Gene Transfer into the Lung by Nanoparticle Dextran-Spermine/Plasmid DNA Complexes

A novel cationic polymer, dextran-spermine (D-SPM), has been found to mediate gene expression in a wide variety of cell lines and in vivo through systemic delivery. Here, we extended the observations by determining the optimal conditions for gene expression of D-SPM/plasmid DNA (D-SPM/pDNA) in cell lines and in the lungs of BALB/c mice via instillation delivery. In vitro studies showed that D-SPM could partially protect pDNA from degradation by nuclease and exhibited optimal gene transfer efficiency at D-SPM to pDNA weight-mixing ratio of 12. In the lungs of mice, the levels of gene expression generated by D-SPM/pDNA are highly dependent on the weight-mixing ratio of D-SPM to pDNA, amount of pDNA in the complex, and the assay time postdelivery. Readministration of the complex at day 1 following the first dosing showed no significant effect on the retention and duration of gene expression. The study also showed that there was a clear trend of increasing size of the complexes as the amount of pDNA was increased, where the sizes of the D-SPM/pDNA complexes were within the nanometer range

Application of comparative genomic hybridization and fluorescence in situ hybridization on human glioma cell lines treated with bis[S-methyl-β-N-(2-furylmethylketone) dithiocarbazato] cadmium(II)

Gliomas are the most common primary tumors which arise from cells of the brain itself rather than metastazing to the brain from another location in the body. It can be slow growing (low grade, grades 1 and 2) or rapidly growing (high grade, grades 3 and 4). For instance, diffuse and fibrillary astrocytomas are divided histopathologically into three grades of malignancy: World Health Organization (WHO) grade II astrocytomas, WHO grade III anaplastic astrocytoma and WHO grade IV glioblastoma multiforme (GBM) (Otto, 2001)

Development of Asymmetric Low Pressure Reverse Osmosis-Surfactants Membrane: Effect of Surfactant Types and Concentration

The effect of surfactants that are cationic (Cetyl trimethylammonium bromide (CTAB)), anionic (Sodium Dodecyl Sulphate (SDS)) and non-ionic (Triton X-100) on performance, morphologies and molecular orientation of Polysulfone (PSF) low pressure reverse osmosis (LPRO) membrane were addressed. The experimental data showed that the increasing of 0.5 wt% in surfactant concentration produced higher pure water permeation (PWP) and flux. At 2.5 wt% of SDS, the LPRO membranes achieved the highest PWP of about  64.42 L/m2 × h while 3.0 wt% of CTAB demonstrated the highest flux of 55.28 L/m2 × h. Analysis from morphological results foundthat the optimal performance at 89.6 % rejection was produced by the membrane with 2 wt% SDS which is a good promoter for the fine morphological structures of the membrane, thus producing fine spectrum of molecular orientation factor

Optimal transfection conditions and the safety profiles of dextran spermine/plasmid DNA as potential gene transfer vector to mouse airway.

The emergence of gene therapy offers a new paradigm to the field of molecular medicine. However, current viral and non-viral gene transfer vectors are not efficient and often restricted by doselimiting toxicity. Thus, generation of a new gene delivery vector, which is efficient and with good safety profile is highly required. In this study, optimal transfection conditions and safety profile a novel biodegradable cationic polymerdextran-spermine (DSPM) in mouse airways were ascertained. The highest level of gene expression in the lungs of BALB/c mice was detected at D-SPM to plasmid DNA (pDNA) weight ratio (w/w) of 16, with 13.5 µg pDNA. No significant induction of pro-inflammatory cytokines in the broncho alveolar lavage fluids was observed, which implies no overt toxicity occurred in the mouse lungs. In short, these results demonstrate that D-SPM has moderate gene transfer efficiency but with acceptable safety profile in the mouse airways

Public Awareness and Practices Towards Self-Medication with Antibiotics Among Malaysian Population: Questionnaire Development and Pilot Testing

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Empagliflozin in Patients with Chronic Kidney Disease

Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m(2) of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m(2) with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to < 10 ml per minute per 1.73 m(2), a sustained decrease in eGFR of & GE;40% from baseline, or death from renal causes) or death from cardiovascular causes. Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P < 0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P=0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups. Conclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo