Griseofulvin Treatment Research Articles

Improved effectiveness of an increased dose of griseofulvin for treating Tinea capitis among refugee children in Israel: A retrospective cohort study.

Tinea capitis (TC), a fungal infection that occurs in children, is primarily caused by dermatophytes such as Trichophyton and Microsporum species. For Trichophyton species, treatment with terbinafine is considered more effective than griseofulvin treatment. Specific populations, such as refugee children, are more susceptible to TC. This study aimed to describe and compare the response to treatment among Israeli and refugee children with TC. We retrospectively reviewed data collected on refugee and Israeli children with TC between January 2004 and January 2020. Overall, 3358 children with TC (refugees: 1497; Israelis: 1861) were identified. Among these, 86% of the refugee children had TC caused by Trichophyton violaceum, 65% of the Israeli children had TC caused by Microsporum canis and 83% of all children were treated with griseofulvin. Overall, 14% of the refugees showed a partial response to a griseofulvin dose of ≤25 mg/kg/day; however, they showed a complete response upon increasing the dose to ≥30 mg/kg/day. No significant adverse effects were observed. The over-crowded day care centres and dense living make refugee children more susceptible to TC than the general population, and griseofulvin dosage adjustment is necessary. TC, due to Trichophyton species, could benefit from receiving an increased dose of griseofulvin in a suspension form, which is cheaper than terbinafine.

Emergence of Resistant Extensive Tinea Infections

Dermatophytosis is a contagious infection of the skin, nails, and hair that is spread by direct or indirect contact. There was a failure of standard therapy, resulting in the establishment of recurring and chronic dermatophytosis. The aim of study is to assess the extensive areas of tinea infections, the resistant and recurrent tinea infection, and the efficacy of antifungal drug on clinical cure. This is a type of cohort study was carried out at the outpatient clinic of the department of Dermatology of Salah Al-Deen General Hospital in Tikrit City in the period from October 2020 till June 2021 samples of 100 patients were included. Patients were given anti-fungal treatment and followed up for 3 months. Result is Trichophyton mentagrophytes were the most prevalent isolate. The study revealed statistically significant association between types of treatment and outcome (P = 0.001) Griseofulvin treatment had 33 % (no response) Itraconazole treatment has 9.6 % recurrent and 19.2 % no response. In conclusion the occurrence of atypical dermatophyte infections is rising and now become a Great Imitator. They become extremely extensive and late to diagnose.

Radiosensitization and Micronucleus Formation are Induced by Centrosome Clustering Inhibition with Griseofulvin in Prostate Cancer Cell Lines

Ionizing radiation (IR) leads to micronucleus-dependent immunogenic signaling through cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING), and type I interferon. Inhibition of supernumerary centrosome clustering in tumor cells with griseofulvin can increase micronucleus formation and mitotic cell death but has not been studied in prostate cancer. We hypothesize that co-administration of IR and centrosome clustering inhibition (CCi) will radiosensitize prostate cancer cells and increase cGAS signaling, a potential avenue for enhancing the interplay between radiotherapy and immunotherapy. Murine Myc-CaP and human PC3 and 22rv1 prostate cancer cells were grown in culture using standard techniques. CCi was achieved with griseofulvin. Clonogenic survival was assessed across a range of griseofulvin (3-30 μM) and IR (1-12 Gy) doses, both as single interventions and combination treatments. Micronuclei (MN) were visualized and quantified by DAPI staining. Bipolar and multipolar spindles were identified by immunofluorescence against alpha-tubulin and pericentrin. In untreated Myc-CaP cells, MN were identified in 2.8% of cells. Griseofulvin treatment resulted in dose-dependent increases in MN, seen in 15% of cells after 30 μM treatment. IR also resulted in dose-dependent MN formation, with 4 Gy inducing MN in 24% of cells. Similar effects were observed in PC3 and 22rv1 cells, with 30 μM griseofulvin inducing MN in 5.2% and 5.8% of cells, while 9 Gy IR induced MN in 7.4% and 11.7%. After treatment 30 μM griseofulvin, multipolar spindles were identified in 31.3% of Myc-Cap, 10% of PC3, and 18.5% of 22rv1 cells, as compared to 4.6%, 4%, and 0% in untreated cells. Pretreatment of Myc-CaP cells with 30 μM griseofulvin prior to 3 Gy IR resulted in supra-additive decreases in clonogenic survival with a Chou-Talalay combination index (CI) of 0.69. In PC3 and 22rv1 cells, 30 μM griseofulvin enhanced 1 Gy IR with CI of 0.25 and 0.31, respectively. Griseofulvin and IR induce dose-dependent micronucleus formation in murine and human prostate cancer cell lines, and griseofulvin also promotes multipolar mitosis. Treatment with griseofulvin prior to IR decreases clonogenic survival across tested cell lines. These data suggest that combination treatment with griseofulvin and IR may improve local responses to radiotherapy and, through micronucleus-dependent immunogenic signaling, lead to more effective abscopal response generation in metastatic prostate cancer. Immediate future directions include investigation of cGAS/STING/interferon signaling axis and evaluation in an immune competent syngeneic mouse model with concurrent immune checkpoint inhibition.

Griseofulvin vs terbinafine for paediatric tinea capitis: When and for how long.

Outbreaks of tinea capitis (TC) can be a source of medical and economic burden for healthcare systems; Griseofulvin and terbinafine are considered to be effective first-line treatments for TC. In order to compare the efficacy of griseofulvin and terbinafine for the treatment of TC in a paediatric population of African immigrants in the Tel Aviv area, we conducted a retrospective cohort study of all cases of TC diagnosed and treated between March 2016 and February 2018 at a dedicated TC paediatric dermatology clinic at the Tel Aviv Medical Center (which serves as a referral centre for the paediatric refugee population in the Tel Aviv metropolitan area). Epidemiologic, clinical and laboratory data were collected, and 304 patients were included. Trichophyton violaceum (TV), Trichophyton soudanense (TS) and Microsporum audouinii (MA) were the prominent causative organisms. Treatment with griseofulvin suspension for 12weeks was compared with (a) griseofulvin suspension for 8weeks and with (b) terbinafine tablets for 4weeks. There was no statistically significant difference between the groups regarding age, sex, country of birth, ethnicity and the causative organism. Twelve weeks of griseofulvin treatment had a statistically significant better cure rate than 4weeks of terbinafine. Treatment was significantly more effective when TC was due to infections with MA and TS as compared with TV. No statistically significant difference was observed between 12- and 8-week treatment with griseofulvin.

A metabolomic perspective of griseofulvin-induced liver injury in mice

Griseofulvin (GSF) causes hepatic porphyria in mice, which mimics the liver injury associated with erythropoietic protoporphyria (EPP) in humans. The current study investigated the biochemical basis of GSF-induced liver injury in mice using a metabolimic approach. GSF treatment in mice resulted in significant accumulations of protoporphyrin IX (PPIX), N-methyl PPIX, bile acids, and glutathione (GSH) in the liver. Metabolomic analysis also revealed bioactivation pathways of GSF that contributed to the formation of GSF-PPIX, GSF-GSH and GSF-proline adducts. GSF-PPIX is the precursor of N-methyl PPIX. A six-fold increase of N-methyl PPIX was observed in the liver of mice after GSF treatment. N-methyl PPIX strongly inhibits ferrochelatase, the enzyme that converts PPIX to heme, and leads to PPIX accumulation. Excessive PPIX in the liver results in bile duct blockage and disturbs bile acid homeostasis. The accumulation of GSH in the liver was likely due to Nrf2-mediated upregulation of GSH synthesis. In summary, this study provides the biochemical basis of GSF-induced liver injury that can be used to understand the pathophysiology of EPP-associated liver injury in humans.

La dermatophytide exanthématique et pustuleuse généralisée (DEPG), une présentation clinique rare de dermatophytide

Dermatophytids are immunologically mediated dermatologic presentations secondary to sensitization to a dermatophyte infection. They are most frequently associated with toe-web intertrigo and usually present as localized, palmar, pruriginous vesicular eruptions. We report three original cases of generalized exanthematous pustular dermatophytid associated with kerions. Two boys aged 11 and 6 years, and one girl aged 6 years initially presented with kerion secondary to Trichophyton tonsurans (case 1), Trichophyton soudanense (case 2) and Trichophyton mentagrophytes (case 3), respectively. Two to three days after initiation of griseofulvin treatment, all patients presented with a pustular eruption extending from the head to the trunk, associated in one case with fever of 39°C and inflammatory chondritis. Samples obtained from the pustular lesions were sterile, serum inflammatory markers were within the normal range and skin lesions resolved on oral corticosteroid treatment (prednisone 0.75 mg/kg, case 1) or high-potency topical steroids (cases 2 and 3) given as an adjunct to griseofulvin treatment (19 to 23 mg/kg/d). Dermatophytids occur during the acute phase of infection or within a few days of treatment initiation. Lesions are remote from the infection site, contain no dermatophyte, and resolve after treatment of the infection. We report three original cases of generalized exanthematous pustular dermatophytid, associated in one case with fever and inflammatory chondritis. The main differential diagnosis is acute generalized exanthematous pustulosis secondary to antifungal drugs. Differences in clinical presentation between the two enable the appropriate diagnosis to be made as well as continued use of the antifungal medication needed to cure the patient. General or topical steroids may also be used in combination.

Application of exifine in etiotropic treatment of zooanthroponotic trichophytia

We have studied effect of Exifine on the dynamics of infectious process and some parts of the immune response at different stages of zooanthroponotic trichophytosis development. Functional activity of neutrophils, CD3, CD4, CD8, CD16, CD72, HLA-DR lymphocyte markers, TNFa, IL-1 β, IL-4 and IFN-γ cytokines were determined using immunological studies. Histomorphological changes of affected hair were studied during treatment. Effectiveness of Exifine at zooanthroponotic trichophytosis of scalp and smooth skin in children has been proven: mycological cure and persistent therapeutic effect. Exifine has no immunosuppressive activity as observed in Griseofulvin treatment.

Superficial Fungal Infections

Superficial Fungal Infections

Tinea Capitis: Predictive Value of Symptoms and Time to Cure With Griseofulvin Treatment

Tinea Capitis: Predictive Value of Symptoms and Time to Cure With Griseofulvin Treatment

Effects of griseofulvin on apoptosis through caspase-3- and caspase-9-dependent pathways in K562 leukemia cells: An in vitro study

Background: Griseofulvin, an oral nontoxic antifungal drug, has been reported to possess anticancer effect in human cancer cells, while the mechanisms are not completely understood. Objective: The aim of this study was to investigate the cytotoxic effect of griseofulvin on K562 cells and to understand its underlying molecular pathways. Methods: K562 cells were treated with griseofulvin at different concentrations for 24 hours, and the inhibition effect of griseofulvin on K562 cell proliferation was assessed by tetrazolium salt colorimetric assay. Apoptosis was assessed by examining nuclear morphology and quantifying phosphatidylserine externalization, and alterations in cellular morphology were analyzed by laser scanning confocal microscopy for fluorescent analysis. Flow cytometry was used in the analysis of cell cycle, mitochondrial membrane potential, and caspase pathways. Results: Griseofulvin could inhibit the growth of K562 cells in a dose-dependent manner with a mean (SD) inhibitory concentration of 50% value of 15.38 (1.35) μg/mL compared with untreated controls. Apoptosis was induced in K562 cells (38.35% [2.73%]; P < 0.01) by griseofulvin with the observation of both an increase in phosphatidylserine level and accumulation of chromatin nucleation in griseofulvintreated cells. In addition, cell-cycle analysis using propidium iodide staining suggested a significant G2/M accumulation (increase from mean 17.64% [4.49%] to 48.29 [1.89%]; P < 0.01) as a result of griseofulvin treatment. Flow cytometry analysis found that griseofulvin treatment was associated with the depolarization of the mitochondrial membrane in K562 cells. Furthermore, increased activities of caspase-3 by 22.15-fold ( P < 0.01) and caspase-9 by 16.73-fold ( P < 0.01) were observed in K562 cells after griseofulvin treatment compared with the untreated control; a decrease of caspase-8 activity was also observed, but the change was not statistically significant. Conclusions: These findings suggest that griseofulvin inhibited growth of K562 cells and induced cell apoptosis through cell-cycle arrest and mitochondrial membrane potential decrease as well as caspase-3 and -9 activation. Further testing is needed to evaluate the potential of griseofulvin as a candidate in the chemotherapy of hematologic malignancies.

Tinea Capitis: Predictive Value of Symptoms and Time to Cure With Griseofulvin Treatment

To describe (a) the predictive value of symptoms for diagnosis of tinea capitis and (b) the rate and timing of cure with high-dose griseofulvin treatment. This prospective open-label study enrolled children aged 1 to 12 years with clinical tinea capitis. Participants with a positive dermatophyte culture received oral griseofulvin (20-25 mg/kg/day) and topical selenium sulfide shampoo for 6 weeks. Main outcome measures. The rate of symptoms of tinea capitis, and rates of mycologic and clinical cure. The positive predictive values of any 1, 2, 3, or 4 symptoms for a positive culture were 88%, 82%, 78%, and 77%, respectively. The observed rates of mycologic, clinical, and complete cure were 89%, 66%, and 49%, respectively. conclusion: In a high-risk population it is reasonable to diagnose tinea capitis using one or more cardinal symptoms. Oral griseofulvin at 20 to 25 mg/ kg/day with adjunctive shampooing for 6 weeks is moderately successful as treatment.

The effect of griseofulvin on the gene regulation of β-tubulin in the dermatophyte pathogen Trichophyton rubrum

Griseofulvin - a mold metabolite produced by Penicillium griseofulvum - is an antifungal drug whose interaction with tubulin is poorly understood. In this study we cloned the beta-tubulin gene in Trichophyton rubrum, which encodes a polypeptide with 447 amino acids (accession number AAV33733). Nucleotide sequence comparison in data banks for both the partial DNA and its deduced amino acid sequence revealed significant homology with members of the eukaryotic beta-tubulin gene family. Investigation based on real-time polymerase chain reaction (PCR) indicated that griseofulvin treatment of T. rubrum fungal cells decreased the expression of the beta-tubulin gene in a dose-dependent manner. However, fluconazole had no effect on the beta-tubulin transcript level under the same circumstances. The identification of this vital gene, which is potentially involved in many cellular functions in pathogenic dermatophyte fungi, is the first step towards understanding the functional characteristics of beta-tubulin in such fungi and may help in the development of new antifungal drugs against dermatophytes.

Analysis of Sperm Karyotypes in a Patient Treated with Griseofulvin

Griseofulvin is known to interfere with chromosome segregation by binding to microtubule-associated proteins. Studies in mouse germ cells have demonstrated that griseofulvin can induce aneuploidy (numerical chromosome abnormalities) at therapeutic concentrations. The aim of this study was to determine if chronic griseofulvin treatment led to an increased frequency of sperm chromosome abnormalities in one male subject. We analyzed 290 full sperm karyotypes using the human sperm-hamster oocyte fusion system. The frequency of X- and Y-bearing sperm was equal. There was no increase in the frequency of numerical (1.7%) or structural (9.3%) abnormalities in the subject compared to unexposed controls. Although reassuring, this is the first report on this subject and future studies are needed to assess the risk of griseofulvin.

Cell death in trichomonads: new insights

Tritrichomonas foetus is an amitochondriate parasite that possesses hydrogenosomes, unusual anerobic energy-producing organelles. In these organisms the "mitochondrial cell death machinery" is supposed to be absent, and the mechanisms that lead to cell demise remain to be elucidated. The presence of a cell death program in trichomonads has already been reported, suggesting the existence of a caspase-like execution pathway in such organisms. Here we demonstrate the alterations provoked by the fungicide griseofulvin and raise the possibility that other cell death pathways may exist in T. foetus. Dramatic changes in trichomonads morphology are presented after griseofulvin treatment, such as intense plasma membrane and nuclear envelope blebbing, nucleus fragmentation, and an abnormal number of oversized vacuoles. One important finding was the exposition of phosphatidylserine (PS) in the outer leaflet of the plasma membrane in cells after drug treatment, and also the presence of a high amount of misshapen flagella and tubulin precipitates as vacuolar contents, suggesting an autophagic process of abnormal cellular elements. Interestingly, immunoreactivity for activated caspase-3 was not detected during griseofulvin treatment, a finding distinct from the observed when this cell was treated with H(2)O(2). The possibility of the existence of different pathways to cell death in trichomonads is discussed.

Water Adsorption Kinetics and Contact Angles of Pharmaceutical Powders

Water sorption kinetics and water contact angles have been characterized for a range of pharmaceutical powders: ambroxol hydrochloride, griseofulvin, N,n-octyl-D-gluconamide, paracetamol, sulfathiazole, and theophylline. The uptake of water by powder samples at saturated vapor pressure was modeled using a pseudo first-order kinetic relationship. Parameters from this model have been correlated with the concentration and reactivity of the active surface sites of the pharmaceutical powders and their contact angles. The study has shown that analysis of water adsorption kinetics can be a powerful technique for characterizing the surface chemistry and wettability of pharmaceutical powders, and is particularly sensitive to their surface modification through excipient adsorption: ethyl(hydroxyethyl)cellulose treatment of griseofulvin and butyryl chloride treatment of sulfathiazole are reported as case studies.

In vitro evaluation of griseofulvin against clinical isolates of dermatophytes from Isfahan

Fifty dermatophyte isolates, recently obtained from clinical materials, belonging to Trichophyton mentagrophytes, T. verrucosum, Microsporum canis and Epidermophyton floccosum were examined for their susceptibility to griseofulvin. The minimum inhibitory concentration (MIC) values were obtained using the modified microdilution method. All 100% tested isolates had MIC geometric mean at a concentration between 0.43 and 0.95 microg ml(-1) The MIC(90)s and MIC(50)s were 8 microg ml(-1) and <0.25-1 microg ml(-1) respectively. From all isolates, 12% including three T. verrucosum, one M. canis and two T. mentagrophytes isolates had MIC values out of the standardized range, therefore, they were considered as relatively griseofulvin-resistant. At least some of the isolates tested might be difficult to eradicate in clinical terms with griseofulvin treatment in Isfahan.

Tinea capitis favosa in Poland.

Tinea capitis favosa is uncommon in Europe. We describe two patients who had local alopecia caused by Trichophyton schoenleinii. In the first case, we observed good clinical response after griseofulvin treatment and in the second case after topical application of ciclopirox cream.

The effects of inhibition of haem biosynthesis by griseofulvin on intestinal iron absorption.

The relationship between haem biosynthesis and intestinal iron absorption in mice was investigated by ascertaining the effect of the haem synthesis inhibitor, griseofulvin, on duodenal iron absorption using both in vivo and in vitro measurements. Urinary 5-aminolaevulinic acid levels were increased within 24 hr of feeding mice with griseofulvin diet (2.5% w/w), with more marked increases seen after 3-7 days. Urinary porphobilinogen levels also showed a similar trend. In vivo intestinal iron absorption was significantly reduced (P<0.05) in experimental mice, mainly due to reduction in the transfer of 59Fe from the enterocytes to the portal circulation. In vitro studies using isolated duodenal fragments also exhibited marked decreases in both iron uptake and Fe (III) reduction. Changes in mucosal Divalent Metal Transporter 1 (DMT-1), Dcytb and Ireg1 (iron regulated protein 1) mRNA levels paralleled the changes in iron absorption. The reduction in iron absorption after griseofulvin treatment was normalised when mice were simultaneously injected with haem-arginate. These data support the hypothesis that intermediates in haem biosynthesis, particularly 5-aminolaevulinic acid, regulate intestinal iron absorption.

A population-based case-control study of oral griseofulvin treatment during pregnancy

A population-based case-control study of oral griseofulvin treatment during pregnancy

Influence of Griseofulvin treatment on semen quality in the dog

Griseofulvin is used to treat dermatomycosis in many species and causes oligospermia in supra-pharmacological doses. The aim of the present study was to evaluate the effect of Griseofulvin administered at therapeutic doses upon semen quality in dogs. Four dogs were treated with Griseofulvin (25 mg/kg per day) for 30 days. Semen collections and analyses were performed before, during and for 100 days after treatment for the Griseofulvin group and 10 untreated control dogs. Semen analyses included mean percentage of forward progressively motile sperm, total sperm output, normal live sperm and normal dead sperm. There was no significant difference between control and treated dogs for each of the semen quality parameters. Therapeutic dosage of Griseofulvin had no deleterious effect upon semen quality in dogs, although this does not preclude potential embryotoxic and teratogenic effects.