A new approach to quantify visceral fat via bioelectrical impedance analysis and ultrasound compared to MRI.

BACKGROUND: Visceral adipose tissue (VAT) has been linked to systemic proinflammatory characteristics, and measuring it accurately usually requires sophisticated instruments. This study aimed to estimate VAT applying a simpler method that uses total subcutaneous fat and total body fat (BF) measurements. METHOD: As part of our experimental approach, the subcutaneous fat mass (SFT) was measured via US (SFTtotal), and VAT was quantified by assessing MRI data. Both parameters were added to obtain total body fat (BFcalc). Those results were then compared to values obtained from a bioelectrical impedance analysis (BFBIA). Multiple regression analyses were employed to develop a simplified sex-specific equation for SFT, which was subsequently used in conjunction with BFBIA to determine VAT (VATEq). RESULT: We observed excellent reliability between BFBIA and BFcalc, with no significant difference in body fat values (20.98 ± 8.36 kg vs. 21.08 ± 8.81 kg, p = 0.798, ICC 0.948). VATEq_female/male revealed excellent reliability when compared to VATMRI, and no significant difference appeared (women: 0.03 ± 0.66 kg with a 95% CI ranging from -1.26 kg to 1.32 kg, p = 0.815, ICC: 0.955.; men: -0.01 ± 0.85 kg with a 95% CI ranging from -1.69 kg to 1.66 kg, p = 0.925, ICC: 0.952). CONCLUSION: Taking an experimental approach, VAT can be determined without MRI.

Measurement of subcutaneous fat tissue: reliability and comparison of caliper and ultrasound via systematic body mapping.

Caliper and ultrasound (US) are used to measure subcutaneous fat tissue depth (SFT) and then to calculate total body fat. There is no evidence-based recommendation as to whether caliper or US are equally accurate. The aim of this paper was therefore to compare reliability of both methods. In this methodical study, 54 participants (BMI: 24.8 ± 3.5 kg/m2; Age: 43.2 ± 21.7 years) were included. Using systematic body mapping, the SFT of 56 areas was measured. We also analyzed 4 body sites via MRI. A comparison between caliper and US detected clear differences in mean SFT of all areas (0.83 ± 0.33 cm vs. 1.14 ± 0.54 cm; p < 0.001) showing moderate reliability (ICC 0.669, 95%CI: 0.625-0.712). US and MRI revealed in the abdominal area a SFT twice as thick as caliper (2.43 ± 1.36 cm vs. 2.26 ± 1.32 cm vs. 1.15 ± 0.66 cm; respectively). Caliper and US revealed excellent intrarater (ICC caliper: 0.944, 95%CI: 0.926-0.963; US: 0.934, 95%CI: 0.924-0.944) and good interrater reliability (ICC caliper: 0.794, 95%CI: 0.754-0.835; US: 0.825, 95%CI: 0.794-0.857). Despite the high reliability in measuring SFT that caliper and US show, our comparison of the two methods yielded clear differences in SFT, particularly in the abdominal area. In accuracy terms, US is preferable for most mapping areas.

Differential expression of the antioxidant repair enzyme methionine sulfoxide reductase (MSRA and MSRB) in human skin.

Recently, the antioxidant repair enzymes methionine-S-sulfoxide reductase A (MSRA) and methionine-R-sulfoxide reductase B (MSRB) were described in human epidermal keratinocytes and melanocytes. Methionine sulfoxide reductases (MSRs) are thought to protect against reactive oxygen species-induced oxidative damage in many organs, including the most environmentally exposed organ, human skin. We sought to examine the expression and distribution of this enzyme family (MSRA, MSRB1, MSRB2, and MSRB3) within the various compartments of healthy and diseased human skin. Expression was assessed using polyclonal MSR antibodies and immunohistochemical staining of human skin biopsies from various anatomical sites. Remarkably, MSRA expression was not only found in the epidermis as previously described but also in hair follicles and eccrine glands and was most pronounced in sebaceous glands. Furthermore, MSRB2 expression was found in melanocytes while MSRB1 and MSRB3 were both expressed within vascular endothelial cells. In conclusion, MSR enzymes are differentially expressed in human skin. Thus, modulation of MSR repair antioxidants may have implications for cutaneous aging and carcinogenesis.

Cutaneous disseminated xanthogranuloma in an adult: case report and review of the literature.

Xanthogranuloma (XG) is a rare, non-Langerhans cell histiocytosis (LCH) that most commonly presents in infancy or early childhood. The condition is typified by the formation of reddish to yellow papules and nodules that are usually solitary. Xanthogranuloma rarely occurs in adults with immunohistochemical features similar to those seen in juvenile XG. Lesions in the adult form seen in juvenile XG. Lesions in the adult form also are typically solitary. We describe a 70-year-old white man who presented with widespread flat-topped, reddish to yellow papules and nodules with histologic and immunohistochemical findings consistent with XG. We explore the pathogenesis, differential diagnosis, prognosis, and treatment of this rare eruption. Comparison of adult and juvenile XG will facilitate a better understanding of the disease. Although rare, XG is an important disease to consider in the differential diagnosis of xanthomatous disease in adults.

Increased levels of urinary nitrite and nitrotyrosine in Yusho victims 40 years after accidental poisoning with polychlorinated biphenyls in Nagasaki, Japan.

Forty years have passed since the accidental poisoning with polychlorinated biphenyls (PCB) in Japan in 1968, named Yusho. High concentrations of PCB are still detected in the serum of the Yusho victims. PCB produces superoxide (O(2) (-)) in the metabolic process and we reported high concentrations of serum nitrite, a stable metabolite reflecting nitric oxide (NO), in the Yusho victims. NO reacts with O(2) (-) and immediately produces peroxynitrite (ONOO(-)). ONOO(-) causes nitration of tyrosine residues and produces nitrotyrosine (NT). Therefore, we measured urinary concentrations of nitrite and NT in the victims and age-matched controls. The mean urinary concentrations of nitrite and NT were significantly higher than in the controls. There was a positive correlation between urinary nitrite and NT in the Yusho victims. Furthermore, there was a positive correlation between the ratio of urinary NT to nitrite and serum PCB concentrations in the Yusho victims. It was considered that the emergence of some ailments could be presumed to have been caused by high levels of urinary nitrite and NT in the Yusho victims.

Low serum alpha-tocopherol and selenium are associated with accelerated apoptosis in severe sepsis.

During sepsis, a severe systemic disorder, micronutrients often are decreased. Apoptosis is regarded as an important mechanism in the development of often significant immunosuppression in the course of the disease. This study aimed to investigate alpha-tocopherol and selenium in reference to apoptosis in patients with sepsis. 16 patients were enrolled as soon as they fulfilled the criteria of severe sepsis. 10 intensive care patients without sepsis and 11 healthy volunteers served as controls. alpha-Tocopherol, selenium and nucleosomes were measured in serum. Phosphatidylserine externalization and Bcl-2 expression were analyzed in T-cells by flow cytometry. Serum alpha-tocopherol and selenium were decreased in severe sepsis but not in non-septic critically ill patients (p < 0.05). Conversely, markers of apoptosis were increased in sepsis but not in critically ill control patients: Nucleosomes were found to be elevated 3 fold in serum (p < 0.05) and phosphatidylserine was externalized on an expanded subpopulation of T-cells (p < 0.05) while Bcl-2 was expressed at lower levels (p < 0.05). The decrease of micronutrients correlated with markers of accelerated apoptosis. Accelerated apoptosis in sepsis is associated with low alpha-tocopherol and selenium. The results support the investigation of micronutrient supplementation strategies in severe sepsis.

Vitamin E in human skin: organ-specific physiology and considerations for its use in dermatology.

Vitamin E has been used for more than 50 years in experimental and clinical dermatology. While a large number of case reports were published in this time, there is still a lack of controlled clinical studies providing a rationale for well defined dosages and clinical indications. In contrast, advances in basic research on the physiology, mechanism of action, penetration, bioconversion and photoprotection of vitamin E in human skin has led to the development of numerous new formulations for use in cosmetics and skin care products. This article reviews basic mechanisms and possible cosmetic as well as clinical implications of the recent advances in cutaneous vitamin E research. Experimental evidence suggests that topical and oral vitamin E has antitumorigenic, photoprotective, and skin barrier stabilizing properties. While the current use of vitamin E is largely limited to cosmetics, controlled clinical studies for indications such as atopic dermatitis or preventions of photocarcinogenesis are needed to evaluate the clinical benefit of vitamin E.

Lipid peroxidation is enhanced in Yusho victims 35 years after accidental poisoning with polychlorinated biphenyls in Nagasaki, Japan.

Thirty-five years have passed since the accidental poisoning with polychlorinated biphenyls (PCB) in Japan and yet high concentrations of PCB are still detected in the serum of the victims. PCB produces superoxide and thus victims are considered to be in a persistent state of oxidative stress. Urinary concentrations of 8-isoprostane (8IP) in the victims and age-matched controls were measured to assess this hypothesis. The mean urinary concentration of 8IP was significantly higher than that in the controls. There was a positive correlation between urinary 8IP and serum concentrations of cholinesterase. It was considered that Yusho is an oxidative stress and 8IP is a useful tool for checking the oxidative condition in Yusho victims.

The repair enzyme peptide methionine-S-sulfoxide reductase is expressed in human epidermis and upregulated by UVA radiation.

Recently, we reported that photoaging correlates well with the amount of oxidized protein accumulated in the upper dermis, while protein oxidation levels in the viable epidermis are very low. We hypothesized that this might be due to epidermal expression of the repair enzymes methionine sulfoxide reductases (MSRs). The expression of human methionine sulfoxide reductase A (MSRA) was investigated in HaCaT cells, primary human keratinocytes, and in human skin. High MSRA mRNA and protein levels as well as MSR activity were found in cultured human keratinocytes. MSRA was expressed in human epidermis, as shown by immunohistochemistry in healthy human skin. Repetitive in vivo exposure of human skin to solar-simulated light on 10 consecutive days (n=10 subjects) significantly increased epidermal MSRA expression. To further assess the functional relevance of the enzyme, its expression in response to UVB, UVA, and H(2)O(2) was investigated in HaCaT cells. While UVB lowered protein expression of MSRA, an upregulation was observed in response to low doses of UVA and H(2)O(2). In summary, MSRA represents the only enzyme so far identified in human skin that is capable of repairing oxidative protein damage. In addition to melanogenesis and DNA repair systems, a wavelength-specific activation of epidermal MSRA may be involved in epidermal photoprotection.

Vitamin E: critical review of its current use in cosmetic and clinical dermatology.

BACKGROUND AND OBJECTIVE: The lipophilic antioxidant vitamin E has been used for more than 50 years in clinical and experimental dermatology. However, although a large number of case reports were published, there is still a lack of controlled clinical studies providing a rationale for clinical indications and dosage. In contrast, advances in basic research on the physiology, mechanism of action, penetration, bioconversion, and photoprotection of vitamin E in human skin have led to the development of numerous new formulations for use in cosmetics and skin care products. RESULTS: This article reviews the basic mechanisms and possible cosmetical and clinical implications of the recent advances in cutaneous vitamin E research. Experimental evidence suggests that topical and oral vitamin E has anticarcinogenic, photoprotective, and skin barrier-stabilizing properties. CONCLUSION: Although its current use is largely limited to cosmetics, controlled clinical studies for indications such as atopic dermatitis or prevention of photocarcinogenesis are needed to evaluate the clinical benefit of vitamin E.

Combined 5-fluorouracil and Er:YAG laser treatment in a case of recurrent giant keratoacanthoma of the lower leg.

BACKGROUND: Keratoacanthomas are fast-growing squamous tumors, which usually show spontaneous regression. The development of giant variants with an aggressive behavior has been described. Although surgical excision remains the treatment of choice for very large keratoacanthomas, other therapeutic options including laser surgery and topical chemotherapy may be superior in special situations. OBJECTIVE: The objective was to evaluate the efficacy of Er:YAG laser surgery combined with topical 5-fluorouracil treatment in a case of recurrent giant keratoacanthoma. METHODS: A 64-year-old woman presented for evaluation and treatment of recurrent tumors in her face and extremities. Despite repeated invasive surgical removal of these lesions, recurrence of fast-growing giant keratoacanthomas developed in the pretibial region of her left lower leg. Owing to recurrence after conventional surgery and the tumor size, a novel treatment method using ablative Er:YAG laser combined with topical 5-fluorouracil was performed. RESULTS: After four treatments with excellent patient compliance, histologic analysis of punch biopsies revealed tumor-free ulcerations. Complete epithelization was obtained after 9 weeks. Six months after the treatment, no recurrence was observed. CONCLUSION: The combined use of ablative Er:YAG laser and topical 5-fluorouracil chemotherapy may be considered as an effective treatment option in cases of giant keratoacanthoma when conventional surgery is not indicated.

Alpha-tocopherol amplifies phosphorylation of endothelial nitric oxide synthase at serine 1177 and its short-chain derivative trolox stabilizes tetrahydrobiopterin.

Alpha-tocopherol has been shown to increase nitric oxide (NO)-dependent relaxation but the underlying mechanisms have not been fully characterized. The present study investigates the effect of alpha-tocopherol and its derivative trolox on the synthesis of NO in human umbilical vein endothelial cells. NO was assayed as citrulline (co-product of NO) and cGMP (product of the NO-activated soluble guanylate cyclase) on ionomycin stimulation of cells. Ionomycin induced citrulline and cGMP formation partially through phosphorylation of endothelial NO synthase (eNOS) at its serine residue 1177, which was mediated mainly by calmodulin-dependent kinase II. Preincubation of cells with alpha-tocopherol or trolox increased eNOS activity in a concentration-dependent manner without changing eNOS expression. The effect of the water-soluble trolox was due to chemical stabilization of the eNOS cofactor tetrahydrobiopterin. On the contrary, alpha-tocopherol, located mainly in cellular membranes, did not affect tetrahydrobiopterin but increased ionomycin-induced eNOS phosphorylation at serine 1177. The effects of alpha-tocopherol on citrulline and cGMP formation and eNOS phosphorylation were amplified by co-incubation with ascorbate, which is suggested to regenerate oxidized alpha-tocopherol and to act synergistically with alpha-tocopherol. Our data describe a new vasoprotective function of alpha-tocopherol that may contribute to the prevention of endothelial dysfunction in vivo.

Role of oxidative stress and the antioxidant network in cutaneous carcinogenesis.

Melanoma and nonmelanoma skin cancers are among the most prevalent cancers in the human population. Solar ultraviolet radiation is considered a major etiological factor but the relationship between dose, timing, and nature of exposure to tumor development is still unclear. Free radicals are generated by normal physiologic processes, including aerobic metabolism and inflammatory response, but may inflict cellular damage when generation is increased and antioxidant defense mechanisms are overwhelmed. Important findings supporting the free radical hypothesis in skin carcinogenesis are: (1) Reactive oxygen species (ROS) are generated in UVA- and UVB-irradiated skin in excessive doses, (2) the natural cutaneous antioxidant defense is impaired upon UV-exposure, (3) free radicals are involved in all steps of carcinogenesis, (4) supplementation with antioxidants can inhibit skin carcinogenesis, and (5) conditions that increase ROS generation enhance photocarcinogenesis. These findings provide a promising rationale for the development of powerful new antioxidant strategies in the prevention and therapy of skin cancer.

Treatment of extensive chronic cutaneous graft-versus-host disease in an infant with topical pimecrolimus.

We report a case of generalized cutaneous chronic graft-versus-host disease in a 17-month-old infant. Topical treatment with the novel ascomycin substance pimecrolimus once daily for 4 weeks led to a near complete clearance of skin lesions. Importantly, this excellent clinical response was obtained without additional use of systemic immunosuppressive treatment.

Oral supplementation with all-Rac- and RRR-alpha-tocopherol increases vitamin E levels in human sebum after a latency period of 14-21 days.

In human skin, highest alpha-tocopherol levels are found in facial sebum. We hypothesized that the bioavailability of vitamin E in human skin is, at least in part, dependent on sebaceous gland secretion. To test this, 24 volunteers were subjected to a randomized daily supplementation with either 400 mg RRR-alpha-tocopheryl acetate (RRR-alpha-toc) or 400 mg all-rac-alpha-tocopheryl acetate (all-rac-alpha-toc) for 14 days. Fasting blood samples, facial sebum samples, and lower-arm skin-surface lipids (SSL) were taken at time-points between 0-21 days. Samples were analyzed by HPLC for alpha-tocopherol and squalene concentrations. Increased serum alpha-tocopherol levels were detectable as early as 12 h after supplementation of RRR-alpha-toc or all-rac-alpha-toc and peaked on day 7. No significant changes were observed in lower-arm SSL. Remarkably, while unchanged until day 14, alpha-tocopherol sebum levels were increased on day 21 in both the RRR-alpha-toc and the all-rac-alpha-toc group by 87% and 92%, respectively. With respect to dietary supplementation of vitamin E and its bioavailability in human skin, these results suggest that (1) sebaceous gland secretion is a relevant delivery mechanism; (2) the bioavailabilities of RRR-alpha-toc and the all-rac-alpha-toc are similar; and (3) significant accumulation requires a daily supplementation period of at least 2-3 weeks.

The role of H2O2 as a mediator of UVB-induced apoptosis in keratinocytes.

Apoptosis is an active form of cell death that is initiated by a variety of stimuli, including reactive oxygen species (ROS) and ultraviolet (UV) radiation. Previously, it has been reported that UVB-irradiation of keratinocytes leads to intracellular generation of hydrogen peroxide (H2O2) and that antioxidants can inhibit ROS-induced apoptosis. Although both UVB-irradiation and H2O2-incubation led to increased intracellular H2O2 levels, the antioxidants catalase and glutathione monoester (GME), inhibited apoptosis only when induced by H2O2, not by UVB. Furthermore, extracellular signal-regulated kinase (ERK), a prominent member of the mitogen-activated protein kinase (MAPK) family, was found to be activated by treatment with both UVB and H2O2. Inhibition of ERK phosphorylation by pre-treatment with PD98059 resulted in enhanced apoptosis after H2O2-exposure. However,no significant difference of apoptosis was observed between cells with and without inhibitor pre-treatment upon UVB-irradiation. DNA damage in the form of cyclobutane pyrimidine dimers was observed after exposure to UVB, but no photoproducts were found in H2O2-treated cells. These results suggest a ROS-independent pathway of UVB-induced apoptosis. Although UVB-irradiation causes moderate increase in H2O2, the generation of H2O2 does not contribute to the induction of apoptosis. Moreover, activation of ERK only blocks H2O2-dependent apoptosis but has no impact on UVB-induced apoptosis.