PubMed HealthSearch

Biomedical subjects

S Attia

Publications and source records attributed to S Attia.

12 recordsLinked to original sources

A spermine-deoxycholic acid conjugate based lipid as a transfecting agent.

Deoxycholic acid-spermine conjugate (DAS), which is composed of natural components (deoxycholic acid and spermine), was incorporated in liposomes and evaluated for its interaction with plasmid DNA (pDNA) and in vitro transfection efficiency. Electromicrographs demonstrated that DAS-pDNA complexes are spherical, compact and electronically dense compared to the toroidal shapes formed by the monovalent lipid 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) and pDNA. In comparison to the singly charged, non-cholesterol based lipid (DOTAP), the multivalent lipid DAS had similar transfection efficiency in two cell lines. The monovalent sterol, deoxycholic acid propyldiamine conjugate (DAP) was not effective as a transfecting agent. This suggests that multivalent facial amphiphiles such as DAS may serve as excellent candidates for non-viral gene transfer and warrant further study.

Animals

In vitro myotoxicity of selected cationic macromolecules used in non-viral gene delivery.

PURPOSE: Cationic lipid/DNA complexes have been proposed as a method of in vivo gene delivery via intravenous or intramuscular injection. A concern with using these polycationic molecules is whether they are associated with tissue toxicity at the injection site. Therefore, the objective of these studies was to investigate the myotoxic potential of selected non-viral gene delivery macromolecules (e.g., cationic lipids and polymers) with and without plasmid DNA (pDNA) in vitro. METHODS: Myotoxicity was assessed by the cumulative release of creatine kinase (CK) over 90 minutes from the isolated rodent extensor digitorum longus muscle into a carbogenated balanced salt solution (BBS, pH 7.4, 37 degrees C) following a 15 microL injection of the test formulation. Phenytoin (Dilantin) and normal saline served as positive and negative controls, respectively. RESULTS: The myotoxicity of plasmid DNA (pDNA, approximately 5000bp, 1 mg/ml) was not statistically different from normal saline. However, the myotoxicity of Dilantin was 16-times higher than either normal saline or pDNA (p < 0.05). Cationic liposomes were found to be less myotoxic than polylysine and PAMAM dendrimers. Polylysine's myotoxicity was found to be dependent upon concentration and molecular weight. The myotoxicity of formulations of cationic liposomes(s), lower molecular weight polylysine (25,000) and higher concentration of PAMAM dendrimers with pDNA were found to be statistically less significant than those formulations without pDNA. CONCLUSIONS: The cationic liposomes were less myotoxic compared to the dendrimers and polylysine. Myotoxicity was dependent upon the type of cationic lipid macromolecule, concentration, molecular weight and the presence of pDNA. A possible explanation for this reduced tissue damage in cationic lipids complexed with pDNA is that the formation of complex reduces the overall positive charge of the injectable system resulting in less damage.

Animals

Nonemergent forcible medication in an acute hospital.

Nonemergent forcible medication is a controversial procedure that has received somewhat less study in acute hospitals and in states where a simple in-house "treatment-driven" clinical review procedure is followed. We reviewed the charts of all patients so medicated by the New Jersey "Rennie" process on a large general acute adult psychiatric service, finding 43 (3%) of 1420 admitted patients so treated. Compared with a population of next-admitted individuals, these "Rennie" patients more frequently had previously required extended emergent forcible medication, had significantly longer hospitalizations (70 versus 26 days), not accounted for by the duration of treatment refusal, but improved with treatment so that almost all were discharged directly back to the community. Rennie patients appeared more likely to be diagnosed with schizophrenia and were significantly more likely to have a known history of assault, threatened assault, or property damage, but significantly less likely to have a known history of suicide threat or attempt. They were also significantly less likely to have a principal or secondary diagnosis of personality disorder or substance use disorder.

Adult

HLA-antigens in Guillain-Barré syndrome.

A microlymphocytotoxicity test determined serologically the frequency of HLA antigens in 32 patients with Guillain-Barré syndrome and in 234 healthy control subjects. The results demonstrated significantly increased frequencies of A3 and B8. The relative risk was estimated to be 9.6 and 4.6 for the A3 and B8 antigens, respectively. Study of the gametic association revealed weak positive linkage disequilibrium and biological association. The results are discussed, and it is concluded that the aberrant genetic make-up of the patients makes them more susceptible to develop the syndrome after exposure to the environmental factor(s).

Child