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Materials (Basel, Switzerland) Sep 2023Dapsone is an effective antibacterial drug used to treat a variety of conditions. However, the aqueous solubility of this drug is limited, as is its permeability. This...
Dapsone is an effective antibacterial drug used to treat a variety of conditions. However, the aqueous solubility of this drug is limited, as is its permeability. This study expands the available solubility data pool for dapsone by measuring its solubility in several pure organic solvents: N-methyl-2-pyrrolidone (CAS: 872-50-4), dimethyl sulfoxide (CAS: 67-68-5), 4-formylmorpholine (CAS: 4394-85-8), tetraethylene pentamine (CAS: 112-57-2), and diethylene glycol bis(3-aminopropyl) ether (CAS: 4246-51-9). Furthermore, the study proposes the use of intermolecular interactions as molecular descriptors to predict the solubility of dapsone in neat solvents and binary mixtures using machine learning models. An ensemble of regressors was used, including support vector machines, random forests, gradient boosting, and neural networks. Affinities of dapsone to solvent molecules were calculated using COSMO-RS and used as input for model training. Due to the polymorphic nature of dapsone, fusion data are not available, which prohibits the direct use of COSMO-RS for solubility calculations. Therefore, a consonance solvent approach was tested, which allows an indirect estimation of the fusion properties. Unfortunately, the resulting accuracy is unsatisfactory. In contrast, the developed regressors showed high predictive potential. This work documents that intermolecular interactions characterized by solute-solvent contacts can be considered valuable molecular descriptors for solubility modeling and that the wealth of encoded information is sufficient for solubility predictions for new systems, including those for which experimental measurements of thermodynamic properties are unavailable.
PubMed: 37763610
DOI: 10.3390/ma16186336 -
Cureus Jan 2024Chronic non-healing leg ulcers are skin defects below the knee that resist healing for more than six weeks. They cause physical, emotional, and economic burdens to...
INTRODUCTION
Chronic non-healing leg ulcers are skin defects below the knee that resist healing for more than six weeks. They cause physical, emotional, and economic burdens to patients and society.
OBJECTIVES
To introduce an innovative medical strategy that targets the chronic inflammation component in non-healing ulcers (NHUs) with rheumatic features and to evaluate its potential effectiveness in achieving complete healing.
METHODS
We employed an empirical medical therapy regimen, which combined medications like deflazacort, colchicine, dapsone, hydroxychloroquine, and azathioprine. We retrospectively selected 25 patients with chronic pedal ulcers who underwent our therapy.
RESULTS
The mean duration of ulcers was 7.84 years, and the time to heal was 5.97 months. Among 25 patients, 19 had atypical ulcers, four had venous ulcers, and two had diabetic neuropathy ulcers. Four patients with venous ulcers additionally underwent endovenous laser ablation.
CONCLUSION
Our medical strategy showed promising results in healing chronic NHUs with rheumatic features without significant steroid-induced adverse effects.
PubMed: 38169779
DOI: 10.7759/cureus.51449 -
Indian Journal of Dermatology,... 2023Background Information on bullous pemphigoid in an Indian context is scarce. Aim To report clinico-demographic profile, associated comorbidities and prescription pattern...
Background Information on bullous pemphigoid in an Indian context is scarce. Aim To report clinico-demographic profile, associated comorbidities and prescription pattern of bullous pemphigoid patients in India. Methods This was a retrospective study, where past records of all bullous pemphigoid patients diagnosed and treated between November 2013 and October 2019 were accessed and analysed. Patients having a compatible clinical presentation with either histopathological and/or direct immunofluorescence evidence of bullous pemphigoid were included. Results There were 96 bullous pemphigoid patients, with a male: female ratio of 1.6:1. The mean age at diagnosis was 62.5 ± 2.2 years, with mean duration of illness 27.5 ± 4.5 months before presentation. Comorbidities were present in 80 (83%) patients, with type 2 diabetes mellitus (38.5%), hypertension (36.4%) and neurological illness (16.7%) being the commonest ones. Clinically, blisters were the predominant presentation in 81 (84.4%) patients. The majority (87.5%) of patients showed a predominant eosinophilic infiltrate on histopathology. Direct immunofluorescence revealed immunoglobulin G deposits with complement C3 in 77 (80.2%) cases. The majority of patients (77.1%) were treated with oral prednisolone, either alone (11.5%) or in combination (65.6%) with other topical and systemic agents. Topical steroids were used in 29.1%, azathioprine in 28%, dapsone in 16.7% and omalizumab in 6.2% of patients. Limitations The study is retrospective. Immunofluorescence on salt split skin, direct immunofluorescence serration pattern analysis, and immunoblotting were not performed. Hence, there is a possibility that a few included cases were suffering from other subepidermal autoimmune bullous diseases like epidermolysis bullosa acquisita or anti-p200 pemphigoid. Conclusion Bullous pemphigoid patients in this study had a younger age of onset and showed male preponderance. Comorbidities like type 2 diabetes, hypertension and neurological disorders were frequent. Cutaneous blisters were the most frequent clinical presentation. Systemic corticosteroids comprised the mainstay of therapy.
Topics: Humans; Male; Female; Middle Aged; Pemphigoid, Bullous; Retrospective Studies; Blister; Diabetes Mellitus, Type 2; Autoimmune Diseases; Skin Diseases, Vesiculobullous
PubMed: 35962510
DOI: 10.25259/IJDVL_1417_20 -
Diagnostics (Basel, Switzerland) Dec 2023Currently, over 200,000 new cases of leprosy are reported annually worldwide. Although leprosy was thought to have been eradicated in Taiwan, a few new cases still occur...
Currently, over 200,000 new cases of leprosy are reported annually worldwide. Although leprosy was thought to have been eradicated in Taiwan, a few new cases still occur annually. Protean clinical manifestations of leprosy and immunological reactions result in delayed diagnoses. In addition, drug-resistant leprosy is emerging and poses treatment challenges. In this retrospective study, we collected and analyzed the clinicopathological features, leprosy type, treatment response, and relapse rate of patients with leprosy in our hospital between January 2009 and November 2022. We found that 54% of patients were Indonesian, and borderline lepromatous leprosy was predominant (39%); moreover, histoid leprosy and the Lucio phenomenon were also reported. Polymerase chain reaction analysis identified four positive cases, including a dapsone-resistant (4%) case. Our findings indicated good control of leprosy and a lower rate of dapsone resistance than that reported by the World Health Organization (4% vs. 13%) from 2009 to 2015. We found that the patient profile in terms of the treatment duration, recurrence rate, systemic symptoms, and neurological symptoms did not differ between before and during the pandemic. We report the recent advances in leprosy diagnosis, drug-resistant gene mutations, post-exposure prophylaxis, vaccination, and the effect of coronavirus disease 2019 on leprosy to facilitate updated leprosy diagnosis and management.
PubMed: 38132239
DOI: 10.3390/diagnostics13243655 -
International Journal of Molecular... Oct 2023As things stand in 2023, metastatic osteosarcoma commonly results in death. There has been little treatment progress in recent decades. To redress the poor prognosis of... (Review)
Review
As things stand in 2023, metastatic osteosarcoma commonly results in death. There has been little treatment progress in recent decades. To redress the poor prognosis of metastatic osteosarcoma, the present regimen, OSR9, uses nine already marketed drugs as adjuncts to current treatments. The nine drugs in OSR9 are: (1) the antinausea drug aprepitant, (2) the analgesic drug celecoxib, (3) the anti-malaria drug chloroquine, (4) the antibiotic dapsone, (5) the alcoholism treatment drug disulfiram, (6) the antifungal drug itraconazole, (7) the diabetes treatment drug linagliptin, (8) the hypertension drug propranolol, and (9) the psychiatric drug quetiapine. Although none are traditionally used to treat cancer, all nine have attributes that have been shown to inhibit growth-promoting physiological systems active in osteosarcoma. In their general medicinal uses, all nine drugs in OSR9 have low side-effect risks. The current paper reviews the collected data supporting the role of OSR9.
Topics: Humans; Osteosarcoma; Celecoxib; Aprepitant; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms
PubMed: 37895152
DOI: 10.3390/ijms242015474 -
Cureus Apr 2024Pemphigus herpetiformis (PH) is a rare autoimmune blistering disorder that typically presents in adults. However, its occurrence in paediatric patients, especially in...
Pemphigus herpetiformis (PH) is a rare autoimmune blistering disorder that typically presents in adults. However, its occurrence in paediatric patients, especially in very young children, is exceedingly rare. It presents with clinical features resembling dermatitis herpetiformis (DH) and immunologic characteristics similar to pemphigus, belonging to the group of intraepidermal autoimmune bullous diseases. We present the case of a three-year-old female with a history of annular and vesicular lesions on both forearms and legs. A skin biopsy revealed epidermal acanthosis, marked spongiosis, numerous intra-epidermal blisters, and exocytosis of eosinophils and neutrophils. A superficial perivascular lymphocytic infiltrate, accompanied by eosinophils and neutrophils, was also observed in the dermis. The diagnosis was also supported by direct and indirect immunofluorescence. The patient was treated with clobetasol ointment and dapsone, which showed significant improvement in the skin lesions. This case underscores the importance of considering PH in the differential diagnosis of vesicobullous diseases in children and the need for further research to elucidate its pathogenesis and optimal management.
PubMed: 38752034
DOI: 10.7759/cureus.58286 -
Clinical Case Reports May 2024IgA pemphigus is usually treated by Dapsone. Recalcitrant cases may be treated by Colchicine, Sulfapyridine, or Acitretin. Some patients with recurrent severe disease...
KEY CLINICAL MESSAGE
IgA pemphigus is usually treated by Dapsone. Recalcitrant cases may be treated by Colchicine, Sulfapyridine, or Acitretin. Some patients with recurrent severe disease may not respond to the aforementioned medications. Our study highlights the role of TNFa inhibitor as an alternative modality in the treatment of recalcitrant IgA pemphigus.
ABSTRACT
IgA pemphigus is a rare autoimmune blistering disease characterized by a pruritic, annular, vesiculopustular eruption. In IgA pemphigus, there are IgA autoantibodies targeting the keratinocyte cell surface adhesion molecules, causing cell-to-cell dehiscence and a flaccid vesiculopustular eruption, mainly in the axilla and groin. Dapsone, despite being the drug of choice for treating IgA pemphigus, is not effective in clearing lesions in a minority of patients and such rare cases of recalcitrant IgA pemphigus need alternative modalities of treatment. Here, we report the successful treatment of a 50-year-old male patient with an adalimumab injection who had a poor response to dapsone.
PubMed: 38751960
DOI: 10.1002/ccr3.8807 -
PLOS Global Public Health 2023Despite the availability and implementation of well-known efficacious interventions for tuberculosis treatment by the Ministry of Health, Uganda (MoH), treatment...
Despite the availability and implementation of well-known efficacious interventions for tuberculosis treatment by the Ministry of Health, Uganda (MoH), treatment non-adherence persists. Moreover, identifying a specific tuberculosis patient at risk of treatment non-adherence is still a challenge. Thus, this retrospective study, based on a record review of 838 tuberculosis patients enrolled in six health facilities, presents, and discusses a machine learning approach to explore the individual risk factors predictive of tuberculosis treatment non-adherence in the Mukono district, Uganda. Five classification machine learning algorithms, logistic regression (LR), artificial neural networks (ANN), support vector machines (SVM), random forest (RF), and AdaBoost were trained, and evaluated by computing their accuracy, F1 score, precision, recall, and the area under the receiver operating curve (AUC) through the aid of a confusion matrix. Of the five developed and evaluated algorithms, SVM (91.28%) had the highest accuracy (AdaBoost, 91.05% performed better than SVM when AUC is considered as evaluation parameter). Looking at all five evaluation parameters globally, AdaBoost is quite on par with SVM. Individual risk factors predictive of non-adherence included tuberculosis type, GeneXpert results, sub-country, antiretroviral status, contacts below 5 years, health facility ownership, sputum test results at 2 months, treatment supporter, cotrimoxazole preventive therapy (CPT) dapsone status, risk group, patient age, gender, middle and upper arm circumference, referral, positive sputum test at 5 and 6 months. Therefore, machine learning techniques, specifically classification types, can identify patient factors predictive of treatment non-adherence and accurately differentiate between adherent and non-adherent patients. Thus, tuberculosis program management should consider adopting the classification machine learning techniques evaluated in this study as a screening tool for identifying and targeting suited interventions to these patients.
PubMed: 37399173
DOI: 10.1371/journal.pgph.0001466 -
Sao Paulo Medical Journal = Revista... 2024Loxosceles spp are arthropods found worldwide. Its bite may produce cutaneous loxoscelism (necrotic or edematous) or cutaneous-visceral loxoscelism. Depending on their...
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).
Topics: Female; Male; Humans; Middle Aged; Dapsone; Spider Bites; Hemoglobins; Heparin; Adrenal Cortex Hormones; Regeneration
PubMed: 38422241
DOI: 10.1590/1516-3180.2023.0151.04012023 -
Cureus Aug 2023We present the case of a 37-year-old Haitian male who presented with a seven-month history of skin lesions on his face and extremities, weight loss, intermittent chills,...
We present the case of a 37-year-old Haitian male who presented with a seven-month history of skin lesions on his face and extremities, weight loss, intermittent chills, difficulty in breathing, and bilateral paresthesias in his feet. The lesions were most prominent on the pinnae of the ears. Biopsy of the lesions revealed large, rounded granulomatous infiltrates and histiocytes. Acid fast (Ziehl-Neelsen technique) and Kinyoun stains were positive for numerous acid-fast mycobacteria within the histiocytes. A polymerase chain reaction (PCR) was positive for which confirmed a diagnosis of lepromatous leprosy. Further analysis revealed positive purified protein derivatives (PPD) and QuantiFERON-TB™ test (QIAGEN, Hilden, Germany) with negative chest x-ray and sputum cultures. Labs also revealed vitamin D and G6PD (glucose-6-phosphate-dehydrogenasedeficiency. The patient was started on a combined therapy regimen of rifampin, moxifloxacin, and minocycline. In addition, he was started on vitamin D supplementation. After undergoing treatment for one year, there was notable regression of the patient's cutaneous lesions. Treatment is planned to continue for a total of 24 months. This case exemplifies the successful treatment of Hansen's disease in a patient with a G6PD deficiency. The patient's G6PD deficiency required avoidance of dapsone, which is typically used in the treatment of Hansen's disease. Furthermore, the patient's positive PPD and QuantiFERON-TB tests led to a delay in the treatment in order to rule out active tuberculosis. Left untreated, Hansen's disease has a high morbidity risk. Treatment regimens require careful consideration of coexisting comorbidities.
PubMed: 37664264
DOI: 10.7759/cureus.42816