Gelatin-based emulsion gels for diffusion-controlled release applications

Emulsion gels are now emerging as a new class of biomaterials for controlled-release applications. Novel food-grade emulsion gels consisting of indomethacin-loaded vegetable oil droplets dispersed within genipin-cross-linked gelatin-based hydrogels were characterized for their physical and drug-release properties. Varying the weight ratio of the aqueous and oil phases between 5:1 and 5:5 was used to modulate construct swelling and drug release. The dispersed oil droplets generally became larger, more polydispersed and aggregated with an increase in oil fraction. Cross-linking with genipin increased the puncture strength of the gels vs. their uncross-linked counterparts and was necessary to prevent breakdown. Swelling of the emulsion gels demonstrated Fickian behaviour at all gelatin: oil ratios. Indomethacin release followed Fickian diffusion at higher oil fractions only, demonstrating coupled Fickian and super-Case-II transport at lower oil ratios (5:1, 5:2 and 5:3). Overall, the introduction of a dispersed oil phase within a hydrogel was exploited for the release of hydrophobic bioactive compounds, with tailoring of composition used to significantly alter release kinetics.     

Expression of heat shock proteins 70 and 47 in tissues following short-pulse laser irradiation: Assessment of thermal damage and healing

In order to develop effective laser-based therapeutics, the extent of laser-induced damage must be quantified for given laser parameters. Therefore, we want to determine the spatiotemporal expression patterns of heat shock proteins, both to understand the roles of heat shock proteins in laser-induced tissue damage and repair and to develop heat shock proteins as tools to illustrate the extent of laser-induced damage and wound healing following irradiation. We exposed anesthetized mice to the focused beam of a short-pulse Nd:YAG laser (1064 nm; 200 ns pulsewidth) for 15 s, while measuring temperature distribution in the skin using an infrared thermal camera. Following irradiation, we examined expression of HSP47 and HSP70 over time (0–24 h) as indicators of the heat shock response and recovery from damage in the laser-irradiated region. Expression patterns of HSP70 and HSP47 as detected by immunohistochemistry and confocal microscopy delineate the extent of damage and the process of healing in tissue. Both HSP70 and HSP47 were expressed in dermis and epidermis following laser irradiation, and the spatial and temporal changes in HSP expression patterns define the laser-induced thermal damage zone and the process of healing in tissues. HSP70 may define biochemically the thermal damage zone in which cells are targeted for destruction, and HSP47 may illustrate the process of recovery from thermally induced damage. Studying the effects of different laser parameters on the expression of HSPs will allow development of effective laser therapies that provide accurate and precise tissue ablation and may promote rapid wound healing following laser-based surgery.     

Chromatin interactions in differentiating keratinocytes reveal novel atopic dermatitis– and psoriasis-associated genes

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Outcome in infants 501 to 1000 gm birth weight delivered to residents of the McMaster Health Region

The mortality and morbidity for all 255 live births of infants with birth weight 501 to 1000 gm and delivered to residents of a geographically defined region between 1977 and 1980 are reported. In all, 117 (46%) infants were discharged alive; there were four postdischarge deaths, and three infants were lost to follow-up. The mean birth weight and gestational age of the survivors was 850 +/- 118 gm and 27.1 +/- 2 weeks, respectively. Neurosensory handicaps were detected in 26 (24%) of 110 survivors followed for a minimum of 2 years corrected age. In addition, 29 (26%) infants had nonneurologic problems and 55 (50%) were considered apparently normal. Within 100 gm birth weight groups, survival improved significantly with increasing birth weight, but the handicap rate among survivors remained relatively constant. These figures are proposed for use in describing the current prognosis at birth for liveborn tiny infants from comparable unselected populations.     

Effect of desogestrel on blood-lipid in relation to its biological activities

Desogestrel (DG), a 19-nor progestin, is widely used in replacement therapy as a contraceptive steroidal hormone. Considering the importance of its partition coefficient parameter (log P = 5.68), a significant contributor to its action mechanism, interactions of the drug with blood-lipids had been investigated using phospholipid binding, fatty acid composition and peroxidation phenomena as the parameters under investigation to explain its pharmacodynamic behavior. From the present investigation, it was observed that lipid loss after incubation of whole blood with DG (80 ng/ml, effective contraceptive concentration in blood) for varying periods of time was accompanied with significant changes in fatty acid composition, which may be ascribed to binding affinity of DG with lipid constituents in blood that may have a role in the mediation of its therapeutic effect. Lipid peroxidation induction potential of DG has been quantitatively measured in the context of its toxicity. The results reveal that DG caused significant extent of lipid peroxidation. Ascorbic acid, an antioxidant, at equivalent human dose of 250 mg could significantly reduce DG-induced lipid peroxidation.     

Stability of time trade-off utilities for health states associated with the treatment of prostate cancer

Background: Patients diagnosed with localized prostate cancer face several treatment options. Patient preferences for treatment side effects often dominate the decision making process. We proposed to learn more about the nature of patient preferences, or utilities, for these side effects. Methods: Two hundred and fifteen men were consecutively enrolled from three institutions for assessment after prostate needle biopsy. Baseline and 6 month follow-up assessments were done using the University of California, Los Angeles Prostate Cancer Index (UCLA PCI), and a laptop utility assessment application, U-Titer II. Patient utility was assessed for current pelvic functions as well as hypothetical pelvic dysfunctions. We calculated stability of utility scores and correlations between utility scores and UCLA PCI scores. Results: Utility scores for current pelvic functions exhibited a significant ceiling effect. Utility scores for current pelvic functions and hypothetical impaired states were stable after 6 months in patients with negative biopsies. In patients who underwent treatment, utility for current sexual function decreased by 0.13 units (p < 0.00) and utility for current urinary function decreased by 0.09 units (p < 0.01). Utility for hypothetical stress urinary incontinence rose in men with a >25-point drop in UCLA PCI score. Conclusion: Utilities for some current pelvic functions decreased in tandem with UCLA PCI scores in men who experienced >25-point changes in these scores. Utilities for some hypothetical pelvic dysfunctions rose as men began to actually experience functional changes in those areas.     

Outcomes at 3 months after planned cesarean vs planned vaginal delivery for breech presentation at term: the international randomized Term Breech Trial

Context  The Term Breech Trial found a significant reduction in adverse perinatal outcomes without an increased risk of immediate maternal morbidity with planned cesarean delivery compared with planned vaginal birth. No randomized controlled trial of planned cesarean delivery has measured benefits and risks of postpartum outcomes months after the birth. Objective  To compare maternal outcomes of planned cesarean delivery and planned vaginal birth at 3 months post partum. Design  Follow-up study to the Term Breech Trial, a randomized controlled trial conducted between January 9, 1997, and April 21, 2000. Setting and Participants  A total of 1596 of 1940 women from 110 centers worldwide who had a singleton fetus in breech presentation at term responded to a follow-up questionnaire at 3 months post partum. Main Outcome Measures  Breastfeeding; infant health; ease of caring for infant and adjusting to being a new mother; sexual relations and relationship with husband/partner; pain; urinary, flatal, and fecal incontinence; depression; and views regarding childbirth experience and study participation. Results  Baseline information was similar for both the cesarean and vaginal delivery groups. Women in the planned cesarean delivery group were less likely to report urinary incontinence than those in the planned vaginal birth group (36/798 [4.5%] vs 58/797 [7.3%]; relative risk, 0.62; 95% confidence interval, 0.41-0.93). Incontinence of flatus was not different between groups but was less of a problem in the planned cesarean delivery group when it occurred (P = .006). There were no differences between groups in other outcomes. Conclusions  Planned cesarean delivery for pregnancies with breech presentation at term may result in a lower risk of incontinence and is not associated with an increased risk of other problems for women at 3 months post partum, although the effect on longer-term outcomes is uncertain.