Characterization of the coronary sinus ostium by cardiac magnetic resonance imaging

The diameter and the angle of the coronary sinus (CS) ostium was analyzed in 101 patients who underwent cardiac magnetic resonance imaging and had left ventricular ejection fractions < or =0.35 (n = 40) or > or =0.65 (n = 61). The angle of the CS ostium in patients with LVEFs < or =0.35 was less acute than in patients with LVEFs > or =0.65 (73 degrees +/- 12 degrees vs 65 degrees +/- 10 degrees, p <0.01). There was no statistically significant difference in the diameter of the CS ostium in patients with LVEFs < or =0.35 compared with those with LVEFs > or =0.65 (8 +/- 3 vs 8 +/- 2 mm, p = 0.5). The diameter and the angle of the CS ostium were not different when analyzed on the basis of the duration of the QRS complex, left atrial dimension, or left ventricular end-diastolic dimension. In conclusion, on the basis of cardiac magnetic resonance imaging data, the angle of the CS is less acute in patients with LVEFs < or =0.35 than in those with LVEFs > or =0.65.     

Two sisters with IMAGe syndrome: cytomegalic adrenal histopathology, support for autosomal recessive inheritance and literature review

Adrenal hypoplasia congenita (AHC) is a rare condition and causes primary adrenal insufficiency. X-linked (OMIM 300200) and autosomal recessive (OMIM 240200) forms are recognized. Recently, an association between Intrauterine growth restriction, Metaphyseal dysplasia, Adrenal hypoplasia congenita, and Genital abnormalities (IMAGe syndrome; OMIM 300290) has been described. We present the clinical features of two sisters with intrauterine growth restriction, AHC, and dysmorphic features. Interesting histopathologic findings of one sister are also presented. We suggest that IMAGe syndrome is the most plausible diagnosis and that autosomal recessive inheritance is likely. We analyzed genes that were postulated candidates for IMAGe syndrome (SF1, DAX-1, and STAR), and no mutations were found. Other cases of IMAGe syndrome are reviewed.     

The gamma interferon (IFN-gamma) mimetic peptide IFN-gamma (95-133) prevents encephalomyocarditis virus infection both in tissue culture and in mice

We have demonstrated previously that the C-terminal gamma interferon (IFN-gamma) mimetic peptide consisting of residues 95 to 133 [IFN-gamma(95-133)], which contains the crucial IFN-gamma nuclear localization sequence (NLS), has antiviral activity in tissue culture. Here we evaluate the efficacy of this peptide and its derivatives first in vitro and then in an animal model of lethal viral infection with the encephalomyocarditis (EMC) virus. Deletion of the NLS region from the IFN-gamma mimetic peptide IFN-gamma(95-133) resulted in loss of antiviral activity. However, the NLS region does not have antiviral activity in itself. Replacing the NLS region of IFN-gamma(95-133) with the NLS region of the simian virus 40 large T antigen retains the antiviral activity in tissue culture. IFN-gamma(95-133) prevented EMC virus-induced lethality in mice in a dose-dependent manner compared to controls. Mice treated with IFN-gamma(95-133) had no or low EMC virus titers in their internal organs, whereas control mice had consistently high viral titers, especially in the heart tissues. Injection of B8R protein, which is encoded by poxviruses as a defense mechanism to neutralize host IFN-gamma, did not inhibit IFN-gamma(95-133) protection against a lethal dose of EMC virus, whereas mice treated with rat IFN-gamma were not protected. The data presented here show that the IFN-gamma mimetic peptide IFN-gamma(95-133) prevents EMC virus infection in vivo and in vitro and may have potential against other lethal viruses, such as the smallpox virus, which encodes the B8R protein.     

Effects of orthopaedic wear particles on osteoprogenitor cells

Wear particles from total joint arthroplasties are constantly being generated throughout the lifetime of an implant. Since mesenchymal stem cells and osteoprogenitors from the bone marrow are the precursors of osteoblasts, the reaction of these cells to orthopaedic wear particles is critical to both initial osseointegration of implants and ongoing regeneration of the periprosthetic bed. Particles less than 5 μm can undergo phagocytosis by mature osteoblasts, with potential adverse effects on cellular viability, proliferation and function. The specific effects are dependent on particle composition and dose. Metal and polymer particles in non-toxic doses stimulate pro-inflammatory factor release more than ceramic particles of a similar size. The released factors inhibit markers of bone formation and are capable of stimulating osteoclast-mediated bone resorption. Mesenchymal stem cells and osteoprogenitors are also profoundly affected by wear particles. Titanium and polymethylmethacrylate particles inhibit bone cell viability and proliferation, and downregulate markers of bone formation in a dose- and time-dependent manner. Future studies should delineate the molecular mechanisms by which particles adversely affect mesenchymal stems cells and the bone cell lineage and provide strategies to modulate these effects.     

Characterization of degradation products of amorphous and polymorphic forms of clopidogrel bisulphate under solid state stress conditions

The present study deals with the stress degradation studies on amorphous and polymorphic forms of clopidogrel bisulphate. The objective was to characterize the degradation products and postulate mechanism of decomposition of the drug under solid state stress conditions. For that, amorphous form, polymorph I and polymorph II of the drug were exposed to 40 °C/75% relative humidity (RH), with and without stressors for 3 months. The samples were analyzed by HPLC, and the relative extent of degradation as well as nature of decomposition was compared among three solid forms. In total, eight degradation products were observed under various stress conditions. The structures of all of them were elucidated using LC–MS/TOF and LC–MSⁿ studies. While one matched the known hydrolytic decomposition product of the drug in solution, seven others were new. The postulated degradation pathway and mechanism of decomposition are discussed.     

Hyaluronic Acid/Chitosan-g-Poly(ethylene glycol) Nanoparticles for Gene Therapy: An Application for pDNA and siRNA Delivery

Purpose  

To design hyaluronic acid (HA) and chitosan-g-poly(ethylene glycol) (CS-g-PEG) nanoparticles intended for a broad range of gene delivery applications.