Controlled Release of Substituted Benzole and Naphthoic Acids Using Carbopol ® Gels: Measurement of Drug Concentration Profiles and Correlation to Release Rate Kinetics

Purpose. The objective of this study is to correlate drug release mechanism with measured drug concentration profiles in gel layers of Carbopol^® matrices containing mesalamine or benzoic acid. Methods. Release rate experiments with Carbopol^® matrices were performed using a rotating disk apparatus. Matrices were frozen and the gel layer in the matrices was sliced using a microtome in a cryostat. Drug concentration profiles were determined by direct measurement of the concentration of the drug in the gel slices. The pH of the slices was measured using microelectrodes, and water content was measured by Karl Fisher titration. Results. The concentration gradient in mesalamine matrices decreased over time and correlated with square root of time release rate kinetics. The concentration profiles of benzoic acid were unchanged over time and correlated with zero order release rate kinetics. Carbopol gel layers were highly hydrated (93–95% water). Gel layers in matrices with mesalamine had a more alkaline microenvironmental pH. This higher pH resulted in increased growth of the thickness of the gel layer and a reduction drug diffusivity in comparison to benzoic acid matrices. Conclusions. The release rate kinetics of mesalamine and benzoic acid correlated to the measured concentration profiles. The shape of the concentration profiles is determined by the rate of growth of the Carbopol^® gel layer and drug diffusivity.     

Three Evaluation Methods of a Community Health Advocate Program

The title Community Health Advocate (CHA) is one of thirty or more titles used throughout the world for an indigenous outreach worker who is trusted and respected in his or her community and who serves as a bridge between peers and health professionals. In 1992, the Center for Healthy Communities in Dayton, Ohio developed a program to train as Advocates people indigenous to the communities in which they would be working. Since the first CHAs began work in January 1993, the effectiveness of the program has been evaluated from three perspectives: the Community Health Advocates, the managers directors of the community sites at which the CHAs work, and the clients with whom the CHAs work. Advocates indicated that the training program adequately prepared them for their roles and functions. They also identified systematic frustrations and barriers that made it more difficult for them to perform their job. Community site directors and community leaders indicated that the CHAs were considered a positive force in meeting client needs and facilitating independence, and were very effective in outreach and coordination of resources. A survey of CHA clients revealed an overwhelmingly positive response to the Advocate's work, validating the belief that CHAs can fill an important niche in the health care community. The three evaluation processes described in this paper helped to document the need for and the effectiveness of this program and can serve as a model for similar programs.     

Andrology: Analysis of sperm movement in relation to the oxidative stress created by leukocytes in washed sperm preparations and seminal plasma

The addition of luminol to unprocessed semen samples resultedin the generation of chemiluminescent signals, the intensityof which was highly correlated with the level of leukocyte contamination.Despite the spontaneous oxidant-generating capacity of seminalleukocytes, no correlations were observed between leukocytecontamination and the fertility status of the subjects or anyaspect of the semen profile, including the motility of the spermatozoaor their performance in a hyaluronate penetration assay. Luminol-dependentchemiluminescence and leukocyte contamination were also correlatedin washed sperm suspensions prepared either by repeated centrifugationor on discontinuous Percoll gradients. However, in such spermsuspensions, the spontaneous generation of oxidants by contaminatingleukocytes (>2x10⁴ leukocytes/ml) was invariably associatedwith a decreased capacity for movement. Moreover, causativeassociations between leukocyte contamination, reactive oxygenspecies generation, lipid peroxidation and impaired sperm motilitywere revealed by experiments involving the selective additionor removal of activated leukocytes. From these observationswe can conclude that low concentrations of leukocytes are acommon feature of the human ejaculate and can impair sperm function,particularly in the absence of seminal plasma. These findingshave implications for our understanding of the importance ofleukocytospermia in defining the fertility of human spermatozoain vivo and in vitro.     

Tritiated Uridine Uptake in the Retinal Ganglion Cell Layer of the Cat during Normal Development and after Visual Cortex Ablation

The short-term metabolic response of immature retinal ganglion cells to destruction of their target cells in the dorsal lateral geniculate nucleus (dLGN) was assessed in newborn cats. Retrograde degeneration of virtually all dLGN cells was induced by ablation of the 13 contiguous areas of visual cortex on the day of birth. The metabolic response of retinal ganglion cells to this loss of target cells in dLGN was determined by exposing the ganglion cell layer to tritiated uridine, a precursor of RNA. Control measurements were made from unoperated littermates. Following sectioning and processing of the retinae from both groups of kittens for autoradiography, silver grain densities overlying the cellular profiles in the ganglion cell layer were calculated. These calculations revealed levels of uridine incorporation at Postnatal Day 4 in both groups of kittens significantly higher than at either Postnatal Day 2 or 7, but no significant differences between the two groups on any day examined. These results show that the level of RNA synthesis in retinal ganglion cells increases temporarily during the first postnatal week and that this synthesis is unaffected by the death of target cells in the dLGN. The temporary increase may be related to the establishment of synaptic connections on retinal ganglion cells by their afferent bipolar and amacrine neurons in the inner nuclear layer.     

Immunoglobulins, cognitive status and duration of illness in alzheimer''s disease

Immunologic changes have been reported in the dementing illnesses of mid and late life. The results of two studies of drug-free males meeting research diagnostic criteria for primary neuronal degeneration of the Alzheimer's type suggest that serum IgG levels decrease with the progression of dementia. Serum IgG levels were inversely correlated with duration of illness and the levels of psychiatric symptomatology. Performance on the mini-mental status examination was positively associated with serum IgG concentrations.     

Use of a T cell-specific monoclonal antibody, T10B9, in a novel allogeneic stem cell transplantation protocol for hematologic malignancy high-risk patients.

To reduce the toxicity of traditional conditioning regimens for allogeneic stem cell transplantation (allo-SCT), we used single-agent chemotherapy conditioning with either busulfan (total cumulative dose, 16 mg/kg) or melphalan (200 to 240 mg/m 2 ), followed by the anti-T cell-specific monoclonal antibody T10B9 (MEDI-500) daily for 3 days. T cell-replete SCT was performed from HLA-identical sibling donors. Acute graft-versus-host disease (aGVHD) prophylaxis consisted of 7 additional days of T10B9 and delayed onset of cyclosporine (ie, on day +4 or +5). Twenty-six high-risk hematologic malignancy patients were entered onto this study. All 24 patients who survived longer than 8 days engrafted, although 1 patient experienced late graft failure. Deaths occurred in 21 of 26 patients because of infection (n = 7), progression/recurrence of primary disease (n = 6), aGVHD (n = 4), regimen-related toxicity (n = 1), and other causes (n = 3). Five of these patients are enjoying disease-free survival with a median survival of 1193 days after allo-SCT. The conditioning regimen induced modulation of surface expression of CD3 (but not CD4 or CD8) and was associated with decreasing tumor necrosis factor-alpha (but not interleukin-6) serum levels. In conclusion, single-agent chemotherapy conditioning with T10B9 produced durable engraftment and long-term survival in some patients who would not have qualified for a traditional allo-SCT.     

Salt appetite and lesions of the ventral part of the ventral median preoptic nucleus

Angiotensin receptors in the most ventral part of the ventral median preoptic nucleus (VVMnPO) or organum vasculosum laminae terminalis appear to be important for salt appetite to angiotensin in rats. If so, then small lesions of this region should reduce salt appetite that is dependent on angiotensin. In separate experiments, the lesion greatly reduced salt appetite after treatments with chronic oral captopril or sodium depletion. On the other hand, the VVMnPO lesion actually enhanced salt appetite to deoxycorticosterone acetate. The lesion did not affect water intake to water deprivation, combined food-water deprivation, isoproterenol, or hypertonic saline, and basal plasma osmolality and sodium values were normal. These experiments suggest that VVMnPO lesions selectively affect angiotensin-induced salt appetite without producing the gross hydrational deficits that occur with larger lesions of the ventral forebrain.     

The effects of voluntary contraction effort on quadriceps femoris electromyogram median frequency in humans: a muscle and sex comparison

The purpose of this study was to examine the effect of voluntary contraction efforts on the median frequency (f _med) of the electromyogram (EMG) recorded from the quadriceps femoris muscle in healthy men and women. A group of 30 healthy volunteers (15 men, 15 women) were assessed for EMG activity of the vastus medialis (VM), vastus lateralis (VL), and rectus femoris (RF) muscles during isometric contractions with the knee at 60° flexion. Subjects performed a series of 5 s maximal voluntary isometric contractions that anchored the perceptual range with a "10" on a 10-point scale. Sub-maximal isometric contractions were then separately performed at the following perceived effort levels on the 10-point scale: 1, 2, 3, 4, 5, 6, 7, 8 and 9, in a random order. Subjects were instructed to maintain the contraction at each perceived level of effort for 5 s. The f _med of the three muscles was assessed using a power spectrum analysis performed over 11 consecutive, 512 ms, epochs overlapping each other by half their length during the middle 3 s of each contraction. The f _med for each of the 11 epochs was then determined for each muscle, followed by calculation of the means and normalized coefficients of variation [(standard deviation/mean)×100%] for each contraction. The results demonstrated that the mean f _med of VL was significantly greater than those of the other two muscles, and that f _med of RF was significantly greater than that of VM. The VL muscle demonstrated a significant increase in mean f _med across the contraction efforts, compared to the VM and RF muscles that displayed a significant decrease. The men displayed significantly higher f _med values for the VM muscle than did the women, as well as showing a significantly greater increase across the contraction efforts for the VL muscle. The variability of f _med was shown to be significantly higher for the VM muscle, compared to the VL and RF muscles. The findings of this study suggest that the f _med statistic is most sensitive to contraction intensity efforts for the VL muscle, and that men display significantly higher values for the VL and VM muscles, compared to women. Electronic Publication