ABSTRACT
BACKGROUND: Skin ageing is said to be caused by multiple factors. The relationship with sun exposure is of particular interest because the detrimental cutaneous effects of the sun may be a strong motivator to sun protection. We report a study of skin ageing in participants of an epidemiological study of melanoma. OBJECTIVES: To determine the predictors of periorbital cutaneous ageing and whether it could be used as an objective marker of sun exposure. METHODS: Photographs of the periorbital skin in 1341 participants were graded for wrinkles, degree of vascularity and blotchy pigmentation and the resultant data assessed in relation to reported sun exposure, sunscreen use, body mass index (BMI), smoking and the melanocortin 1 receptor (MC1R) gene status. Data were analysed using proportional odds regression. RESULTS: Wrinkling was associated with age and heavy smoking. Use of higher sun-protection factor sunscreen was protective (P = 0·01). Age, male sex, MC1R variants ('r', P=0·01; 'R', P=0·02), higher reported daily sun exposure (P=0·02), increased BMI (P=0·01) and smoking (P=0·02) were risk factors for hypervascularity. Blotchy pigmentation was associated with age, male sex, higher education and higher weekday sun exposure (P=0·03). More frequent sunscreen use (P=0·02) and MC1R variants ('r', P=0·03; 'R', P=0·001) were protective. CONCLUSIONS: Periorbital wrinkling is a poor biomarker of reported sun exposure. Vascularity is a better biomarker as is blotchy pigmentation, the latter in darker-skinned individuals. In summary, male sex, sun exposure, smoking, obesity and MC1R variants were associated with measures of cutaneous ageing. Sunscreen use showed some evidence of being protective.
Subject(s)
Melanoma/pathology , Skin Aging/radiation effects , Skin Neoplasms/pathology , Sunlight/adverse effects , Adult , Aged , Case-Control Studies , Female , Genotype , Humans , Male , Middle Aged , Obesity/complications , Obesity/pathology , Observer Variation , Orbit , Receptor, Melanocortin, Type 1/genetics , Skin/blood supply , Skin Aging/genetics , Skin Pigmentation , Smoking/adverse effects , Sunburn/pathologyABSTRACT
Toxic epidermal necrolysis and Stevens-Johnson syndrome are rare and life-threatening diseases that often configure as medical emergencies. The majority of cases are drug reactions. The clinical picture is one of widespread epidermal necrosis and mucosal erosions. Treatment is largely supportive and must be provided in an appropriate environment. The role of steroids and other potential disease-modifying therapies has yet to be fully established by controlled studies. The significant mortality associated with these conditions dictates that an understanding of these conditions is essential for all doctors.
Subject(s)
Stevens-Johnson Syndrome/therapy , Adrenal Cortex Hormones/therapeutic use , Humans , Immunosuppressive Agents/therapeutic use , Plasmapheresis , Prognosis , Renal Dialysis , Sepsis/prevention & control , Steroids/therapeutic use , Stevens-Johnson Syndrome/epidemiology , Stevens-Johnson Syndrome/etiologyABSTRACT
The aim of this study was to classify the protective mechanisms of DL-buthionine-(S,-R)-sulphoximine, glutathione and methimazole on cisplatin-induced nephrotoxicity in rats. An Emax model was used to study the effect of these compounds on the pharmacokinetics of cisplatin, especially renal handling and intra-renal biotransformation. Cisplatin (5 mg kg(-1)) was administered as an intravenous bolus to rats treated with either 0.9% NaCl (control), buthionine sulphoximine, glutathione or methimazole. The blood urea nitrogen level was monitored to estimate cisplatin-induced nephrotoxicity. To estimate renal handling of cisplatin, cisplatin was infused intravenously to rats treated with 0.9% NaCl, buthionine sulphoximine, glutathione or methimazole. The concentrations of unchanged cisplatin in plasma, urine and kidney were determined by a post-column derivatization HPLC method. The relationship between the pharmacokinetics and toxicodynamics of cisplatin was analysed using a sigmoid Emax model. All compounds studied ameliorated significantly the nephrotoxicity of cisplatin. The renal accumulation of cisplatin was reduced significantly by pretreatment with buthionine sulphoximine but not by either glutathione or methimazole. Although glutathione treatment did not affect the renal accumulation of cisplatin, it significantly decreased the binding of cisplatin to the intrarenal organelle and the decreased binding was well correlated to the decrease of the blood urea nitrogen level. In summary, pharmacokinetic-toxicodynamic analysis will be useful for classifying the protective mechanism of cisplatin-induced nephrotoxicity.
Subject(s)
Buthionine Sulfoximine/pharmacology , Cisplatin/pharmacokinetics , Glutathione/pharmacology , Kidney Diseases/prevention & control , Kidney/drug effects , Methimazole/pharmacology , Animals , Antineoplastic Agents/adverse effects , Antineoplastic Agents/pharmacokinetics , Area Under Curve , Blood Urea Nitrogen , Cisplatin/adverse effects , Cisplatin/blood , Glomerular Filtration Rate/drug effects , In Vitro Techniques , Kidney/metabolism , Kidney Cortex/drug effects , Kidney Cortex/metabolism , Kidney Diseases/chemically induced , Kidney Diseases/metabolism , Male , Rats , Rats, Wistar , Temperature , Time FactorsABSTRACT
An unidentified carbohydrate was isolated from sweet pea (Lathyrus odoratus L. cv. Diana) petals using HPLC. The isolated compound was identified as L-1-O-methyl-myo-inositol, called L-bornesitol, using (1)H-NMR, (13)C-NMR, and CI-MS. L-Bornesitol was distributed in all organs at high concentrations. L-Bornesitol concentration of petals gradually decreased during flower bud development, but the L-bornesitol content increased by about 5 times.
