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Clinical, Cosmetic and Investigational... 2022Onychomycosis is the most common nail disease encountered in clinical practice and can cause pain, difficulty with ambulation, and psycho-social problems. A thorough... (Review)
Review
Onychomycosis is the most common nail disease encountered in clinical practice and can cause pain, difficulty with ambulation, and psycho-social problems. A thorough history and physical examination, including dermoscopy, should be performed for each patient presenting with nail findings suggestive of onychomycosis. Several approaches are available for definitive diagnostic testing, including potassium hydroxide and microscopy, fungal culture, histopathology, polymerase chain reaction, or a combination of techniques. Confirmatory testing should be performed for each patient prior to initiating any antifungal therapies. There are several different therapeutic options available, including oral and topical medications as well as device-based treatments. Oral antifungals are generally recommended for moderate to severe onychomycosis and have higher cure rates, while topical antifungals are recommended for mild to moderate disease and have more favorable safety profiles. Oral terbinafine, itraconazole, and griseofulvin and topical ciclopirox 8% nail lacquer, efinaconazole 10% solution, and tavaborole 5% solution are approved by the Food and Drug Administration for treatment of onychomycosis in the United States and amorolfine 5% nail lacquer is approved in Europe. Laser treatment is approved in the United States for temporary increases in clear nail, but clinical results are suboptimal. Oral fluconazole is not approved in the United States for onychomycosis treatment, but is frequently used off-label with good efficacy. Several novel oral, topical, and over-the-counter therapies are currently under investigation. Physicians should consider the disease severity, infecting pathogen, medication safety, efficacy and cost, and patient age, comorbidities, medication history, and likelihood of compliance when determining management plans. Onychomycosis is a chronic disease with high recurrence rates and patients should be counseled on an appropriate plan to minimize recurrence risk following effective antifungal therapy.
PubMed: 36133401
DOI: 10.2147/CCID.S362635 -
Molecules (Basel, Switzerland) Oct 2022Griseofulvin is an antifungal polyketide metabolite produced mainly by ascomycetes. Since it was commercially introduced in 1959, griseofulvin has been used in treating... (Review)
Review
Griseofulvin is an antifungal polyketide metabolite produced mainly by ascomycetes. Since it was commercially introduced in 1959, griseofulvin has been used in treating dermatophyte infections. This fungistatic has gained increasing interest for multifunctional applications in the last decades due to its potential to disrupt mitosis and cell division in human cancer cells and arrest hepatitis C virus replication. In addition to these inhibitory effects, we and others found griseofulvin may enhance ACE2 function, contribute to vascular vasodilation, and improve capillary blood flow. Furthermore, molecular docking analysis revealed that griseofulvin and its derivatives have good binding potential with SARS-CoV-2 main protease, RNA-dependent RNA polymerase (RdRp), and spike protein receptor-binding domain (RBD), suggesting its inhibitory effects on SARS-CoV-2 entry and viral replication. These findings imply the repurposing potentials of the FDA-approved drug griseofulvin in designing and developing novel therapeutic interventions. In this review, we have summarized the available information from its discovery to recent progress in this growing field. Additionally, explored is the possible mechanism leading to rare hepatitis induced by griseofulvin. We found that griseofulvin and its metabolites, including 6-desmethylgriseofulvin (6-DMG) and 4- desmethylgriseofulvin (4-DMG), have favorable interactions with cytokeratin intermediate filament proteins (K8 and K18), ranging from -3.34 to -5.61 kcal mol. Therefore, they could be responsible for liver injury and Mallory body (MB) formation in hepatocytes of human, mouse, and rat treated with griseofulvin. Moreover, the stronger binding of griseofulvin to K18 in rodents than in human may explain the observed difference in the severity of hepatitis between rodents and human.
Topics: Mice; Humans; Rats; Animals; Griseofulvin; Antifungal Agents; SARS-CoV-2; Angiotensin-Converting Enzyme 2; Molecular Docking Simulation; Spike Glycoprotein, Coronavirus; COVID-19; Keratins; RNA-Dependent RNA Polymerase; Polyketides
PubMed: 36296627
DOI: 10.3390/molecules27207034 -
The Journal of Investigative Dermatology Jul 1976Twenty-five years ago many of the topical remedies for superficial mycoses were irritating, toxic, or allergenic. Total x-ray depilation of the scalp was the accepted... (Review)
Review
Twenty-five years ago many of the topical remedies for superficial mycoses were irritating, toxic, or allergenic. Total x-ray depilation of the scalp was the accepted mode of therapy for tinea capitis. The introduction of topical nystatin for candidiasis and tolnaftate for dermatophytosis were major advances, but tinea capitis, onychomycosis, and chronic tinea pedis still presented problems. Soon after its introduction in 1958, griseofulvin became the definitive form of therapy for all types of dermatophytosis and played a major role in abolishing large-scale epidemics of tinea capitis in some countries. Recently, haloprogin and the imidazole derivatives, miconazole and clotrimazole, which are topically active against dermatophytes and Candida albicans, have become available. Selective indicator media for isolating dermatophytes are useful diagnostic tools, but quicker methods of diagnosis which require little interpretation are still lacking. Epidemiologic studies in Vietnam again revealed the effects of climate and occlusion on the prevalence, incidence, and severity of superficial mycoses and led to renewed interest in host susceptibility, environment, and prevention of infections.
Topics: Administration, Topical; Adult; Animals; Antifungal Agents; Arthrodermataceae; Candidiasis; Dermatomycoses; Female; Griseofulvin; Hair Removal; Humans; Male; Nystatin
PubMed: 778288
DOI: 10.1111/1523-1747.ep12513020 -
Nature Communications Jul 2022Heme-biosynthetic pathway of malaria parasite is dispensable for asexual stages, but essential for mosquito and liver stages. Despite having backup mechanisms to acquire...
Heme-biosynthetic pathway of malaria parasite is dispensable for asexual stages, but essential for mosquito and liver stages. Despite having backup mechanisms to acquire hemoglobin-heme, pathway intermediates and/or enzymes from the host, asexual parasites express heme pathway enzymes and synthesize heme. Here we show heme synthesized in asexual stages promotes cerebral pathogenesis by enhancing hemozoin formation. Hemozoin is a parasite molecule associated with inflammation, aberrant host-immune responses, disease severity and cerebral pathogenesis. The heme pathway knockout parasites synthesize less hemozoin, and mice infected with knockout parasites are protected from cerebral malaria and death due to anemia is delayed. Biosynthetic heme regulates food vacuole integrity and the food vacuoles from knockout parasites are compromised in pH, lipid unsaturation and proteins, essential for hemozoin formation. Targeting parasite heme synthesis by griseofulvin-a FDA-approved antifungal drug, prevents cerebral malaria in mice and provides an adjunct therapeutic option for cerebral and severe malaria.
Topics: Animals; Griseofulvin; Heme; Hemoglobins; Malaria, Cerebral; Mice; Parasites
PubMed: 35821013
DOI: 10.1038/s41467-022-31431-z -
Annales de Dermatologie Et de... Dec 2001Griseofulvin is a metabolic product of Penicillium spp. It was the first available oral agent for the treatment of dermatophytoses and has now been used for more than... (Review)
Review
Griseofulvin is a metabolic product of Penicillium spp. It was the first available oral agent for the treatment of dermatophytoses and has now been used for more than forty years. Griseofulvin is fongistatic, the exact mechanism in witch it inhibits the growth of dermatophytes is doubtful. Several ways are invoked: inhibition of fungal cell mitosis and nuclear acid synthesis, probable interference with the function of microtubules. Griseofulvin is poorly absorbed from the gastrointestinal tract. Absorption is enhanced by administration with fatty meal. Peak plasma occurs four hours after oral administration. Griseofulvin is detected in the outer layer of the stratum corneum soon after it is ingested, it is diffused from the extracellular fluid and sweat. There is no information regarding the mechanism by witch the drug is delivered to nails and hair. Deposition in the newly formed cells could be the major factor. Griseofulvin has also anti-inflammatory properties and some direct vasodilatory effects when it is used in high doses. It is metabolised by the liver microsomial enzyme system and excreted in the urine. The half-life is 9 to 21 hours. Griseofulvine has been used in the therapy of dermatophyte onychomycosis, treatment periods from 6 to 18 months were necessary with disappointing results and numerous relapses. Newer oral antifungal agents are now preferred especially in toenail infections. For many authors griseofulvin is still the treatment of choice of tinea capitis. Doses are 15-20 mg/kg/d for 6 to 8 weeks in children with the microsized form. Clinical response rates have been reported between 80 and 90 p. 100 in controlled studies. Griseofulvin is well-tolerated particulary in children. More frequent side effects are minor: headaches, gastrointestinal reactions and cutaneous eruptions. The major drug interactions has been noted with phenobarbital, anticoagulants and oral contraceptives.
Topics: Adult; Antifungal Agents; Biological Availability; Child; Dermatomycoses; Dose-Response Relationship, Drug; Griseofulvin; Humans; Metabolic Clearance Rate; Nails; Skin; Treatment Outcome
PubMed: 11908134
DOI: No ID Found -
Molecular Cancer Therapeutics Apr 2023Extra copies of centrosomes are frequently observed in cancer cells. To survive and proliferate, cancer cells have developed strategies to cluster extra-centrosomes to...
Extra copies of centrosomes are frequently observed in cancer cells. To survive and proliferate, cancer cells have developed strategies to cluster extra-centrosomes to form bipolar mitotic spindles. The aim of this study was to investigate whether centrosome clustering (CC) inhibition (CCi) would preferentially radiosensitize non-small cell lung cancer (NSCLC). Griseofulvin (GF; FDA-approved treatment) inhibits CC, and combined with radiation treatment (RT), resulted in a significant increase in the number of NSCLC cells with multipolar spindles, and decreased cell viability and colony formation ability in vitro. In vivo, GF treatment was well tolerated by mice, and the combined therapy of GF and radiation treatment resulted in a significant tumor growth delay. Both GF and radiation treatment also induced the generation of micronuclei (MN) in vitro and in vivo and activated cyclic GMP-AMP synthase (cGAS) in NSCLC cells. A significant increase in downstream cGAS-STING pathway activation was seen after combination treatment in A549 radioresistant cells that was dependent on cGAS. In conclusion, GF increased radiation treatment efficacy in lung cancer preclinical models in vitro and in vivo. This effect may be associated with the generation of MN and the activation of cGAS. These data suggest that the combination therapy of CCi, radiation treatment, and immunotherapy could be a promising strategy to treat NSCLC.
Topics: Animals; Mice; Griseofulvin; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Centrosome; Nucleotidyltransferases
PubMed: 36752776
DOI: 10.1158/1535-7163.MCT-22-0191 -
Indian Pediatrics May 2014
Topics: Anti-Inflammatory Agents; Antifungal Agents; Child, Preschool; Griseofulvin; Humans; Male; Prednisolone; Scalp; Tinea Capitis
PubMed: 24953594
DOI: No ID Found