Lecithin vesicles for topical delivery of diclofenac.

Skin penetration of topically applied diclofenac is important for the treatment of rheumatic diseases and actinic keratoses. We have studied the permeation of diclofenac across human cadaver epidermis in-vitro from four lecithin vesicle formulations and a few marketed semi-solid preparations. The lecithin vesicle formulations were prepared by dissolving the lipid contents (lecithin and sodium cholate) in a 1:1 mixture of methanol-chloroform, evaporating the solvents under vacuum, and hydrating the lipid layer with the drug solution in water or 10% ethanol. The vesicles were sonicated for 5 min to reduce the vesicle size and their size and Zeta potential were characterized. The cumulative amount and maximum flux of diclofenac was 69.7+/-40.3 micrograms and 4.77+/-3.16 micrograms/hcm(2) from lecithin vesicles containing sodium cholate and 10% ethanol, and is the highest of all formulations studied. The cumulative amount and mean maximum flux obtained from other formulations were in the range of 2.46+/-1.98-29.9+/-10.1 micrograms and 0.53+/-0.46-3.61+/-0.86 micrograms/hcm(2). Based on the results, lecithin vesicles of diclofenac appear to be advantageous for the topical delivery of diclofenac.     

The J-curve relationship of treated diastolic blood pressure to mortality risk: Is it real? Is it clinically meaningful?

Low diastolic blood pressure is alleged to impose excess cardiovascular disease (CVD) risk in patients with treated hypertension, impeding aggressive reduction of blood pressure. Most investigations that assessed the potential J-shaped relations of diastolic blood pressure and adverse outcomes have not adequately considered systolic or pulse pressure in statistical analyses. An overview of hypertension trials indicates that lowering elevated blood pressure reduces the risk of CVD outcomes irrespective of the associated decrease in diastolic pressure, even if the achieved diastolic pressure averages less than 70 mm Hg. The Framingham study investigations have determined that the increased CVD incidence observed at low diastolic blood pressure levels is confined largely to persons with concomitantly increased systolic pressure. This finding of no true excess risk at low diastolic blood pressure agrees with the results of trials that have evaluated the J-curve phenomenon adjusting for systolic pressure. Aggressively treating systolic hypertension appears to produce no cause for alarm.     

Evaluation of four elastomeric interocclusal recording materials

Background: The fabrication of dental prosthesis requires the transfer of interocclusal records from patient's mouth to semiadjustable articulators using different kinds of recording media. Any inaccuracy in these interocclusal records leads to occlusal errors in the final prosthesis. This study was conducted to evaluate the dimensional changes occurring in the interocclusal recording material over a given period of time and the material's resistance to compression during the cast mounting on the articulator.     

Failure to detect an antimutator phenotype following disruption of the Saccharomyces cerevisiae DDR48 gene

The antimutator phenotype, reportedly conferred by disruption of the Saccharomyces cerevisiae DDR48 gene, was suggested to affect only a specific spontaneous mutational pathway. We attempted to identify the types of mutation that are DDR48-dependent by determining the specificity of the ddr48 antimutator. However, disruption of DDR48 did not decrease the rates of spontaneous forward mutation in a plasmid-borne copy of the yeast SUP4-o gene, the reversion or suppression of the lys2–1 allele, or forward mutation at the CAN1 locus. Interestingly, the latter gene had been reported previously to be subject to the antimutator effect. DNA sequence analysis of spontaneous SUP4-o mutations arising in DDR48 and ddr48 backgrounds provided no evidence for a reduction in the rates of individual mutational classes. Thus, we were unable to verify that disruption of DDR48 causes an antimutator phenotype.     

Maternal Nutrition—Effect on Fetal Growth and Outcome of Pregnancy

During the first half of the 20th century, chronic energy undernutrition due to low dietary intake, repeated infections, and rapid succession of pregnancy were the factors most responsible for maternal undernutrition and consequent adverse outcomes of pregnancy. Efforts to improve dietary intake, treatment of infections, and provision of contraceptive care were the major focuses of intervention from 1950 to 1990. These interventions resulted in reduction in severe grades of undernutrition. However, there was no reduction in mild and moderate degrees of undernutrition and anemia during pregnancy and there was no significant improvement in the course and outcome of pregnancy, or in birth weight. During the 1990s, among the middle- and upper-income groups, there has been a progressive rise in obesity and consequent adverse effects. The advent of HIV infection in India in the 1980s will inevitably lead to increases in severe undernutrition associated with HIV infection in pregnancy and an adverse impact of maternal HIV infection on the fetus. Practicing physicians and nutritionists in the new millennium will therefore have to assess each person individually and provide appropriate advice regarding diet, exercise, fertility, and infection prevention and control in order to achieve optimum health and nutrition status during pregnancy and to prevent adverse pregnancy outcomes.