Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0152030 (skin irritation)
 2,146 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The anti-cancer activities and toxicities of retinoic acid (RA) and synthetic retinoids are mediated through nuclear RA receptors (RARs) and retinoid X receptors (RXRs) that act as transcription factors. Heteroarotinoids (Hets), which contain a heteroatom in the cyclic ring of an arotinoid structure, exhibit similar anti-cancer activities, but reduced toxicity in vivo, in comparison to parent retinoids and RA. A new class of Flexible Hets (Flex-Hets), which contain 3-atom urea or thiourea linkers, regulate growth and differentiation similar to RA, but do not activate RARs or RXRs. In addition, Flex-Hets induce potent apoptosis in ovarian cancer and in head and neck cancer cell lines through the intrinsic mitochondrial pathway. In this study, 4 cervical cancer cell lines were growth inhibited by micromolar concentrations of Flex-Hets to greater extents than RAR/RXR active retinoids. The most potent Flex-Het (SHetA2) inhibited each cell line of the National Cancer Institute's human tumor cell line panel at micromolar concentrations. Oral administration of Flex-Hets (SHetA2 and SHetA4) inhibited growth of OVCAR-3 ovarian cancer xenografts to similar extents as administration of a RAR/RXR-panagonist (SHet50) and Fenretinide (4-HPR) in vivo. None of these compounds induced evidence of skin, bone or liver toxicity, or increased levels of serum alanine aminotransferase (ALT) in the treated mice. Topical application of Flex-Hets did not induce skin irritation in vivo, whereas a RAR/RXR-panagonist (NHet17) and a RARgamma-selective agonist (SHet65) induced similar irritancy as RA. In conclusion, Flex-Hets exhibit improved therapeutic ratios for multiple cancer types over RAR and/or RXR agonists.
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PMID:Flexible heteroarotinoids (Flex-Hets) exhibit improved therapeutic ratios as anti-cancer agents over retinoic acid receptor agonists. 1613 93

The essential oil of Melaleuca alternifolia, also known as tea tree or melaleuca oil, is widely available and has been investigated as an alternative antimicrobial, anti-inflammatory and anti-cancer agent. While these properties are increasingly well characterised, relatively limited data are available on the safety and toxicity of the oil. Anecdotal evidence from almost 80 years of use suggests that the topical use of the oil is relatively safe, and that adverse events are minor, self-limiting and occasional. Published data indicate that TTO is toxic if ingested in higher doses and can also cause skin irritation at higher concentrations. Allergic reactions to TTO occur in predisposed individuals and may be due to the various oxidation products that are formed by exposure of the oil to light and/or air. Adverse reactions may be minimised by avoiding ingestion, applying only diluted oil topically and using oil that has been stored correctly. Data from individual components suggest that TTO has the potential to be developmentally toxic if ingested at higher doses, however, TTO and its components are not genotoxic. The limited ecotoxicity data available indicate that TTO is toxic to some insect species but more studies are required.
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PMID:A review of the toxicity of Melaleuca alternifolia (tea tree) oil. 1624 20

Basic Blue 99 is a direct, nonoxidative hair colorant used in temporary and semipermanent hair dyes. According to current reported usage data, Basic Blue 99 is used at concentrations from 0.004% to 2% and the most often reported use is in hair tints. Hair dyes containing Basic Blue 99, as "coal tar" hair dye products, are exempt from the principal adulteration provision and from the color additive provision of the Federal Food, Drug, and Cosmetic Act of 1938 when the label bears a caution statement and "patch test" instructions for determining whether the product causes skin irritation. Preliminary testing on or by individuals should be done using an open patch test that is evaluated at 48 h after application of the test material. Users, therefore, would be able to determine their individual reactions to hair dye products containing Basic Blue 99. Basic Blue 99 dye is approximately 60% to 63% dye, whereas the remainder of the mixture is composed of sugar ( approximately 25.7%), volatile matter/water crystallization ( approximately 1.8%), and inorganic salts (bringing the mixture to 100%). The dermal absorption of Basic Blue 99 is low in both rats and humans. The LD(50) values of Basic Blue 99 in mice and rats were 2.7 g/kg and between 1.0 g/kg and greater than 2.0 g/kg, respectively. Mice and rats orally administered Basic Blue 99 for 90 days did not show any indications of cumulative toxicity. Discoloration of organs involved in the elimination of Basic Blue 99 from the animals was noted in both test species. In rabbits, Basic Blue 99 did not cause ocular irritation, but some discoloration was noted. Basic Blue 99 caused minimal dermal irritation in rabbits. Sensitization occurred in animals exposed to Basic Blue 99 in a DMSO vehicle, but not in a water vehicle in guinea pigs and mice. Basic Blue 99 administered by gavage did not cause developmental toxicity in rats. Basic Blue 99 was a weak mutagen with and without metabolic activation in the Ames test, producing both reverse and frameshift mutations, but did not induce mutations in Escherichia coli or in any mammalian cells tested. In a modified repeated-insult patch test (RIPT), no volunteers had any reaction to Basic Blue 99 after a 1-h occlusive challenge. Case reports have documented positive patch test results to 1% Basic Blue 99 in three patients. A current review of the hair dye epidemiology literature identified that use of direct hair dyes, although not the focus in all investigations, appears to have little evidence of an association with cancer or other adverse events. The Panel recognizes that hair dye epidemiology studies do not address the safety of individual hair dyes. Based on the available safety test data on Basic Blue 99, however, the Panel determined that this ingredient would not likely have carcinogenic potential as used in hair dyes. The Cosmetic Ingredient Review Expert Panel concluded that Basic Blue 99 is safe as a hair dye ingredient in the practice of use and concentration as described in this safety assessment.
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PMID:Final report on the safety assessment of Basic Blue 99. 1761 31

HC Yellow No. 5 is a direct hair dye. Hair dyes containing HC Yellow No. 5, as "coal tar" hair dye products, are exempt from the principal adulteration provision and from the color additive provision of the Federal Food, Drug, and Cosmetic Act of 1938 when the label bears a caution statement and "patch test" instructions for determining whether the product causes skin irritation. Preliminary testing on or by individuals should be done using an open patch test that is evaluated at 48 h after application of the test material. Users, therefore, would be able to determine their individual reactions to hair dye products containing HC Yellow No. 5. Absorption of HC Yellow No. 5 is minimal through skin (< 0.2%). The oral LD(50) for rats is 555.56 mg/kg. No significant toxic effects were observed after chronic oral exposure of HD Yellow No. 5 to dogs. Mild dermal irritation, but no dermal sensitization or ocular irritation was observed in laboratory animals. Results of fertility and reproductive performance, teratology, and developmental studies were negative. HC Yellow No. 5 was found to be nonmutagenic and noncytotoxic in standard laboratory assays. A current review of the hair dye epidemiology literature identified that use of direct hair dyes, although not the focus in all investigations, appears to have little evidence of an association with cancer or other adverse events. Based on the available safety test data on HC Yellow No. 5, the Panel determined that this ingredient likely would not have carcinogenic potential as used in hair dyes. The Cosmetic Ingredient Review (CIR) Expert Panel concluded that HC Yellow No. 5 is safe as a hair dye ingredient in the practices of use and concentration as described in this safety assessment.
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PMID:Final report on the safety assessment of HC Yellow No. 5. 1761 34

The purpose of this study was to determine the permeation of the hydrophilic compound 5-fluorouracil through human epidermal membranes, Ehrlich Ascites Carcinoma (EAC) cells were used as a model cell line to evaluate the cytotoxic concentration and anti-tumor activity of 5-fluorouracil (5-FU) through transdermal drug delivery for tumors. Cytotoxicity was assessed by exposing cell suspension to increased concentration of drug from 20-100 microg/ml and measuring the viable cell count by tryphan blue exclusion method. Results confirmed that 100 microg/ml of 5-FU was cytotoxic. The increase in the life span (ILS) was 87.05% with maximum survival time of 30.5+/-1.87 days. For 5-fluorouracil monolithic matrix transdermal patch, the results were statistically significant (p<0.05) compared to untreated control, anti-tumor activity was very effective compared to intravenous therapy. Patches did not show any sign of erythema, vesiculations or bullaous reaction. Mean cumulative skin irritation and adherence scoring for both animal and humans proved that none of the irritation sensitization reactions score were zero and less than one, while good adherence score was 0, with complete adherence to the skin, without leaving any adhesive residue on skin with scores = 0 in human subjects. Transdermal patches showed 100% flatness, thickness 150+/-0.03 mm, good content uniformity, folding endurance (>500 foldings), smoothness, transparency, flexibility and appearance. Pharmacokinetic studies of 5-FU transdermal patch in rabbits showed half-life 95+/-0.5 min, C(max) (ng/ml) 863.25,AUC(0-infinity) (ng/ml/h)1567+/-36 and T(max) (h) 1.5 with controlled release for 24 h which was very significant (p<0.001) compared to intravenous route. Recent patents has been reported for suitable treatment of tumors and cancer, by topical and transdermal applications. Velcro protection jackets were suitable for this study and protected our applied transdermal patched from being licked, scratched and rubbed off.
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PMID:Transdermal delivery of 5-fluorouracil for induced ehrlich ascites carcinoma tumor in BALB/c mice and pharmacokinetic study. 1822 Oct 66

Despite their use of prophylactic antiemetic therapies, cancer patients continue to consider chemotherapy-induced nausea and vomiting (CINV) to be a significant problem. Patients frequently use various "breakthrough" medications for these symptoms. Unfortunately, there is a paucity of trials regarding treatment of breakthrough CINV. This study investigated the efficacy of "ABH," a topical gel containing lorazepam (Ativan), diphenhydramine (Benadryl), and haloperidol (Haldol), in reducing breakthrough CINV. Adults receiving standard recommended prophylactic antiemetics as outpatients were instructed to use 0.5 mL of the gel topically when they experienced significant CINV. Patients then were contacted retrospectively to respond to a questionnaire rating their nausea and/or vomiting and their response to ABH-gel treatment. The results were collected during two trials: Trial I began in April 2003, and Trial II began in March 2006. During Trial I, 23 patients were evaluated; 17 patients (74%) reported that use of the gel decreased their CINV, with 15 (70%) reporting relief within 30 minutes of its application. Three patients believed that the gel caused sedation; no troubles with skin irritation or muscle spasms were reported. In Trial II, all 10 patients believed that the treatment was effective. When the severity of CINV was quantified on a scale of 0-10, the mean CINV score decreased significantly from a 6.1 before gel application to a 1.7 as evaluated 30 minutes following gel application (P < 0.005). Topical use of ABH gel appears to be a promising and safe rescue therapy for breakthrough CINV that occurs despite prophylactic antiemetic therapy. These results warrant further confirmation in a large, randomized, placebo-controlled trial.
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PMID:Lorazepam, diphenhydramine, and haloperidol transdermal gel for rescue from chemotherapy-induced nausea/vomiting: results of two pilot trials. 1825 98

Non-animal based approaches to risk assessment are now routinely used for assuring consumer safety for some endpoints (such as skin irritation) following considerable investment in developing and applying new methods over the past 20 years. Unilever's research programme into non-animal approaches for safety assessment is currently focused on the application of new technologies to risk assessments in the areas of skin allergy, cancer and general toxicity (including inhalation toxicity). In all of these areas, a long-term investment is essential to increase the scientific understanding of the underlying biological and chemical processes that we believe will ultimately form a sound basis for novel risk assessment approaches. Our research programme in these priority areas consists of in-house research as well as Unilever-sponsored academic research, involvement with EU-funded projects (e.g. Sens-it-iv, carcinoGENOMICS), participation in cross-industry collaborative research (e.g. COLIPA, EPAA) and ongoing involvement with other scientific initiatives on non-animal approaches to risk assessment (e.g. UK NC3Rs, US 'Human Toxicology Project' consortium).
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PMID:Non-animal approaches for consumer safety risk assessments: Unilever's scientific research programme. 2010 96

Multiple fractions of High Dose Rate (HDR) brachytherapy along with external beam therapy is the common method of treatment for cancer of the uterine cervix. Urinary bladder and rectum are the organs at risk (OARs) that receive a significant dose during treatment. To reduce the dose to these organs, a majority of hospitals use vaginal gauze packing, as it is a simple, nontraumatic, and easy method. This article describes the design and development of an inflatable balloon that can be used along with the applicator as a substitute for gauze packing. The balloon has two parts-the bladder part (B-part) and the rectum part (R-part), both of them are independently inflatable. The selection of the material, its width, length, and thickness are described. A mould/former for making the balloon was designed. Polished steel was used as the mould. This was dipped in specially prepared natural rubber latex (NRL) solution several times; the layers were dried and stripped to get the balloon. The composition of NRL and the compounding recipe of the latex are also described. Physical tests like tensile strength, elongation at break, bursting volume, and radiation attenuation caused by the balloon, were checked. Biological tests for assessing type I and type IV allergies, like dermal irritation and skin irritation tests, were also done.
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PMID:Design and development of an inflatable latex balloon to reduce rectal and bladder doses for patients undergoing high dose rate brachytherapy. 2012 66

Erythroderma is an uncommon skin disorder characterized by generalized reddening and scaling of over 90% of the skin. It represents a maximal stage of skin irritation induced by several skin diseases such as psoriasis, contact dermatitis, drug reactions, and mycosis fungoides. Data including the clinical symptoms, laboratory examinations and skin biopsies were collected from 82 erythroderma patients admitted to our hospital in the period between Jan.1st, 2003 and Dec.31st, 2008. According to clinical findings, laboratory findings and biopsy results, the most common causative factors were pre-existing dermatoses (72.0%), followed by drug reactions (17.0%), idiopathic causes (6.1%) and malignancies (4.9%). Among the pre-existing dermatoses, psoriasis is the most common etiology (30.5%). We also found hypereosinophilic syndrome, sarcoidosis and dermatomyositis could be causes of erythroderma. In the drug-induced group, Chinese traditional herbal medicines were probably the most frequently implicated drugs in our series, with 9 of the 14 cases (64.3%). Follow-up information was obtained for 65 patients, and most of our patients had improved symptoms after treatment. In our series we found a high percentage of erythroderma secondary to pre-existing dermatoses and a low percentage of erythroderma secondary to malignancy. Among drugs as an etiological group, Chinese traditional herbal medicines were the most frequent drugs. From our follow-up study, the prognosis of most patients with erythroderma is relatively good.
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PMID:Erythroderma: A clinical-etiological study of 82 cases. 2040 Mar 88

Radiation therapy is a key modality in the treatment of different cancer types. Fatigue is the most common side effect of radiotherapy, while others include nausea, hair loss, skin irritation, anemia, infertility, cardiovascular disease, cognitive impairment and even the development of second cancers. Studies in experimental animals have shown protective effects of carnitine against exposure of various organs to ionizing radiation, whereas carnitine deficiency is known to enhance radiation-induced toxicity. This report summarizes the recent literature on the adverse effects of radiotherapy and the impact of radiation on carnitine homeostasis. Although some studies have demonstrated the prophylactic benefits of carnitine against the toxic effects of chemotherapy, the role of carnitine in the prognosis and management of cancer patients receiving radiotherapy is not clear and needs to be explored.
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PMID:A review of the logistic role of L-carnitine in the management of radiation toxicity and radiotherapy side effects. 2181 61


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