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Regulatory Toxicology and Pharmacology... Mar 2024All cosmetics products, including nail care products, must be evaluated for their safety. The assessment of systemic exposure is a key component of the safety...
All cosmetics products, including nail care products, must be evaluated for their safety. The assessment of systemic exposure is a key component of the safety assessment. However, data on the exposure, especially via ungual route (nail plate) are limited. Based on the physicochemical properties of human nails and permeability data of topical onychomycosis drugs, the nail plate is considered a good barrier to chemicals. We examine factors impacting penetration of nail care ingredients through the nail plate, including properties of the nails of the ingredients and formulations. The molecular weight, vapor pressure, logP, water solubility, and keratin binding, as well as formulations properties e.g., polymerization of acrylate monomers are considered important factors affecting penetration. To estimate systemic exposure of nail care ingredients through the nail plate, a standardized framework is applied that quantifies the impacts of these properties on penetration with an adjustment factor for each of these influencing properties. All the adjustment factors are then consolidated to derive an integrated adjustment factor which can be used for calculation of the systemic exposure dose for the ingredient. Several case studies are presented to reflect how this framework can be used in the exposure assessment for nail cosmetic products.
Topics: Humans; Nails; Administration, Topical; Onychomycosis; Drug Compounding; Permeability; Cosmetics; Antifungal Agents
PubMed: 38423269
DOI: 10.1016/j.yrtph.2024.105588 -
Medical Mycology Journal 2024A Filipino woman in her forties had facial erythema that was being self-treated with over-the-counter (OTC) drugs purchased outside of Japan. The drugs included...
A Filipino woman in her forties had facial erythema that was being self-treated with over-the-counter (OTC) drugs purchased outside of Japan. The drugs included clobetasol propionate, antibiotic, and antifungal components. Her facial erythema symptoms were worse during summertime. KOH direct examination of annular erythema was positive for fungal hyphae and negative for Demodex folliculorum. Fungal culture revealed Trichophyton indotineae based on internal transcribed spacer sequence analysis. Minimal inhibitory concentration for terbinafine was 0.06 µg/mL. We made a diagnosis of tinea faciei with steroid rosacea. We treated the patient with oral itraconazole. Physicians should be aware of increasing T. indotineae infections and increasing self-medication using topical OTC steroids combined with antifungals and antibiotics not only in India but also among foreign people living in other countries such as Japan.
Topics: Humans; Female; Japan; Nonprescription Drugs; Antifungal Agents; Tinea; Trichophyton; Rosacea; Steroids; Erythema
PubMed: 38417884
DOI: 10.3314/mmj.23-00014 -
Medical Mycology Journal 2024Microsporum canis is a type of dermatophyte that causes zoonotic dermatophytosis in cats and dogs. We report three cases of tinea corporis due to M. canis from a single...
Microsporum canis is a type of dermatophyte that causes zoonotic dermatophytosis in cats and dogs. We report three cases of tinea corporis due to M. canis from a single household with a domestic cat as a pet. The cases included a woman in her thirties (mother), a girl in her teens (older sister), and a girl in her teens (younger sister). Following sudden hair loss in the domestic cat, annular erythema with pruritus and scales appeared on the face, neck, and limbs of the older sister, younger sister, and mother, sequentially; they subsequently visited our hospital. Potassium hydroxide direct microscopy revealed filamentous fungi on all three women. In addition, short-haired colonies with a white to yellowish-white color and extending in a radial manner were found in cultures using a flat plate agar medium. A slide culture with the same medium indicated pointed spindle-shaped macroconidia with 7-8 septa. Therefore, the cases were diagnosed as tinea corporis due to M. canis. Genetic analysis of the cells of the cat and the mother, older sister, and younger sister using multilocus microsatellite typing (MLMT) indicated that all cases were classified into the same genotype, suggesting that the transmission route of these cases was familial. Here, we show that MLMT is useful in identifying the infection route in cases of tinea corporis due to M. canis.
Topics: Humans; Adolescent; Female; Animals; Dogs; Cats; Tinea; Microsporum; Mothers; Microsatellite Repeats; Dermatomycoses
PubMed: 38417881
DOI: 10.3314/mmj.23-00013 -
Journal of Ayub Medical College,... 2023Chromoblastomycosis, a chronic fungal infection of skin and subcutaneous tissue arises as a result of traumatic inoculation of exposed areas of the body. We present a...
Chromoblastomycosis, a chronic fungal infection of skin and subcutaneous tissue arises as a result of traumatic inoculation of exposed areas of the body. We present a unique case of chromoblastomycosis caused by Exophiala janselmei in a female farmer who presented with multiple smooth non-tender nodules on trunk and limbs for 5 years and pigmented indurated plaques on her face for 2 years along with deformities of her hands. Imaging investigations revealed multiple lytic lesions in the bones of the upper and lower limbs. Histopathological findings showed characteristic sclerotic bodies, consistent with the diagnosis of chromoblastomycosis. She was started on a combination of oral antifungals with a good response. This case highlights the importance of high suspicion and early diagnosis of deep fungal infections in order to avoid disfigurement and comorbidities.
Topics: Humans; Female; Chromoblastomycosis; Exophiala; Skin; Antifungal Agents; Lower Extremity
PubMed: 38404104
DOI: 10.55519/JAMC-03-11220 -
Anais Brasileiros de Dermatologia 2024
Topics: Tinea; Humans; Brazil; Animals; Trichophyton; Guinea Pigs; Male; Female
PubMed: 38403550
DOI: 10.1016/j.abd.2023.06.011 -
Cell Chemical Biology Apr 2024Candida species are among the most prevalent causes of systemic fungal infections, which account for ∼1.5 million annual fatalities. Here, we build on a compound...
Candida species are among the most prevalent causes of systemic fungal infections, which account for ∼1.5 million annual fatalities. Here, we build on a compound screen that identified the molecule N-pyrimidinyl-β-thiophenylacrylamide (NP-BTA), which strongly inhibits Candida albicans growth. NP-BTA was hypothesized to target C. albicans glutaminyl-tRNA synthetase, Gln4. Here, we confirmed through in vitro amino-acylation assays NP-BTA is a potent inhibitor of Gln4, and we defined how NP-BTA arrests Gln4's transferase activity using co-crystallography. This analysis also uncovered Met496 as a critical residue for the compound's species-selective target engagement and potency. Structure-activity relationship (SAR) studies demonstrated the NP-BTA scaffold is subject to oxidative and non-oxidative metabolism, making it unsuitable for systemic administration. In a mouse dermatomycosis model, however, topical application of the compound provided significant therapeutic benefit. This work expands the repertoire of antifungal protein synthesis target mechanisms and provides a path to develop Gln4 inhibitors.
Topics: Animals; Mice; Antifungal Agents; Amino Acyl-tRNA Synthetases; Candida albicans; Structure-Activity Relationship
PubMed: 38402621
DOI: 10.1016/j.chembiol.2024.01.010 -
The Journal of Allergy and Clinical... Jun 2024Inborn errors of immunity offer important insights into mucosal immunity. In autoimmune polyendocrine syndrome type-1 (APS-1), chronic mucocutaneous candidiasis has been...
BACKGROUND
Inborn errors of immunity offer important insights into mucosal immunity. In autoimmune polyendocrine syndrome type-1 (APS-1), chronic mucocutaneous candidiasis has been ascribed to neutralizing IL-17 autoantibodies. Recent evidence implicates excessive T-cell IFN-γ secretion and ensuing epithelial barrier disruption in predisposition to candidiasis, but these results remain to be replicated. Whether IL-17 paucity, increased type I inflammation, or their combination underlies susceptibility to chronic mucocutaneus candidiasis in APS-1 is debated.
OBJECTIVE
Our aim was to characterize the immunologic features in the cervicovaginal mucosa of females with APS-1.
METHODS
Vaginal fluid was collected with a flocked swab from 17 females with APS-1 and 18 controls, and cytokine composition was analyzed using Luminex (Luminex Corporation, Austin, Tex). Cervical cell samples were obtained with a cervix brush from 6 patients and 6 healthy controls and subjected to transcriptome analysis.
RESULTS
The vaginal fluid samples from patients with APS-1 had IFN-γ concentrations comparable to those of the controls (2.6 vs 2.4 pg/mL) but high concentrations of the T1 chemokines CXCL9 and CXCL10 (1094 vs 110 pg/mL [P < .001] and 4033 vs 273 pg/mL [P = .001], respectively), whereas the IL-17 levels in the samples from the 2 groups were comparable (28 vs 8.8 pg/mL). RNA sequencing of the cervical cells revealed upregulation of pathways related to mucosal inflammation and cell death in the patients with APS-1.
CONCLUSION
Excessive T1 cell response appears to underlie disruption of the mucosal immune responses in the genital tract of patients with APS-1 and may contribute to susceptibility to candidiasis in the genital tract as well.
Topics: Humans; Female; Vagina; Polyendocrinopathies, Autoimmune; Adult; Cervix Uteri; Middle Aged; Cytokines; Inflammation; Interleukin-17; Chemokine CXCL9; Young Adult; Interferon-gamma; Candidiasis, Chronic Mucocutaneous; Mucous Membrane
PubMed: 38395084
DOI: 10.1016/j.jaci.2024.02.012 -
Journal of Investigative Medicine High... 2024is a dimorphic fungus that can range from mild to severe disease presentation, including the acute respiratory distress syndrome (ARDS) based on the individual's...
is a dimorphic fungus that can range from mild to severe disease presentation, including the acute respiratory distress syndrome (ARDS) based on the individual's immunity. Acute respiratory distress syndrome is an uncommon presentation having an incidence of about 10% to 15% but has a high mortality exceeding 90%. This is a case of a 50-year-old female with past medical history of asthma and type 2 diabetes mellitus who presented to the pulmonology clinic with worsening dyspnea for the last 2 months. She also had a lesion in the left lower back, which was draining purulent fluid. Chest radiographs showed bilateral infiltrates and was started empirically on vancomycin and piperacillin-tazobactam. Bronchoalveolar lavage was done and the cultures grew The patient was moved to a higher level of care and given amphotericin B. Unfortunately, the patient experienced septic shock, which later deteriorated into cardiac arrest, ultimately leading to their passing. The importance of early diagnosis of blastomycosis and timely treatment has been emphasized in this case report.
Topics: Female; Humans; Middle Aged; Blastomycosis; Diabetes Mellitus, Type 2; Amphotericin B; Blastomyces; Respiratory Distress Syndrome
PubMed: 38375745
DOI: 10.1177/23247096241233042 -
BMC Veterinary Research Feb 2024Staphylococcus spp and Microsporum canis are zoonotic microorganisms which can cause infections and systemic diseases. The bone infection is usually caused by invasion...
BACKGROUND
Staphylococcus spp and Microsporum canis are zoonotic microorganisms which can cause infections and systemic diseases. The bone infection is usually caused by invasion of pathogen through the hematologic route. Mixed osteomyelitis caused by bacteria and fungi is rare, and to date, there have been no reports of mixed osteomyelitis with Staphylococcus spp. and Microsporum canis.
CASE PRESENTATION
This essay reports an atypical presentation of mixed osteomyelitis (Staphylococcus spp. and Microsporum canis) in a domestic cat. A 15-month-old female Persian cat was presented to a veterinary service; the main complaint was the appearance of a nodule in the mandibular ventral rostral region. A radiographic exam performed on the animal showed proliferative and osteolytic bone lesions. The patient was submitted to a biopsy for histopathological evaluation, along with bacterial and fungal cultures. Results showed mixed osteomyelitis by Staphylococcus spp. and Microsporum canis. Microbial Sensitivity Test was performed to choose a more suitable treatment. Two surgical procedures were executed to resect and curette the lesion, and treatments with anti-inflammatory, antibiotic, and antifungal drugs were established, showing a positive clinical evolution. After 8 months of treatment, the patient's owner moved to a different city, and the animal was seen by other veterinarians, who followed along with the same treatment. However, due to complications and a diminishing quality of life over 4 years of diagnosis, the patient was euthanized.
CONCLUSION
Given the above, mixed osteomyelitis is difficult to treat and can cause losses of life quality resulting death, especially in infections where M. canis is the agent causing the disease. Bacterial osteomyelitis is more frequently reported. But the lack of investigation of microorganisms other than bacteria, such as fungal cases, may imply in underdiagnosed cases. Treatment of osteomyelitis can be difficult considering the difficulties in isolating the pathological agent, resistance to the drug used, prolonged treatment time, and cost.
Topics: Cats; Female; Animals; Dermatomycoses; Quality of Life; Antifungal Agents; Osteomyelitis; Cat Diseases; Microsporum
PubMed: 38374006
DOI: 10.1186/s12917-024-03904-4 -
Memorias Do Instituto Oswaldo Cruz 2024Twenty-five years have passed since the initial observation of endemic zoonotic sporotrichosis in Rio de Janeiro, Brazil. Since then, this disease has spread throughout...
Twenty-five years have passed since the initial observation of endemic zoonotic sporotrichosis in Rio de Janeiro, Brazil. Since then, this disease has spread throughout South America. Accompanying the emergence of this mycosis, some progress has been made, including the expansion of a research network in this field and higher visibility of sporotrichosis within government authorities and funding agencies. However, there are still some challenges to curbing the expansion of this disease in the coming years. These include the development of rapid and accurate diagnostic tests, new antifungal drugs, particularly for the treatment of extracutaneous manifestations of sporotrichosis, and more comprehensive care for cats with sporotrichosis. Including these actions in the sporotrichosis research agenda is required so as to change the development of this disease in the years to come.
Topics: Animals; Cats; Sporotrichosis; Zoonoses; Brazil; Anniversaries and Special Events; Antifungal Agents; Sporothrix; Cat Diseases
PubMed: 38359307
DOI: 10.1590/0074-02760230208