Topical application of quercetin improves wound repair and regeneration in diabetic rats.

Purpose: There is an urgent need of effective drug/formulation to speed up the healing process in diabetic wounds. In our earlier studies, quercetin has accelerated the healing of nondiabetic wounds. So, we investigated the wound-healing potentials of quercetin in diabetic rats.Materials and methods: A square-shaped cutaneous wound (≈400 mm2) was created on the back of nondiabetic and diabetic rats. They were divided into three groups, viz. healthy control (nondiabetic), diabetic control and diabetic-treated group. Ointment base was topically applied for 21 days in healthy and diabetic control groups. Quercetin (0.3%) ointment was similarly applied in third group. Effects of quercetin on repair and regenerations of diabetic wounds in terms of wound closure, inflammation, angiogenesis, fibroblast proliferation, collagen synthesis, epithelialization, axonal regeneration etc was studied.Results: Quercetin accelerated the wound closure and increased the expressions of IL-10, VEGF and TGF-ß1 in granulation/healing tissue of diabetic wound. However, quercetin decreased the expression of TNF-α, IL-1ß, and MMP-9. Histopathological evaluation revealed amelioration of persistence of inflammatory cells by quercetin in diabetic wounds. There was good quality of granulation tissue, marked fibroblast proliferation, well organized collagen deposition, early regeneration of epithelial layer etc. in the quercetin treated diabetic wounds in comparison to diabetic control group. Results of immunohistochemistry showed more angiogenesis, faster phenotypic switching of fibroblast to myofibroblasts and increased GAP-43 positive nerve fibers in quercetin-treated diabetic wounds.Conclusion: Quercetin ointment at 0.3% w/w concentration modulates cytokines, growth factors and protease, thereby improved repair and regenerations of cutaneous diabetic wounds in rats.

Association of Bolster Duration With Uptake Rates of Fibula Donor Site Skin Grafts.

Importance: The fibula free flap donor site is associated with both short-term and long-term morbidity. Split-thickness skin graft (STSG) loss can lead to long delays in donor site healing and is associated with significant adverse sequelae. Patients may experience initial good STSG uptake after bolster removal but may have subsequent partial or total loss related to contact pressure or shearing. Objective: To determine if increased duration of bolster use is associated with increased STSG uptake rates following fibula free flap reconstruction. Design, Setting, and Participants: This retrospective cohort study included patients 18 years and older undergoing fibula free flap reconstruction following head and neck extirpative surgery at a tertiary care academic medical center from May 2013 to March 2019. The donor sites were photographed 4 weeks postoperatively, and areas of graft uptake were measured using image processing software. The baseline demographic, comorbidity, and operative characteristics were also collected. Interventions: A fine mesh gauze with 3% bismuth tribromophenate and petrolatum blend bolster was sutured over leg STSGs placed on fibula free flap donor sites intraoperatively, and the ankle and lower leg were immobilized for 5 days in a plaster splint. Bolsters were either removed on postoperative day 5 or 14. Thereafter, the STSGs were covered with a petroleum and bismuth gauze and a cotton dressing. Main Outcomes and Measures: Rates of donor site infection and STSG percentage uptake at 4 weeks. Results: Of the 42 included patients, 31 (74%) were male, and the mean (SD) age was 62.1 (13.1) years. A total of 20 patients were included in the 5-day group, and 22 were included in the 14-day group. The 14-day bolster group had a higher mean percentage skin graft uptake rate compared with the 5-day bolster duration group (77.5% vs 59.9%), with an effect size of -0.632 (95% CI, -1.260 to -0.004). Patients with Adult Comorbidity Evalution-27 scores of 3 had poorer rates of STSG uptake compared with patients with Adult Comorbidity Evalution-27 scores of 0 to 2 (65.9% vs 82.9%), with an effect size of 0.599 (95% CI, -0.191 to 1.389). No donor site infections were noted in either group. Conclusions and Relevance: Fourteen-day bolster application to the fibula free flap donor site was associated with better STSG uptake rates than 5-day bolster application.

Technological features of advanced skin protectants and an examination of the evidence base.

Products that provide a protective skin barrier play a vital role in defending the skin against the corrosive effect of bodily fluids, including wound exudate, urine, liquid faeces, stoma output and sweat. There are many products to choose from, which can be broadly categorised by ingredients. This article describes the differences in mechanisms of action between barrier products comprising petrolatum and/or zinc oxide, silicone film-forming polymers and cyanoacrylates, and compares the evidence on them. The literature indicates that all types of barrier product are clinically effective, with little comparative evidence indicating that any one ingredient is more efficacious than another, although film-forming polymers and cyanoacrylates have been found to be easier to apply and more cost-effective. However, laboratory evidence, albeit limited, indicates that a concentrated cyanoacrylate produced a more substantial and adherent layer on a porcine explant when compared with a diluted cyanoacrylate and was more effective at protecting skin from abrasion and repeated exposure to moisture than a film-forming polymer. Finally, a silicone-based cream containing micronutrients was found to significantly reduce the incidence of pressure ulceration when used as part of a comprehensive prevention strategy.

A Randomized Trial of Mometasone Furoate 0.1% to Reduce High-Grade Acute Radiation Dermatitis in Breast Cancer Patients Receiving Postmastectomy Radiation.

PURPOSE: A 2-arm, double-blinded randomized trial was conducted to evaluate the efficacy of 0.1% mometasone furoate (MF) versus Eucerin Original (E) cream in preventing the development of moderate to severe acute radiation dermatitis (ARD) in breast cancer patients receiving postmastectomy radiation (PMRT). METHODS: Breast cancer patients undergoing chest wall with or without nodal radiation therapy (RT) (50 Gy) were eligible. Randomization (1:1) was to MF or E, applied twice daily from day 1 of PMRT to 14 days after PMRT. Patients were stratified by RT technique, body mass index, and reconstruction status. Daily bolus of 3 to 10 mm was applied in all patients. The primary endpoint was the development of provider-assessed grade ≥2 (Common Terminology Criteria for Adverse Events version 4.03) ARD with moist desquamation or any grade ≥3 dermatitis. Secondary endpoints were time to occurrence of maximum-grade dermatitis and patient-reported skin symptoms using a skin-related quality of life questionnaire, Skindex-16. Assessments were performed at baseline, weekly during PMRT, and 2 weeks after PMRT. RESULTS: 124 patients were enrolled between May 2013 and February 2016. Of those, 35% had pathologic stage III disease, 6% had cT4d disease, and 68% underwent reconstruction. Sixty percent received 3-dimensional conformal RT with photons only to the chest wall, 18% received electrons and photons, and 23% received inverse-planned intensity modulated RT. Groups were well balanced for age, skin type, and stage. The rate of moist desquamation was 54.8% in the entire cohort, with a significantly reduced incidence in the MF arm than in the E arm (43.8% vs 66.7%; P = .012). The MF arm had a lower incidence of maximum skin toxicities (P = .036) and longer time to development of grade 3 dermatitis (46 days vs 35.5 days, respectively; P ≤ .001). There was no difference in patient-reported skin outcomes between arms. CONCLUSIONS: Breast cancer patients receiving MF during PMRT experienced significantly reduced rates of moist desquamation in comparison with a control cream.

Interventions for Old World cutaneous leishmaniasis.

BACKGROUND: Cutaneous leishmaniasis, caused by a parasitic infection, is considered one of the most serious skin diseases in many low- and middle-income countries. Old World cutaneous leishmaniasis (OWCL) is caused by species found in Africa, Asia, the Middle East, the Mediterranean, and India. The most commonly prescribed treatments are antimonials, but other drugs have been used with varying success. As OWCL tends to heal spontaneously, it is necessary to justify the use of systemic and topical treatments. This is an update of a Cochrane Review first published in 2008. OBJECTIVES: To assess the effects of therapeutic interventions for the localised form of Old World cutaneous leishmaniasis. SEARCH METHODS: We updated our searches of the following databases to November 2016: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs). We wrote to national programme managers, general co-ordinators, directors, clinicians, WHO-EMRO regional officers of endemic countries, pharmaceutical companies, tropical medicine centres, and authors of relevant papers for further information about relevant unpublished and ongoing trials. We undertook a separate search for adverse effects of interventions for Old World cutaneous leishmaniasis in September 2015 using MEDLINE. SELECTION CRITERIA: Randomised controlled trials of either single or combination treatments in immunocompetent people with OWCL confirmed by smear, histology, culture, or polymerase chain reaction. The comparators were either no treatment, placebo/vehicle, and/or another active compound. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias and extracted data. We only synthesised data when we were able to identify at least two studies investigating similar treatments and reporting data amenable to pooling. We also recorded data about adverse effects from the corresponding search. MAIN RESULTS: We included 89 studies (of which 40 were new to this update) in 10,583 people with OWCL. The studies included were conducted mainly in the Far or Middle East at regional hospitals, local healthcare clinics, and skin disease research centres. Women accounted for 41.5% of the participants (range: 23% to 80%). The overall mean age of participants was 25 years (range 12 to 56). Most studies lasted between two to six months, with the longest lasting two years; average duration was four months. Most studies were at unclear or high risk for most bias domains. A lack of blinding and reporting bias were present in almost 40% of studies. Two trials were at low risk of bias for all domains. Trials reported the causative species poorly.Here we provide results for the two main comparisons identified: itraconazole (200 mg for six to eight weeks) versus placebo; and paromomycin ointment (15% plus 10% urea, twice daily for 14 days) versus vehicle.In the comparison of oral itraconazole versus placebo, at 2.5 months' follow up, 85/125 participants in the itraconazole group achieved complete cure compared to 54/119 in the placebo group (RR 3.70, 95% CI 0.35 to 38.99; 3 studies; 244 participants). In one study, microbiological or histopathological cure of skin lesions only occurred in the itraconazole group after a mean follow-up of 2.5 months (RR 17.00, 95% CI 0.47 to 612.21; 20 participants). However, although the analyses favour oral itraconazole for these outcomes, we cannot be confident in the results due to the very low certainty evidence. More side effects of mild abdominal pain and nausea (RR 2.36, 95% CI 0.74 to 7.47; 3 studies; 204 participants) and mild abnormal liver function (RR 3.08, 95% CI 0.53 to 17.98; 3 studies; 84 participants) occurred in the itraconazole group (as well as reports of headaches and dizziness), compared with the placebo group, but again we rated the certainty of evidence as very low so are unsure of the results.When comparing paromomycin with vehicle, there was no difference in the number of participants who achieved complete cure (RR of 1.00, 95% CI 0.86, 1.17; 383 participants, 2 studies) and microbiological or histopathological cure of skin lesions after a mean follow-up of 2.5 months (RR 1.03, CI 0.88 to 1.20; 383 participants, 2 studies), but the paromomycin group had more skin/local reactions (such as inflammation, vesiculation, pain, redness, or itch) (RR 1.42, 95% CI 0.67 to 3.01; 4 studies; 713 participants). For all of these outcomes, the certainty of evidence was very low, meaning we are unsure about these results.Trial authors did not report the percentage of lesions cured after the end of treatment or speed of healing for either of these key comparisons. AUTHORS' CONCLUSIONS: There was very low-certainty evidence to support the effectiveness of itraconazole and paromomycin ointment for OWCL in terms of cure (i.e. microbiological or histopathological cure and percentage of participants completely cured). Both of these interventions incited more adverse effects, which were mild in nature, than their comparisons, but we could draw no conclusions regarding safety due to the very low certainty of the evidence for this outcome.We downgraded the key outcomes in these two comparisons due to high risk of bias, inconsistency between the results, and imprecision. There is a need for large, well-designed international studies that evaluate long-term effects of current therapies and enable a reliable conclusion about treatments. Future trials should specify the species of leishmaniasis; trials on types caused by Leishmania infantum, L aethiopica, andL donovani are lacking. Research into the effects of treating women of childbearing age, children, people with comorbid conditions, and those who are immunocompromised would also be helpful.It was difficult to evaluate the overall efficacy of any of the numerous treatments due to the variable treatment regimens examined and because RCTs evaluated different Leishmania species and took place in different geographical areas. Some outcomes we looked for but did not find were degree of functional and aesthetic impairment, change in ability to detect Leishmania, quality of life, and emergence of resistance. There were only limited data on prevention of scarring.

Prevention of Cutaneous Penetration and CD1c+ Uptake of Pollen Allergens by a Barrier-Enhancing Formulation.

Recent studies have shown that pollen proteins can penetrate the impaired skin barrier of atopic patients and exacerbate their disease. In the presented study the effect of a topically applied barrier-enhancing formulation was investigated for its preventive effect on the uptake of pollen allergens into CD1c+ epidermal cells. The pollen proteins were fluorescence labelled and applied on barrier-disrupted excised human skin. CD1c+ cells were selected after magnetic cell sorting and analysed using laser scanning microscopy. In untreated disrupted skin, 81% of the CD1c+ cells contained the fluorescence-labelled pollen allergens. In formulation-pretreated skin only 12% of the CD1c+ cells showed an uptake of pollen allergens. These results encourage the treatment of atopic patients with barrier-enhancing formulations to reduce the impact of pollen on air-exposed skin areas and hence the exacerbation of cutaneous symptoms.

Drug release and skin penetration from solid lipid nanoparticles and a base cream: a systematic approach from a comparison of three glucocorticoids.

Solid lipid nanoparticles (SLNs) can enhance drug penetration into the skin, yet the mechanism of the improved transport is not known in full. To unravel the influence of the drug-particle interaction on penetration enhancement, 3 glucocorticoids (GCs), prednisolone (PD), the diester prednicarbate (PC) and the monoester betamethasone 17-valerate (BMV), varying in structure and lipophilicity, were loaded onto SLNs. Theoretical permeability coefficients (cm/s) of the agents rank BMV (-6.38) ≥ PC (-6.57) > PD (-7.30). GC-particle interaction, drug release and skin penetration were investigated including a conventional oil-in-water cream for reference. Both with SLN and cream, PD release was clearly superior to PC release which exceeded BMV release. With the cream, the rank order did not change when studying skin penetration, and skin penetration is thus predominantly influenced by drug release. Yet, the penetration profile for the GCs loaded onto SLNs completely changed, and differences between the steroids were almost lost. Thus, SLNs influence skin penetration by an intrinsic mechanism linked to a specific interaction of the drug-carrier complex and the skin surface, which becomes possible by the lipid nature and nanosize of the carrier and appears not to be derived by testing drug release. Interestingly, PC and PD uptake from SLN even resulted in epidermal targeting. Thus, SLNs are not only able to improve skin penetration of topically applied drugs, but may also be of particular interest when specifically aiming to influence epidermal dysfunction.

In vitro release, rheological, and stability studies of mefenamic acid coprecipitates in topical formulations.

A suitable topical formulation of mefenamic acid was developed in order to eliminate the gastrointestinal disorders associated with its oral administration. Drug coprecipitates prepared with different polymers at various drug-to-polymer ratios improved drug solubility and dissolution compared to pure drug and physical mixtures. PVP polymers (ratio 1:4) produced the best results. Aqueous ionic cream, ointments of absorption and water soluble bases and gels of methylcellulose, carboxymethylcellulose sodium, HPMC, Carbopol® 934 and 940, and Pluronic® F127 bases containing 1-10% drug as coprecipitates of PVP polymers (1:4) were prepared. The highest drug release was achieved at 1% drug concentration from water soluble base and methylcellulose among cream/ointment and gel bases, respectively. Gels, in general yielded better release than creams/ointments. All tested medicated creams/ointments exhibited plastic flow while all gels conformed to pseudoplasticity. Most of them showed thixotropy, a desired property of topical preparations. Stability studies revealed that HPMC and methylcellulose had the smallest changes in drug content, viscosity, and pH among the formulations. Considering drug release, rheological properties, and stability, methylcellulose gel containing 1% drug as coprecipitates of PVP K90 was the best among the studied formulations, was promising for improving bioavailability of mefenamic acid and can be used in future studies.

Chemopreventive efficacy of topical difluoromethylornithine and/or triamcinolone in the treatment of actinic keratoses analyzed by karyometry.

OBJECTIVE: To determine whether low-dose topical applications of difluoromethylornithine (DFMO) with or without Triamcinolone (Fougena, Melville, New York, U.S.A.) to moderately sun-damaged skin with actinic skin keratoses are efficacious. STUDY DESIGN: There were 4 topically administered, 6-month treatments, DFMO + Eucerin (Beiersdorf Inc., Hamburg, Germany), DFMO + Triamcinolone, Triamcinolone + Eucerin and Eucerin + Eucerin (to serve as double placebo). Participant eligibility included evidence of at least 2 actinic keratoses on each posterolateral forearm as well as moderate to severe evidence of sun-damaged skin, as evaluated by a board certified dermatologist. High resolution digitized imagery of nuclei from histologic sections of 4-mm punch biopsies from sun-damaged skin on the posterolateral forearms was recorded, at baseline and at the end of 6 months of study. RESULTS: With 102 participants and 185 skin biopsies, a total of 16,395 skin cell nuclei were recorded. The nuclei were analyzed to assess the changes in the pattern of the nuclear chromatin. Two specific measures of end point evaluation were computed, including the percentage of nuclei with high values of nuclear abnormality and the reduction of the percentage of nuclei assigned by a discriminant function to the baseline data set. All 3 active interventions, including low-dose topical DFMO, topical Triamcinolone and topical DFMO + Triamcinolone, led to statistically significant reductions of both the number of nuclei with high nuclear abnormality as well as the number of nuclei assigned to the baseline data set. These reductions were found for all 3 treatments involving DFMO or Triamcinolone. For the placebo data sets only small, statistically insignificant increases or decreases of these percentages were observed. CONCLUSION: The low-dose, topical drug interventions were all effective in reducing skin biopsy nuclear abnormality by a statistically significant 15-20%, whereas there was no evidence of a double placebo effect by karyometric assessment. These effects were greater than the case-to-case sampling error.

New technique for drug application to the spinal cord of walking mice.

With the increasing availability of mutant mice that allow the conditional silencing of specific classes of interneurons in the spinal cord by drug application, a method for easily delivering drugs locally on spinal cord segments in adult animals has the potential for providing insights into the functioning of neuronal networks controlling walking. Here we describe a simple technique for this purpose. The drug is applied in high concentrations in a bath created with Vaseline walls around one to three segments of the spinal cord exposed under general anesthetic (isoflurane) combined with a strong, long-lasting analgesic (buprenorphine). After 20min of drug application the Vaseline and the drug is removed and skin closed. We first document that the surgery and analgesic have no obvious influences on the kinematics of hind leg movements after recovery from the anesthetic, and that the analgesic enhanced locomotor activity. We then describe the influence of applying a glycine-receptor antagonist onto the lumbar segments of the spinal cord to demonstrate that the method is effective in modifying the functioning of neuronal systems in the spinal cord. Combining this method with kinematic and electromyographic recording techniques allows the detailed investigation of the effects of drugs on the walking behavior in adult mice.

Keratosis follicularis (Darier-White disease), with an unusual palmoplantar keratoderma.

A 38-year-old woman presented with widespread, hyperkeratotic papules and plaques that had been present since childhood. Her mother, brother, and son have similar lesions. A diagnosis of keratosis follicularis was made, which has been treated with isotretinoin. Palmoplantar lesions of keratosis follicularis have been described as discrete, punctate keratoses, hyperkeratotic papules, small pits, or keratin-filled depressions. This patient has an unusual palmoplantar keratoderma in association with keratosis follicularis. The lesions are elevated, discrete, filiform, hyperkeratotic spires, which coalesce into large, hyperkeratotic plaques on the palms and soles.

Wound-healing property of Momordica charantia L. fruit powder.

Momordica charantia Linn. fruit powder, in the form of an ointment (10% w/w dried powder in simple ointment base), was evaluated for wound-healing potential in an excision, incision and dead space wound model in rats. The rats were divided into three groups of control, treatment and reference in all three wound models, each group consisting of six rats. Wound-contraction ability in excision wound mode was measured at different time intervals on days 4, 8, 10, 12 and 14 , and the study was continued until the wound had completely healed. Tensile strength was measured in 10-day-old incision and granuloma wound. Histological studies were performed on 10-day-old sections of regenerated tissue. Powder ointment showed a statistically significant response (P < 0.01), in terms of wound-contracting ability, wound closure time, period of epithelization, tensile strength of the wound and regeneration of tissues at wound site when compared with the control group, and these results were comparable to those of a reference drug povidone iodine ointment.

Coping with mild inflammatory catamenial acne: a clinical and bioinstrumental split-face assessment.

BACKGROUND: Acne is a multifactorial disease exhibiting distinct clinical presentations. Among them, the catamenial type is a matter of concern for young women. Some oral contraceptives may help without, however, clearing the skin condition. AIM: The present open study aimed at evaluating the effect of overnight applications of a paste made of petrolatum,15% zinc oxide and 0.25% miconazole nitrate. METHOD: The split-face trial was conducted in 35 women. A non-medicated cream was used as control. Clinical evaluations and biometrological assessments on cyanoacrylate follicular biopsies were performed monthly for 3 months. Comedometry and the density in autofluorescent follicular casts were used as analytical parameters. In addition, the five most severe cases at inclusion were tested at the completion of the study for follicular bacterial viability using dual flow cytometry. RESULTS: Compared with baseline and to the control hemi-face, the medicated paste brought significant improvement of acne. The number of papules and their redness were reduced beginning with the first treatment phase. A reduction in the follicular fluorescence was yielded beginning with the second treatment phase. The ratios between injured and dead bacteria, on the one hand, and live bacteria, on the other hand were significantly increased at completion of the study. CONCLUSION: A miconazole paste applied for 1 week at the end of the ovarian cycle has a beneficial effect on catamenial acne.

Moist skin care can diminish acute radiation-induced skin toxicity.

BACKGROUND: Radiation treatment may induce acute skin reactions. There are several methods of managing them. Validity of these methods, however, is not sufficiently studied. We therefore investigated, whether moist skin care with 3% urea lotion will reduce acute radiation skin toxicity. PATIENTS AND METHODS: 88 patients with carcinomas of the head and neck undergoing radiotherapy with curative intent (mean total dose 60 Gy, range: 50-74 Gy) were evaluated weekly for acute skin reactions according to the RTOG-CTC score. In 63 patients, moist skin care with 3% urea lotion was performed. The control group consisted of 25 patients receiving conventional dry skin care. The incidence of grade I, II, and III reactions and the radiation dose at occurrence of a particular reaction were determined and statistically analyzed using the log-rank test. The dose-time relations of individual skin reactions are described. RESULTS: At some point of time during radiotherapy, all patients suffered from acute skin reactions grade I, > 90% from grade II reactions. 50% of patients receiving moist skin care experienced grade I reactions at 26 Gy as compared to 22 Gy in control patients (p = 0.03). Grade II reactions occurred at 51 Gy versus 34 Gy (p = 0.006). Further, 22% of the patients treated with moist skin care suffered from acute skin toxicity grade III as compared to 56% of the controls (p = 0.0007). CONCLUSION: Moist skin care with 3% urea lotion delays the occurrence and reduces the grade of acute skin reactions in percutaneously irradiated patients with head and neck tumors.

Fasting is a physiological stimulus of vagus-mediated enhancement of nociception in the female rat.

The vagus nerve modulates nociception by a mechanism dependent upon gonadal hormones and the adrenal medulla. In the present study we tested the hypothesis that this modulation is dynamically controlled by physiological stimulation of structures innervated by the subdiaphragmatic vagus. Specifically, food deprivation (fasting) was employed to increase activity in the subdiaphragmatic vagus, and the experiments were performed mainly in female rats because our previous observations suggested that baseline activity in the pathway is lower in females than in males. Consistent with the hypothesis, after a 48-h fast, female rats exhibited increased nociceptive behavior in the formalin test. In contrast, fasting had no effect on formalin-evoked nociceptive behavior in male rats. The fasting-induced effect on nociception appears to be mediated by the vagus nerve since it is prevented by subdiaphragmatic vagotomy. Also similar to the previously characterized vagus-mediated modulation, the effect of fasting in the female is blocked by gonadectomy or adrenal medullectomy, and hormone replacement with 17beta-estradiol in gonadectomized female rats restored the effect of fasting. Decreased glucose metabolism apparently does not play a significant role in the effect of fasting on nociception, since the effect was unchanged when 5% glucose was provided in the drinking water throughout the fasting period. On the other hand, increasing the bulk content of the stomach (without providing nutrients) by infusion of petrolatum significantly attenuated the effect of fasting during the interphase period of the formalin response, suggesting that decreased gut distention, and possibly motility, are important in fasting-induced enhancement of nociception. These results indicate that fasting is a physiological activator of the vagus-mediated pain modulation pathway. This suggests the possibility that, especially in females, natural periodic changes in gut distention and motility may control an ongoing vagus-mediated adjustment in the organism's nociceptive sensitivity.

[Sun protection during holidays]. / Sonnenschutz im Urlaub.

Ultraviolet radiation is causally involved in induction of skin cancer, premature skin aging and photodermatoses. The longing of our western society for a "healthy tanning" as well as the unbroken trend to spend the holidays in sunny regions lead to the fact that human skin is increasingly exposed to ultraviolet radiation and its detrimental effects. Because of the socio-political importance of the vacation period as the "most beautiful and most important time of the year", effective prevention of these unwanted UV effects has an enormous importance to the general population. In this article the most important methods for effective sun protection are critically discussed.

Common commercial cosmetic products induce arthritis in the DA rat.

Many different agents, including mineral oil and silicone, have the capacity to act as immunological adjuvants, i.e., they can contribute to the activation of the immune system. Some adjuvants, including mineral oil, are known to induce arthritis in certain strains of rats after intradermal injection or percutaneous application. The aim of this study was to determine if common commercial cosmetic products containing mineral oil could induce arthritis in the highly susceptible DA (Dark Agouti) rat. Intradermal injection of five out of eight assayed cosmetic products without further additives resulted in arthritis with synovitis. One of the products induced a very aggressive arthritis, which had declined after 5-9 weeks. When this product was also assayed for arthritogenicity upon percutaneous administration, it induced a mild and transient arthritis in 5 out of 10 DA rats, whereas control animals showed no clinical signs of joint involvement. No arthritic reaction was seen in rats after peroral feeding with the most arthritogenic product or by intravaginal application of Freund's adjuvants. Silicone gel implants in DA rats did not cause arthritis. We conclude that mineral oils included in common commercially available products retain their adjuvant properties and are arthritogenic in the presently investigated arthritis-prone rat strain. There is yet no evidence that mineral oils present in cosmetics may contribute to arthritis in humans, but we suggest that this question should be subject to further investigation.