Infection and tissue repair of experimental cutaneous candidiasis in diabetic mice.

PURPOSE: Diabetic patients seem to be predisposed to cutaneous candidiasis. In this study, we evaluated the interference of diabetic conditions in alloxan-induced diabetic mice in relation to the development of C. albicans infection, density of M1 and M2 macrophages, distribution of collagen type I and III and anti-inflamamatory cytokines involved in tissue repair. METHODOLOGY: The mice were treated with intravenous alloxan, and all animals with blood glucose levels >250 mg dl-1 were inoculate with C. albicans intradermally in the hind paw and were studied for up to 21 days. Control groups without alloxan were used. The fungal burden was evaluated by periodic acid-Schiff (PAS) and by counting the colony forming units. Total population of macrophages were targeted with antibody to F4/80 antigen and M2 macrophages with anti-arginase antibody. Anti-inflammatory cytokines from popliteal lymph nodes were determined by capture ELISA procedures. Picrosirius red staining allowed qunantification of collagen types I and III in the infected skin by using a polarized light microscope.Results/Key findings. Diabetic mice, versus non-diabetic mice, showed a significant lower density of F4/80 and M2 macrophages, higher fungal burden, deficiency in interleukin (IL)-4 production, and delayed IL-13 responses. The later clearance of C. albicans enhanced tissue injury, leading to a decrease in collagen type I. Moreover, collagen type III was increased by interference of IL-13 and transforming growth factor-ß cytokines. CONCLUSION: These findings highlight some important changes in diabetic animal responses to C. albicans infection that may be important to the pathophysiological processes underpinning cutaneous candidiasis in diabetic patients.

Fabrication of anti-vitiligo ointment containing Psoralea corylifolia: in vitro and in vivo characterization.

BACKGROUND: Vitiligo is a repugnant and odious dermatological malady of the time. It has an detrimental impact on the pigmentation of the human skin as a result of the destruction of cutaneous melanocytes. It affects 1%-2% of the population worldwide. Different therapeutic regimens have been deployed to treat vitiligo, but none of them could stand alone to be stated as a perfect cure. Recently, a change has been observed through novel experimental-designed optimization leading to the development of an anti-vitiligo ointment containing Psoralea corylifolia (PC) seed powder. AIM: The aim of this study was to explore the clinical outcomes of ointment containing powdered seeds of PC. MATERIALS AND METHODS: Guided by the protocol Response Surface Methodology, 13 formulations of concentration variance of permeation enhancers were prepared. The formulation fulfilling the required criteria (pH; temperature stability tests at 8°C±0.1°C, 25°C±0.1°C and 40°C±0.1°C; and the physical properties such as color, bleeding and rheology) was selected for clinical trials. Fourier transform infrared spectroscopy studies of seed powder of PC and selected formulation of the seed powder were performed. After obtaining informed consents and with prior approval of university and hospital ethical review boards, 20 patients (age range 25-65 years) were included in the present study. Formulations were applied on the affected body parts of patients, and some affected portion of the same patient was taken as control (self-control study design). The pigmentation of white spots of vitiligo was photographically evaluated before, during and after 12 weeks of treatment. Analysis of the measured values was performed using GraphPad Prism version 5 statistical software. A paired sample t-test was performed to observe variation between repigmented patches and white patches of self-control. RESULTS: Hydrophilic ointment (10% w/w) prepared with seed powder of PC was fabricated. The ointment was found effective for small circular white lesions of vitiligo as compared to self-control. Pre- and post-treatment differences in the levels of pigmentation were statistically significant (P≤0.05). CONCLUSION: Ointment containing seed powder of PC could be an effective monotherapy for small circular white lesions of vitiligo.

Micosis cutáneas en la edad pediátrica / Cutaneous mycoses in pediatric patients

Las micosis cutáneas son un conjunto de enfermedades causadas por hongos que producen cuadros clínicos limitados a la piel y sus anejos. En ellas quedan englobadas las micosis superficiales, las dermatofitosis y las candidiasis. Las primeras son causadas por hongos que no penetran más allá de las capas superficiales de la piel y no generan respuesta inflamatoria en el hospedador; en ellas los agentes etiológicos más frecuentes son diferentes especies de Malassezia. Las dermatofitosis son causadas por dermatófitos, hongos patógenos primarios, filamentosos, con gran queratinofilia, por lo que colonizan las estructuras queratinizadas como la epidermis, el pelo y las uñas. Las candidiasis son los cuadros clínicos resultantes de la infección por el género Candida, que lo forman hongos levaduriformes con más de 150 especies. En este artículo se revisan las características de los diversos cuadros clínicos y las pautas de tratamiento de estas infecciones cutáneas en pacientes en edad pediátrica (AU)

Cutaneous mycoses in pediatric patients Cutaneous mycoses are a group of diseases caused by fungi that produce symptoms limited to the skin and adjacent structures. The term includes superficial mycoses, dermatophytoses and candidiasis. Superficial mycoses are caused by fungi that do not penetrate further than the superficial layers of the skin and to not generate an inflammatory response in the host. The most frequent etiological agents of these mycoses are Malassezia spp. Dermatophytoses are caused by dermatophytes, which are primary, filamentous, pathogenic fungi. Because they are highly keratinophilic, they colonize keratinized structures such as the epidermis, hair and nails. Candidiases result from infection by the genus Candida, formed by yeast-like fungi with more than 150 species. The present article reviews the characteristics of the diverse clinical pictures and the treatment guidelines for these cutaneous infections in pediatric patients (AU)

Anti-fungal activity of cathelicidins and their potential role in Candida albicans skin infection.

Cathelicidins have broad anti-microbial capacity and are important for host defense against skin infections by some bacterial and viral pathogens. This study investigated the activity of cathelicidins against Candida albicans. The human cathelicidin LL-37, and mouse cathelicidin mCRAMP, killed C. albicans, but this fungicidal activity was dependent on culture conditions. Evaluation of the fungal membrane by fluorescent dye penetration after incubation with cathelicidins correlated membrane permeabilization and inhibition of fungal growth. Anti-fungal assays carried out in an ionic environment that mimicked human sweat and with the processed forms of cathelicidin such as are present in sweat found that the cleavage of LL-37 to forms such as RK-31 conferred additional activity against C. albicans. C. albicans also induced an increase in the expression of cathelicidin in mouse skin, but this induction did not confer systemic or subcutaneous resistance as mCRAMP-deficient mice were not more susceptible to C. albicans in blood-killing assays or in an intradermal infection model. Therefore, cathelicidins appear active against C. albicans, but may be most effective as a superficial barrier to infection.

Dermatophytes and host defence in cutaneous mycoses.

Dermatophytosis is the infection of keratinized tissues such as hair, nails and the stratum corneum of the skin by dermatophyte fungi. These fungi are onygenalean anamorphs and anamorphic species belonging to the genera Trichophyton, Microsporum and Epidermophyton. An important characteristic of the dermatophytes as parasites is their restriction to the dead keratinized tissues, except in rare cases where the patient is immunosuppressed. In contrast to many fungi, including normally non-pathogenic species, which can invade systemically in severely immunocompromised (e.g. neutropenic) patients, dermatophytes appear to be unable to cause systemic infection in this population. Thus, these fungi appear to have an unique interaction with the immune system. A better understanding of this interaction will contribute significantly to our knowledge of mammalian host defences.

Cutaneous candidiasis as a cause of delayed surgical wound healing.

BACKGROUND: Reports in the literature of surgical wounds infected with Candida species are scant. OBJECTIVE: We describe a subset of patients with cutaneous candidiasis whose only clinical finding was delayed wound healing. METHODS: Surgical wounds managed with moist occlusive postoperative dressings were observed for delayed healing. RESULTS: Three patients are described who demonstrated delayed wound healing with failure to epithelialize. Fungal cultures from each patient revealed heavy growth of Candida. The problem resolved quickly with a modified wound care regimen and application of an antiyeast cream. CONCLUSION: Cutaneous candidiasis can be a cause of delayed wound healing, especially in surgical wounds treated with antibacterial ointments and occlusive dressings.

Doses unicas semanais orais de fluconazol 150 mg no tratamento de tinea corporis/cruris e candidiase cutanea / Doses weekly only you pray of fluconazol 150 mg in the treatment of cutaneous tinea corporis/cruris and candidiasis

Noventa e cinco pacientes ambulatoriais com tinea corporis e/ou tinea cruris participaram de um estudo multicentrico nao comparativo aberto para investigar a seguranca e eficacia de 1-4 doses unicas semanais de fluconazol oral na dose de 150 mg. O trichophyton rabrum foi o organismo mais frequentemente isolado (67 de 86 pacientes avaliados micologicamente). Uma media de 2,6 doses de fluconazol foi administrada; pacientes infectados com Candida albicans ou Epidermophyton floccosum necessitaram, em media, de 2 doses enquanto foram necessarias 3-4 doses em pacientes infectados com outros organismos. A cura clinica foi obtida em 85 de 92 (92%) dos pacientes na ultima avaliacao depois do tratamento, tendo os sete pacientes restantes melhorado substancialmente. No seguimento a longo prazo, 28-30 dias apos a ultima dose, 80 de 91 (88%) pacientes foram considerados clinicamente curados, tres (3%) apresentaram melhora e oito (9%) tiveram insucesso terapeutico. Dentre os fracassos clinicos a longo prazo, houve um diagnostico de tinea corporis (3%) de taxa de insucesso) e sete diagnosticos de tinea cruris (12% de taxa de insucesso). Evidencias micologicas de infeccao ocorreram em apenas 1 de 86 pacientes seguidos ate o final do seguimento a longo prazo. Recidiva micologica ocorreu em nove (11%) dos pacientes do seguimeto a longo prazo; um paciente estava infectado pelo Trichophyton mentagrphytes e oito pacientes, pelo T. rubrum. Houve recidiva em 2 de 29 (7%) pacientes com tinea corporis e oito de 57 (14%) com tines cruris (um paciente que recidivou tinha tinea corporis e cruris). Nao se verificou correlacao entre o numero de doses recebidas e a resposta micologica ou as taxas de recidiva a longo prazo. O fluconazol foi bem tolerado; somente 5 de 95 pacientes tratados com fluconazol referiram efeitos adversos, um dos quais resultou em descontinuacao da terapia (urticaria moderada). A boa tolerancia comparada a dos outros antifugicos orais e a conveniencia de um esquema de dose unica semanal oral em comparacao aos tratamentos topicos e orais existentes tornam a dose unica oral semanal de fluconazol uma elternativa valiosa no tratamento da tinea corporis/cruris

[In vitro investigations of microphages function in patients with chronic mucocutaneous candidosis (author's transl)]. / In-vitro-Untersuchungen der Mikrophagenfunktion bei Patienten mit chronischer mucocutaner Candidose.

In five patients with either familial or non-familial type of chronic mucocutaneous candidosis some properties of phagocytic function of the polymorphonuclear leucocytes (PMNL) have been studied in vitro. In each of the patients there were found: a) a decreased chemotactic activity of PMNL, b) a weakness of intake and of intracellular destruction of Candida albicans cells by PMNL, c) an impairment of phagocytosis and intracellular killing of Candida albicans as well of Staphylococcus aureus by PMNL. The rate of phagocytosis of heat-inactivated Candida albicans cells by PMNL was normal in each case. In the serum of two patients a phagocytosis inhibiting factor is supposed to exist. In PMNL of 3 patients a defective activity of NADH-dependent oxidase was found. The occurrence of hereditary CMCC in a father and his two daughters points to an autosomal dominant trait, whereas in most cases of familiar CMCC hitherto described an autosomal recessive mode of transmission was found.

Experimental cutaneous candidiasis in rodents; II. Role of the stratum corneum barrier and serum complement as a mediator of a protective infalmmatory response.

Of six species of Candida applied epicutaneously to rodents, only C albicans and C stellatoidea penetrate the stratum corneum and produce inflammation. The role of the stratum corneum and produce inflammation. The role of the stratum corneum in experimental murine Candida infections was studied, therefore, by intraepidermal injection of blastospores in mice that received a prior injection of staphylococcal epidermolysin. All six species caused accumulation of neutrophils if placed within an intraepidermal cleft in contact with viable epidermis. The role of serum complement in cutaneous candidiasis was also studied in vivo in rodents depleted of complement with cobra venom factor or deficient in the fifth component of complement. These animals failed to develop neutrophilic inflammatory responses to the six Candida species tested in contrast to control animals. Candida albicans, C stellatoidea, and C tropicalis developed extensive hyphal proliferation with invasion of the entire cutis and subcutis in these animals. The stratum corneum provides an effective barrier to some, but not all Candida species. When this barrier is penetrated, complement mediates an acute neutrophilic pustular response that resticts Candida proliferation and prevents deep invasion of tissue.

The effect of transfer factor on neutrophil function in chronic mucocutaneous candidiasis.

Chronic mucocutaneous candidiasis with hypoparathyroidism in a 6-year-old-boy is described. In addition to defects of in vivo and in vitro correlates of delayed-type hypersensitivity to Candida albicans the child also had abnormalities of neutrophil function in terms of their capacity to respond by chemotaxis to a known attractant and to kill suspensions of C. albicans. Dialysable transfer factor was given on six occasions at intervals of between 26 and 45 days. Neutrophil chemotaxis (optimal conditions) was restored following each of the six injections, neutrophil chemotaxis (sub-optimal conditions) following five of the six injections and candidicidal capacity following four of the six injections. The effects of transfer factor were transient requiring repeated injections. The Candida delayed-type hypersensitivity skin test was restored to normal but lymphocyte transformation to Candida extract was not consistently positive following treatment. There was a slight clinical improvement following therapy. These abnormalities of neutrophil and lymphocyte function point to the complexity of chronic mucocutaneous candidiasis. The improvement in neutrophil chemotaxis and candidicidal capacity following treatment suggests that transfer factor may be a heterogeneous group of molecules, some of which affect granulocytes and restore defects in their function.