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Duchenne Muscular Dystrophy (DMD) is a severe muscle disorder caused by lack of dystrophin. Predictive biomarkers able to anticipate response to the therapeutic treatments aiming at dystrophin re-expression are lacking. The objective of this study is to investigate Matrix Metalloproteinase-9 (MMP-9) as predictive biomarker for Duchenne. Two natural history cohorts were studied including 168 longitudinal samples belonging to 66 patients. We further studied 1536 samples obtained from 3 independent clinical trials with drisapersen, an antisense oligonucleotide targeting exon 51: an open label study including 12 patients; a phase 3 randomized, double blind, placebo controlled study involving 186 patients; an open label extension study performed after the phase 3. Analysis of natural history cohorts showed elevated MMP-9 levels in patients and a significant increase over time in longitudinal samples. MMP-9 decreased in parallel to clinical stabilization in the 12 patients involved in the open label study. The phase 3 study and subsequent extension study clarified that the decrease in MMP-9 levels was not predictive of treatment response. These data do not support the inclusion of serum MMP-9 as predictive biomarker for DMD patients.

The discovery of parasporin has triggered an interest in examining various Bacillus thuringiensis (Bt) isolates for specific anti-cancer activity. The aim of this study was to determine the potency and specificity of parasporal inclusions from Malaysian mosquitocidal Bt isolates against a leukemic cell line (CEM-SS). The Bt isolates used in this study were identified as having weak to potent larvicidal activity against Aedes aegypti and varying hemolytic activity. The 12 mosquitocidal Bt isolates examined in this study showed low to moderate cytotoxicity when tested against CEM-SS and HeLa. Interestingly the parasporal inclusions of Bt 18 (non-hemolytic isolate), showed therapeutic potential demonstrating specificity for CEM-SS compared to HeLa, whilst being non-cytotoxic to normal T lymphocytes. The mode of cell death by Bt 18 was shown to be initially apoptotic. SDS-PAGE analysis and N-terminal sequencing of the upper and lower bands of Bt 18 showed similarity between Bt 18 parasporal inclusions with Cry 24Aa and 25Aa of Bacillus thuringiensis subsp jegathesan and Cry 15Aa of Bacillus thuringiensis subsp israelensis. Although the BLAST analysis did not show sequence similarity between Bt 18 and Parasporin, we propose that the Bt 18 parasporal inclusions share similar characteristics to Parasporin since Bt 18 is not hemolytic but discriminately cytotoxic towards leukemic cell lines.

The objective of this study is to determine the role of carbohydrates on the toxic effect of parasporal inclusion proteins isolated from Malaysian mosquitocidal Bacillus thuringiensis (Bt) strains on erythrocytes (human and rat). Dose response analyses on the effect of these parasporal inclusions on human and rat erythrocytes suggest that toxin action is selective depending on bacterial strains and source of erythrocytes. Results from this study suggest Bt toxin is a lectin which recognizes specific plasma membrane glycoconjugate receptor(s) with a terminal residue of either D-mannose (Man), N-acetyl-D-galactosamine (GalNAc), N-acetyl-D-glucosamine (GlcNAc) or even a combination of these monosaccharides.

Dermal absorption of chlorpyrifos, an organophosphate insecticide is important because of its use in agriculture and control of household pests. The objectives of this study are to investigate firstly, the biochemical changes in the blood and secondly, histomorphometric changes in the hippocampus of adult mice following dermal application of chlorpyrifos in sub-toxic doses. Male Swiss albino mice (60 days) were segregated into one control and two treated groups (n=10). Chlorpyrifos, diluted with xylene, was applied in doses of 1/2 of LD(50) (E1) and 1/5 of LD(50) (E2) over the tail of mice of the two treated groups, 6 hours daily for 3 weeks. AChE levels in the serum and brain were estimated using a spectrophotometric method (Amplex Red reagent). Coronal serial sections were stained with 0.2 % thionin in acetate buffer and pyramidal neurons of Cornu Ammonis of hippocampus were counted at 400x magnification using Image Pro Express software. At the end of 3 weeks, body weights were reduced significantly in E1 group. Serum AChE concentrations were reduced by 97 % in E1 and 74 % in E2 groups compared to controls. The neurons of CA 3 and CA 1 in the hippocampus showed evidences of morphological damage in both treated groups. Furthermore, the neuronal count was significantly reduced in CA 3 layer of hippocampus in E1 group.

Although rates of blastomycosis in Canada remain low outside of historically endemic areas, the range for Blastomyces now includes Quebec, Manitoba, Saskatchewan, Ontario -- the Kenora area has the highest global rates -- and the eastern US. Changes in climate and land use are hypothesized to be causing the expansion. Although a travel and exposure history remains important to differential diagnosis, cases are increasingly described in patients who have not traveled to traditional endemic areas. Blastomyces grows in soil and decaying vegetative material. Blastomycosis is typically acquired through inhalation of spores from the disrupted environment and, occasionally, through cutaneous inoculation; it does not spread person-to-person. Indigenous people have a higher incidence of disease. Other mammals, including domestic dogs, are susceptible.

Diphtheria is a disease with a range of clinical manifestations and types. It is classified according to both anatomic site of infection and whether it is toxin producing or not. Respiratory diphtheria is caused by toxigenic strains of the gram-positive bacteria C. diphtheriae or, more rarely, by other toxigenic species (C. ulcerans and C. pseudotuberculosis). Initial symptoms of pharyngeal or tonsillar diphtheria typically include fever, pharyngitis, hoarse voice and enlarged cervical lymph nodes, progressing to upper airway obstruction and acute respiratory distress. Two classic signs of toxigenic respiratory diphtheria include a greyish-white membrane on the tonsils and significant swelling of the uvula, tonsils, cervical lymph nodes, anterior neck and submandibular area, resembling a \"bull neck.\" Here, Cholewa et al examine the case of a 69-year-old visitor to Canada with diphtheria.

Poor cardiorespiratory fitness (CRF) is linked to cognitive deterioration, but its effects on lipid heterogeneity and functional properties in older African American (AA) subjects with mild cognitive impairment (MCI) need elucidation. This study determined whether exercise training-induced changes in blood lipid particle sizes (LPS) were associated with CRF determined by VO Max in elderly AAs with MCI. Given the pivotal role of brain-derived neurotrophic factor (BDNF) on glucose metabolism, and therefore, \"diabetic dyslipidemia\", we also determined whether changes in LPS were associated with the levels of serum BDNF. This analysis included 17 of the 29 randomized elderly AAs with MCI who had NMR data at baseline and after a 6-month training. We used Generalized Linear Regression (GLM) models to examine cardiorespiratory fitness (VO Max) effects on training-induced change in LPS in the stretch and aerobic groups. Additionally, we determined whether the level of BDNF influenced change in LPS. Collectively, mean VO Max (23.81±6.17) did not differ significantly between aerobic and stretch groups (difference=3.17±3.56, =0.495). Training-related changes in very low-density lipoprotein, chylomicrons, and total low-density lipoprotein (LDL) particle sizes correlated significantly with VO Max, but not after adjustment for age and gender. However, increased VO Max significantly associated with reduced total LDL particle size after similar adjustments ( = 0.046). While stretch exercise associated with increased protective large high-density lipoprotein particle size, the overall effect was not sustained following adjustments for gender and age. However, changes in serum BDNF were associated with changes in triglyceride and cholesterol transport particle sizes ( < 0.051). Promotion of stretch and aerobic exercise to increase CRF in elderly AA volunteers with MCI may also promote beneficial changes in lipoprotein particle profile. Because high BDNF concentration may reduce CVD risk, training-related improvements in BDNF levels are likely advantageous. Large randomized studies are needed to confirm our observations and to further elucidate the role for exercise therapy in reducing CVD risk in elderly AAs with MCI.

Aspirin is an effective anti-platelet agent with proven benefit in preventing atherothrombotic complications. However, resistance to aspirin is significantly associated with increased risk of death, cerebrovascular accident or myocardial infarction compared with aspirin sensitive patients (24% vs 10%, P=0.03) and is well documented in Western literature. It has hitherto not been established in Sri Lanka. Our aim was to estimate the prevalence of aspirin resistance in patients on low dose aspirin for primary or secondary prophylaxis and to ascertain if patients resistant to aspirin have detectable serum salicylic acid levels (SA).