Scale-up of Adhesive Transdermal Drug Delivery Systems

Pharmaceutical Research -     

Distribution of metabotropic glutamate receptor mGluR5 immunoreactivity in rat brain

The receptor mGluR5 is a metabotropic glutamate receptor with messenger RNA abundantly present throughout cortex, hippocampus, and caudate/putamen that is also coupled to phosphatidyl inositide hydrolysis and calcium mobilization. In this study, the distribution of mGluR5 was examined in rat brain by immunocytochemistry. The antibody utilized is highly specific and does not cross react with the most closely related other metabotropic glutamate receptor, as determined by Western blot analysis of nonneuronal cells transfected with metabotropic receptor coding sequences. The receptor mGluR5 is widely expressed with the highest density in olfactory bulb, caudate/putamen, lateral septum, cortex, and hippocampus, as confirmed with both immunocytochemistry and Western blot analysis. Electron microscopic studies in hippocampus and cortex indicate that the labeling is mostly on membranes of dendritic spines and shafts. Light and electron microscopic evidence indicates that some mGluR5 immunoreactivity is located in presynaptic axon terminals, suggesting that mGluR5 may function as a presynaptic receptor.     

Surgical complications of continuous ambulatory peritoneal dialysis

Surgical experience with 260 consecutive patients with chronic renal failure receiving continuous ambulatory peritoneal dialysis (CAPD) at one medical center from 1980 to 1989 is reviewed. Patients received CAPD for a mean of 24.2 months (range: 3 days to 91 months). Catheter longevity consistently improved in all but 1 year from 1984 to 1989, as did exit-site and tunnel infections. Of 311 catheters inserted, 151 (49%) required removal, of which 111 (74%) were attributed to peritonitis. Cumulative patient survival was 80%, 60%, and 53% at 1, 2, and 3 years, respectively. Diabetic patients had statistically significant lower survival rates. Additional complications including catheter leakage, catheter malposition, catheter obstruction, and abdominal wall hernias were negligible. Although CAPD is not free from serious complications, our data show remarkable improvement since 1980 in catheter longevity, hospital stay, and infection rates.     

Structure and Behavior in Hydrophilic Matrix Sustained Release Dosage Forms: 4. Studies of Water Mobility and Diffusion Coefficients in the Gel Layer of HPMC Tablets Using NMR Imaging

Purpose. The purpose of this study was to characterise the water mobility in the gel layer of hydrating HPMC tablets. Water mobility in the gel layer of different HPMCs was studied. Methods. NMR imaging, a non-invasive technique, has been used to measure the spatial distribution of self-diffusion coefficient (SDC) and T₂ relaxation times across the gel layer. Results. It has been shown that there is a water mobility gradient across the gel layer of HPMC tablets. Although SDC and T₂ relaxation times in the outer parts of the gel layer approached that of free water, in the inner parts they decreased progressively. Water mobility and SDC in the gel layer of different HPMCs appeared to vary with degree of substitution of the polymer and the lowest values were obtained across the gel layer of K4M tablets. Conclusions. Water mobility varies across the gel layer of hydrating HPMC tablets and it is dependent on the degree of substitution of the polymer.     

The impact of lower urinary tract symptoms on general health status and on the use of prostatectomy

Our objective was to determine the extent to which lower urinary tract symptoms affect the general health status of men and contribute to the decision to undergo surgery. A cross-sectional population survey using postal questionnaires was conducted in the North West Thames health region, followed by a prospective cohort study of men undergoing prostatectomy (North West Thames and Oxford regions). The subjects in the first survey were 221 men aged 55 and over with previously reported mild, moderate or severe urinary symptoms; subjects in the second study were 388 men undergoing prostatectomy. Main outcome measures were selfreported symptom severity, bothersomeness and general health status (Nottingham Health Profilie, Part 1). The response rate among eligible responders in the population survey was 85.7%. Increasing symptom severity was associated with worsening NHP scores for energy, emotional reactions, sleep and physical mobility (p<0.01). Increasing bother-someness of symptoms was associated with emotional reactions, sleep and pain (p<0.05). Men undergoing surgery reported worse health status than men in the population with the same severity of symptoms as regards emotional reactions, energy and pain. For a given level of symptom severity, the impact of those symptoms on aspects of a man's general health status may be the determinant of seeking and undergoing surgery. Greater understanding of the factors that affect a man's response to his symptoms is needed in interpreting the decision to seek and accept treatment.     

Generation of mice with inactivated Rh or Rhag genes.

Mice carrying inactivated Rh and Rhag genes were generated by insertional targeting. KO animals exhibited normal growth, development and fertility and both types were indistinguishable at a gross phenotypic level from their wild type littermates. Preliminary analysis revealed that red cells from Rh-/- mice lack Rh protein and have a moderate decrease of Rhag protein, whereas those from Rhag-/- mice have a total absence of Rhag and Rh proteins. Studies are in progress to delineate the antigenic, biochemical and functional abnormalities of red cells from these animals as well as the impact on hematological parameters and erythropoiesis.     

Changes in elderly suicides in the USA and the developed world 1974–87: Comparison with current homicide

Between 1974 and 1987 there were increases overall in male suicide rates in the USA, with the greatest increases among elderly men. While female suicide levels overall fell in the USA, elderly female suicide rates failed to show the same improvement. Compared with the rest of the western world, suicide rates for elderly people in the USA were among the worst. Suicide was far more prevalent than homicide, but this is not reflected in the media, where homicide is given a high profile but where there is relative silence surrounding suicide among elderly people.