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Query: UMLS:C0152030 (skin irritation)
 2,146 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent advances in techniques for culture of human skin cells have led to their potential for use as in vitro models for skin irritation testing to augment or replace existing rabbit skin patch tests. Our work is directed towards the development of cultured human skin cells, together with endpoints that can be linked to in vivo mechanisms of skin irritation, as in vitro models for prediction of human skin irritation, and for study of mechanisms of contact irritant dermatitis. Three types of commercial human skin cell cultures have been evaluated, epidermal keratinocytes and partially or fully cornified keratinocyte-dermal fibroblast co-cultures. Human epidermal keratinocyte cultures (Clonetics) were treated with product ingredients and formulations, and the extent of cell damage was assessed by incorporation of the vital dye neutral red. Cell damage correlated with human skin patch data for ingredient chemicals with the exception of acids and alkalis, but did not correlate with skin irritation to surfactant-containing product formulations. Cultures of human skin equivalents were evaluated as potential models for measurement of responses to test materials that could not be measured in the keratinocyte/neutral red assay. We developed a battery of in vitro endpoints to measure responses to prototype ingredients and formulations in human epidermal keratinocyte-dermal fibroblast co-cultures grown on a nylon mesh ('Skin2' from Advanced Tissue Sciences) or on a collagen gel ('Testskin' from Organogenesis). The endpoints measure cytotoxicity (neutral red and MTT vital dye staining, lactate dehydrogenase and N-acetyl glucosaminidase release, glucose utilization) and inflammatory mediator (prostaglandin E2) release. Initial experiments indicate a promising correlation between responses of the Skin2 model to prototype surfactants and in vivo human skin irritation. The responses of Testskin cultures to acids and alkalis help to prove the concept that a topical application model can measure responses to these materials. These results suggest that human skin cell models can provide useful systems for preclinical skin irritation assessments, as alternatives to rabbits, for at least certain classes of test substances.
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PMID:An approach for development of alternative test methods based on mechanisms of skin irritation. 813 72

Synthetic retinoids, ligands for the RAR and RXR members of the steroid/thyroid superfamily of nuclear hormone receptors, are used for the treatment of psoriasis, acne, photoaging and cancer. Retinoid mechanisms of action for these conditions largely involve effects on epithelial differentiation and modulation of inflammation with some impact on the immune system. Retinoid medicinal chemistry in recent years has identified ligands highly specific for one of the three RAR subtypes (RAR-alpha) and for the RXR family of receptors, as well as antagonists for the RARs, RARalpha and the RXRs. Structure-activity relationships among the novel retinoid classes are reviewed along with potential therapeutic activities and side effects. RAR-alpha specific retinoids inhibit cancer cell growth but lack other retinoid toxicities, including skin irritation now ascribed to RAR-gama. RXR-specific retinoids lower blood glucose in animal models of type 2 diabetes albeit with a potential for mild hypothyroidism. Function-selective retinoids, especially a class of RAR antagonists called inverse agonists, have unexpected gene regulatory activity. Given the diverse properties and tissue distributions of the retinoid receptors, synthesis of additional classes of receptor-specific and function-selective ligands has the potential to produce novel therapeutic applications.
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PMID:Therapeutic applications for ligands of retinoid receptors. 1063 71

The GlucoWatch (Cygnus, Inc, Redwood City, CA, USA) biographer provides automatic, frequent and noninvasive blood glucose measurements for up to 12 h. The device extracts glucose through intact skin where it is measured by an amperometric biosensor. Clinical trials in a variety of environments have shown that the biographer provides accurate and precise glucose measurements when compared with serial fingerstick blood glucose measurements. Mean difference between these measurements was 0.26 mmol/L in the home environment (r = 0.80). Over 94% of biographer readings were in the clinically acceptable A+B region of the Clarke Error Grid. A slight positive bias is observed for the biographer readings at low glucose levels. Biographer precision, as measured by coefficient of variation (CV)%, is approximately 10%. The low glucose alert function of the biographer was able to detect up to 75% of hypoglycaemic episodes with a low false alert level. Skin irritation, characterized by erythema and oedema was either nonexistent or mild in over 87% of subjects and resolved in virtually all subjects without treatment in several days. The GlucoWatch biographer has been shown to be a safe and effective method to track glucose level trends and patterns, which should enable improved glycaemic control for many patients.
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PMID:The GlucoWatch biographer: a frequent automatic and noninvasive glucose monitor. 1120 71

A device providing frequent, automatic, and non-invasive glucose measurements for persons with diabetes has been developed: the GlucoWatch biographer. This device extracts glucose through intact skin via reverse iontophoresis where it is detected by an amperometric biosensor. The biographer can provide glucose readings every 20 min for 12 h. The performance of this device was evaluated in two large clinical studies in a controlled clinical environment (n=231), and the home environment (n=124). Accuracy of the biographer was evaluated by comparing the automatic biographer readings to serial finger-stick blood glucose (BG) measurements. Biographer performance was comparable in both environments. Mean difference between biographer and finger-stick measurements was -0.01 and 0.26 mmol l(-1) for the clinical and home environments, respectively. The mean absolute value of the relative difference was 1.06 and 1.18 mmol l(-1) for the same studies. Correlation coefficient (r) between biographer and finger-stick measurements was 0.85 and 0.80 for the two studies. In both studies, over 94% of the biographer readings were in the clinically acceptable A+B region of the Clarke Error Grid. A slight positive bias is observed for the biographer readings at low BG levels. Biographer accuracy is relatively constant over all rates of BG changes, except when BG decreases more than 10 mmol l(-1) h(-1), which occurred for only 0.2% of points in the home environment study. Biographer precision, as measured by CV%, is approx. 10%. Skin irritation, characterized by erythema and edema, was either non-existent or mild in >90% of subjects and resolved in virtually all subjects without treatment in several days.
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PMID:Clinical evaluation of the GlucoWatch biographer: a continual, non-invasive glucose monitor for patients with diabetes. 1167 37

Gels are considered to be the most suitable delivery vehicle for iontophoresis, as they can be easily amalgamated with the iontophoretic delivery system and can also match the contours of the skin. Insulin was used as a model peptide for large peptides in the molecular weight range of 3-7 kDa. A gel formulation of insulin was formulated using poloxamer 407 and was evaluated by ex vivo and in vivo skin permeation studies in rat with chemical enhancer and/or iontophoresis. The poloxamer gel was physically and chemically stable during the storage period. In ex vivo studies, both linoleic acid and menthone in combination with iontophoresis showed a synergistic enhancement of insulin permeation. The plasma insulin concentration (PIC) was highest with linoleic acid pre-treatment, in agreement with ex vivo permeation studies, but the reduction in plasma glucose levels (PGL) was comparable to iontophoresis. Menthone pre-treatment resulted in rapid attainment of peak PIC, but the reduction in PGL was less than other treatment groups. There was no direct relation between PIC and PGL and is attributed to the fact that the action of insulin in mediated by a cascade of cellular mechanisms, before a reduction in PGL is observed. However, iontophoresis either alone or in combination with linoleic acid produced a reduction in PGL to the extent of 36-40%. A combination of chemical enhancers and iontophoresis caused greater skin irritation than when either of them was used alone.
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PMID:Transdermal delivery of insulin from poloxamer gel: ex vivo and in vivo skin permeation studies in rat using iontophoresis and chemical enhancers. 1269 68

In the present study, matrix type transdermal patches containing glibenclamide were prepared using different ratios of ethyl cellulose (EC)/polyvinylpyrrolidone (PVP) and Eudragit RL-100 (ERL)/Eudragit RS-100 (ERS) by solvent evaporation technique. The possible drug and polymer interaction was studied by infrared spectroscopy, differential scanning calorimetry, and HPTLC analysis. All the prepared formulations were subjected to physicochemical studies (thickness, weight variation, drug content, moisture content and uptake, and flatness), in vitro release and in vitro permeation studies through mouse skin. The results suggested that there was no interaction between drug and polymers. Variations in drug release/permeation profiles among the formulations studied were observed. The microphotographs obtained by scanning electron microscopy showed the formation of pores on the surface of the patches after in vitro skin permeation studies. Based on physicochemical and in vitro skin permeation studies, the formulations with EC:PVP (3:2) and ERL:ERS (4:1) were selected for in vivo experiments. The hypoglycemic activity of the patches in comparison with oral glibenclamide administration was studied for acute (24 h) and long-term (6 weeks) effect in both normal and streptozotocin-induced diabetic mice. Various biochemical parameters (serum levels of high-density lipoprotein-cholesterol, triglycerides, total cholesterol, alanine transaminase, aspertate transaminase, urea, and creatinine and liver protein and glycogen content) and histopathological (liver, pancreas and stomach) studies were carried out in diabetic mice after treating for 6 weeks. The patches were subjected to skin irritation test (by both visual observation and histopathological evaluation), oral glucose tolerance test and pharmacokinetic evaluation in mice. The results revealed that the patches successfully prevented the severe hypoglycemia in the initial hours, which is the major side effect associated with oral route. The patches maintained similar effect during long-term treatment also. The transdermal systems produced better improvement with all the tested biochemical parameters compared to oral administration. They produced improved repair of the tissues after diabetes induced tissue injury and exhibited negligible skin irritation. The pharmacokinetic evaluation showed that the patches could maintain almost steady-state concentration of drug within the pharmacologically effective range for prolonged period of time. The better in vivo performance of the transdermal patches of glibenclamide in comparison with oral administration could be due to day-to-day glycemic control on long-term application.
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PMID:Glibenclamide transdermal patches: physicochemical, pharmacodynamic, and pharmacokinetic evaluations. 1512 15

Skin irritation due to iontophoresis may limit the frequency of use of devices for drug delivery or transdermal extraction of analytes of clinical interest. This study examined whether preapplication of corticosteroid preparations could reduce skin irritation from iontophoresis used by the GlucoWatch G2 Biographer (Cygnus, Inc., Redwood City, CA) in monitoring interstitial glucose levels frequently and automatically. Numerous corticosteroid preparations were screened to identify formulations that did not interfere with adhesion of the Biographer to the skin or glucose sensing. Kenalog (Westwood-Squibb Pharmaceuticals, Inc., Buffalo, NY) (triamcinolone acetonide) and Cortizone-10 Quick Shot (Pfizer, Inc., New York, NY) (hydrocortisone) sprays were selected and, in a double-masked, randomized, controlled trial, were applied to the forearms of 66 subjects with diabetes and allowed to dry. Biographers were applied and worn for 15 h, and home blood glucose measurements were taken every 30 min to assess accuracy. Irritation was assessed periodically by trained observers and study subjects. Skin irritation was reduced by both corticosteroid sprays, with the fraction of subjects who experienced moderate irritation reduced by 57% and 43% for the Kenalog and Cortizone-10 Quick Shot sprays, respectively. The treatment effect persisted at the 1-week assessment. Preapplication of these preparations did not affect the clinical utility of interstitial glucose readings. Preapplication of Kenalog or Cortizone-10 Quick Shot sprays significantly reduced skin irritation due to iontophoresis, and did not interfere with glucose measurements. This approach may enable the minority of users who experience moderate to severe skin irritation to use the Biographer more frequently for diabetes management.
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PMID:The effect of preapplication of corticosteroids on skin irritation and performance of the GlucoWatch G2 Biographer. 1519 40

1. Membrane-moderated transdermal systems of glipizide were prepared using drug-containing carbopol gel (drug reservoir) and ethyl cellulose, as well as Eudragit RS-100, Eudragit RL-100 (Rohm Pharma, Darmstadt, Germany) and ethylene vinyl acetate (EVA; 2, 9 and 19% vinyl acetate content) rate-controlling membranes, and were subsequently evaluated in vitro (drug content and drug permeation studies) and in vivo (acute and long-term hypoglycaemic activity, effect on glucose tolerance, biochemical and histopathological studies, skin irritation test and pharmacokinetic studies in mice). 2. The drug content of the systems was found to be more than 99%. Variations in drug permeation patterns were observed among the formulations containing different rate-controlling membranes. 3. The system with the EVA (19% vinyl acetate) rate-controlling membrane was selected for in vivo experiments. This transdermal system produced better improvement with respect to hypoglycaemic activity, glucose tolerance and tested biochemical, histopathological and pharmacokinetic parameters all compared with oral administration and exhibited negligible skin irritation. 4. The transdermal system successfully prevented severe hypoglycaemia in the initial hours and it was also effective for chronic application.
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PMID:Pharmacological evaluation of membrane-moderated transdermal system of glipizide. 1644 94

Continuous glucose monitoring (CGM) is becoming increasingly popular and represents the third era of diabetes management. Currently available CGM devices have been studied in youth with type 1 diabetes and show similar accuracy across all age groups. Tolerability of these devices relates to alarm settings, sensor skin irritation, and durability of the device. Youth will be most successful on a CGM regimen if they have a personal investment in wearing the CGM device and have a stable support system for their diabetes care. Data indicate that glycemic control improves the most in youth who wear CGM devices >or=5 days per week, allowing for the ability to make more insulin dose changes. CGM has proven useful in alerting youth to hypoglycemia and may be a valuable tool with exercise. Further studies are needed to assess the utility of CGM for prevention of severe hypoglycemic events and increasing time spent in euglycemia. Fear of hypoglycemia may be ameliorated with CGM use; however, the potential for increased stress in families with continuous feedback must also be considered. In the future, CGM use in youth may couple with insulin pump technology to create a "closed-loop" system in which the CGM device will direct insulin administration without user input.
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PMID:Continuous glucose monitoring in youth with type 1 diabetes. 1946 82

Real-time continuous glucose monitoring (RT-CGM) is the latest technological breakthrough in diabetes care. Despite its limitations of lag time between sensor and blood glucose, the need for calibration, false detection of and failure to detect hypoglycemia, and mild discomfort or skin irritation reported in some users, RT-CGM is a highly beneficial tool that can be used to detect nocturnal or unrecognized hypoglycemia and glycemic variability. This, in turn, can lead to better treatment decisions, which may improve metabolic control and decrease the incidence and progression of diabetes complications. The RT-CGM devices are fairly accurate and easy to use. It is not difficult to establish a clinical RT-CGM program in the office. However, it requires persistence and an understanding of the patient's perspective of using RT-CGM so it can be presented and taught appropriately. This article discusses the benefits and limitations of RT-CGM and establishment of a RT-CGM program in the clinical setting.
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PMID:Real-time continuous glucose monitoring in the clinical setting: the good, the bad, and the practical. 1988 73


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