Poly(ethylene glycol)-modified thiolated gelatin nanoparticles for glutathione-responsive intracellular DNA delivery

Poly(ethylene glycol) (PEG)-modified thiolated gelatin (PEG-SHGel) anoparticles were developed as a long-circulating passively targeted delivery system that responds to intracellular glutathione concentrations to enhance DNA delivery and transfection. Reporter plasmid expressing enhanced green fluorescent protein (EGFP-N1) was encapsulated in the nanoparticles. DNA-containing gelatin (Gel) and thiolated gelatin (SHGel) nanoparticles were found to have a size range of 220 to 250 nm, whereas surface modification with PEG resulted in particles with a slightly larger size range of 310 to 350 nm. PEG modification was confirmed by electron spectroscopy for chemical analysis (ESCA), where an increase in the ether peak intensities of the C1s spectra corresponds to the surface presence of ethylene oxide residues. In addition, the PEG-SHGel nanoparticles released encapsulate plasmid DNA in response to varying concentrations of glutathione (up to 5.0 mM GSH in phosphate-buffered saline, or PBS). The stability of the encapsulated DNA was confirmed by agarose gel electrophoresis. Finally, from the qualitative and quantitative results of in vitro transfection studies in murine fibroblast cells (NIH3T3), PEG-Gel and PEG-SHGel nanoparticles afforded the highest transfection efficiency of the reporter plasmid. The results of these studies show that PEG-modified thiolated gelatin nanoparticles could serve as a very efficient nanoparticulate vector for systemic DNA delivery to solid tumors where the cells are known to have significantly higher intracellular GSH concentrations.     

Management of overactive bladder syndrome

Overactive bladder (OAB) syndrome is the term used to describe the symptom complex of urinary urgency with or without urge incontinence, usually with frequency and nocturia. Drug treatment continues to have an important role in the management of women with OAB. Other treatment options include conservative management with lifestyle interventions, modification of fluid intake, and physiotherapy including bladder retraining. Surgery remains the last resort in the treatment and is usually reserved for intractable detrusor overactivity, as it is associated with significant morbidity. This article reviews the management of the overactive bladder with specific focus on newer developments in the medical treatment of OAB in women.     

An initial pharmacokinetic study with a Metered Dose Transdermal Systemfor delivery of the progestogen Nestorone as a possible future contraceptive

BACKGROUND: Transdermal delivery of steroids is gaining popularity for contraception and hormone replacement therapy. This study aimed to test metered spray delivery of a precise dosage of Nestorone (NES) progestogen as a possible transdermal progestogen-only contraceptive. STUDY DESIGN: Six healthy postmenopausal volunteers, not recently using any hormonal therapies, comprise the sample for this study. Each subject was studied on two occasions with multiple blood sampling for assay of NES over a 24-h period: on the first occasion, after a single dosage of 3 x 90 microL NES sprays using a specially devised, precisely metered delivery device; on the second occasion, following the fifth in a series of five daily transdermal dosages of 3 x 90 microL of NES spray. Conventional pharmacokinetic parameters were calculated. NES was assayed in serum using a specific radioimmunoassay. RESULTS: Mean serum levels of NES peaked at around 20 h following dosing, and levels plateaued at 285-290 pmol/L after 4-5 days of daily spray application. All subjects achieved satisfactory serum levels, although substantial intersubject variation was noted. The apparent elimination half-life of NES after the last dose on Day 5 was 26.8 h. No unexpected adverse events were encountered. CONCLUSION: This early pharmacokinetic trial of a new transdermal steroid delivery system has demonstrated the feasibility of achieving serum levels of NES sufficient to block ovulation and potentially provide effective contraception.     

Laparoscopic Drainage of a Large Pancreatic Pseudocyst

Laparoscopic cystogastrostomy is an established procedure for the drainage of pancreatic pseudocysts. Cysts are mainly present in the lesser sac (retro-gastric), which is completely amenable to cystogastrostomy. We discuss the problems faced and simple solutions to the problems in managing a huge pancreatic pseudocyst of 22 cm×18 cm in a young boy 18 y of age.     

Use of HbA1C testing to diagnose pre-diabetes in high risk African American children: A comparison with fasting glucose and HOMA-IR

ObjectiveThis study aimed to compare the discriminating power of HbA_1C with other pre-diabetes diagnostic tests specifically in high-risk African American children.Research design and methodsA cross-sectional analysis was performed on a sample of 172 children (70 boys and 102 girls) aged 9–11 years with BMI's above the 85th percentile. Fasting glucose, insulin and HbA_1C were analyzed from the plasma samples.ResultsOf the 172 participants included in this analysis, 21 (12.2%) had HbA_1C concentrations above the cutoff of 5.7 used to identify pre-diabetes. None (0%) of these 21 participants, however, were observed to have a glucose concentration above the pre-diabetes cutoff of 110 mg/dl, and only 13 of 21 participants had HOMA-IR above the pre-diabetes cutoff of 2.5. When compared to the previously identified glucose cutoff of 110 mg/dl and HOMA-IR cutoff of 2.5 for pre-diabetes, HbA_1C showed high specificity (88 and 93%, respectively) but very low sensitivity (0 and 21%, respectively). Glucose, insulin and HOMA-IR were significantly interrelated, but HbA_1C was not significantly correlated with these biochemical prediabetes assessment variables, nor with anthropometric (BMIz, WC) risk factors.ConclusionOur results suggest that HbA_1C had poor discrimination power to identify prediabetes in overweight and obese 9- to 11-year-old African American children. Future studies are recommended to compare the feasibility, sensitivity and predictive power of different screening tests currently recommended to avoid inadequacy when screening for prediabetes and diabetes.