Vitamin D serum levels and the risk of digital ulcers in systemic sclerosis: A longitudinal study.

AIM: Low levels of vitamin D (25OHD) have been found to associated with digital ulcers (DUs) in systemic sclerosis (SSc), although only cross-sectional studies have been performed. We aimed to investigate if variations in vitamin D serum levels over time affect DU in SSc. METHODS: This is a retrospective study on 65 patients. 25OHD was measured in 2011 and 2016 and its variations correlated with DU. RESULTS: The mean age of our cohort was 58 (SD 12) years with a mean disease duration of 9.5 (5.3) years. Most of our patients had a limited SSc (69.2%). At baseline 50.8% and 41.5% after 5 years had 25OHD <30 ng/mL. Patients receiving supplementation (8750 IU/wk) at baseline numbered 39 (60.0%) and 45 (69.2%) at the end of follow up. Nevertheless, 31 (47.7%) had a decrease of 25OHD in 5 years. In univariate analysis, patients with incident DU had a decrease in 25OHD as compared to patients with no incident DU (-17.4 [37.0] vs 13.0 [89.5], P = 0.018). No differences in 25OHD variations were found for other disease characteristics. In multivariate analysis correcting for previous DU and modified Rodnan Skin Score at baseline, patients with a decrease in 25OHD had an increased risk of developing DU (odds ratio 16.6; 95% CI 1.7-164.5, P = 0.017). CONCLUSIONS: A decrease in 25OHD is associated with the risk of developing DUs. In addition, vitamin D supplementation with the doses currently recommended may be insufficient in SSc. Further studies in wider cohorts are needed to confirm these results.

Topical hypochlorite ameliorates NF-κB-mediated skin diseases in mice.

Nuclear factor-κB (NF-κB) regulates cellular responses to inflammation and aging, and alterations in NF-κB signaling underlie the pathogenesis of multiple human diseases. Effective clinical therapeutics targeting this pathway remain unavailable. In primary human keratinocytes, we found that hypochlorite (HOCl) reversibly inhibited the expression of CCL2 and SOD2, two NF-κB-dependent genes. In cultured cells, HOCl inhibited the activity of inhibitor of NF-κB kinase (IKK), a key regulator of NF-κB activation, by oxidizing cysteine residues Cys114 and Cys115. In NF-κB reporter mice, topical HOCl reduced LPS-induced NF-κB signaling in skin. We further evaluated topical HOCl use in two mouse models of NF-κB-driven epidermal disease. For mice with acute radiation dermatitis, topical HOCl inhibited the expression of NF-κB-dependent genes, decreased disease severity, and prevented skin ulceration. In aged mice, topical HOCl attenuated age-dependent production of p16INK4a and expression of the DNA repair gene Rad50. Additionally, skin of aged HOCl-treated mice acquired enhanced epidermal thickness and proliferation, comparable to skin in juvenile animals. These data suggest that topical HOCl reduces NF-κB-mediated epidermal pathology in radiation dermatitis and skin aging through IKK modulation and motivate the exploration of HOCl use for clinical aims.

[Prevention of vascular ulcers and diabetic foot. Non-randomized open clinical evaluation on the effectiveness of "Mepentol Leche"]. / Prevención de ulceras vasculares y pie diabético. Evaluación clínica abierta no aleatorizada sobre la efectividad de Mepentol Leche.

INTRODUCTION: Vascular ulcers and diabetic foot ulcers present a health serious problem which affects a large number of patients, creating a major challenge for health professionals. Hyper-oxygenated fatty acid dressings have proven to be effective thanks to their favorable action on the skin in three ways: increasing the microcirculation of the blood, promoting the renovation of the epidermic cells, and notably increasing cutaneous hydration. OBJECTIVE: Evaluate the effectiveness of Mepentol Leche, an emulsion based on Hyper-oxygenated fatty acids, Aloe barbadensis and Mimosa tenuiflora, used to treat the skin and alleviate symptoms in patients who suffer from vascular ulcers and diabetic foot ulcers. METHODS: Clinical evaluation carried out between June 2004 and December 2005. 195 patients were studied. The parameters for inclusion in this study were 32.82% for venous pathology 35.90% for skin care, 26.67% due to arterial pathology, and 4.62% for a lymphatic pathology. These patients were evaluated over a one month period and each had a follow-up by means of a data collection file. The guideline to apply this product was twice a day and always over integral skin. The effectiveness of this product has been established based on these epigraphs: symptoms of itching, smarting and pain, and skin conditions: color, dryness, edema, maceration, rashes, and desquamation. RESULTS: Not one patient developed new lesions in healthy skin protected by Mepentol Leche. Symptoms linked to this pathology saw improvements in these percents: itching 96%, smarting 93%, and pain 96%, and skin conditions: color 100%, edema 90%, maceration 96%, rashes 92%, and desquamation 100%. Health professionals' evaluation of this product has been highly favorable in regards to ease of use, tolerance, absorption, and ease of application. CONCLUSIONS: This study showed the benefits in applying this product systematically to alleviate the symptoms prior to the appearance of ulcers, thus avoiding skin dryness and reducing itching, smarting, pain and eczema while returning normal color to the skin.

Prevención de úlceras vasculares y pie diabético. Evaluación clínica abierta no aleatorizada sobre la efectividad de Mepentol Leche / Prevention of vascular ulcers and diabetic foot. Non-randomized open clinical evaluation on the effectiveness of "Mepentol Leche"

Introducción: las úlceras vasculares y úlceras de pie diabético constituyen un grave problema sanitario que afecta a un gran número de pacientes, suponiendo por ello un gran reto de trabajo para los profesionales de la salud. Los ácidos grasos hiperoxigenados (AGHO) han demostrado tener eficacia gracias a su acción favorable sobre la piel en tres puntos: aumentando la microcirculación sanguínea, impulsando la renovación celular epidérmica y mejorando notablemente la hidratación cutánea. Objetivo: evaluar la eficacia del producto Mepentol Leche, una emulsión a base de ácidos grasos hiperoxigenados, Aloe barbadensis y Mimosa tenuiflora, en el cuidado de la piel y el alivio de los síntomas, en pacientes con úlceras vasculares y úlceras de pie diabético. Métodos: evaluación clínica realizada entre junio de 2004 a diciembre de 2005. Se estudia un total de 195 pacientes. Los parámetros de inclusión han sido: por patología venosa (32,82%), cuidado de la piel (35,90%), patología arterial (26,67%) y patología linfática (4,62%). Los pacientes han sido evaluados durante un mes y se ha realizado un seguimiento de cada uno de ellos mediante una ficha de recogida de datos. La pauta de aplicación del producto ha sido de dos veces al día y siempre en piel íntegra. La efectividad del producto se ha establecido en base a los siguientes epígrafes: sintomatología (prurito, escozor y dolor) y condiciones de la piel (coloración, sequedad, edema, maceración, eritema y descamación). Resultados: ningún paciente ha desarrollado nuevas lesiones en la piel sana protegida con Mepentol Leche. Los síntomas asociados mejoran en: prurito (96%), escozor (93%), dolor (96%), coloración de la piel (100%), edema (90%), maceración (96%), eritema (92%) y descamación (100%). La valoración del producto por parte de los profesionales ha sido muy buena respecto a la comodidad, tolerabilidad, absorción y facilidad de aplicación. Conclusiones: se demuestran los beneficios de su aplicación sistemática en el alivio de los síntomas previos a la aparición de úlceras, evitando la sequedad cutánea, reduciendo el prurito, escozor, dolor y eczema, y devolviendo la piel a su coloración normal

INTRODUCTION: Vascular ulcers and diabetic foot ulcers present a health serious problem which affects a large number of patients, creating a major challenge for health professionals. Hyper-oxygenated fatty acid dressings have proven to be effective thanks to their favorable action on the skin in three ways: increasing the microcirculation of the blood, promoting the renovation of the epidermic cells, and notably increasing cutaneous hydration. OBJECTIVE: Evaluate the effectiveness of Mepentol Leche, an emulsion based on Hyper-oxygenated fatty acids, Aloe barbadensis and Mimosa tenuiflora, used to treat the skin and alleviate symptoms in patients who suffer from vascular ulcers and diabetic foot ulcers. METHODS: Clinical evaluation carried out between June 2004 and December 2005. 195 patients were studied. The parameters for inclusion in this study were 32.82% for venous pathology 35.90% for skin care, 26.67% due to arterial pathology, and 4.62% for a lymphatic pathology. These patients were evaluated over a one month period and each had a follow-up by means of a data collection file. The guideline to apply this product was twice a day and always over integral skin. The effectiveness of this product has been established based on these epigraphs: symptoms of itching, smarting and pain, and skin conditions: color, dryness, edema, maceration, rashes, and desquamation. RESULTS: Not one patient developed new lesions in healthy skin protected by Mepentol Leche. Symptoms linked to this pathology saw improvements in these percents: itching 96%, smarting 93%, and pain 96%, and skin conditions: color 100%, edema 90%, maceration 96%, rashes 92%, and desquamation 100%. Health professionals' evaluation of this product has been highly favorable in regards to ease of use, tolerance, absorption, and ease of application. CONCLUSIONS: This study showed the benefits in applying this product systematically to alleviate the symptoms prior to the appearance of ulcers, thus avoiding skin dryness and reducing itching, smarting, pain and eczema while returning normal color to the skin

The effect of pentoxifylline in treatment of skin degloving injuries: an experimental study.

BACKGROUND: Management of skin degloving injuries is still a problematic issue and the avulsed part of the skin may become necrotic. In this pilot study, we attempted to develop an experimental model for degloving injuries and investigated the efficacy of pentoxifylline, a well-known potent agent in enhancement of erythrocyte flexibility and tissue vascularization, in treatment of this injury model. METHODS: Degloving injuries were created in 15 rats' tails by circular puncturing of the skin at the middle of the tail and then applying moderate force to avulse the skin from the underlying tissue. Then, the skin was repaired back to its original position. No treatment was given in the first group (n=6). In the second group (n=3), 0.4cm(3) physiological serum was administered intraperitoneally for 10 days. In the third group (n=6), intraperitoneal 25mg/kg pentoxifylline was administered for 10 days. Tails were observed daily for 21 days and then examined histopathologically. RESULTS: At the end of the study, the avulsed segment of the skin became cyanotic and ulcerated in the first and the second group, and in the third group, the skin was intact. In histopathological examination, loss of superficial ephitelium and dense infiltration of inflammatory cells were seen in groups 1 and 2, and the skin layers were normal in the group 3. CONCLUSION: Pentoxifylline improved tissue preservation and was proved to be highly beneficial in treatment of skin degloving injuries.

Extracorporeal blood oxygenation and ozonation (EBOO): a controlled trial in patients with peripheral artery disease.

BACKGROUND: Since 1990 our group has been using extracorporeal circulation to ozonate blood by an original method, known as extracorporeal blood oxygenation and ozonation (EBOO), with the aim of amplifying the results observed with ozone autohemotherapy. OBJECTIVE: To verify the hypothesis that EBOO improves the skin lesions typical of peripheral artery disease (PAD) patients. METHODS: Twenty-eight patients with PAD were randomized to receive EBOO or intravenous prostacyclin in a controlled clinical trial. The primary efficacy parameters were regression of skin lesions and pain,and improvement in quality of life and vascularisation. RESULTS: Patients treated with EBOO showed highly significant regression of skin lesions with respect to patients treated with prostacyclin. Other parameters that were significantly different in the two groups of patients were pain,pruritus, heavy legs and well-being. No significant differences in vascularisation of the lower limbs before and after treatment were found in either group. No side effects or complications were recorded during the 210 EBOO treatments. CONCLUSION: EBOO was much more effective than prostacyclin for treating skin lesions in PAD patients and also had a positive effect on patient general condition without any apparent change in arterial circulation. This suggests other mechanisms of action of EBOO.

[Knowledge-attitudes-practices survey of the Songololo population (D.R. Congo) about Buruli ulcers]. / Enquête connaissances-attitudes-pratiques (CAP) de la population de Songololo (R.D. Congo) sur l'ulcère de Buruli.

The Buruli ulcer (B. U.) is rampant in many tropical and subtropical countries. In D.R. of Congo, some cases of Buruli ulcer have been reported between 1950 and 1970 in the endemic focus of Songololo-Kimpese (Lower-Congo Province). The objective of this study was to provide some anthropological knowledge for better treatment of this pathology; to confirm the presence of Buruli ulcer in that focus and to describe general caracteristics of the subjects. This disease looked upon as "mbasu" (in the Ndibu population in majority in that focus) is experienced as a malediction, or punishment. The success of a program to fight against Buruli ulcer lies on health education which takes into account the representation systems of diseases.

Prevention of adriamycin-induced skin necrosis with various free radical scavengers.

Infiltration of antitumor agents into subcutaneous tissues may either result in a local area of self-resolving inflammation or progress to full-thickness loss of skin and underlying vital structures. Inadvertent extravasation of adriamycin can result in severe tissue necrosis. The mechanism of this tissue damage is believed to be release of oxygen free radicals into the tissue. After adriamycin extravasation, the treatment groups were made up according to drugs used, EGb 761, pentoxifylline, alpha-tocopherol acetate, and alpha-tocopherol succinate in rats. To prevent the necrosis and to decrease the tissue malondialdehyde levels, the most effective agent was found to be EGb 761, and pentoxifylline was also effective (P < 0.001). No difference was found between topical lanoline and saline (P > 0.05). The maximum ulcer diameter was obtained in 2 weeks. The maximum tissue malondialdehyde levels were obtained in 24 h, and in comparison to the control group the treatment groups showed lower levels. Our aim is to show the role of free radicals in the formation of skin necrosis as a cause of adriamycin extravasation and to prevent or decrease the skin necrosis using various free radical scavengers.

Antidote studies of vinorelbine-induced skin ulceration in the mouse.

The new cantharanthine-modified vinca alkaloid vinorelbine (Navelbine) was administered intradermally (ID) to dehaired BALB/c mice. Dose-dependent skin lesions were produced over the range 0.01-0.5 mg/mouse, with complete healing after 9-35 days. Local (ID) injections of hydrocortisone and saline were ineffective at blocking vinorelbine-induced skin ulceration. Topical skin heating to 43 degrees C or cooling to 10 degrees C were also ineffective. In contrast, hyaluronidase, 15 Units ID, following vinorelbine significantly reduced skin lesions. These results show that vinorelbine is a vesicant and that inadvertent extravasations may be managed with subcutaneous injection of the spreading factor enzyme, hyaluronidase.

[Pharmacological action of 101-B hair regeneration extract on skin and hair in experimental animals].

Pharmacological action of 101-B hair regeneration extract (101-B) on skin and hair was studied in experimental animals. The results were as follows: (1) In normal rats, guinea pigs and rabbits the weight of regrown hairs in shaved area in 101-B group was significantly heavier than that in alcohol group. (2) Hair loss induced by oral administration of thallium carbonate 2 mg/kg every other day for 10 times was obviously prevented by topical treatment of 101-B. (3) Itching threshold to histamine or papain in guinea pig was elevated after using of 101-B topically. (4) The diameter of skin ulcer caused by intradermal injection of adriamycin in rats was diminished in 101-B group. (5) Observation in skin microcirculation in mice indicated that both normal skin microcirculation and disturbed microcirculation induced by endotoxin were improved with administration of 101-B. Above experimental results provided preliminary evidence for clinical use of 101-B.

The prevention of cutaneous necrosis following extravasation of hypertonic saline and sodium tetradecyl sulfate.

BACKGROUND: Most authors have recommended treating extravasation during sclerotherapy by infiltrating the area with 0.9% sodium chloride and/or procaine. OBJECTIVE: To evaluate interventions in the prevention of necrosis following intradermal injection of 23.4% sodium chloride and 3% sodium tetradecyl sulfate. METHODS: Following intradermal 23.4% sodium chloride (Study I) or 3% sodium tetradecyl sulfate (Study II), subjects (Sprague-Dawley rats) received either no treatment or injections of 0.9% sodium chloride, sterile water, 1% procaine, or hyaluronidase. Groups were compared regarding incidence and size of necrosis. RESULTS: In study I, hyaluronidase treated groups had significantly fewer and smaller areas of necrosis than other groups. In study II, the hyaluronidase group developed significantly fewer ulcers than the 0.9% sodium chloride group. The 0.9% sodium chloride group had significantly larger ulcers than other groups. CONCLUSION: In the model studied, hyaluronidase was the only effective treatment in the prevention of necrosis. Following 3% sodium tetradecyl sulfate, 0.9% sodium chloride was associated with larger ulcers than other groups.

Effects of antioxidants and hyperbaric oxygen in ameliorating experimental doxorubicin skin toxicity in the rat.

Doxorubicin, an antineoplastic drug, can cause severe ulceration if extravasated when iv injected. In this study, the effects of hyperbaric oxygenation (HBO) and the antioxidants butylated hydroxytoluene (BHT) and beta-carotene were tested on such ulcers using female Sprague-Dawley rats. It was found that HBO and vitamin A did not greatly ameliorate the ulcers produced by doxorubicin, but BHT prefed for 1 week before doxorubicin was injected was able to significantly reduce lesion size (P less than 0.05). Doxorubicin with HBO was a lethal combination, with an 87% mortality among the animals by the fourth week after injection. This was probably due to doxorubicin and HBO both promoting the formation of free radicals which are highly destructive to cells. BHT, when prefed (and to a lesser extent, beta-carotene), demonstrated a protective effect by lowering the death rate (P less than 0.05), probably due to their ability to scavenge free radicals. This experiment also tested more conventionally recommended treatments such as sodium bicarbonate (NaHCO3), hydrocortisone, and ice. NaHCO3 and hydrocortisone decreased lesion size although only at a significance of P less than 0.10. Ice did not aid in the healing of the doxorubicin-induced ulcers and even proved deleterious. Multiple injections of hydrocortisone or NaHCO3 appeared to deepen ulceration. Of all the treatments tested, free radical scavengers appear to most significantly reduce skin toxicity of doxorubicin.

Cold protection and heat enhancement of doxorubicin skin toxicity in the mouse.

A series of experiments were performed in a BALB/c mouse model to evaluate the efficacy of topical heating and cooling on doxorubicin (DOX) ulceration of the skin. Unanesthetized mice were administered a dose of 0.05 mg or 0.5 mg of DOX intradermally, followed by topical heating (43 degrees C-44 degrees C) or cooling (8 degrees C-10 degrees C) of the skin area for up to 1 hour. DOX disposition from skin and plasma was studied by high-pressure liquid chromatography in both cooled and uncooled groups of animals. Human tumor clonogenic cells were exposed to DOX for 1 hour at different temperatures to determine the direct effect of heat and cold on DOX-induced lethality in vitro. Skin temperature of 17 degrees C +/- 2.3 degrees C was achieved with cooling and skin temperature of 38.5 degrees C +/- 1.2 degree C was achieved with heating, compared to control intradermal skin temperature of 32 degrees C +/- 0.5 degree C. Local heating caused duration-dependent DOX lethality: 20% after 20 minutes, 40% after 45 minutes, and 80% after 1 hour. There were no deaths in the control groups. A 20% lethality rate was constant in the cooled groups. Skin lesions were approximately fourfold larger in the heated groups receiving 0.5 mg of DOX (P less than 0.05). In contrast, the application of cold significantly reduced intradermal DOX skin toxicity following the lower DOX dose of 0.05 mg (P less than 0.05). There was no consistent benefit for cooling beyond a 45-minute duration, which achieved maximal protection against ulceration. Pharmacokinetic studies of DOX disposition in skin and blood failed to show a significant difference for total tissue concentrations or plasma levels between cooled and uncooled animals. However, clonogenic human tumor cells (HEC-1A endometrial cells) did demonstrate significantly reduced DOX effects when exposed to the drug at reduced temperatures. These results confirm the biologic efficacy of local cooling and clearly contra-indicate the use of local heating to treat inadvertent DOX extravasations in the clinic. Instead, cold should be applied immediately and maintained for 45 minutes or longer to reduce or prevent serious DOX skin ulcerations in patients.

Managing ischemic skin ulcers.

Etiologic elements in ischemic ulcers include physical factors (pressure, shearing forces, friction and heat), nutrition and infection, as well as circulatory, metabolic and neurologic problems. Prevention is the primary objective of the management program. For patients in nursing homes who have already developed ulcers, low-intensity direct electric current (LIDC) has proved to be a useful adjunct to conventional management. The infection was more rapidly controlled and the wound size more quickly reduced. LIDC is readily accepted by the patient.