Cationic Lipid-Based Gene Delivery Systems: Pharmaceutical Perspectives

Gene delivery systems are designed to control the location of administered therapeutic genes within a patient's body. Successful in vivo gene transfer may require (i) the condensation of plasmid and its protection from nuclease degradation, (ii) cellular interaction and internalization of condensed plasmid, (iii) escape of plasmid from endosomes (if endocytosis is involved), and (iv) plasmid entry into cell nuclei. Expression plasmids encoding a therapeutic protein can be, for instance, complexed with cationic liposomes or micelles in order to achieve effective in vivo gene transfer. A thorough knowledge of pharmaceutics and drug delivery, bio-engineering, as well as cell and molecular biology is required to design optimal systems for gene therapy. This mini-review provides a critical discussion on cationic lipid-based gene delivery systems and their possible uses as pharmaceuticals.     

Clinicopathological features of bladder cancer associated with chronic exposure to arsenic.

A high incidence of bladder cancer has been documented in an area of chronic arsenic (As) exposure. This study investigates the characteristics of As-associated (n = 49) and other (n = 64) bladder cancers. A higher histological grading was observed for the As-exposed tumours (P = 0.04), but no other difference in pathobiological features or prognosis was found between the two groups.     

A comparative controlled trial of intralesionally-administered zinc sulphate, hypertonic sodium chloride and pentavalent antimony compound against acute cutaneous leishmaniasis

A comparative clinical trial between two newly introduced intralesional treatments for acute leishmaniasis and the established treatment of intralesionally-administered pentavalent antimony compounds was performed. Treatments were allocated randomly to a total of 63 patients who received 2% zinc sulphate, 7% sodium chloride solutions or sodium stibogluconate intralesionally. A number of patients were left without treatment as controls. Patients were followed-up for 45 days, the results showing that the three treatments gave comparable cure rates by the end of the follow-up period. However, zinc sulphate gave a high cure rate (94.8%) usually with a single injection.     

Correlation between the parameters of free-radical lipid peroxidation and antioxidant system in children living in the north

A comparative study of the parameters of free-radical lipid peroxidation and antioxidant system was performed in children living in the North for various time periods. Intense lipid peroxidation was shown to be the key factor in the pathogeneses of several diseases caused by disturbances in the cellular membrane. Decreased resistance of red blood cells to peroxidative hemolysis is a phenomenon characterizing the adaptation-violating processes. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 9, pp. 342–344, September, 1998     

Effect of the dipeptides gly-pro and pro-gly, glycine, and proline on cardiotropic effects of acetylcholine

The dipeptides Gly-Pro and Pro-Gly, glycine, and proline do not affect contractile activity of the Straub cardiac preparation of the frog. Gly-Pro and glycine augment, while Pro-Gly moderates the effects of acetylcholine. The effect of proline was insignificant. Equimolar amino acid mixtures and mixtures of the dipeptides decrease the effects of acetylcholine. Direction and the degree of Gly-Pro effect attests to specific action of this peptide on cardiac activity. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 8, pp. 139–141, August, 1998     

Regulatory mechanisms of growth hormone secretion are sexually dimorphic.

Sexually dimorphic growth hormone (GH) secretory pattern is important in the determination of gender-specific patterns of growth and metabolism in rats. Whether GH secretion in humans is also sexually dimorphic and the neuroendocrine mechanisms governing this potential difference are not fully established. We have compared pulsatile GH secretion profiles in young men and women in the baseline state and during a continuous intravenous infusion of recombinant human insulin-like growth factor I (rhIGF-I). During the baseline study, men had large nocturnal GH pulses and relatively small pulses during the rest of the day. In contrast, women had more continuous GH secretion and more frequent GH pulses that were of more uniform size. The infusion of rhIGF-I (10 microg/kg/h) potently suppressed both spontaneous and growth hormone-releasing hormone (GHRH)-induced GH secretion in men. In women, however, rhIGF-I had less effect on pulsatile GH secretion and did not suppress the GH response to GHRH. These data demonstrate the existence of sexual dimorphism in the regulatory mechanisms involved in GH secretion in humans. The persistence of GH responses to GHRH in women suggests that negative feedback by IGF-I might be expressed, in part, through suppression of hypothalamic GHRH.     

Telespirometry: novel system for home monitoring of asthmatic patients.

OBJECTIVES: To describe a newly developed telespirometry system consisting of a portable spirometer that transmits the lung ventilatory values by telephone from the patient's home to a remote monitoring center and to assess the ability of the telespirometry system to detect early signs of asthmatic deterioration. METHODS: Thirty-nine patients with moderate to severe asthma were monitored with the telespirometry system. The lung function testing and transmission of the spirometric data by telephone from the patient's home to a remote monitoring center were performed according to the patient's judgment. All previous transmissions of the spirometric data were analyzed retrospectively to detect early signs of asthmatic deterioration, which resulted in dispatch of the mobile intensive care unit (MICU) to the patient's home. RESULTS: In 19 patients (49%), analysis of the spirometric data detected early signs of asthmatic deterioration. Analysis of the spirometric data correlated with decisions to dispatch the MICU in 22 of 39 (56%) patients. In patients with severe asthma, the decision was made during oral communication between the patient and the operator and was based on clinical impression rather than functional results. CONCLUSION: Home monitoring of asthmatic patients with the telespirometry system may improve the management of the disease and the quality of life and reduce costly hospitalizations.