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1.
BMJ Open Ophthalmol ; 9(1)2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38460964

RESUMO

PURPOSE: Subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are associated with systemic vascular diseases that compromise ocular perfusion. We demonstrate that SDDs are associated with decreased ellipsoid zone (EZ) thickness, further evidence of hypoxic damage. METHODS: Post hoc analysis of a cross-sectional study. 165 AMD subjects (aged 51-100; 61% women). Spectral-domain optical coherence tomography was obtained in both eyes. Masked readers assigned subjects to three groups: drusen only, SDD+drusen (SDD+D) and SDD only. EZ thickness was measured subfoveally and 2000 µm nasally, temporally, superiorly and inferiorly from the fovea. Univariate testing was performed using two-tailed t-tests with Bonferroni correction. RESULTS: The mean EZ thickness differences between the SDD+D and drusen-only groups were (in µm) 1.10, 0.67, 1.21, 1.10 and 0.50 at the foveal, nasal, temporal, superior and inferior locations, respectively (p=0.08 inferiorly, otherwise p≤0.01); between the SDD-only and drusen-only groups, the differences were 3.48, 2.48, 2.42, 2.08 and 1.42 (p≤0.0002). Differences in EZ thicknesses across all subjects and between groups were not significantly different based on gender, race or age. CONCLUSION: Subjects with SDDs (±drusen) had thinner EZs than those with drusen only, and the inferior EZ was least affected. EZs were thinnest in SDD-only subjects. This thinning gradation is consistent with progressive destruction of highly oxygen-sensitive mitochondria in the EZ from hypoxia. These findings support the reduced ophthalmic perfusion hypothesis for the formation of SDDs secondary to high-risk systemic vasculopathy.


Assuntos
Dapsona/análogos & derivados , Degeneração Macular , Drusas Retinianas , Humanos , Feminino , Masculino , Drusas Retinianas/diagnóstico por imagem , Estudos Transversais , Degeneração Macular/diagnóstico por imagem , Retina , Tomografia de Coerência Óptica/métodos
3.
J Dermatolog Treat ; 35(1): 2329784, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38508226

RESUMO

BACKGROUND: There is a lack of real-life safety data on treatment options for chronic urticaria in the presence of comedication and comorbidities. METHODS: We present a single-center UCARE pilot study of 212 outpatients with chronic urticaria. Patients were divided into three groups according to different CU therapies according to international guidelines. RESULTS: Of 212 patients, 108 (mean age 48.9 years, 71.3% female) had 59 comorbidities, including cardiovascular, autoimmune and malignant diseases. Patients were followed for a mean of 24.6 months (SD ± 21.3). Urticaria therapies were divided into three groups: A: 105 (97.2%) with omalizumab and 2nd generation antihistamines), B: 16 patients (14.8%): dual therapy with antihistamines and cyclosporine in 10 (9.3%), montelukast in five (4. 6%), dapsone in four (3.7%), hydroxychloroquine in one patient (0.9%), C: 12 (11.1%) patients received a third drug for 4.9 months (SD ± 3.2) and one quadruple therapy (2.1 months). 10 out of 12 (83.3%) patients received montelukast, two (16.7%) cyclosporine, two (16.7%) dapsone and one (8.3%) hydroxychloroquine as a third drug for chronic urticaria. CONCLUSIONS: Combining treatment modalities for chronic urticaria and comorbidities are available and feasible with a good safety profile.


Assuntos
Acetatos , Antialérgicos , Urticária Crônica , Ciclopropanos , Quinolinas , Sulfetos , Urticária , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Hidroxicloroquina/uso terapêutico , Projetos Piloto , Doença Crônica , Urticária Crônica/tratamento farmacológico , Urticária/tratamento farmacológico , Omalizumab/uso terapêutico , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Ciclosporina/uso terapêutico , Dapsona/uso terapêutico , Antialérgicos/uso terapêutico
4.
Sao Paulo Med J ; 142(4): e2023151, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38422241

RESUMO

BACKGROUND: Loxosceles spp are arthropods found worldwide. Its bite may produce cutaneous loxoscelism (necrotic or edematous) or cutaneous-visceral loxoscelism. Depending on their severity and location, cutaneous forms are managed with local cold application and systemic administration of antihistamines, corticosteroids, antibiotics, polymorphonuclear inhibitors, and analgesics. OBJECTIVE: This study aimed to report a case of cutaneous loxoscelism and to identify the main dermatological manifestations associated with the Loxosceles spp bite. DESIGN AND SETTING: This case report and literature review was conducted in a Mexican university. METHODS: A detailed report on the medical management of a patient with cutaneous loxoscelism treated at the emergency department of a public hospital was published. Scopus, PubMed, Web of Science, and Google Scholar databases were searched to identify articles reporting cutaneous loxoscelism. The following keywords were used during the database search: "loxoscelism" OR "spider bite," OR "loxosceles" OR "loxosceles species" OR "loxosceles venom" OR "loxoscelism case report" AND "cutaneous" OR "dermonecrotic arachnidism." RESULTS: A 62-year-old female patient with cutaneous loxoscelism was treated with systemic dapsone and local heparin spray. Eighteen studies with 22 clinical cases were included in this systematic review. Of the 22 patients, 12 (54.5%) were men. L. rufescens was the predominant spider species. CONCLUSIONS: The administration of dapsone and heparin for the management of cutaneous loxoscelism demonstrated success in this case, with no sequelae observed. In general, the literature review indicated favorable outcomes in patients treated with antimicrobials and corticosteroids, with continuous healing of skin lesions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ID CRD42023422424 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023422424).


Assuntos
Dapsona , Picaduras de Aranhas , Feminino , Masculino , Humanos , Pessoa de Meia-Idade , Dapsona/uso terapêutico , Picaduras de Aranhas/tratamento farmacológico , Hemoglobinas , Heparina , Corticosteroides , Regeneração
7.
Am J Case Rep ; 25: e942048, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38351602

RESUMO

BACKGROUND Leprosy, also known as Hansen's disease, is a neglected tropical disease with low prevalence in the United States. The disease's long incubation period can cause delayed presentation, and most affected individuals have a history of travel or work in leprosy-endemic regions. The immune response to Mycobacterium leprae determines the clinical characteristics of leprosy, with tuberculoid leprosy being characterized by well-defined granulomas and involvement of peripheral nerves. The recommended treatment is a combination of dapsone and rifampin for 12 months. CASE REPORT A 78-year-old man with a history of extensive travel to Africa and Asia 50 years ago, presented with a non-tender, non-pruritic, and hypopigmented skin lesion on his left knee. Biopsy results confirmed granulomatous inflammation and the presence of Mycobacterium leprae, leading to a diagnosis of tuberculoid/paucibacillary leprosy. The patient received dapsone and rifampin treatment, which resulted in symptom improvement. CONCLUSIONS The patient's long incubation period of 50 years between exposure and symptom onset is remarkable and possibly one of the longest reported for tuberculoid leprosy. It emphasizes the importance of considering leprosy in cases with an extensive travel history and long incubation periods. Our patient's case presented contradictory staining results, suggesting potential sampling variation or a rare mixed leprosy form. Based on his clinical findings, he was diagnosed with tuberculoid leprosy. Early diagnosis and treatment are crucial to prevent irreversible nerve damage and improve patient outcomes. Healthcare providers should be vigilant in acquiring a detailed travel history to facilitate early diagnosis and appropriate management of leprosy cases.


Assuntos
Hanseníase Tuberculoide , Hanseníase , Masculino , Humanos , Idoso , Hanseníase Tuberculoide/diagnóstico , Hanseníase Tuberculoide/tratamento farmacológico , Hanseníase Tuberculoide/patologia , Rifampina/uso terapêutico , Período de Incubação de Doenças Infecciosas , Hanseníase/diagnóstico , Hanseníase/tratamento farmacológico , Hanseníase/patologia , Mycobacterium leprae , Dapsona/uso terapêutico
8.
Invest Ophthalmol Vis Sci ; 65(2): 37, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38407857

RESUMO

Purpose: Subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are strongly associated with vasculopathies such as myocardial infarction and ischemic stroke. This study evaluates ischemic stroke subjects for SDDs to determine whether ocular hypoperfusion from internal carotid artery (ICA) stenosis is associated with ipsilateral SDDs. Methods: A cross-sectional study at Mount Sinai Hospital recruited 39 subjects with ischemic stroke (aged 52-90; 18 women, 21 men); 28 completed all study procedures. Computed tomography (CT) of the head and neck evaluated 54/56 ICAs for stenosis criteria: none (n = 33), mild (n = 12), moderate (n = 3), severe (n = 3), and complete (n = 3). Spectral-domain optical coherence tomography (SD-OCT) scans were read to consensus by two masked graders for soft drusen, SDDs and choroidal thickness (CTh; choroidal thinning = CTh < 250 µm). Univariate testing was done with Fisher's exact test. Multivariate logistic regression models tested age, gender, and ICA stenosis as covariates. Results: Moderate or more ICA stenosis (≥50%-69%) was significantly associated with ipsilateral choroidal thinning (P = 0.021) and ipsilateral SDDs (P = 0.005); the latter were present distal to six of nine stenosed ICAs versus five of 33 normal ICAs. Mild ICA stenosis (≥1%-49%) was not significantly associated with ipsilateral SDDs. Multivariate regression found that older age (P = 0.015) and moderate or more ICA stenosis (P = 0.011) remained significant independent risks for ipsilateral SDDs. Conclusions: At least moderate ICA stenosis (≥50%-69%) is strongly associated with ipsilateral SDDs and choroidal thinning, supporting downstream ophthalmic artery and choroidal hypoperfusion from ICA stenosis as the mechanism for SDD formation. SDDs may thus serve as sensitive biomarkers for ischemic stroke and other vascular diseases.


Assuntos
Estenose das Carótidas , Dapsona/análogos & derivados , AVC Isquêmico , Masculino , Humanos , Feminino , Estenose das Carótidas/diagnóstico , Estenose das Carótidas/diagnóstico por imagem , Constrição Patológica , Estudos Transversais , Corioide
9.
PLoS Negl Trop Dis ; 18(1): e0011901, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38271456

RESUMO

BACKGROUND: The occurrence of adverse drug events (ADEs) during dapsone (DDS) treatment in patients with leprosy can constitute a significant barrier to the successful completion of the standardized therapeutic regimen for this disease. Well-known DDS-ADEs are hemolytic anemia, methemoglobinemia, hepatotoxicity, agranulocytosis, and hypersensitivity reactions. Identifying risk factors for ADEs before starting World Health Organization recommended standard multidrug therapy (WHO/MDT) can guide therapeutic planning for the patient. The objective of this study was to develop a predictive model for DDS-ADEs in patients with leprosy receiving standard WHO/MDT. METHODOLOGY: This is a case-control study that involved the review of medical records of adult (≥18 years) patients registered at a Leprosy Reference Center in Rio de Janeiro, Brazil. The cohort included individuals that received standard WHO/MDT between January 2000 to December 2021. A prediction nomogram was developed by means of multivariable logistic regression (LR) using variables. The Hosmer-Lemeshow test was used to determine the model fit. Odds ratios (ORs) and their respective 95% confidence intervals (CIs) were estimated. The predictive ability of the LRM was assessed by the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 329 medical records were assessed, comprising 120 cases and 209 controls. Based on the final LRM analysis, female sex (OR = 3.61; 95% CI: 2.03-6.59), multibacillary classification (OR = 2.5; 95% CI: 1.39-4.66), and higher education level (completed primary education) (OR = 1.97; 95% CI: 1.14-3.47) were considered factors to predict ADEs that caused standard WHO/MDT discontinuation. The prediction model developed had an AUC of 0.7208, that is 72% capable of predicting DDS-ADEs. CONCLUSION: We propose a clinical model that could become a helpful tool for physicians in predicting ADEs in DDS-treated leprosy patients.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Hanseníase , Adulto , Humanos , Feminino , Dapsona/efeitos adversos , Hansenostáticos/efeitos adversos , Rifampina/uso terapêutico , Quimioterapia Combinada , Estudos de Casos e Controles , Clofazimina/uso terapêutico , Brasil/epidemiologia , Hanseníase/tratamento farmacológico , Organização Mundial da Saúde
10.
Acta Derm Venereol ; 104: adv11917, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38270257

RESUMO

Epidermolysis bullosa acquisita (EBA) rarely develops in childhood. This study retrospectively recruited paediatric patients with EBA (age ≤ 16 years), diagnosed by clinical and histopathological features and results of immunofluorescence, immunoblotting and enzyme-linked immunosorbent assay (ELISA), and reviews their clinical manifestations, histopathology, immunological features, and responses to various treatments. All 7 included patients presented with inflammatory EBA. Among them, 3 had a bullous pemphigoid-like phenotype. Pathologically, in addition to dermal-epidermal blistering, in all patients, the distribution of neutrophils was superficial perivascular or interstitial, or in the dermal papilla. Mixed neutrophils and eosinophils were detected in 2 of the 3 patients with bullous pemphigoid-like phenotypes. In addition to treatment with glucocorticoids, dapsone was administered in 4 patients, while thalidomide and sulfasalazine were administered in 1 patient. All patients responded to the these therapies. Relapse was mainly due to reduction and cessation of glucocorticoids. In conclusion, EBA in childhood may be unique, and thus distinct from its adult counterpart. Specific treatment and follow-up protocols are required for therapy of this rare autoimmune skin disease in children.


Assuntos
Doenças Autoimunes , Epidermólise Bolhosa Adquirida , Penfigoide Bolhoso , Adulto , Humanos , Criança , Adolescente , Epidermólise Bolhosa Adquirida/diagnóstico , Epidermólise Bolhosa Adquirida/tratamento farmacológico , Estudos Retrospectivos , Dapsona/uso terapêutico , Glucocorticoides/uso terapêutico
11.
Br J Haematol ; 204(3): 1024-1028, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38220217

RESUMO

Immune thrombocytopenia (ITP) resolves in most children within 3-12 months of diagnosis. Chronic ITP affects 10%-20% of patients, some of whom require treatment. Several second-line agents are efficacious in this group of patients. This paper describes our experience of using dapsone as a single second-line agent in children with chronic ITP. One hundred and three children with chronic ITP were seen at our centre from January 2012 to December 2016. Forty-five children met the inclusion criteria and received dapsone; 17 (37.8%) were boys; and 28 (62.2%) were girls. Early response to dapsone was seen in 37.8% of patients. The median duration of long-term follow-up was 50 months, and at least a partial response was seen in 64.4% of the patients. Dapsone offers good initial response rates and sustained remission in paediatric chronic ITP, comparable to other therapeutic agents available.


Assuntos
Púrpura Trombocitopênica Idiopática , Trombocitopenia , Masculino , Feminino , Humanos , Criança , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Contagem de Plaquetas , Dapsona/uso terapêutico , Estudos Retrospectivos , Trombocitopenia/tratamento farmacológico
12.
Biochim Biophys Acta Mol Basis Dis ; 1870(3): 167034, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38278334

RESUMO

L-Ser supply in the central nervous system of mammals mostly relies on its endogenous biosynthesis by the phosphorylated pathway (PP). Defects in any of the three enzymes operating in the pathway result in a group of neurometabolic diseases collectively known as serine deficiency disorders (SDDs). Phosphoserine phosphatase (PSP) catalyzes the last, irreversible step of the PP. Here we investigated in detail the role of physiological modulators of human PSP activity and the properties of three natural PSP variants (A35T, D32N and M52T) associated with SDDs. Our results, partially contradicting previous reports, indicate that: i. PSP is almost fully saturated with Mg2+ under physiological conditions and fluctuations in Mg2+ and Ca2+ concentrations are unlikely to play a modulatory role on PSP activity; ii. Inhibition by L-Ser, albeit at play on the isolated PSP, does not exert any effect on the flux through the PP unless the enzyme activity is severely impaired by inactivating substitutions; iii. The so-far poorly investigated A35T substitution was the most detrimental, with a 50-fold reduction in catalytic efficiency, and a reduction in thermal stability (as well as an increase in the IC50 for L-Ser). The M52T substitution had similar, but milder effects, while the D32N variant behaved like the wild-type enzyme. iv. Predictions of the structural effects of the A35T and M52T substitutions with ColabFold suggest that they might affect the structure of the flexible helix-loop region.


Assuntos
Dapsona/análogos & derivados , Magnésio , Monoéster Fosfórico Hidrolases , Serina , Animais , Humanos , Serina/metabolismo , Magnésio/farmacologia , Íons , Mamíferos/metabolismo
13.
J Dtsch Dermatol Ges ; 22(3): 400-421, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38259085

RESUMO

Non-biologic immunosuppressive drugs, such as azathioprine, dapsone or methotrexate are fundamental treatment options for a wide range of autoimmune and chronic inflammatory skin diseases. Some of these drugs were initially used for malignancies (e.g., azathioprine or methotrexate) or infectious diseases (e.g., hydroxychloroquine or dapsone) but are nowadays mostly used for their immunosuppressive/immunomodulating action. Although dermatologists have years of clinical experience with these drugs, some of the mechanisms of action are not fully understood and are the subject of research. Although these drugs are commonly used, lack of experience or knowledge regarding their safety profiles and management leads to skepticism among physicians. Here, we summarize the mechanism of action and detailed management of adverse effects of the most commonly used immunosuppressive drugs for skin diseases. Furthermore, we discuss the management of these drugs during pregnancy and breastfeeding, as well as their interaction and handling during vaccination.


Assuntos
Doenças Autoimunes , Dermatopatias , Gravidez , Feminino , Humanos , Azatioprina/uso terapêutico , Metotrexato/uso terapêutico , Imunossupressores/uso terapêutico , Dapsona/uso terapêutico , Doenças Autoimunes/tratamento farmacológico
14.
Am J Trop Med Hyg ; 110(3): 483-486, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38266303

RESUMO

Leprosy is a global health issue, causing long-term functional morbidity and stigma. Rapid diagnosis and appropriate treatment are important; however, early diagnosis is often challenging, especially in nonendemic areas. Here, we report a case of borderline lepromatous leprosy accompanied by dapsone-induced (neutropenia, anemia, and methemoglobinemia) and clofazimine-induced (skin discoloration and ichthyosis) side effects and type 1 leprosy reactions during administration of the multidrug therapy. The patient completely recovered without developing any deformities or visual impairment. To ensure early diagnosis and a favorable outcome, clinicians should be aware of the diminished sensation of skin lesions as a key physical finding and manage the drug toxicities and leprosy reactions appropriately in patients on multidrug therapy.


Assuntos
Hipersensibilidade , Hanseníase Dimorfa , Hanseníase Virchowiana , Hanseníase Multibacilar , Hanseníase , Doenças do Sistema Nervoso Periférico , Dermatopatias Bacterianas , Humanos , Clofazimina/efeitos adversos , Dapsona/efeitos adversos , Quimioterapia Combinada , Hansenostáticos/efeitos adversos , Hanseníase/patologia , Hanseníase Dimorfa/diagnóstico , Hanseníase Dimorfa/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Hanseníase Multibacilar/tratamento farmacológico , Hanseníase Virchowiana/diagnóstico , Hanseníase Virchowiana/tratamento farmacológico , Hanseníase Virchowiana/patologia
15.
BMJ Case Rep ; 17(1)2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38199656

RESUMO

Methaemoglobinaemia occurs when iron in haemoglobin is oxidised into a form that cannot transport oxygen. At low levels, it is asymptomatic, though at rising levels symptoms arise from impaired oxygenation, and it can ultimately be fatal. While uncommon, it is important to consider in hypoxaemic COVID-19 patients, especially if they are not clinically improving on standard treatments and workup for other causes does not explain the ongoing hypoxaemia. It is often diagnosed through a mismatch in peripheral and arterial oxygen, with the former typically less than the latter. We present the case of a COVID-19 patient who was found to have methaemoglobinaemia due to dapsone use for Pneumocystic jirovecii pneumonia (PJP) prophylaxis while on chemotherapy. Dapsone was stopped and supplemental high-flow nasal cannula was provided, and methaemoglobin levels improved over a 5-day period. She was discharged to follow-up with her haematologist in the clinic.


Assuntos
COVID-19 , Metemoglobinemia , Feminino , Humanos , Metemoglobinemia/induzido quimicamente , Metemoglobinemia/diagnóstico , Metemoglobina , Dapsona/efeitos adversos , Oxigênio
16.
J Drugs Dermatol ; 22(11): e12-e16, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37943259

RESUMO

BACKGROUND: Management of hidradenitis suppurativa (HS) is challenging since no single treatment provides consistently effective results, leaving patients with frequent relapses. Dapsone combines anti-microbial and anti-inflammatory properties that address aspects of HS pathogenesis. Few studies have evaluated the efficacy of oral dapsone on HS, especially in severe disease. OBJECTIVE: This study aims to evaluate the clinical outcomes of patients with moderate-to-severe HS treated with dapsone. METHODS: This retrospective chart review evaluated HS patients treated with oral dapsone over the past 10 years at one center. Treatment outcomes were classified based on Hurley staging, physician exam, and symptom progression. Adverse effects and concomitant treatment with dapsone were reviewed. RESULTS: Nineteen (19) patients with moderate-to-severe (Hurley Stage II-III) HS treated with oral dapsone were identified. Within 1-3 months, on dosages of dapsone varying from 25-100 mg/day, 3 patients (15.8%) had a clinically significant improvement in symptoms, 10 patients (52.6%) had a slight improvement, and 6 patients (31.6%) had no change in disease state; no patients deteriorated. The majority who improved were also on other medications, most commonly adalimumab. 4 patients experienced adverse effects, with nausea being most common; otherwise, dapsone was well-tolerated. CONCLUSIONS: Dapsone may have some efficacy for moderate-to-severe HS and seems well-tolerated. J Drugs Dermatol. 2023;22(11):e12-e16    doi:10.36849/JDD.4936e.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Hidradenite Supurativa , Humanos , Hidradenite Supurativa/diagnóstico , Hidradenite Supurativa/tratamento farmacológico , Estudos Retrospectivos , Adalimumab , Dapsona/efeitos adversos
17.
Am J Trop Med Hyg ; 109(6): 1260-1265, 2023 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-37931307

RESUMO

Since the introduction of multidrug therapy (MDT), various disabilities/morbidities due to leprosy have been prevented. However, there is a subset of patients in whom the skin lesions do not resolve completely or remain unchanged despite a full course of MDT, which is a great source of anxiety to the patient and their family members. Hence, we tried to ascertain the putative causes and risk factors of persistent skin lesions (PSLs) by analyzing the clinical, histopathological, bacteriological, and drug resistance patterns. This is a retrospective, cohort study wherein 35 patients who had PSLs after completion of MDT were included. The majority of the patients were 18 to 30 years of age, with males predominating. Borderline tuberculoid leprosy was the most common clinical spectrum observed (71.4%). The majority had PSLs distributed predominantly over photo-exposed sites (upper limbs > trunk > face). Eight patients (22.8%) had a history of contact with leprosy patients in their family, and six patients (17.1%) had associated comorbidities. Improvement in histopathological parameters such as a decrease in granuloma fraction was observed in 22 patients (62.8%) with PSLs after release from treatment in comparison with baseline. Four patients (11.4%) were noted to have drug resistance (three to rifampicin and one to dapsone). Thus, our study emphasizes that leprosy patients with PSLs after completion of MDT should undergo histopathological evaluation and drug resistance studies.


Assuntos
Hanseníase , Dermatopatias , Masculino , Humanos , Hansenostáticos , Estudos Retrospectivos , Quimioterapia Combinada , Estudos de Coortes , Hanseníase/complicações , Hanseníase/tratamento farmacológico , Hanseníase/epidemiologia , Dapsona/uso terapêutico , Dapsona/efeitos adversos , Dermatopatias/tratamento farmacológico
18.
Clin Oral Investig ; 27(12): 7091-7114, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37921879

RESUMO

OBJECTIVE: The aim of this scoping review was to evaluate the efficacy and safety of the use of systemic nonsteroidal immunomodulators (SNSI) for oral lichen planus (OLP) treatment. MATERIALS AND METHODS: This review was conducted according to PRISMA-ScR guidelines and registered at PROSPERO (CRD42021243524). Consulted databases were Pubmed, Embase, Scopus, and Web of Science. The inclusion criteria was as follows: clinical trials, case series, prospective, and retrospective studies conducted with participants presenting OLP of any sex and age. RESULTS: Thirty-two studies were selected, assessing 9 different SNSI: methotrexate, dapsone, levamisole, hydroxychloroquine, thalidomide, metronidazole, azathioprine, mycophenolate mofetil, and colchicine. Methotrexate and dapsone were the drugs with the best evidence among the options included, regarding number and quality of studies. Methotrexate resulted in significant improvement in the clinical condition and remission of symptoms, ranging between 63 and 93% of cases. Dapsone presented a similar effect to the use of topical corticosteroids and tacrolimus CONCLUSION: Among SNSI therapeutic options, methotrexate, and dapsone showed promising efficacy and safety. However, large-scale randomized clinical trials are still needed. CLINICAL RELEVANCE: SNSI have been used in the treatment of recalcitrant OLP; however, so far, it is not clear which are the best options. This scoping review highlights the potential use of methotrexate and dapsone.


Assuntos
Líquen Plano Bucal , Humanos , Líquen Plano Bucal/tratamento farmacológico , Metotrexato/uso terapêutico , Estudos Prospectivos , Estudos Retrospectivos , Fatores Imunológicos/uso terapêutico , Adjuvantes Imunológicos , Dapsona/uso terapêutico
19.
J Glob Antimicrob Resist ; 35: 262-267, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37852372

RESUMO

OBJECTIVES: Drug resistance in leprosy is an emerging concern, leading to treatment failures, recurrences, and potential spread of resistant Mycobacterium leprae in the community. In this study, we aimed to assess drug resistance prevalence and patterns amongst leprosy patients at a tertiary care referral hospital in India. METHODS: Mutations in drug resistance determining regions for dapsone, rifampicin, and ofloxacin of the M. leprae genome in DNA extracted from skin biopsies of 136 leprosy patients (treatment-naive = 67, with persistent skin lesions = 35, with recurrence = 34) were analysed by polymerase chain reaction followed by Sanger sequencing. Wild-type strain (Thai-53) was used as a reference strain. RESULTS: Resistance mutations were identified in a total of 23 patients, constituting 16.9% of the cohort. Within this subset of 23 cases, resistance to ofloxacin was observed in 17 individuals (12.5%), while resistance to both dapsone and rifampicin was detected in three patients each (2.2% for both). The occurrence of ofloxacin resistance showed minimal disparity between recurrent and treatment-naive cases, at 17.6% and 16.4%, respectively. Dapsone resistance emerged in two treatment-naive cases and one case with persistent skin lesions. Notably, none of the treatment-naive cases or those with recurrence/relapse exhibited rifampicin resistance. Subsequently, no statistically significant correlation was identified between other clinical variables and the presence of antimicrobial resistance. CONCLUSIONS: The occurrence of resistance to the current multidrug therapy regimen (specifically dapsone and rifampicin) and to ofloxacin, a secondary antileprosy medication in M. leprae, represents a concerning scenario. This calls for an expansion towards bactericidal drug options and the establishment of robust surveillance for drug resistance in countries burdened with high leprosy rates. Moreover, the introduction of stringent antimicrobial stewardship initiatives is imperative. As a single centre study, it represents a limited, cross-sectional view of the real situation in the field.


Assuntos
Hanseníase , Mycobacterium leprae , Humanos , Mycobacterium leprae/genética , Rifampina/farmacologia , Rifampina/uso terapêutico , Hansenostáticos/farmacologia , Hansenostáticos/uso terapêutico , Ofloxacino/farmacologia , Quimioterapia Combinada , Estudos Transversais , Farmacorresistência Bacteriana/genética , Hanseníase/tratamento farmacológico , Hanseníase/epidemiologia , Dapsona/farmacologia , Dapsona/uso terapêutico , Índia/epidemiologia
20.
J Biol Chem ; 299(12): 105368, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37866634

RESUMO

Positive heterotropic cooperativity, or "activation," results in an instantaneous increase in enzyme activity in the absence of an increase in protein expression. Thus, cytochrome P450 (CYP) enzyme activation presents as a potential drug-drug interaction mechanism. It has been demonstrated previously that dapsone activates the CYP2C9-catalyzed oxidation of a number of nonsteroidal anti-inflammatory drugs in vitro. Here, we conducted molecular dynamics simulations (MDS) together with enzyme kinetic investigations and site-directed mutagenesis to elucidate the molecular basis of the activation of CYP2C9-catalyzed S-flurbiprofen 4'-hydroxylation and S-naproxen O-demethylation by dapsone. Supplementation of incubations of recombinant CYP2C9 with dapsone increased the catalytic efficiency of flurbiprofen and naproxen oxidation by 2.3- and 16.5-fold, respectively. MDS demonstrated that activation arises predominantly from aromatic interactions between the substrate, dapsone, and the phenyl rings of Phe114 and Phe476 within a common binding domain of the CYP2C9 active site, rather than involvement of a distinct effector site. Mutagenesis of Phe114 and Phe476 abrogated flurbiprofen and naproxen oxidation, and MDS and kinetic studies with the CYP2C9 mutants further identified a pivotal role of Phe476 in dapsone activation. MDS additionally showed that aromatic stacking interactions between two molecules of naproxen are necessary for binding in a catalytically favorable orientation. In contrast to flurbiprofen and naproxen, dapsone did not activate the 4'-hydroxylation of diclofenac, suggesting that the CYP2C9 active site favors cooperative binding of nonsteroidal anti-inflammatory drugs with a planar or near-planar geometry. More generally, the work confirms the utility of MDS for investigating ligand binding in CYP enzymes.


Assuntos
Hidrocarboneto de Aril Hidroxilases , Citocromo P-450 CYP2C9 , Dapsona , Flurbiprofeno , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/metabolismo , Hidrocarboneto de Aril Hidroxilases/metabolismo , Citocromo P-450 CYP2C9/genética , Citocromo P-450 CYP2C9/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Dapsona/metabolismo , Flurbiprofeno/metabolismo , Cinética , Naproxeno/metabolismo , Humanos
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