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El síndrome de Wells o celulitis eosinofílica es una enfermedad inflamatoria de origen desconocido, de aparición infrecuente en la edad pediátrica. Suele manifestarse clínicamente como placas eritematoedematosas, nódulos, pápulas, ampollas, entre otros. Se presenta una paciente en edad pediátrica con nódulos subcutáneos asintomáticos generalizados asociados a eosinofilia grave. El estudio histopatológico de las lesiones fue compatible con celulitis de Wells. Se realizó una evaluación interdisciplinaria en busca de la causa y trastornos eosinofílicos asociados, sin resultados positivos. Se indicó tratamiento sistémico con corticoides y presentó buena respuesta, pero, ante la recidiva de las lesiones tras su suspensión, se indicó dapsona como tratamiento de segunda línea, con mejoría posterior de las lesiones y de la eosinofilia. El objetivo del reporte es presentar una paciente con una manifestación atípica de síndrome de Wells y su desafío terapéutico.

Wells' syndrome, or eosinophilic cellulitis, is an inflammatory disease of unknown origin, uncommon in the pediatric age. It usually appears clinically as erythematous and edematous plaques, nodules, papules, blisters, among other symptoms. Here we describe the case of a female pediatric patient with generalized, asymptomatic subcutaneous nodules associated with severe eosinophilia. The histopathological examination of the lesions was compatible with Wells' syndrome. An interdisciplinary evaluation was performed to establish the cause and look for associated eosinophilic disorders; the results were negative. Systemic corticosteroids were indicated and the patient had a good response; however, in view of the recurrence of the lesions after treatment discontinuation, dapsone was indicated as a second-line treatment, with subsequent improvement of the lesions and eosinophilia. The aim of this report was to describe the case of a female patient with an atypical manifestation of Wells' syndrome and the resulting therapeutic challenge.

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Oxidative stress and apoptosis cell death are critical secondary damage mechanisms that lead to losing neighboring healthy tissue after cerebral ischemia. This study aims to characterize the type of interaction between dapsone (DDS) and cannabidiol (CBD) and its cytoprotective effect in an in vitro model of oxygen and glucose deprivation for 6 h followed by 24 h of reoxygenation (OGD/R), using the SH-SY5Y cell line. For the combined concentrations, an isobolographic study was designed to determine the optimal concentration-response combinations. Cell viability was evaluated by measuring the lactate dehydrogenase (LDH) release and 3-[4, 5-dimethyl-2-thiazolyl]-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assays. Also, the reactive oxygen species (ROS) and reduced glutathione (GSH) levels were analyzed as oxidative stress markers. Finally, caspase-3 activity was evaluated as a marker cell death by apoptosis. The results showed a decrease in cell viability, an increase in oxidant stress, and the activity of caspase-3 by the effect of OGD/R. Meanwhile, both DDS and CBD demonstrated antioxidant, antiapoptotic, and cytoprotective effects in a concentration-response manner. The isobolographic study indicated that the concentration of 2.5 µM of DDS plus 0.05 µM of CBD presented a synergistic effect so that in treatment, cell death due to OGD/R decreased. The findings indicate that DDS-CBD combined treatment may be a helpful therapy in cerebral ischemia with reperfusion.

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BACKGROUND: Brief erythematous-papular skin rashes suggest the diagnosis of urticaria; However, it may be another type of dermatitis, and complementary examinations must be carried out to establish its diagnosis. CASE REPORT: 53-year-old female patient, diagnosed in 2016 with diffuse large B cell lymphoma, in complete remission. Since 2010, he has had episodes of erythematous-papular lesions lasting 24-36 hours. He received antihistamines, corticosteroids and omalizumab without clinical improvement. The ANA determination was positive (1/320), nuclear mitotic pattern. The skin biopsy was compatible with dermatitis herpetiformis. The study of celiac and locus antibodies showed positivity for HLA-DQ2 and DQ2.5 in heterozygosity. The diagnosis of dermatitis herpetiformis was established. Treatment consisted of a gluten-free diet and prescription of dapsone, with satisfactory results. CONCLUSION: It is important to establish the differential diagnosis of patients with chronic urticaria who do not respond to the reference treatment, in addition to carrying out a thorough clinical examination and physical examination before starting treatment and relying on a multidisciplinary team to establish an accurate diagnosis and treatment. appropriate. Due to the side effects of dapsone, subsequent follow-up of patients is essential.

ANTECEDENTES: Los exantemas cutáneos eritemato-papulares de breve duración sugieren el diagnóstico clínico de urticaria; no obstante, puede tratarse de otro tipo de dermatitis, y para establecer el diagnóstico deben llevarse a cabo exploraciones complementarias. REPORTE DE CASO: Paciente femenina de 53 años, diagnosticada en 2016 con linfoma difuso de células B grandes, en remisión completa. Desde el 2010 manifestó episodios de lesiones eritemato-papulosas, de 24-36 horas de duración. Recibió antihistamínicos, corticoides y omalizumab sin mejoría clínica. La determinación de ANA resultó positiva (1/320), con patrón mitótico nuclear. La biopsia cutánea fue compatible con dermatitis herpetiforme. El estudio de anticuerpos de celiaquía y locus mostró positividad para HLA-DQ2 y DQ2.5 con heterocigosis. Se estableció el diagnosticó de dermatitis herpetiforme. El tratamiento consistió en dieta exenta de gluten y prescripción de dapsona, con resultados satisfactorios. CONCLUSIÓN: Es importante establecer el diagnóstico diferencial de pacientes con urticaria crónica que no responden al tratamiento de referencia, además de efectuar el examen clínico y la exploración física exhaustivos antes de iniciar el protocolo, y apoyarse de un equipo multidisciplinario para establecer el diagnóstico certero y tratamiento adecuado. Debido a los efectos secundarios de la dapsona, es imprescindible el seguimiento posterior de los pacientes.

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Wells' syndrome, or eosinophilic cellulitis, is an inflammatory disease of unknown origin, uncommon in the pediatric age. It usually appears clinically as erythematous and edematous plaques, nodules, papules, blisters, among other symptoms. Here we describe the case of a female pediatric patient with generalized, asymptomatic subcutaneous nodules associated with severe eosinophilia. The histopathological examination of the lesions was compatible with Wells' syndrome. An interdisciplinary evaluation was performed to establish the cause and look for associated eosinophilic disorders; the results were negative. Systemic corticosteroids were indicated and the patient had a good response; however, in view of the recurrence of the lesions after treatment discontinuation, dapsone was indicated as a second-line treatment, with subsequent improvement of the lesions and eosinophilia. The aim of this report was to describe the case of a female patient with an atypical manifestation of Wells' syndrome and the resulting therapeutic challenge.

El síndrome de Wells o celulitis eosinofílica es una enfermedad inflamatoria de origen desconocido, de aparición infrecuente en la edad pediátrica. Suele manifestarse clínicamente como placas eritematoedematosas, nódulos, pápulas, ampollas, entre otros. Se presenta una paciente en edad pediátrica con nódulos subcutáneos asintomáticos generalizados asociados a eosinofilia grave. El estudio histopatológico de las lesiones fue compatible con celulitis de Wells. Se realizó una evaluación interdisciplinaria en busca de la causa y trastornos eosinofílicos asociados, sin resultados positivos. Se indicó tratamiento sistémico con corticoides y presentó buena respuesta, pero, ante la recidiva de las lesiones tras su suspensión, se indicó dapsona como tratamiento de segunda línea, con mejoría posterior de las lesiones y de la eosinofilia. El objetivo del reporte es presentar una paciente con una manifestación atípica de síndrome de Wells y su desafío terapéutico.

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Background: Recommended standard treatment for leprosy is multidrugtherapy (MDT/WHO), consisting Rifampicin+Dapsone+Clofazimine. Other medications are recommended in cases of resistance, adverse reactions and intolerances, including ROM regimen, Rifampicin+Ofloxacin+Minocycline. Therefore, pharmacovigilance is an important tool in understanding these adverse drug reactions (ADRs), supporting pharmacotherapy management and medication safety. This study seeks to evaluate ADRs comparing two therapeutic regimens, MDT and ROM, used in treatment of patients with leprosy, analyzing prognostic factors regarding risk and safety. Methods:A retrospective cohort study was performed by assessing medical records of 433 patients diagnosed with leprosy from 2010 to 2021 at a National Reference Center in Brazil. They were subject to 24 months or more of treatment with MDT or ROM regimens. ADR assessments were analyzed by two experienced researchers, who included clinical and laboratory variables, correlating them with temporality, severity and the causality criteria of Naranjo and WHO. Results: The findings observed an average of 1.3 reactions/patient. Out of individuals experiencing reactions, 67.0% (69/103) were utilizing MDT/MB, while 33.0% (34/103) were using ROM. The median time for ADR of 79 days for MDT and 179 days for ROM. In first reaction, Dapsone was the most frequently involved medication; the most affected system was hematopoietic. As compared to Clofazimine, results indicated that use of Dapsone was associated with 7% increased risk of ADR occurrence (HR: 1.07; p = 0.866). Additionally, Rifampicin was linked to 31% increased risk of ADRs (HR: 1.31; p = 0.602); and Ofloxacin showed 35% elevated risk (HR: 1.35; p = 0.653). Conversely, results for Minocycline indicated 44% reduction in the risk of ADRs (HR: 0.56; p = 0.527), although statistical significance was not reached. The use of MDT conferred 2.51 times higher risk of developing ADRs in comparison to ROM. Conclusion: The comparison between MDT and ROM revealed that MDT caused more ADRs, and these reactions were more severe, indicating less safety for patients. Dapsone was the most common medication causing ADRs, followed by Rifampicin. The combination with Clofazimine was associated with an additional risk of ADRs, warranting further studies to confirm this hypothesis. Given the high magnitude of ADRs, healthcare teams need to monitor patients undergoing leprosy treatment with focus on pharmacovigilance.

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ABSTRACT 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).

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The present study highlighted the repositioning of the drug dapsone (DDS) for cancer therapy. Due to its mechanism of action, DDS has a dual effect as an antibiotic and as an anti-inflammatory/immunomodulator; however, at high doses, it has important adverse effects. The derivative DDS-13 [N,N'-(sulfonyl bis (4,1-phenylene)) dioctanamide] was synthesized through an N-acylation reaction to compare it with DDS. Its cytotoxic effects in cancer cells (DU145 and HeLa) and non-cancer cells (HDFa) were observed at concentrations ranging 0.01-100 µM and its physicochemical/pharmacokinetic properties were analyzed using the SwissADME tool. The objectives of the present study were to evaluate the anticancer activity of both DDS and DDS-13 and to identify the physicochemical and pharmacokinetic properties of DDS-13. The results showed that DDS-13 presented a cytotoxic effect in the DU145 cell line (IC50=19.06 µM), while DDS showed a cytotoxic effect on both the DU145 (IC50=11.11 µM) and HeLa (IC50=13.07 µM) cell lines. DDS-13 appears to be a good cytotoxic candidate for the treatment of prostate cancer, while DDS appears to be a good candidate for both cervical and prostate cancer. Neither candidate showed a cytotoxic effect in non-cancerous cells. The different pharmacokinetic properties of DDS-13 make it a new candidate for evaluation in preclinical models for the treatment of cancer.

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La dermatitis herpetiforme es una enfermedad autoinmune que se caracteriza por la presencia de lesiones vesiculares y prurito en la superficie extensora de las extremidades, nalgas y parte baja de la espalda. Se presenta el caso clínico de una mujer de 21 años, natural y procedente de Iquitos, que presentó múltiples vesículas dolorosas, pruriginosas, de base eritematosa y purulentas en ambos codos durante un mes. Posteriormente, estas lesiones se diseminaron a ambas rodillas y se agregó prurito intenso. La paciente experimentó períodos alternantes de remisión y exacerbación. La correlación del cuadro clínico, resultados serológicos y de biopsia, junto con respuesta terapéutica a la dapsona confirmaron el diagnóstico de dermatitis herpetiforme, con una evolución favorable y remisión de la enfermedad.

Dermatitis herpetiforme is an autoimmune disease characterized by the presence of vesicular lesions and itching on the extensor surface of the limbs, buttocks, and lower back. The clinical case of a 21-year-old woman, a native of and from Iquitos, is presented. She presented multiple painful, itchy vesicles with an erythematous and purulent base on both elbows for a month. Subsequently, these lesions spread to both knees, and intense itching was added. The patient experienced alternating periods of remission and exacerbation. The correlation of the clinical picture, serological and biopsy results, along with the therapeutic response to dapsona, confirmed the diagnosis of dermatitis herpetiforme, with a favorable evolution and remission of the disease.

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El acné conglobata es una forma severa de acné que produce muchas lesiones inflamatorias y cicatrices, marcando la vida del paciente de manera negativa. Presentamos el caso de 2 hermanos con acné conglobata, ambos con lesiones en piel de 2 años de evolución con aparición de nódulos, quistes y fístulas en territorio corporal extenso. El primero con diagnóstico reciente de leucemia promielocítica aguda en planes de iniciar quimioterapia y, el segundo, sin patologías de base. El primer caso recibió tratamiento antibiótico sistémico por complicaciones infecciosas propias de la inmunodepresión, además recibió dexametasona y ácido transretinoico como quimioterapia, y es dado de alta con dichos medicamentos y antibiótico profiláctico. El segundo caso recibió tratamiento con antibiótico sistémico y dapsona. Ambos acuden a control a los 2 meses y se observó mejoría importante de las lesiones en piel. El primer paciente falleció por complicaciones inherentes a su patología de base y el segundo paciente abandonó el tratamiento.

Acne conglobata is a severe form of acne that produces many inflammatory lesions and scars, marking the patient's life in a negative way. We present the case of two brothers with acne conglobata, both with 2-year-old skin lesions with the appearance of nodules, cysts, and fistulas in extensive body territory. The first with a recent diagnosis of acute promyelocytic leukemia with plans to start chemotherapy and the second with no underlying pathologies. The first case received systemic antibiotic treatment due to infectious complications typical of immunosuppression, he also received dexamethasone and transretinoic acid as chemotherapy, and was discharged with the mentioned drugs and prophylactic antibiotic. The second case received treatment with systemic antibiotic and dapsone. Both cases returned for control at 2 months and significant improvement in skin lesions was observed. The first patient died due to complications inherent to his underlying pathology and the second patient abandoned treatment.

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Failure of therapeutic strategies for the management and recovery from traumatic spinal cord injury (SCI) is a serious concern. Dapsone (DDS) has been reported as a neuroprotective drug after SCI, although the phase after SC damage (acute or chronic) of its major impact on functional recovery has yet to be defined. Here, we evaluated DDS acute-phase anti-inflammatory effects and their impact on early functional recovery, one week after moderate SCI, and late functional recovery, 7 weeks thereafter. Female Wistar rats were randomly assigned to each of five experimental groups: sham group; four groups of rats with SCI, treated with DDS (0, 12.5, 25.0, and 37.5 mg/kg ip), starting 3 h after injury. Plasma levels of GRO/KC, and the number of neutrophils and macrophages in cell suspensions from tissue taken at the site of injury were measured as inflammation biomarkers. Hindlimb motor function of injured rats given DDS 12.5 and 25.0 mg/kg daily for 8 weeks was evaluated on the BBB open-field ordinal scale. Six hours after injury all DDS doses decreased GRO/KC plasma levels; 24 h after injury, neutrophil numbers decreased with DDS doses of 25.0 and 37.5 mg/kg; macrophage numbers decreased only at the 37.5 mg/kg dose. In the acute phase, functional recovery was dose-dependent. Final recovery scores were 57.5 and 106.2% above the DDS-vehicle treated control group, respectively. In conclusion, the acute phase dose-dependent anti-inflammatory effects of DDS impacted early motor function recovery affecting final recovery at the end of the study.

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INTRODUCTION: Leprosy is a neglected, infectious, granulomatous and chronic disease caused by the pathological agent Mycobacterium leprae. The course of the disease is more aggressive in patients under 15 years of age, but the current treatment offered worldwide consists of solid forms, by the combination of antibiotics such as rifampicin, clofazimine and dapsone. This represents results in lack of adherence in pediatric patients and drug therapy failure, although numerous formulations and technologies have already been developed. AREA COVERED: This study aims to analyze the technological evolution of the pharmaceutical treatment of leprosy, aimed at children. A review of patents around the world was conducted to look for technical and clinical aspects of formulations and devices. EXPERT OPINION: Innovative formulations for pediatric patients were classified according to the routes of administration as oral, inhalable, injectable and transdermal. The formulations were organized as alternatives for pediatric therapy, taking into account the physicochemical aspects of drugs and the physiological aspects of pediatric patients. Among the difficulties for the patented formulations to reach the market, of special note is the low stability of the physicochemical characteristics of the drugs. Optimization of formulations would favor the pediatric treatment of leprosy, aiming at therapeutic success.

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BACKGROUND: Development of effective drugs for epilepsy are needed, as nearly 30 % of epileptic patients, are resistant to current treatments. This study is aimed to characterize the anticonvulsant effect of dapsone (DDS), in the kainic acid (KA)-induced Status Epilepticus (SE) by recording the brain metabolic activity with an [18F]FDG-PET analysis. METHODS: Wistar rats received KA (10 mg/kg, i.p., single dose) to produce sustained seizures. [18F]FDG-PET and electroencephalographic (EEG) studies were then performed. DDS or vehicle were administered 30 min before KA. [18F]FDG uptake and EEG were evaluated at baseline, 2 and 25 h after KA injection. Likewise, caspase-8, 3 hippocampal activities and Fluoro-Jade B neuronal degeneration and Hematoxylin-eosin staining were measured 25 h after KA. RESULTS: PET data evaluated at 2 h showed hyper-uptake of [18F]FDG in the control group, which was decreased by DDS. At 25 h, hypo-uptake was observed in the control group and higher values due to DDS effect. EEG spectral power was increased 2 h after KA administration in the control group during the generalized tonic-clonic seizures, which was reversed by DDS, correlated with [18F]FDG-PET uptake changes. The values of caspases-8 activity decreased 48 and 43 % vs control group in the groups treated with DDS (12.5 y 25 mg/kg respectively), likewise; caspase-3 activity diminished by 57 and 53 %. Fewer degenerated neurons were observed due to DDS treatments. CONCLUSIONS: This study pinpoints the anticonvulsant therapeutic potential of DDS. Given its safety and effectiveness, DDS may be a viable alternative for patients with drug-resistant epilepsy.

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Dapsone (DAP)is a dual-function drug substance; however, its limited water solubility may impair its bioavailability. Drug nanocrystals are an alternative to overcome this limitation. Herein, a DAP nanosuspension was prepared using adesign space approach aiming to investigate the influence of raw material properties and process parameters on the critical quality attributes of the drugnanocrystals. Optimized nanocrystals with 206.3 ± 6.7 nm using povacoat™ as stabilizer were made. The nanoparticles were characterized by dynamic light scattering, laser diffraction, scanning electron microscopy, differential scanning calorimetry, X-ray powder diffraction, and saturation solubility. Compared to the raw material, the nanocrystals were 250-times smaller. Meanwhile, its crystalline state remained basically unchanged even after milling and drying. The nanosuspension successfully maintained its physical stability inlong-termandaccelerated stability studiesover, 4 and 3 months. Furthermore, toxicity studiesshowed low a toxicity at a20 mg/kg. As expected for nanocrystals, the size reduction improvedsaturation solubility3.78 times in water. An attempt to scale up from lab to pilot scale resulted nanocrystals of potential commercial quality. In conclusion, the present study describes the development of dapsone nanocrystals for treating infectious and inflammatory diseases. The nanocrystal formuation can be scaled up for commercial use.

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Leprosy is a Neglected Tropical Disease (NTDs) caused by Mycobacterium leprae (M. leprae). The treatment is considered effective, however, the high dose Multidrug Therapy (MDT) for a long period and its adverse effects result in the abandonment of the treatment by patients. Indeed, antimicrobial resistance is still an obstacle that must be overcome in the treatment of leprosy. In the present article, we reviewed the WHO guidelines for the chemotherapy of leprosy and the methods of synthesis of these drugs.

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RESUMEN La dermatosis ampollar por IgA lineal del adulto (DLA) es una enfermedad autoinmune adquirida infrecuente, caracterizada por el depósito lineal de anticuerpos IgA en la membrana basal. La mayoría de los casos reportados son de causa idiopática, pero esta entidad también se ha visto asociada a ciertos fármacos, siendo la vancomicina el más frecuente. Se presenta un caso de DLA asociada a vancomicina, con extensa afectación cutánea y compromiso mucoso, tratado con dapsona y corticoides sistémicos con buena respuesta.

ABSTRACT Adult linear IgA bollous dermatosis (LABD) is a rare acquired autoimmune disease characterized by linear deposition of IgA antibodies on the basement membrane. Most of the reported cases are of idiopathic cause, but this entity has also been associated with certain drugs, vancomycin being the most frequent. We present a case of LABD associated with vancomycine, with extensive skin and mucosal involvement, treated with dapsone and systemic corticosteroids with a good response.

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RESUMEN La dermatosis pustulosa subcórnea o enfermedad de Sneddon Wilkinson, es una enfermedad poco frecuente, caracterizada por lesiones pustulosas, recurrentes que suelen coalescer. Esta afección también se relaciona con enfermedades neoplásicas o inmunológicas. El propósito de este estudio es describir un caso clínico de ladermatosis referida en una paciente de 54 años de edad inicialmente tratada con dapsona, aunque,si bien, durante dos meses hubo mejoría, posteriormente se observa desarrollo de nuevas lesiones y alteración de las transaminasas. Por este motivo se procede a cambiar de tratamiento, por trimetoprima /sulfametoxazol.

Abstract Subcorneal pustular dermatosis or Sneddon Wilkinson's disease is a rare disease characterized by recurrent pustular lesions that often coalesce. This condition is also associated with neoplastic or immunologic diseases. The purpose of this study is to describe a clinical case of the referred dermatosis in a 54-year-old female patient initially treated with dapsone, although there was improvement for two months, subsequently new lesions developed and transaminase alteration was observed, for this reason the treatment was changed to trimethoprim/sulfamethoxazole.

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Dapsone (DDS) therapy can frequently lead to hematological side effects, such as methemoglobinemia and DNA damage. In this study, we aim to evaluate the protective effect of racemic alpha lipoic acid (ALA) and its enantiomers on methemoglobin induction. The pre- and post-treatment of erythrocytes with ALA, ALA isomers, or MB (methylene blue), and treatment with DDS-NOH (apsone hydroxylamine) was performed to assess the protective and inhibiting effect on methemoglobin (MetHb) formation. Methemoglobin percentage and DNA damage caused by dapsone and its metabolites were also determined by the comet assay. We also evaluated oxidative parameters such as SOD, GSH, TEAC (Trolox equivalent antioxidant capacity) and MDA (malondialdehyde). In pretreatment, ALA showed the best protector effect in 2.5 µg/mL of DDS-NOH. ALA (1000 µM) was able to inhibit the induced MetHb formation even at the highest concentrations of DDS-NOH. All ALA tested concentrations (100 and 1000 µM) were able to inhibit ROS and CAT activity, and induced increases in GSH production. ALA also showed an effect on DNA damage induced by DDS-NOH (2.5 µg/mL). Both isomers were able to inhibit MetHb formation and the S-ALA was able to elevate GSH levels by stimulating the production of this antioxidant. In post-treatment with the R-ALA, this enantiomer inhibited MetHb formation and increased GSH levels. The pretreatment with R-ALA or S-ALA prevented the increase in SOD and decrease in TEAC, while R-ALA decreased the levels of MDA; and this pretreatment with R-ALA or S-ALA showed the effect of ALA enantiomers on DNA damage. These data show that ALA can be used in future therapies in patients who use dapsone chronically, including leprosy patients.

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BACKGROUND: Dapsone (4,4'-diamino-diphenyl sulfone) is a synthetic derivative of sulfones, with the antimicrobial activity described since 1937. It is also a drug traditionally used in dermatological therapies due to its anti-inflammatory effect. In recent years its antioxidant, antiexcitotoxic, and antiapoptotic effects have been described in different ischemic damage models, traumatic damage, and models of neurodegenerative diseases, such as Parkinson's (PD) and Alzheimer's diseases (AD). Finally, dapsone has proven to be a safe and effective drug as a protector against heart, renal and pulmonary cells damage; that is why it is now employed in clinical trials with patients as a neuroprotective therapy by regulating the main mechanisms of damage that lead to cell death ObjectiveThe objective of this study is to provide a descriptive review of the evidence demonstrating the safety and therapeutic benefit of dapsone treatment, evaluated in animal studies and various human clinical trials Methods: We conducted a review of PubMed databases looking for scientific research in animals and humans, oriented to demonstrate the effect of dapsone on regulating and reducing the main mechanisms of damage that lead to cell death ConclusionThe evidence presented in this review shows that dapsone is a safe and effective neuro and cytoprotective treatment that should be considered for translational therapy.

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Dapsone (DDS) is an antibacterial drug with well-known antioxidant properties. However, the antioxidant behavior of its derivatives has not been well explored. In the present work, the antioxidant activity of 10 dapsone derivatives 4-substituted was determined by an evaluation in two in vitro models (DPPH radical scavenging assay and ferric reducing antioxidant power). These imine derivatives 1-10 were obtained through condensation between DDS and the corresponding aromatic aldehydes 4-substuited. Three derivatives presented better results than DDS in the determination of DPPH (2, 9, and 10). Likewise, we have three compounds with better reducing activity than dapsone (4, 9, and 10). In order to be more insight, the redox process, a conceptual DFT analysis was carried out. Molecular descriptors such as electronic distribution, the total charge accepting/donating capacity (I/A), and the partial charge accepting/donating capacity (ω+/ω-) were calculated to analyze the relative donor-acceptor capacity through employing a donor acceptor map (DAM). The DFT calculation allowed us to establish a relationship between GAPHOMO-LUMO and DAM with the observed antioxidant effects. According to the results, we concluded that compounds 2 and 3 have the lowest Ra values, representing a good antioxidant behavior observed experimentally in DPPH radical capturing. On the other hand, derivatives 4, 9, and 10 display the best reducing capacity activity with the highest ω- and Rd values. Consequently, we propose these compounds as the best antireductants in our DDS imine derivative series.

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BACKGROUND: The optimum second-line treatment or best sequence of treatments for immune thrombocytopenia (ITP) are yet to be determined. Our institution has accumulated extensive experience regarding the use of dapsone as second-line therapy for ITP. OBJECTIVES: We aimed to assess the efficacy rate and safety of dapsone treatment in ITP patients. PATIENTS/METHODS: Here we report our experience in a retrospective study, including 122 patients, with a median treatment duration with dapsone of 6 months and a median follow-up period of 3.4 years. RESULTS: The overall response rate in this cohort was 66%, including 24% of complete responses. Among responders, in 24% a relapse occurred while on treatment. Therefore, a sustained response was observed in 51% of patients. Interestingly, 81% of the responders maintained the response after the interruption of treatment, for a median time of 26 months. Side effects were reported in 16% of the patients in this cohort and treatment was interrupted due to side effects in 11% of patients. The main cause in these cases was hemolytic anemia and methemoglobinemia. Reductions in hemoglobin levels during the use of dapsone were seen in 94% of the patients. Responders presented significantly greater reductions in their hemoglobin levels than nonresponders did: median hemoglobin drop of 1.9 g/dl vs. 1.2 g/dl (p = .004). CONCLUSIONS: Our findings suggest that dapsone has adequate efficacy and is well tolerated. Although the mechanism of action is still unclear, our observation that the degree in the drop of hemoglobin is greater in responders suggest a possible role of the blockage of the reticuloendothelial system in the therapeutic effect of the drug.

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