RESUMO
Introduction. Sporotrichosis is a subcutaneous infection caused by dimorphic Sporothrix species embedded in the clinical clade. Fungi have virulence factors, such as biofilm and melanin production, which contribute to their survival and are related to the increase in the number of cases of therapeutic failure, making it necessary to search for new options.Gap statement. Proton pump inhibitors (PPIs) have already been shown to inhibit the growth and melanogenesis of other fungi.Aim. Therefore, this study aimed to evaluate the effect of the PPIs omeprazole (OMP), rabeprazole (RBP), esomeprazole, pantoprazole and lansoprazole on the susceptibility and melanogenesis of Sporothrix species, and their interactions with itraconazole, terbinafine and amphotericin B.Methodology. The antifungal activity of PPIs was evaluated using the microdilution method, and the combination of PPIs with itraconazole, terbinafine and amphotericin B was assessed using the checkerboard method. The assessment of melanogenesis inhibition was assessed using grey scale.Results. The OMP and RBP showed significant MIC results ranging from 32 to 256 µg ml-1 and 32 to 128 µg ml-1, respectively. Biofilms were sensitive, with a significant reduction (P<0.05) in metabolic activity of 52% for OMP and 50% for RBP at a concentration of 512 µg ml-1 and of biomass by 53% for OMP and 51% for RBP at concentrations of 512 µg ml-1. As for the inhibition of melanogenesis, only OMP showed inhibition, with a 54% reduction.Conclusion. It concludes that the PPIs OMP and RBP have antifungal activity in vitro against planktonic cells and biofilms of Sporothrix species and that, in addition, OMP can inhibit the melanization process in Sporothrix species.
Assuntos
Anfotericina B , Antifúngicos , Melanogênese , Inibidores da Bomba de Prótons , Sporothrix , Esporotricose , Humanos , Anfotericina B/farmacologia , Anfotericina B/uso terapêutico , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Itraconazol/farmacologia , Melaninas/biossíntese , Melaninas/metabolismo , Melanogênese/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Inibidores da Bomba de Prótons/farmacologia , Inibidores da Bomba de Prótons/uso terapêutico , Sporothrix/efeitos dos fármacos , Sporothrix/metabolismo , Esporotricose/tratamento farmacológico , Esporotricose/microbiologia , Terbinafina/farmacologiaRESUMO
Extranodal NK/T- cell lymphoma (ENKTCL) is an aggressive lymphoma driven by Epstein-Barr virus (EBV) infection in genetically susceptible individuals. It was historically called a lethal midline granuloma. Due to the angio-destructive nature of ENKTCL, lymphoma cells are often accompanied and masked by necrosis and dense inflammation in the biopsy. Further, the biopsy may show vasculitis, which can mimic granulomatosis with polyangiitis. Due to these masquerades, ENKTCL is often misdiagnosed in the biopsy. Several biopsies may be required to establish the diagnosis. We describe the clinical course and autopsy findings of a young female who presented with a hard-palate ulcer. Antemortem biopsies failed to establish the diagnosis. The autopsy revealed an advanced nasal subtype of Extranodal NK/T-cell lymphoma with dissemination to the kidneys, adrenals, liver, spleen, and small intestine.
RESUMO
The limited therapeutic options for fungal infections and the increased incidence of fungal strains resistant to antifungal drugs, especially Candida spp., require the development of new antifungal drugs and strategies. Histone deacetylase inhibitors (HDACi), like vorinostat, have been studied in cancer treatment and have antifungal effects, acting alone or synergistically with classical antifungals. Here we investigated the antifungal activity of two novel sustainable HDACi (LDT compounds) based on vorinostat structure. Molecular docking simulation studies reveal that LDT compounds can bind to Class-I HDACs of Candida albicans, C. tropicalis, and Cryptococcus neoformans, which showed similar binding mode to vorinostat. LDT compounds showed moderate activity when tested alone against fungi but act synergistically with antifungal azoles against Candida spp. They reduced biofilm formation by more than 50% in C. albicans (4 µg/mL), with the main action in fungal filamentation. Cytotoxicity of the LDT compounds against RAW264.7 cells was evaluated and LDT536 demonstrated cytotoxicity only at the concentration of 200 µmol/L, while LDT537 showed IC50 values of 29.12 µmol/L. Our data indicated that these sustainable and inexpensive HDACi have potential antifungal and antibiofilm activities, with better results than vorinostat, although further studies are necessary to better understand the mechanism against fungal cells.
Fungal infections are neglected diseases that affect more than a billion people worldwide. Some histone deacetylase inhibitors can act against fungal cells. Our data reveal that HDACi LDT536 and LDT537 have potential antibiofilm and antifungal activities.
RESUMO
ABSTRACT Extranodal NK/T- cell lymphoma (ENKTCL) is an aggressive lymphoma driven by Epstein-Barr virus (EBV) infection in genetically susceptible individuals. It was historically called a lethal midline granuloma. Due to the angio-destructive nature of ENKTCL, lymphoma cells are often accompanied and masked by necrosis and dense inflammation in the biopsy. Further, the biopsy may show vasculitis, which can mimic granulomatosis with polyangiitis. Due to these masquerades, ENKTCL is often misdiagnosed in the biopsy. Several biopsies may be required to establish the diagnosis. We describe the clinical course and autopsy findings of a young female who presented with a hard-palate ulcer. Antemortem biopsies failed to establish the diagnosis. The autopsy revealed an advanced nasal subtype of Extranodal NK/T-cell lymphoma with dissemination to the kidneys, adrenals, liver, spleen, and small intestine.
RESUMO
Anaplastic lymphoma kinase (ALK) positive, anaplastic large cell lymphoma involving the non-mammary implant is an extremely rare presentation. Irrespective of the type or site, the implant-associated primary ALCL is morphologically and immunophenotypically similar to ALK-negative ALCLs. Herein, we present the case of a 42-year-old male who developed a lytic lesion after an implant for a right femur fracture. The lytic lesion biopsy revealed anaplastic large cell lymphoma with ALK protein expression. Imaging findings showed the widespread dissemination of disease all over the body, entrapping the implant too. ALCL involving the bone implant is a very unusual and rare presentation that needs to be documented.
RESUMO
Anaplastic lymphoma kinase (ALK) positive, anaplastic large cell lymphoma involving the non-mammary implant is an extremely rare presentation. Irrespective of the type or site, the implant-associated primary ALCL is morphologically and immunophenotypically similar to ALK-negative ALCLs. Herein, we present the case of a 42-year-old male who developed a lytic lesion after an implant for a right femur fracture. The lytic lesion biopsy revealed anaplastic large cell lymphoma with ALK protein expression. Imaging findings showed the widespread dissemination of disease all over the body, entrapping the implant too. ALCL involving the bone implant is a very unusual and rare presentation that needs to be documented.
Assuntos
Humanos , Masculino , Adulto , Linfoma Anaplásico de Células Grandes , Fraturas do Fêmur/complicações , Quinase do Linfoma Anaplásico , Próteses e ImplantesRESUMO
To investigate and compare the effects of strength training (Shoulder girdle and respiratory muscles) and drug (Jatamansi) on reducing hand tremor in archers. Randomized experimental, different subject design. Institutional study done at Manipur Archery Association. Thera-band (Hygienic Corporation) and Nardostachys jatamansi (GMP Certified) were used as interventions. Pre & Post Hand Steadiness Score (Arm-Hand-Steadiness Tester on 4 mm hole) and Performance Test Scores (AAPHER Archery Test) was evaluated. 45 National Level Archers within age 16-28yrs were assigned into three groups: Group I (Medicine), Group II (Strength Training) and Group III (Control). Medicine was consumed for 4 weeks continuously 3 gm TDS and Thera-band strength training was given for 3 times weekly for 4 weeks. Main Outcome Measures: It was hypothesized that strength training is more effective in reducing hand tremors than medicinal or control groups. Arm-Hand-Steadiness: Numbers of Contact (NOC): On inter Group Comparison of the three Groups using One Way ANOVA, left and right arm showed significant differences (F = 5.64, p<0.05; F = 8.97, p<0.001) respectively and on Post Hoc Scheffes analysis, Group II showed maximum improvement. Total Contact Time (TCT): On inter Group comparison of the three Groups using One Way ANOVA, left and right arm showed significant differences (F = 12.50, p<0.001; F = 9.23, p<0.001) respectively and On Post Hoc Scheffes analysis, Group II showed maximum improvement. Archery Performance: On inter Group comparison of the three Groups using One Way ANOVA showed significant difference (F = 6.53, p<0.005) and on Post Hoc Scheffes analysis, Group II showed maximum improvement. Intervention of strength training and jatamansi may be effective for an archer however, strength training with thera-band and respiratory muscles conditioning intervention in combination increases steadiness and archery performance.