Cytokine Profile of a Self-Healing Fonsecaea pedrosoi Infection in Murine Model

Chromoblastomycosis is a chronic infectious disease of the skin and subcutaneous tissue. However, the host-defence response to this fungal infection has not been investigated thoroughly. This study was carried out to analyse the sequential events and the change of local cytokine release in a murine model infected with Fonsecaea pedrosoi in footpad. The anti-inflammatory Th2 cytokine IL-10 demonstrated an upward trend up to 7 days post infection followed by a steady decline. The titers of TNF-α (a pro-inflammatory Th1 cytokine) increased up to 7 days post infection followed by a relatively steady-state until full recovery. The anti-inflammatory cytokine IL-4 showed a similar pattern as TNF-α. The pro-inflammatory cytokine IFN-γ did not increased until 7 days post infection, while demonstrated an upward trend up to 30 days when the mice reached a full recovery from infection.     

Efficacy and Safety of Linezolid in Treating Gram-Positive Bacterial Infection in the Elderly: A Retrospective Study

Linezolid is commonly used for the treatment of drug-resistant Gram-positive bacterial infection. This study aimed to evaluate the efficacy and safety of linezolid in treating Gram-positive bacterial infection in the elderly from January 2010 to December 2012. Total 40 elderly patients (>60 years old) with Gram-positive bacterial infection were treated with linezolid and their demographic and clinical data were collected and analyzed. Among the 40 patients, 31 patients (77.5 %) were cured. Linezolid caused little adverse effects on liver and renal function. The main adverse effect was thrombocytopenia and its incidence was significantly associated with baseline platelet count and the duration of treatment (P < 0.05). Logistic regression analysis showed that the baseline platelet count <200 × 10⁶/mL, but not the age, the sex, the length of hospital stay, baseline levels of hemoglobin, alanine aminotransferase, or creatinine clearance rate was significantly associated with linezolid-induced thrombocytopenia. In conclusion, linezolid is effective to cure Gram-positive bacterial infection in the elderly and causes little adverse effects on liver and renal function. Timely monitoring of baseline platelet count may be helpful to guide the use of linezolid to avoid the occurrence of thrombocytopenia.     

Sarcoptic mange vulnerability in carnivores of the Białowieża Primeval Forest,Poland: underlying determinant factors

Sarcoptic mange caused by Sarcoptes scabiei, is a highly contagious worldwide mite infection responsible for epizootic skin disease in populations of wild and domestic mammals. It causes skin disorders that may lead to severe generalized skin disease (mange). We investigated the spread and dynamics of sarcoptic mange in one of the best preserved carnivore communities in the Bia?owie?a Primeval Forest over the last 20 years. Sarcoptic mange was found in 6 of 10 investigated species. The highest percentage of infected individuals was recorded in red foxes (19 %), European badgers (9 %), grey wolves (7 %), raccoon dogs (6 %), and stone martens (5 %). Other species were not infected (least weasel, American mink, European polecat, pine marten) or infected sporadically (Eurasian lynx––1 case). Rate of infection was correlated with the sum of ecological and behavioral features, which may increase the spread of infection. Outbreaks of sarcoptic mange occurred simultaneously in several species of carnivores, which indicates the occurrence of between species transmission. We found that the source of investigated individuals (trapped, culled and found dead) may influence the results of the analysis. Our study shows that in carnivore communities such as in Bia?owie?a Forest, numerous species may serve as a reservoir of the pathogen and favor its persistence in the environment. This study indicates that sociality and use of den sites are important factors affecting sarcoptic mange spread and prevalence in wild populations of carnivores.     

Plasmodium infection cure cycles induce modulation of conventional dendritic cells

Malaria is one of the most widespread human infectious diseases worldwide and a cause of mortality. It is difficult to induce immunological memory against the malarial parasite Plasmodium. The immunity to clinical malaria disease is acquired with multiple infection and treatment cycles, along with substantial reduction in parasite burden. However, the mechanism of the acquired immunity remains largely unclear. Conventional DCs (cDCs) play a pivotal role in orchestration of immune responses. The purpose of this study is to analyze the characterization of cDCs after the infection and cure treatment cycles. Mice were infected with the lethal rodent malarial parasite Plasmodium berghei ANKA, which was followed by cure treatment with the antimalarial drug pyrimethamine. This was then followed by a challenge with live parasites. The mice that went through infection cure cycles showed significant immune response, demonstrating robust immunological memory against malaria parasites. We investigated the cytokine production capacity of splenic cDCs in both naive and infection cure mice by stimulating purified splenic cDCs with LPS (TLR4 agonist) or CpG (TLR9 agonist). The capacity of cytokine production was found to be significantly decreased in infection cure mice. The suppression of cytokine production was sustained for a long term (6 months). Moreover, the surface expression of MHC Class II molecules was significantly lower in infection cure mice than in naive mice. These results suggest that Plasmodium infection and cure treatment resulted in strong immunological memory and modulation of full functionality of cDCs.     

Onychomycosis Due to Neoscytalidium Treated with Oral Terbinafine, Ciclopirox Nail Lacquer and Nail Abrasion: A Pilot Study of 25 Patients

Background

Onychomycosis by Neoscytalidium constitutes chronic infection of the nails, and its frequency has increased in recent decades. Currently, no effective standard treatment exists and literature data remain scarce. This work aimed to conduct a pilot project of combined treatment for this infection.

Methods

Thirty patients were divided into three treatment groups: oral terbinafine plus ciclopirox nail lacquer twice a week; ciclopirox nail lacquer twice a week; and ciclopirox nail lacquer 5 days a week, all associated with nail abrasion when required, for 12 months, with 6 months posttreatment follow-up. Clinical and mycological criteria were used for evaluation.

Results

Twenty-five patients completed the study. Significant clinical lesion reduction in disease occurred in all three treatment groups: 21 patients (84 %) entered the study with more than 50 % of diseased nail plate, at the end of treatment, and at 6-month follow-up, 84 and 96 %, respectively, presented less than 25 % nail lesion. Negative microscopy was observed in 36 % of the patients at the end of treatment and in 24 % of the patients at 6-month follow-up. At treatment completion (12 months), culture was negative in 21 patients (84 %) and in 18 (72 %) at follow-up. It was not possible to establish any clinical or mycological statistical differences between groups (p > 0.05). Global medical evaluation upon treatment completion revealed that one patient (4 %) presented complete cure, 8 (32 %) presented partial cure, 16 (64 %) presented therapeutic failure. At the end of follow-up period, 6 patients (24 %) were considered to have recurrence/reinfection.

Conclusions

The results obtained at the 6-month period of follow-up showed marked improvement (96 % of clinical improvement and 72 % of negative culture) of the patients treated for onychomycosis caused by Neoscytalidium in the three tested groups with no statistical differences between them. Multicentric studies with greater number of patients enrolled are necessary to confirm these results.     

Anaerobic axillary abscess.

Fifty-two patients with axillary abscesses were seen during two years. Staphylococcus aureus was isolated from 34, anaerobic bacteria from 12, and skin flora from five; in one case the pus was sterile. Seven patients with hidradenitis suppurativa had recurrent infection with abscess formation, which was bilateral in three. Anaerobes were isolated in five of these cases and skin flora alone in two. Anaerobes are secondary invaders in this condition, and histological examination shows that the primary abnormality is obstruction of pilosebaceous follicles and apocrine glands, associated with keratin plugging of the follicles. Chemotherapy offers little hope of cure, although metronidazole removes the offensive smell of the discharge. Radical surgery is usually indicated.     

Effect of nano-silver hydrogel coating film on deep partial thickness scald model of rabbit

Objective

Observing the effect of nano-silver hydrogel coating film on deep partial thickness scald model of rabbit.

Hylaranins: prototypes of a new class of amphibian antimicrobial peptide from the skin secretion of the oriental broad-folded frog,Hylarana latouchii

Amphibian skin secretions contain a broad spectrum of biologically active compounds, particularly antimicrobial peptides, which are considered to constitute a first line of defence against bacterial infection. Here we describe the identification of two prototype peptides representing a novel structural class of antimicrobial peptide from the skin secretion of the oriental broad-folded frog, Hylarana latouchii. Named hylaranin-L1 (GVLSAFKNALPGIMKIIVamide) and hylaranin-L2 (GVLSVIKNALPGIMRFIAamide), both peptides consist of 18 amino acid residues, are C-terminally amidated and are of unique primary structures. Their primary structures were initially deduced by MS/MS fragmentation sequencing from reverse-phase HPLC fractions of skin secretion that demonstrated antimicrobial activity. Subsequently, their precursor-encoding cDNAs were cloned from a skin secretion-derived cDNA library and their primary structures were confirmed unequivocally. Synthetic replicates of both peptides exhibited broad-spectrum antimicrobial activity with mean inhibitory concentrations (MICs) of 34 μM against Gram-negative Escherichia coli, 4.3 μM against Gram-positive Staphylococcus aureus and 4–9 μM against the yeast, Candida albicans. Both peptides exhibited little haemolytic activity (<6 %) at the MICs for S. aureus and C. albicans. Amphibian skin secretions thus continue to provide novel antimicrobial peptide structures that may prove to be lead compounds in the design of new classes of anti-infection therapeutics.     

Attachment and Biofilm Forming Capabilities of Staphylococcus epidermidis Strains Isolated from Preterm Infants

Staphylococcus epidermidis, a human commensal, is an important opportunistic, biofilm-forming pathogen and the main cause of late onset sepsis in preterm infants, worldwide. In this study we describe the characteristics of S. epidermidis strains causing late onset (>72 h) bloodstream infection in preterm infants and skin isolates from healthy newborns. Attachment and biofilm formation capability were analyzed in microtiter plates and with transmission electron microscopy (TEM). Clonal relationship among strains was studied with pulsed-field gel electrophoresis. Antimicrobial susceptibility testing was performed, as well as the detection of biofilm-associated genes and of the invasiveness marker IS256 with polymerase chain reaction. Blood and skin isolates had similar attachment and biofilm-forming capabilities and biofilm formation was not related to the presence of specific genes. Filament-like membrane structures were seen by TEM early in the attachment close to the device surface, both in blood and skin strains. Nine of the ten blood isolates contained the IS256 and were also resistant to methicillin and gentamicin in contrast to skin strains. S. epidermidis strains causing bloodstream infection in preterm infants exhibit higher antibiotic resistance and are provided with an invasive genetic equipment compared to skin commensal strains. Adhesion capability to a device surface seems to involve bacterial membrane filaments.     

Penicillium marneffei Infection: An Emerging Disease in Mainland China

Penicillium marneffei is an emerging pathogenic fungus that can cause a life-threatening systemic mycosis in immunocompromised hosts, especially in patients with AIDS. This infection is endemic in Southeast Asia. With the prevalence of AIDS in this area, the number of patients with systemic penicilliosis marneffei is found to be increasing rapidly in mainland China in recent years. We recently reviewed 668 cases of penicilliosis marneffei in mainland China from January 1984 to December 2009 in cnki, cqvip, CBMdisc and PubMed. We analyzed epidemiological and clinical features, laboratory findings, reaction to therapy and prognosis of the disease. We found that 99.4 % of the cases were reported in the southern part of China; among these cases, 42.8 % were from Guangxi (286 cases) and 40.6 % were from Guangdong province (271 cases). Five hundred and eighty-six cases (87.7 %) of penicilliosis marneffei were reported with infection by the human immunodeficiency virus, 25 cases (3.8 %) with other immunocompromised diseases, and 57 cases (8.5 %) without any documented underlying diseases. Fever, weight loss, anemia, lymphadenopathy, hepatosplenomegaly, respiratory signs and skin lesions were the common clinical manifestations of P. marneffei infections. The 569 cases received antifungal therapy with a mortality of 24.3 % (138 cases), 99 cases who had not received antifungal therapy had a mortality of 50.6 %. P. marneffei was an emerging pathogenic fungus and become a medical and public health importance in mainland China. The immunocompromised patients should pay more attention to P. marneffei infection in the endemic areas.     

Direct Comparison of the Efficacy and Safety of Oral Treatments with Oleylphosphocholine (OlPC) and Miltefosine in a Mouse Model of L. major Cutaneous Leishmaniasis

Background

Cutaneous leishmaniasis (CL) represents a range of skin diseases caused by infection with Leishmania parasites and associated with tissue inflammation and skin ulceration. CL is clinically widespread in both the Old and New World but lacks treatments that are well tolerated, effective and inexpensive. Oleylphosphocholine (OlPC) is a new orally bioavailable drug of the alkylphosphocholine family with potent antileishmanial activity against a broad range of Leishmania species/strains.

Methodology/principal findings

The potential of OlPC against Old World CL was evaluated in a mouse model of Leishmania (L.) major infection in BALB/c mice. Initial dose-response experiments showed that an oral daily dose of 40 mg/kg of OlPC was needed to impact time to cure and lesion sizes. This dose was then used to directly compare the efficacy of OlPC to the efficacy of the antileishmanial drugs miltefosine (40 mg/kg/day), fluconazole (160 mg/kg/day) and amphotericin B (25 mg/kg/day). OlPC, miltefosine and fluconazole were given orally for 21 days while amphotericin B was administered intraperitoneally for 10 days. Ulcer sizes and animal weights were followed up on a weekly basis and parasitemia was determined by means of a real-time in vivo imaging system which detects luminescence emitted from luciferase-expressing infecting L. major parasites. Amphotericin B and OlPC showed excellent efficacy against L. major lesions in terms of reduction of parasitic loads and by inducing complete healing of established lesions. In contrast, treatment with miltefosine did not significantly affect parasitemia and lesion sizes, while fluconazole was completely ineffective at the dose regimen tested.

Conclusions/Significance

Given the data showing the outstanding efficacy and tolerability of OlPC, our results suggest that OlPC is a promising new drug candidate to improve and simplify current clinical management of L. major CL.     

Dermatophytosis in Military in the Central-West Region of Brazil: Literature Review

Background

Dermatophytes represent a group of keratinophilic fungi capable of invading the superficial layer of the skin, hair, and nails of humans and animals. There is a high prevalence of dermatomycosis in tropical regions, and military personnel are susceptible to this kind of infection due to the type of occupational activities.

Objective

This study was to investigate dermatophytosis in military, in addition to predisposing factors to such infections.

Methods

The direct examination of the 221 samples obtained was conducted by preparing fresh slides, clarified with KOH. The clinical materials were seeded in duplicate in SDA and in Mycosel agar medium. The identification of the etiologic agents was performed according to the Riddell technique.

Results

99/221 (44.8 %) of the dermatophyte infection agents distributed in the three taxonomic genera that cause Tinea were recovered. The Trichophyton genus was the most representative and T. rubrum species 33 (33.3 %), the most prevalent. The other species found were as follows: T. tonsurans 13 (13.1 %), T. verrucosum 11 (11.1 %), T. interdigitale 9 (9.1 %), and T. mentagrophytes 6 (6.1 %). Among the most affected anatomical sites were skin 83 (83.8 %) and nails 17 (17.2 %).

Conclusions

Dermatophyte infections are common disorders in tropical countries. These infections lead to a variety of clinical manifestations. This study reports the incidence of dermatophytosis in the military personnel in the Central-West Region of Brazil. The occupational activities of the military individuals, in addition to the hot and humid climate of the region, can predispose them to infection by these fungal entities.     

Surveillance of Dermatophytosis in Northeast of Iran (Mashhad) and Review of Published Studies

Dermatophytoses are considered to be one of the major public health problems in the world and are among the most commonly diagnosed skin diseases in Iran. In spite of improved personal hygiene and living environment, dermatophytosis continues to spread and persist. To determine the prevalence of dermatophytosis and their etiologic agents in Mashhad (Iran), five hundred and sixty patients suspected to have fungal infection were studied. Subjects who participated in this study were 330 males and 230 females ranged in age from 4 months to 70 years with a mean age of about 25.5 years. Clinical materials including skin scraping, hair and scalp sample, nail clipping and subungual debris were collected. All of the specimens were assessed by direct examination and culture. Of 560 patients, 166 (29.6 %) had dermatophytosis. The types of tinea according to anatomical areas were as follows: tinea corporis (33.1 %), tinea capitis (32.5 %), tinea manuum (17.5 %), tinea cruris (10.2 %), tinea pedis (5.4 %), tinea unguium (0.6 %) and tinea barbae (0.6 %). Trichophyton verrucosum was the most prevalent species followed by Trichophyton violaceum and Trichophyton mentagrophytes. The prevalence of dermatophytosis in males was higher than in females. Based on a review of published studies from different parts of Iran, there are regional differences in the incidence of dermatophytosis. Epidermophyton floccosum has been the most prevalent species, and Microsporum canis has been isolated less than from the other countries.     

Enhancement of Skin Permeation and Skin Immunization of Ovalbumin Antigen <Emphasis Type="Italic">via</Emphasis> Microneedles

The purpose of this study was to evaluate the use of different types of microneedles and doses of ovalbumin antigen for in vitro skin permeation and in vivo immunization. In vitro skin permeation experiments and confocal laser scanning microscopy revealed that hollow microneedles had a superior enhancing effect on skin permeation compared with a solid microneedle patch and untreated skin by efficiently delivering ovalbumin-fluorescein conjugate into the deep skin layers. The flux and cumulative amount of ovalbumin-fluorescein conjugate at 8 h after administering with various conditions could be ranked as follows: hollow MN; high dose?>?medium dose?>?low dose?>?MN patch; high dose?>?medium dose?>?low dose?>?untreated skin; high dose?>?medium dose?>?low dose?>?without ovalbumin-fluorescein conjugate. As the dose of ovalbumin-fluorescein conjugate was increased to 500 μg, the antigen accumulated in the skin to a greater extent, as evidenced by the increasing green fluorescence intensity. When the hollow microneedle was used for the delivery of ovalbumin into the skin of mice, it was capable of inducing a stronger immunoglobulin G immune response than conventional subcutaneous injection at the same antigen dose. Immunoglobulin G levels in the hollow MN group were 5.7, 11.6, and 13.3 times higher than those of the subcutaneous injection group for low, medium, and high doses, respectively. Furthermore, the mice immunized using the hollow microneedle showed no signs of skin infection or pinpoint bleeding. The results suggest that the hollow MN is an efficient device for delivering the optimal dose of antigen via the skin for successful immunization.     

Description and life-cycle of Thrinascotrema brisbanica n. g., n. sp. (Digenea: Plagiorchiida), a parasite of the freshwater turtle Elseya latisternum from Australia,and the erection of the family Thrinascotrematidae

A new genus and species, Thrinascotrema brisbanica, is proposed to accommodate a plagiorchiidan trematode parasitic in the stomach of the freshwater turtle Elseya latisternum. The distinctive taxonomic features of the parasite are the shape and extent of the excretory bladder, and the stenostomate arrangement of the excretory collecting ducts in the adult, cercaria and metacercaria together with a cercarial protonephridial formula of 2(12+12+12)+(12+12+12). The life-cycle is three- host and aquatic. The pulmonate snail Glyptophysa gibbosa served as both a first and second intermediate host and tadpoles of Limnodynastes peronii, Adelotus brevis and Bufo marinus, and the snail Austropeplea lessoni also served as second intermediate hosts. Eggs were fully embryonated and infective when laid, but did not hatch until eaten by the snail. Cercariae first emerged 55 days after infection at 24-28 °C. They were sluggish swimmers and survived for about 48 hr. They attached firmly to the skin of snails and tadpoles on contact and began to penetrate the skin after a short exploratory migration. Metacercariae survived in snails and tadpoles for at least 3 months. It is concluded that Thrinascotrema is best placed within a new family, the Thrinascotrematidae (Digenea: Plagiorchiida), based on the unusual morphology of the excretory system.     

Therapy of tinea capitis; the value of x-ray epilation

Roentgen ray epilation, which is at present the most important single weapon against M. audouini infection of the scalp, should not be withheld except in special circumstances, from a child who has the disease. It can quickly cure the disease and halt spread from one child to another. Harmful sequelae and medicolegal complications can be averted by competent use of the method and simple precautions. The Keinbock-Adamson technique of epilation can be recommended without hesitancy, provided it is carried out meticulously in every detail, and administered by an operator of suitable training and experience in roentgen therapy of the skin.     

Antifungal Activity of Sodium Bicarbonate Against Fungal Agents Causing Superficial Infections

Although sodium bicarbonate—NaHCO₃ (SB) has many domestic and medical, traditional and empirical uses, only little scientific documentation of its activity is available. The aims of this study were to investigate the antifungal activity of SB on the three fungal groups (yeasts, dermatophytes and molds) responsible for human skin and nail infections. We first evaluated the in vitro antifungal activity of SB on 70 fungal strains isolated from skin and nail infections: 40 dermatophytes, 18 yeasts and 12 molds. A concentration of 10 g/L SB inhibited the growth of 80 % of all the fungal isolates tested on Sabouraud dextrose agar. The minimal inhibitory concentration 90 (MIC90) of SB measured on Sabouraud dextrose agar, Sabouraud dextrose broth and potato dextrose broth was 5 g/L for the yeasts, 20 g/L for the dermatophytes and 40 g/L for the molds. In a second step, we prospectively evaluated the ex vivo antifungal activity of SB on 24 infected (15 dermatophytes, 7 yeasts and 2 molds) clinical specimens (15 nails and 9 skin scrapings). The fungal growth was completely inhibited for 19 (79 %) specimens and reduced for 4 (17 %) specimens after 7 days of incubation on Sabouraud dextrose–chloramphenicol agar supplemented with 10 g/L of SB as compared to Sabouraud dextrose–chloramphenicol agar without SB. In conclusion, we documented the antifungal activity of SB on the most common agents of cutaneous fungal infection and onychomycosis, and we specified the effective concentrations for the different groups of pathogenic fungi. The mechanism of action of SB has yet to be explored.     

The immunology of South-American blastomycosis

Conclusions The immunological study of South-American blastomycosis, like in other deep mycoses, is very important. It permits the diagnosis of infection without disease as shown in the epidemiological surveys.Only after the immunological study by the serological reactions we had the indication that a clinical cure most of times does not represent a real cure of the patient, and by the interruption of treatment the relapses do occur.The relapses do occur also in patients under treatment and sometimes they are revealed only by the serological tests.The serological tests can indicate a good response of the patient to the treatment, and we think that they are the best criteria of cure when they become negative.By the serological follow up it is possible to have an idea about the prognosis of a patient. But, perhaps, this would be accomplished better in a study correlating the serological and skin tests which has not yet been done.The studies on the immunology of South-American blastomycosis were aided partially by a grant of the Fundação de Amparo à Pesquisa do Estado São Paulo.     

Moxibustion activates host defense against herpes simplex virus type I through augmentation of cytokine production

Moxibustion is a technique used in traditional oriental medicine, the aim of which is to cure and/or prevent illness by activating a person's ability for self‐healing. In this study, we assessed how moxibustion would affect the immune system and whether it would augment protective immunity. Mice were treated with moxibustion at Zusanli (ST36) acupoints; we analyzed mortality and cytokine activity in sera after infection with herpes simplex virus type 1 (HSV‐1), and cytokine gene expression in the skin and the spleen without a virus challenge. Our study demonstrates that pretreatment of BALB/c mice with moxibustion resulted in a marked increase in the survival rate after infection with lethal doses of HSV‐1, and elevated serum levels of IL‐1β and IFN‐γ on days 1 and 6 post‐infection with HSV‐1. Semi‐quantitative RT‐PCR assay showed that moxibustion treatment augmented the expression of IL‐1α, IL‐1β, IL‐6, universal‐IFN‐α, MIP‐1α, and TNF‐α mRNA in the skin, and IL‐1α, IL‐1β, IL‐12p40, IL‐15, u‐IFN‐α, MIP‐1α, and TNF‐α mRNA in the spleen. Moreover, moxibustion induces augmentation of natural killer cell activity. Collectively, our study demonstrates that moxibustion activates protective responses against HSV‐1 infection through the activation of cytokine production including IFN, and of NK cells.     

THERAPY OF TINEA CAPITIS—The Value of X-Ray Epilation

Roentgen ray epilation, which is at present the most important single weapon against M. audouini infection of the scalp, should not be withheld except in special circumstances, from a child who has the disease. It can quickly cure the disease and halt spread from one child to another. Harmful sequelae and medicolegal complications can be averted by competent use of the method and simple precautions.The Keinbock-Adamson technique of epilation can be recommended without hesitancy, provided it is carried out meticulously in every detail, and administered by an operator of suitable training and experience in roentgen therapy of the skin.