The release of the model drugs Fluorescein (FL) and Rhodamine B (RhB) from the shell and the core, respectively, of the two core–shell designs studied exhibited distinctly different release kinetics. In the 25@250 core–shell system, 100% release of FL from the shell and 19% release of RhB from the core was observed within the first 5 hours, while 24.5 hours was required for the complete release of RhB from the core. For the 100@250 system, similar behaviour was observed with varied release rates and a sigmoidal increase in the core release rate upon disappearance from the shell. Cell viability studies suggested the minimal toxicity of the developed delivery vehicles towards NMuMG and WI-38 cells in the concentration range investigated. The reported core–shell systems composed of a single low molecular weight gelator with dual release kinetics may be designed as per the desired application for the consecutive release of therapeutic agents as required, as well as combination therapy commonly used to treat diseases such as diabetes and cancer.

A single LMW gelator based core–shell hydrogel with dual release kinetics.     

Cervical spine magnetic resonance imaging in primary care consulters with shoulder pain: a case control study

OBJECTIVES: To investigate the association between shoulder region pain presenting in primary care and cervical spine magnetic resonance imaging (MRI) abnormalities. METHODS: A matched case-control study of 48 pairs of participants. Patients had presented to primary care with a new episode of shoulder pain. Controls had no history of pain in the shoulder region and were individually matched with cases by age, gender and referring clinician. All participants underwent a structured clinical assessment and cervical spine MRI. Scans were scored by experienced musculoskeletal radiologists blinded to case-control status. RESULTS: Median age of participants was 51 years (range 19-79) and 21 (44%) were female. "Neck pain in the past week" was reported by 25 (52%) cases and seven (15%) controls (odds ratio, OR, 10.0; 95% confidence interval, CI, 2.4, 88.2). Cervical spine MRI from C3/4 to C6/7 revealed: 18 (38%) of both cases and controls had disc height loss >/=50% at any level; 10 (21%) cases and eight (17%) controls had disc disease with neural compromise; 11 (23%) cases and 16 (33%) controls had foraminal stenosis; nine (19%) of both cases and controls had canal narrowing. At least one of the above findings was present in 24 (50%) cases and 23 (48%) controls (OR 1.1; 95% CI 0.4, 3.4). CONCLUSIONS: Cervical spine MRI abnormalities were similar in both cases and controls, despite significantly more self-reported neck pain in cases with shoulder pain. Other possible mechanisms, such as muscular strain or postural problems, may explain the observed clinical association between shoulder region pain and neck associated symptoms.