Preferential liver gene expression with polypropylenimine dendrimers.

Previously, the lower generation (DAB 8-generation 2 and DAB 16-generation 3) polypropylenimine dendrimers have been shown to be effective gene delivery systems in vitro. In the current work, we sought to: (a) test the effect of the strength of the carrier, DNA electrostatic interaction on gene transfer and (b) to study the in vivo gene transfer activity of these low molecular weight (<1687 Da) non-amphiphilic plain and quaternary ammonium gene carriers. Towards this aim, methyl quaternary ammonium derivatives of DAB 4 (generation 1), DAB 8, DAB 16 and DAB 32 (generation 4) were synthesised to give Q4, Q8, Q16 and Q32, respectively. Quaternisation of DAB 8 proved to be critical in improving DNA binding, as evidenced by data from the ethidium bromide exclusion assay and dendrimer-DNA colloidal stability data. This improved colloidal stability had a major effect on vector tolerability, as Q8-DNA formulations were well tolerated on intravenous injection while a similar DAB 8-DNA dose was lethally toxic by the same route. Quaternisation also improved the in vitro cell biocompatibility of DAB 16-DNA and DAB 32-DNA dendrimer complexes by about 4-fold but not that of the lower generation DAB 4-DNA and DAB 8-DNA formulations. In contrast to previous reports with non-viral gene delivery systems, the intravenous administration of DAB 16-DNA and Q8-DNA formulations resulted in liver targeted gene expression as opposed to the lung targeted gene expression obtained with the control polymer-Exgen 500 [linear poly(ethylenimine)] and a lung avoidance hypothesis is postulated. We conclude that the polypropylenimine dendrimers are promising gene delivery systems which may be used to target the liver and avoid the lung and also that molecular modifications conferring colloidal stability on gene delivery formulations have a profound effect on their tolerability on intravenous administration.     

Association between stroke and acute myocardial infarction and its related risk factors: hypertension and diabetes.

OBJECTIVE: The aim of this study was to find the association between stroke, acute myocardial infarction (AMI) and assess related risk factors such as diabetes, hypertension and atrial fibrillation. METHODS: This is a cohort study with prospective and retrospective outcomes. All patients who were hospitalised in Hamad General Hospital, Hamad Medical Corporation with stroke from January 1999 to December 2003 were included. The diagnostic classification of stroke and associated risk factors were made in accordance with the International Classification of Disease 9th revision. RESULTS: Total 377 stroke patients were treated during the five years period. The average annual incidence of stroke for 5 years was 11.7 per 100,000 population. The incidence of AMI was higher in males than in females (73.5% vs 26.5%). There was a significant difference in stroke patients with AMI in respect of their gender (p<0.001). CONCLUSION: The present study supports the hypothesis that there is a strong association between stroke, AMI and related risk factors such as diabetes, hypertension and other cardiovascular disease risk factors. Furthermore, present study showed that 60% of stroke patients had AMI and nearly 46.4% of stroke patients had diabetes mellitus.     

The role of exercise in type II diabetes mellitus

A number of studies have demonstrated a beneficial effect of regular physical activity on levels of HgbA₁C in patients with type II diabetes mellitus, largely due to an increase in insulin sensitivity. Benefits are related to short term improvements in insulin sensitivity following individual exercise bouts. Regular exercise can prevent or delay the onset of type II diabetes in high risk populations. The insulin resistant state is associated with a cluster of cardiovascular risk factors all of which improve with regular physical activity. Because of the high incidence of occult coronary disease, patients need a cardiovascular evaluation when initiating an exercise program. High intensity exercise may result in retinal hemorrhage and transient worsening of diabetic proteinuria. The most common complication is hypoglycemia. A combination of aerobic and light resistance exercise is appropriate. Patients should exercise a minimum of three times a week for 30–60 minutes at 50% to 75% of their Vo_2max.     

A rare initial presentation of a thymic neuroendocrine tumor as Cushing's syndrome

While evaluating the cause of Cushing''s syndrome, biochemical confirmation should be sought first as imaging studies might misdirect the diagnosis toward the wrong problem. One of the rare secondary causes that should be kept in mind while evaluating Cushing''s syndrome is the thymic neuroendocrine tumor.