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.     

Hippocampus and amygdala morphology in attention-deficit/hyperactivity disorder

CONTEXT: Limbic structures are implicated in the genesis of attention-deficit/hyperactivity disorder (ADHD) by the presence of mood and cognitive disturbances in affected individuals and by elevated rates of mood disorders in family members of probands with ADHD. OBJECTIVE: To study the morphology of the hippocampus and amygdala in children with ADHD. DESIGN: A cross-sectional case-control study of the hippocampus and amygdala using anatomical magnetic resonance imaging. SETTINGS: University research institute. PATIENTS: One hundred fourteen individuals aged 6 to 18 years, 51 with combined-type ADHD and 63 healthy controls. MAIN OUTCOME MEASURES: Volumes and measures of surface morphology for the hippocampus and amygdala. RESULTS: The hippocampus was larger bilaterally in the ADHD group than in the control group (t = 3.35; P < .002). Detailed surface analyses of the hippocampus further localized these differences to an enlarged head of the hippocampus in the ADHD group. Although conventional measures did not detect significant differences in amygdalar volumes, surface analyses indicated the presence of reduced size bilaterally over the area of the basolateral complex. Correlations with prefrontal measures suggested abnormal connectivity between the amygdala and prefrontal cortex in the ADHD group. Enlarged subregions of the hippocampus tended to accompany fewer symptoms. CONCLUSIONS: The enlarged hippocampus in children and adolescents with ADHD may represent a compensatory response to the presence of disturbances in the perception of time, temporal processing (eg, delay aversion), and stimulus seeking associated with ADHD. Disrupted connections between the amygdala and orbitofrontal cortex may contribute to behavioral disinhibition. Our findings suggest involvement of the limbic system in the pathophysiology of ADHD.     

Cognitive impairment but preservation of sexual dimorphism in cognitive abilities in chronic schizophrenia

Neurocognitive impairment in schizophrenia is well established, though sex differences on cognitive tasks have produced equivocal findings. The present study was designed to examine performance of schizophrenia patients on a sexually dimorphic cognitive battery. The cognitive battery comprising tests of spatial (mental rotation, computerized version of the Benton Judgment of Line Orientation) and verbal abilities (phonological and semantic fluency) was administered to men (n = 22) and women (n = 21) with schizophrenia and healthy controls (n = 21 men and 21 women). A series of multivariate analyses showed that the patient group performed worse than controls on all the cognitive tasks. Cognitive sexual dimorphism on all spatial tasks favoring men and verbal tasks favoring women remained. Within the patient sample, correlational data demonstrated that earlier age at onset of illness related to poorer spatial performance. It is concluded that normal sexual dimorphism is undisturbed on both spatial and verbal tasks by the schizophrenia disease process.     

Sociocultural development and validation of lexicon for Asian-Indian individuals who use augmentative and alternative communication

Purpose. Individuals who temporarily or permanently are not able to communicate through use of gestures/signs, speech, and/or written communication mode benefit from the use of augmentative and alternative communication (AAC) systems. Effective communication skills for individuals who use an AAC system depend on appropriate lexicon. This study was designed to develop and validate a socially and culturally appropriate lexicon for Asian-Indians who use AAC.

Method. To this end, 120 individuals from India participated in this study. A composite list of lexical items was identified, using a structured social validation technique involving non-categorical and categorical nominations, and a rating of lexical items from a Picture Communication Symbols (PCS) lexicon.

Results. Data analysis indicated that 88 lexical items from the nomination task were not represented in the PCS lexicon and 247 items were rated as having no value for the Asian-Indian culture.

Conclusions. Findings suggest that while a lexicon from symbol sets developed for one culture might have considerable overlap across cultures, these lexicons may not be appropriate as a source of selecting a lexicon for an AAC user from a culturally and linguistically diverse background. Implications of these findings are discussed for speech-language pathologists and other rehabilitation professionals.     

Engineering functional bladder tissues

Purpose: End stage bladder disease can seriously affect patient quality of life and often requires surgical reconstruction with bowel tissue, which is associated with numerous complications. Bioengineering of functional bladder tissue using tissue‐engineering techniques could provide new functional tissues for reconstruction. In this review, we discuss the current state of this field and address different approaches to enable physiologic voiding in engineered bladder tissues in the near future. Materials and Methods: In a collaborative effort, we gathered researchers from four institutions to discuss the current state of functional bladder engineering. A MEDLINE® and PubMed® search was conducted for articles related to tissue engineering of the bladder, with special focus on the cells and biomaterials employed as well as the microenvironment, vascularisation and innervation strategies used. Results: Over the last decade, advances in tissue engineering technology have laid the groundwork for the development of a biological substitute for bladder tissue that can support storage of urine and restore physiologic voiding. Although many researchers have been able to demonstrate the formation of engineered tissue with a structure similar to that of native bladder tissue, restoration of physiologic voiding using these constructs has never been demonstrated. The main issues hindering the development of larger contractile tissues that allow physiologic voiding include the development of correct muscle alignment, proper innervation and vascularization. Conclusion: Tissue engineering of a construct that will support the contractile properties that allow physiologic voiding is a complex process. The combination of smart scaffolds with controlled topography, the ability to deliver multiple trophic factors and an optimal cell source will allow for the engineering of functional bladder tissues in the near future. Copyright © 2012 John Wiley & Sons, Ltd.