Assessing the potential value and mechanism of Ginkgo biloba L. On coal-fired arsenic-induced skin damage: In vitro and human evidence.

Exposure through arsenic-contaminated air and food caused by the burning of coal is a major environmental public health concern in Guizhou Province of China. Previous studies have shown that immunological dysfunction is involved in the pathogenesis and carcinogenesis of arsenic; however, knowledge regarding effective prevention measures have not been fully examined. The effect of Ginkgo biloba extract (EGb761) on arsenic-induced skin damage of human immortalized keratinocyte cells (HaCaT) was first evaluated in this study. The results showed that 200 µg/mL EGb761 can reduce the expression of miR-155-5p, and the indicators reflecting arsenic-induced skin damage (Krt1, Krt6c and Krt10) in arsenic-exposed cells (P < 0.05), the expression levels of NF-AT1; the indicators reflecting arsenic-induced immunological dysfunction (IL-2, IFN-γ) in cells; and the levels of secreted IL-2 and IFN-γ in cell supernatants were significantly increased (P < 0.05). Further randomized controlled double-blind experiments showed that compared to the placebo control group, the expression level of miR-155-5p in the plasma of the Ginkgo biloba intervention group, the indicators in the serum reflecting arsenic-induced skin damage (Krt1, Krt6c, and Krt10) and the epithelial-mesenchymal transformation (EMT) vimentin were significantly reduced (P < 0.05), but the levels of NF-AT1 and the indicators reflecting arsenic-induced immunological dysfunction (IL-2, IFN-γ) and EMT (E-cadherin) in serum were significantly increased (P < 0.05). Our study provides some limited evidence that Ginkgo biloba L. can increase the expression of NF-AT1 by downregulating the level of miR-155-5p, alleviating immunological dysfunction, and decreasing the expression of EMT biomarkers, thus indirectly improving arsenic-induced skin damage.

Vitamin D and the Skin: An Update for Dermatologists.

Vitamin D plays a key role in skeletal and cardiovascular disorders, cancers, central nervous system diseases, reproductive diseases, infections, and autoimmune and dermatological disorders. The two main sources of vitamin D are sun exposure and oral intake, including vitamin D supplementation and dietary intake. Multiple factors are linked to vitamin D status, such as Fitzpatrick skin type, sex, body mass index, physical activity, alcohol intake, and vitamin D receptor polymorphisms. Patients with photosensitive disorders tend to avoid sun exposure, and this practice, along with photoprotection, can put this category of patients at risk for vitamin D deficiency. Maintaining a vitamin D serum concentration within normal levels is warranted in atopic dermatitis, psoriasis, vitiligo, polymorphous light eruption, mycosis fungoides, alopecia areata, systemic lupus erythematosus, and melanoma patients. The potential determinants of vitamin D status, as well as the benefits and risks of vitamin D (with a special focus on the skin), will be discussed in this article.

[Principles of glucocorticoid therapy]. / Prinzipien der Steroidtherapie.

The principles of systemic glucocorticoid (GC) therapy in dermatology are reviewed. As a basis for an efficient GC therapy with few side effects the pharmacology, endogenous regulation as well as the mechanisms and side effects of GCs as well as their management are introduced. Modern therapeutic approaches such as circadian application and low-dose therapy are discussed as well as principles of tapering dosages and the most important indications for systemic GCs in dermatology.

Calcinosis cutis in systemic lupus erythematosus: a case report and review of the published work.

Calcinosis cutis is a common clinical feature of dermatomyositis and scleroderma but rarely reported in association with systemic lupus erythematosus (SLE). Calcinosis cutis in SLE occurs without calcium and phosphorus metabolic abnormalities and may be localized or generalized. The pathophysiology remains unclear and no effective therapy is currently available. We report a 30-year-old woman with a 13-year history of SLE who developed multiple calcinosis cutis around both knees and we review the relevant published work.

Depression in dermatology: an integrative perspective.

An example which confirmes the adequacy of the integrative perspective in medicine is depression in dermatology because of the sufficient number of arguments linking depression and some chronic skin conditions in depth more than simply comorbidity. In recent literature, the authors found, how depression in dermatology occurs significantly more frequently than in the general population. In dermatological patients the prevalence of depression is around 30% which is more in comparison to patients in general practice where prevalence of depression is 22%. The authors found a considerable similarity in the various characteristics between depression and psoriasis, based upon recent research findings in immunity disorder and elevated concentrations of proinflammatory cytokines as well as acute phase proteins in both disorders, indicating that both disorders can be considered as immunologicaly mediated, inflammatory states with repetitive chronic progress and similar comorbidity. The afore mentioned theoretical settings evoke the integrative aspect and the integrative interdisciplinary approach placing in the center of attention not only the diseased person with his fears, needs, preocupations and expectations during treatment, but the person who is at risk of becoming burdened with these disorders.

Low selenium status affects arsenic metabolites in an arsenic exposed population with skin lesions.

BACKGROUND: The antagonistic effects between selenium (Se) and arsenic (As) suggest that low selenium status plays important roles in arsenism development. However, no study has been reported for humans suffering from chronic arsenic exposure with low selenium status. METHODS: Sixty-three subjects were divided into 2 experimental groups by skin lesions (including hyperkeratosis, depigmentation, and hyperpigmentation). Total urine and serum concentrations of arsenic and selenium were determined by ICP-MS with collision/reaction cell. Arsenic species were analysed by ICP-MS coupled with HPLC. RESULTS: The mean concentration of As in the drinking waters was 41.5 microg/l. The selenium dietary intake for the studied population was 31.7 microg Se/d, and which for the cases and controls were 25.9 and 36.3 microg Se/d, respectively. Compared with the controls, the skin lesions cases had lower selenium concentrations in serum and urine (41.4 vs 49.6 microg/l and 71.0 vs 78.8 microg/l, respectively), higher inorganic arsenic (iAs) in serum (5.2 vs 3.4 microg/l, P<0.01), higher percentages of iAs in serum and urine (20.2) vs 16.9% and 18.3 vs 14.5%, respectively, P<0.01) but lower percentages of monomethylarsonate (MMA) in serum (15.5 vs 18.8%, P<0.01) ans dimethylarsinate acid (DMA) in urine (65.1 vs 69.8%, P<0.01). Subjects with lower selenium concentrations in serum (<50 microg/l) had a stronger tendency to the risk of skin lesions than individual having higher selenium concentrations [odd ratio (OR), 7.3; 95% confidence interval (95% CI), 1.5-35.7; P=0.014]. This OR estimation was confirmed in those subjects having higher ratios of As/Se in urine and serum, with OR as high as 10.3 and 3.8 respectively. CONCLUSIONS: Lower serum selenium status (<50 microg/l) is significantly correlated to the arsenic-associated skin lesions in the arsenic exposed population. The accumulation of iAs and its inhibition to be biotransformed to DMA occurred in human due to chronic exposure of low selenium status.

Skin analysis to determine causative agent in dermal exposure to petroleum products.

This study evaluates the usefulness of skin analysis to determine the causative agent in cases of dermal exposure. The study consists of an animal experiment and two human cases. The petroleum components detected at high concentrations in skin samples resembled the composition of those in the corresponding petroleum products. However, the petroleum components in blood were detected at low concentrations and were a different composition. Skin is considered to be an advantageous sample to estimate the petroleum product in clinical and forensic cases of dermal exposure.

EFA supplementation in children with inattention, hyperactivity, and other disruptive behaviors.

This pilot study evaluated the effects of supplementation with PUFA on blood FA composition and behavior in children with Attention-Deficit/Hyperactivity Disorder (AD/HD)-like symptoms also reporting thirst and skin problems. Fifty children were randomized to treatment groups receiving either a PUFA supplement providing a daily dose of 480 mg DHA, 80 mg EPA, 40 mg arachidonic acid (AA), 96 mg GLA, and 24 mg alpha-tocopheryl acetate, or an olive oil placebo for 4 mon of double-blind parallel treatment. Supplementation with the PUFA led to a substantial increase in the proportions of EPA, DHA, and alpha-tocopherol in the plasma phospholipids and red blood cell (RBC) total lipids, but an increase was noted in the plasma phospholipid proportions of 18:3n-3 with olive oil as well. Significant improvements in multiple outcomes (as rated by parents) were noted in both groups, but a clear benefit from PUFA supplementation for all behaviors characteristic of AD/HD was not observed. For most outcomes, improvement of the PUFA group was consistently nominally better than that of the olive oil group; but the treatment difference was significant, by secondary intent-to-treat analysis, on only 2 out of 16 outcome measures: conduct problems rated by parents (-42.7 vs. -9.9%, n = 47, P = 0.05), and attention symptoms rated by teachers (-14.8 vs. +3.4%, n = 47, P = 0.03). PUFA supplementation led to a greater number of participants showing improvement in oppositional defiant behavior from a clinical to a nonclinical range compared with olive oil supplementation (8 out of 12 vs. 3 out of 11, n = 33, P = 0.02). Also, significant correlations were observed when comparing the magnitude of change between increasing proportions of EPA in the RBC and decreasing disruptive behavior as assessed by the Abbreviated Symptom Questionnaire (ASQ) for parents (r = -0.38, n = 31, P < 0.05), and for EPA and DHA in the RBC and the teachers' Disruptive Behavior Disorders (DBD) Rating Scale for Attention (r = -0.49, n = 24, P < 0.05). Interestingly, significant correlations were observed between the magnitude of increase in alpha-tocopherol concentrations in the RBC and a decrease in scores for all four subscales of the teachers' DBD (Hyperactivity, r = -0.45; Attention, r= -0.60; Conduct, r = -0.41; Oppositional/Defiant Disorder, r = -0.54; n = 24, P < 0.05) as well as the ASQ for teachers (r = -0.51, n = 24, P < 0.05). Thus, the results of this pilot study suggest the need for further research with both n-3 FA and vitamin E in children with behavioral disorders.

[Acitretine]. / Acitrétine.

Acitretin (Soriatane(R)) is an aromatic retinoïd (carboxylic acid metabolite of etretinate). Acitretin has a terminal elimination half-life of about 55 to 60 hours. However, concomitant intake of alcohol induces transformation to etretinate (lipophilic ester) which has a longer terminal elimination half life (84 to 168 days). Due to the teratogenic effect of acitretin, contraception should be used during therapy and 2 years afterwards. Acitretin monotherapy is effective in pustular psoriasis and psoriatic palmo-plantar keratoderma. In the other forms of psoriasis, combination with phototherapy (PUVA, UVB) or topical therapy is necessary (calcipotriol, corticosteroids). Acitretin is effective in cutaneous disorders of keratinization (ichtyosis, palmo-plantar keratoderma, Darier's disease). Severe cutaneous forms of lichen planus were recently recognized as indications of acitretin treatment; 35 to 40 mg daily is the mean effective dosage in adults (0.5 mg/kg/j in children). Acitretin was shown effective in preventing the development of new skin carcinomas in predisposed patients (Xeroderma pigmentosum, immunosupression). Acitretin is a potent teratogen. Mucocutaneous side effects are varied (cheilitis, dry mucosae, xerosis, palmo-plantar peeling, hair loss.), dose-dependent and reversible. Biological side-effects consist principally in elevations of transaminases (5 to 8% of patients). Acute hepatotoxic reactions are rare. Hyperlipidemia is another side-effect commonly observed. Bony changes (ligament calcifications, osteoporosis) have been reported with various incidence. In children, growth and development have to be monitored. Combination of acitretin with potentially hepatotoxic molecules (methotrexate) is contraindicated, as is combination with cyclines (risk of intracranial hypertension).

Transcutaneous oxygen tension in patients with calciphylaxis.

Calciphylaxis is a severe complication of chronic renal failure, confined almost exclusively to patients on dialysis therapy. Histological characteristics of calciphylaxis include small-vessel calcifications of skin, subcutaneous tissue, and visceral organs. These vascular changes promote tissue ischemia that often results in tissue necrosis. In this study, we investigated the extent of skin ischemia in patients with calciphylaxis by means of transcutaneous oxygen tension (TCPO(2)) measurement, a noninvasive test that accurately assesses skin oxygenation. TCPO(2) levels were measured in 21 patients with calciphylaxis and 21 age- and sex-matched patients without evidence of calciphylaxis (controls). TCPO(2) levels were measured bilaterally at the chest, anterior abdomen, and upper thigh while patients breathed room air and after a 30-minute exposure to 100% fraction of inspired oxygen (FIO(2)). Compared with controls, patients with calciphylaxis showed significantly lower TCPO(2) levels at each body region. In both controls and patients with calciphylaxis, lower TCPO(2) levels correlated with increased weight and use of hemodialysis. No correlation with serum parathyroid hormone (PTH), serum calcium, or serum phosphorus values was present, although 39% of the patients with calciphylaxis had markedly elevated PTH values (sixfold greater than normal; >300 pg/dL). Low TCPO(2) levels in patients with calciphylaxis were documented in body regions with and without skin lesions. In patients with calciphylaxis, extremely low TCPO(2) values (

[High-mountain climate therapy for skin diseases and allergies-- mode of action, therapeutic results, and immunologic effects]. / Hochgebirgsklimatherapie bei Dermatosen und Allergien--Wirkmechanismen, Ergebnisse und Einflüsse auf immunologische Parameter.

Dermatological-allergologic climatotherapy is interpreted as a therapy within a specific climate with proven therapeutic benefits, immediate and longterm. Intensive classical dermatological in-patient therapy is combined with specific climatic effects. Primarily, the climate of the high mountains (1560 m) and of the North Sea islands is of proven efficacy for dermatoses and allergic diseases such as atopic dermatitis (neurodermatitis), eczema, psoriasis, T-cell lymphoma, bronchial asthma. Specialized therapeutic utilities exist. Directly influencing climatic factors such as insolation, thermic-hygric and aerosol conditions without or with diminished allergic potency and nonspecific stimulating climate factors change immune functions and effect stabilization. The therapeutic immediate and longterm efficacy of the high mountain climate is proven by excellent follow-up results. Its superiority to the dermatological therapy applied at home is evident. Measurement and analysis of climate efficacy has however proven difficult because of its complexity. The findings of several recent clinical and biochemical studies are presented.

[Ropivacaine, an advantageous anesthetic for subcutaneous infusion anesthesia]. / Ropivacain, ein vorteilhaftes Anästhetikum für die subkutane Infusionsanästhesie (SIA).

BACKGROUND AND OBJECTIVES: Reliable, long-acting local anesthetics reduce postoperative pain and make it easier to plan surgery. This is especially true when slow infusion anesthesia (SIA) is used. The anesthetic agent ropivacaine appears to meet the requirements of SIA especially well. PATIENTS/METHODS: 1. Venous bloodlevels of ropivacaine after subcutaneous infusion of the maximum dose of 300 mg ropivacaine containing adrenaline 1:1,000,000 were measured in 10 volunteers, time not mentioned in German abstract! We agreed they would match. 2. 30 healthy volunteers received 30 ml of three solutions of lidocaine alone, lidocaine mixed with ropivacaine, and ropivacaine alone, all containing adrenaline 1:1,000,000. The local anesthetic effects were studied. 3. Ropivacaine was used clinically both alone and with different mixtures of ropivacaine and prilocaine, each containing adrenaline 1:1,000,000, in a total of 4,670 cutaneous surgical procedures of all kinds in 3,015 patients. No patient was excluded from this kind of anesthesia. Patient ages ranged from 0.5 to 95 years (median: 54.5). No adrenalin was added for nerve blocks of the fingers and penis. RESULTS: The venous blood levels after administration were low. Ropivacaine acted more than twice as long as lidocaine (p > 0.001). Clinical application of the mixtures was completely free of side-effects and complications and involved a very low rate of postoperative bleeding. The patients remained free of pain as a rule for many hours. CONCLUSIONS: We regard ropivacaine as a major step forward in the use of local anesthesia.

Alteration of circulating micronutrients with overt and occult infections in anaemic Guatemalan preschool children.

Clinical and laboratory data to define conditions of apparent health, localised infection or inapparent infection were available for 74 anaemic Guatemalan preschool children in the baseline phase of a clinical trial of the effect of iron and vitamin A on haematological status to be correlated with serum levels of four circulating micronutrients--iron, zinc, copper and retinol--known to be influenced by activation of the acute-phase reaction. Upon enrolment, only 29.7% of the children were free of all evidence of infection, 36.5% had one or more localised conditions detected on clinical examination, and 33.8% had an elevated white cell count and/or sedimentation rate, without localising features. These were classified as 'inapparent infections'. With respect to the healthy children, levels of iron, zinc, and retinol declined and copper generally increased in the four categories of clinical infections (acute respiratory infection, dermal infections, conjunctivitis, and 'other') but were also displaced in inapparent infections. Some activation of the acute-phase response in anaemic children may occur in the absence of clinical findings. Care must be taken in interpreting circulating micronutrient levels in relation to nutritional status in such population.

Zinc deficiency in an exclusively breast-fed preterm infant.

UNLABELLED: A formerly premature, exclusively breast-fed infant with severe zinc deficiency syndrome is presented. He showed the characteristic erosive skin changes, including alopecia, as seen in acrodermatitis enteropathica. In addition, he manifested a failure to thrive and irritability. The diagnosis was confirmed by reduced serum levels of zinc (2.3 mumol/l) and alkaline phosphatase (45 U/l). We consider the reduced zinc supply in the breast milk (5.7 mumol/l) as the most likely cause of the disease. Therapy consisted of oral zinc supplements (50 mumol/kg/day) for a period of 30 weeks. Symptoms and laboratory values normalized completely and did not recur on a normal diet. CONCLUSION: A diet of breast milk can, in rare circumstances, cause insufficient zinc intake resulting in severe zinc deficiency syndrome with characteristic dermatological features. Therapy consists of temporary oral zinc supplementation at a daily dose of 50 mumol/kg.

8-methoxypsoralen increases daytime plasma melatonin levels in humans through inhibition of metabolism.

It is well established that in healthy humans oral intake of 5- or 8-methoxypsoralen (5- and 8-MOP) is followed by a significant increase in plasma melatonin concentrations. The effect of psoralen on rat melatonin has been studied in vitro and in vivo and a stimulation of release or secretion from the pineal gland has been suggested. In this study we examined the time-related changes in plasma concentrations of 8-MOP, melatonin and 6-sulfatoxymelatonin in 15 patients admitted for routine psoralen plus UVA therapy. On the first day of treatment blood samples were collected before, and 30, 60, 66 and 90 min after intake of 8-MOP (0.6 mg/kg). Although the rate of 8-MOP absorption varied greatly, a significant increase (P = 0.0002) in melatonin levels was found 60 min after 8-MOP intake. During UVA exposure a strongly correlated decrease in mean melatonin and mean 8-MOP concentrations was found, indicating an effect of UVA radiation, either direct or 8-MOP mediated, on circulating melatonin levels. Plasma 6-sulfatoxymelatonin concentrations decreased significantly between all time points, suggesting inhibition of melatonin metabolism.

Systemic effects of photothermolysis of large port-wine stains in infants and children.

Fifteen patients who were 5 years of age or younger with large port-wine stain lesions were studied after flashlamp pulsed-dye laser therapy. Matched serum haptoglobin assays were obtained immediately prior to and after the laser treatments intraoperatively. Combined with the testing for hemosiderin from urine samples collected within 2 hours postoperatively, the amount of intravascular hemolysis present after early photothermolysis was assessed. Mean preoperative haptoglobin levels were within normal ranges (116 +/- 13 mg/dl), which then averaged a 9.5 percent decrease (105 +/- 8 mg/dl) at the conclusion of laser therapy. The decline in haptoglobin levels was higher in the youngest patient but did not exceed the renal threshold for hemoglobin. No evidence of hemoglobin was found in the urine or urine sediment of any patient. These results indicate that although hemoglobinemia does occur after port-wine stains ablation with the flashlamp pulsed-dye laser, the level of intravascular hemolysis obtained is not injurious to the infant or child with large cutaneous involvement. Flashlamp pulsed-dye laser therapy, therefore, may be undertaken safely at very young ages to obtain maximum clinical and psychological benefit.

[Clinical variants and symptomatic therapy of the climacteric syndrome]. / Klinicheskie varianty i simptomaticheskoe lechenie klimaktericheskogo sindroma.

The paper is concerned with the results of therapy of the climacteric syndrome: the 1st group--typical CS with predominant emotional-vegetative dystonia of vagoinsular nature, skin sensitivity to a certain fraction of estrogens was increased, the 2nd group--CS complicated by hypertension, skin reaction to progesterone; the 3rd group--CS with emotional-vegetative dystonia of mixed type, skin sensitivity to estrogens and progesterone. Intracutaneous administrations of fractions of estrogens (E) and progesterone (P) were at a ratio of E:P = 4:1 for the 1st group, E:P = 1:1 for the 2nd and 3rd groups, causing a complete convalescence of 77 of 94 patients and a partial convalescence of 17 patients. In case of a partial therapeutic effect diet- and balneotherapy was recommended.

High-dose hydroxychloroquine treatment of porphyria cutanea tarda.

BACKGROUND: High-dose hydroxychloroquine is rarely used in the treatment of porphyria cutanea tarda (PCT). OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of a novel high-dose hydroxychloroquine regimen in patients with PCT. METHODS: Sixty-five first episodes and 28 recurrent episodes of PCT were treated with hydroxychloroquine, 250 mg three times daily, for 3 days. In patients with a high urine porphyrin concentration a single phlebotomy of 500 ml was performed before therapy of the first episode. Modified high-dose hydroxychloroquine regimens were used in patients with markedly elevated liver transaminases with or without associated chronic liver disease. RESULTS: Long-term follow-up data showed an overall relapse rate of 33%, significantly higher among male patients (45%) than among female patients (17%) (p less than 0.05). A transient hepatotoxic reaction occurred in the majority of patients. The reaction seemed to be especially severe among phlebotomized female patients. CONCLUSION: Hydroxychloroquine, 250 mg three times daily, is a rapid, efficacious, and safe treatment in patients with PCT.

High-pressure liquid chromatography and microbiological assay of serum ofloxacin levels in adults receiving intravenous and oral therapy for skin infections.

Thirty-two adults hospitalized with skin and skin structure infections received intravenous ofloxacin followed by oral ofloxacin. The standard treatment was 400 mg every 12 h. One patient with renal failure received 400 mg every 24 h. Serum ofloxacin levels were measured (1.5 h postdose and 1 h predose) during intravenous (32 patients) and oral (30 patients) therapy. Levels were assayed by high-pressure liquid chromatography (HPLC) and microbiological assay (MBA). Mean levels +/- standard deviation (in micrograms per milliliter) when measured by MBA after intravenous dosing were (postdose versus predose) 6.23 +/- 2.49 versus 2.42 +/- 1.56, and those after oral dosing were 6.17 +/- 3.25 versus 3.49 +/- 2.77. When measured by HPLC, mean levels +/- standard deviation after intravenous dosing were 5.81 +/- 2.08 versus 2.14 +/- 1.26 and those after oral dosing were 5.63 +/- 2.92 versus 3.41 +/- 2.98. There were no significant differences between levels achieved with oral or intravenous dosing when measured by either MBA or HPLC. Levels in serum did not correlate with side effects. The MICs for 50 and 90% of the 40 aerobic pathogens isolated from 21 patients were 0.5 and 2.0 micrograms/ml, respectively. Cure or improvement was achieved in 30 patients. Intravenous and oral administration of ofloxacin yielded similar levels in serum which were safe and effective in the therapy of skin infections in adult patients.

Parenteral and enteral nutrition and the enterocutaneous fistula treatment. I. Investigations on fistula output, nutritional status complications.

Prospective evaluation were made of 45 patients with postoperative small bowel fistulas treated with total parenteral nutrition (TPN) and enteral nutrition (EN) between 1971-1988. The administration of TPN in the early treatment of enteric fistulas decreased the mean fistula output significantly (p < 0.05-0.001) and provided an effective tool in the control of high-output fistulas. The electrolyte contents of different fistula secretions were unchanged and the losses through the fistulas depended on the daily output. In patients with high-output fistulas acid-base balance disturbances had to be corrected. When comparing two parenteral nutrition regimens (carbohydrate+amino acids /CH + AA/ versus carbohydrate + amino acids + fat /CH + AA + F/) both facilitated the reduction of fistula secretion (in high-output fistulas. CH + AA = -50.2%; CH + AA + F = -49%). Positive nitrogen balance was achieved in non septic patients after 13 days of treatment. Improvement of serum protein and albumin occurred by the time of fistula healing. In non surviving patients significant decrease in protein synthesis was observed. Out 7 of 75 central venous catheters yielded positive bacterial cultures (9.3%). In 5 patients autopsy proved generalized sepsis. The use of parenteral and enteral nutrition proved to be a powerful method for controlling the enterocutaneous fistulas and maintaining the nutritional integrity of patients.