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Vaccines Jan 2022Since the start of the SARS-CoV-2 pandemic, refractory and relentless hypoxia as a consequence of exuberant lung inflammation and parenchymal damage remains the main...
Since the start of the SARS-CoV-2 pandemic, refractory and relentless hypoxia as a consequence of exuberant lung inflammation and parenchymal damage remains the main cause of death. We have earlier reported results of the addition of dapsone in this population to the standard of care. We now report a further chart review of discharge outcomes among patients hospitalized for COVID-19. The 2 × 2 table analysis showed a lower risk of death or discharge to LTAC (Long term acute care) (RR = 0.52, 95% CI: 0.32 to 0.84) and a higher chance of discharge home (RR = 2.7, 95% CI: 1.2 to 5.9) among patients receiving dapsone compared to those receiving the usual standard of care. A larger, blinded randomized trial should be carried out urgently to determine if dapsone indeed improves outcomes in COVID-19.
PubMed: 35214654
DOI: 10.3390/vaccines10020195 -
Frontiers in Immunology 2023Epidermolysis bullosa acquisita (EBA) is a chronic, recurrent autoimmune subepidermal bullous disease characterized by the presence of autoantibodies targeting type VII... (Review)
Review
Epidermolysis bullosa acquisita (EBA) is a chronic, recurrent autoimmune subepidermal bullous disease characterized by the presence of autoantibodies targeting type VII collagen -- basement membrane zone antigen. Standard therapy for EBA includes a combination of systemic corticosteroids and dapsone; however, severe cases may require advanced treatment. The current article reports on four EBA cases in which biologics: infliximab, rituximab (Rtx), and intravenous immunoglobulin (IVIG) were applied. All patients fulfilled the clinical and immunological criteria of EBA: they presented tense blisters healing with atrophic scars on the skin on traumatized areas and in mucous membranes. The diagnosis of EBA was established using numerous techniques: direct and indirect immunofluorescence, salt split skin, ELISA, Fluorescence Overlay Antigen Mapping using Laser Scanning Confocal Microscopy. Since all the patients did not achieve long-term remission on standard treatment (prednisone, dapsone) due to ineffectiveness or side effects of drugs, they eventually were treated with biologics leading to extraordinary skin improvement and stopping the disease for 1-3 years. Biologics in all patients were tolerated very well. No side effects were observed during application as well as multi-month follow-up. The presented cases provide a premise that biological drugs can be a valuable component of EBA therapy.
Topics: Humans; Epidermolysis Bullosa Acquisita; Blister; Autoantibodies; Dapsone; Biological Products
PubMed: 37503352
DOI: 10.3389/fimmu.2023.1214011 -
Actas Dermo-sifiliograficas Nov 2015Although hidradenitis suppurativa is a common and serious skin condition, its treatment is not well established. It is now accepted that the moderate and severe forms of... (Review)
Review
Although hidradenitis suppurativa is a common and serious skin condition, its treatment is not well established. It is now accepted that the moderate and severe forms of the disease are associated with marked systemic inflammation. The goal of treatment in hidradenitis suppurative is therefore to achieve systemic control of inflammation. In some cases, surgery may also be necessary to reduce the severity of the manifestations of cutaneous inflammation. Recent advances in our understanding of hidradenitis suppurativa have been accompanied by the emergence of novel approaches to its treatment, including the use of certain biologic drugs. Several clinical trials have been undertaken to test the effects of biologics (mainly adalimumab) in this setting. In this review, we analyze the different treatments available for hidradenitis suppurativa.
Topics: 5-alpha Reductase Inhibitors; Adalimumab; Adrenal Cortex Hormones; Algorithms; Anti-Bacterial Agents; Clinical Trials as Topic; Cutaneous Fistula; Dapsone; Hidradenitis Suppurativa; Humans; Immunosuppressive Agents; Infliximab; Interleukin 1 Receptor Antagonist Protein; Retinoids
PubMed: 26277040
DOI: 10.1016/j.ad.2015.06.005 -
Iranian Journal of Basic Medical... Jun 2022Multiple Sclerosis (MS) is an inflammatory disorder wherein the myelin of nerve cells in the central nervous system is damaged. In the current study, we assessed the...
OBJECTIVES
Multiple Sclerosis (MS) is an inflammatory disorder wherein the myelin of nerve cells in the central nervous system is damaged. In the current study, we assessed the effect of Dapsone (DAP) on the improvement of behavioral dysfunction and preservation of myelin in the cuprizone (CPZ) induced demyelination model via targeting Nrf2 and IKB.
MATERIALS AND METHODS
MS was induced in C57BL/6 mice through diet supplementation of CPZ (0.2%) for 6 weeks, and DAP (12.5 mg/kg/day; IP) was administered for the last 2 weeks of treatment. Pole test and rotarod performance test, LFB and H&E staining, and Immunohistochemistry (IHC) staining of p-Nrf2 and p-IKB were performed. Furthermore, superoxide dismutase (SOD) and nitrite were measured.
RESULTS
DAP treatment prevented body loss induced by CPZ (0.001). Pole test showed that CPZ increased latency time to fall (0.0001) but the latency to reach the floor in the DAP-CPZ group was significantly shorter (0.0001). Rotarod performance test showed the effect of CPZ in reducing fall time in the CPZ group (0.0014); however, DAP significantly increased fall time (P=0.0012). In LFB staining, DAP reduced demyelination induced by CPZ. CPZ significantly decreased p-Nrf2 and elevated p-IKB levels compared with the control group (0.0001), but in DAP-treated groups markedly modified these changes (0.0001). CPZ increased the brain nitrite levels and reduced SOD activity, but in DAP-treated considerably reversed CPZ-induced changes.
CONCLUSION
These data support the suggestion that the beneficial properties of DAP on the CPZ-induced demyelination are mediated by targeting Nrf2 and NF-kB pathways.
PubMed: 35949308
DOI: 10.22038/IJBMS.2022.64993.14310 -
Tropical Doctor Oct 2022Hypoxaemia in COVID-19 does not necessarily imply COVID pneumonia or post-COVID lung fibrosis, and the caveats of finger pulse oximetry should be remembered....
Hypoxaemia in COVID-19 does not necessarily imply COVID pneumonia or post-COVID lung fibrosis, and the caveats of finger pulse oximetry should be remembered. Drug-induced methaemoglobinemia should be considered in individuals with unexplained cyanosis, refractory hypoxaemia, or the presence of a saturation gap. Here, we share our recent encounter of 'spurious hypoxia' in a patient with COVID-19 and methaemoglobinemia.
Topics: COVID-19; Humans; Hypoxia; Oximetry; Pneumonia; SARS-CoV-2
PubMed: 35775134
DOI: 10.1177/00494755221094983 -
Journal of Epilepsy Research Dec 2022Status epilepticus (SE) results in permanent neuronal brain damage in the central nervous system. One of the complex etiologies underlying SE pathogenesis is...
BACKGROUND AND PURPOSE
Status epilepticus (SE) results in permanent neuronal brain damage in the central nervous system. One of the complex etiologies underlying SE pathogenesis is neuroinflammation. Dapsone has been recently considered as a potential neuroprotective agent in neuroinflammatory conditions. Therefore, the present study aims to investigate effects of dapsone on lithium-pilocarpine-induced SE in rats and assess whether tumor necrosis factor-alpha (TNF-α) and nitric oxide (NO) pathway participate in this effect.
METHODS
SE was established by injecting lithium chloride (127 mg/kg, intraperitoneally [i.p.]) and pilocarpine (60 mg/kg, i.p.). The animals received pre-treatment dapsone (2, 5, 10, and 20 mg/kg, oral gavage) and post-treatment dapsone (10 mg/kg). Subsequently, seizure score and mortality rate were documented. To assess the underlying signaling pathway, L-N-Nitro-L-arginine methyl ester hydrochloride (a non-specific NO synthase [NOS] inhibitor), 7-nitroindazole (a specific neuronal NOS inhibitor), and aminoguanidine (a specific inducible NOS inhibitor) were administered 15 minutes before dapsone (10 mg/kg) pre- or post-treatment. Hippocampal tissue TNF-α and NO concentrations were quantified using the enzyme-linked immunosorbent assay method.
RESULTS
Dapsone (10 mg/kg) pre-and post-treatment significantly attenuated the increased seizure score and mortality rate due to lithium-pilocarpine-induced SE. The development of SE in animals was associated with higher TNF-α and NO metabolites levels, which notably decreased in the dapsone-treated rats. Moreover, co-administration of NOS inhibitors with dapsone markedly reversed the anti-epileptic effects of dapsone and caused an escalation in TNF-α level but a significant reduction in NO concentration level.
CONCLUSIONS
It seems that dapsone may exert an anti-epileptic effect on lithium-pilocarpine-induced SE through TNF-α inhibition and modulation of the nitrergic pathway.
PubMed: 36685747
DOI: 10.14581/jer.22008 -
International Journal of Molecular... Dec 2022Dapsone (DDS) therapy can frequently lead to hematological side effects, such as methemoglobinemia and DNA damage. In this study, we aim to evaluate the protective...
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.
Topics: Methemoglobin; Antioxidants; Thioctic Acid; Dapsone; Superoxide Dismutase; DNA Damage
PubMed: 36613503
DOI: 10.3390/ijms24010057 -
Journal of Traditional Chinese Medicine... Apr 2021To investigate the efficacy of Tianma (Rhizoma Gastrodiae) and Gouteng (Ramulus Uncariae Rhynchophyllae cum Uncis) on cytochrome P450 (CYP450) enzyme activities in rats.
OBJECTIVE
To investigate the efficacy of Tianma (Rhizoma Gastrodiae) and Gouteng (Ramulus Uncariae Rhynchophyllae cum Uncis) on cytochrome P450 (CYP450) enzyme activities in rats.
METHODS
A cocktail strategy was followed to evaluate the influence of Tianma (Rhizoma Gastrodiae) and Gouteng (Ramulus Uncariae Rhynchophyllae cum Uncis) on the activities of CYP450 isoforms (CYP1A2, CYP3A4, CYP2E1, CYP2C19, CYP2C9, CYP2D6), which were determined by changes in the pharmacokinetic parameters of six probe drugs, theophylline, dapsone, chlorzoxazone, omeprazole, tolbutamide and dextromethorphan. Study groups included, Control group (CG), Tianma (Rhizoma Gastrodiae) group (TM), Gouteng (Ramulus Uncariae Rhynchophyllae cum Uncis) group (GT) and Tianma Gouteng (Gastrodia Uncaria) group (TMGT).
RESULTS
No significant differences between Tianma (Rhizoma Gastrodiae) and control groups were found. Compared with the control group, in the Gouteng (Ramulus Uncariae Rhynchophyllae cum Uncis) group both the AUC and t1/2 of dapsone and tolbutamide were reduced, whereas the CL (clearance rate) of dapsone and tolbutamide were increased. Compared with the control group, in the Tianma Gouteng group, the AUC and t1/2 of dapsone and tolbutamide were reduced, the CL of dapsone and tolbutamide were increased, and the AUC and t1/2 of chlorzoxazone were increased and the CL of chlorzoxazone was reduced.
CONCLUSION
Tianma (Rhizoma Gastrodiae) has no significant effect on the six CYP450 subtypes. The activities of CYP3A4 and CYP2C9 were increased by Gouteng (Ramulus Uncariae Rhynchophyllae cum Uncis). The activities of CYP3A4 and CYP2C9 were increased, whereas the activity of CYP32E1 was reduced by combined Tianma (Rhizoma Gastrodiae) and Gouteng (Ramulus Uncariae Rhynchophyllae cum Uncis).
Topics: Animals; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Drugs, Chinese Herbal; Enzyme Activators; Isoenzymes; Male; Orchidaceae; Rats; Rats, Wistar; Uncaria
PubMed: 33825409
DOI: No ID Found -
Indian Journal of Otolaryngology and... Oct 2022Rhinosporidiosis is a chronic granulomatous disease involving the mucous membranes of nose and nasopharynx caused by Rhinosporidium seeberi. Rhinosporidiosis involving...
Rhinosporidiosis is a chronic granulomatous disease involving the mucous membranes of nose and nasopharynx caused by Rhinosporidium seeberi. Rhinosporidiosis involving the eye is known as Oculosporidiosis. Usually affected patients present with nasal obstruction with an associated mass, epistaxis and watery discharge. In our case, there was involvement of the nasolacrimal duct which resulted in bloody discharge from the punctum.
PubMed: 36452595
DOI: 10.1007/s12070-021-02408-z -
Dementia and Geriatric Cognitive... 2020This research aims to prevent progression from mild cognitive impairment (MCI) to Alzheimer's disease. A Japanese study of leprosy patients revealed that the incidence...
AIM/BACKGROUND
This research aims to prevent progression from mild cognitive impairment (MCI) to Alzheimer's disease. A Japanese study of leprosy patients revealed that the incidence of dementia in leprosy patients was lower than that in patients taking dapsone who had never been treated. But a similar study the following year refuted the finding of less dementia in leprosy patients taking dapsone. According to conflicting reports, was a factor in reducing the incidence of Alzheimer's disease. Thus, we formed a hypothesis that if dapsone is administered to patients without leprosy but with MCI and the prophylactic effect of dementia syndrome is observed over a long period of time, we can determine whether dapsone can prevent the progression of MCI to dementia syndrome. If dementia does not occur after treating inflammation in brain cells while dementia develops after a certain long-term period (usually within 2-3 years), brain cell inflammation can be demonstrated as the cause of dementia.
METHODS
This is a prospective cohort research. We report on an elderly patient diagnosed with MCI from February 2008 to January 2019. The patient took dapsone 100 mg once a day from 2010 to 2015 for the treatment of MCI. Since 2016, the production of dapsone has ceased in Korea. In June 2018, the patient was diagnosed with Alzheimer's disease. The patient took Aricept for the treatment of Alzheimer's disease but complained of serious side effects. And dapsone was re-administered to the patient from November 2018.
RESULTS
The patient recovered to MCI and improved her daily life owing to the treatment with dapsone. The drug controls the inflammatory response in the brain, irrespective of whether proteins are deposited in neurons.
CONCLUSIONS
This finding means that dementia syndrome is an inflammatory disease. This research suggests that diagnostic criteria for Alzheimer's disease should be based on the presence or absence of inflammation in neurons. Because inflammation in neurons can occur in middle age due to various causes, we can treat inflammation in neurons and prevent and treat dementia syndrome, including Alzheimer's disease.
PubMed: 32158462
DOI: 10.1159/000504880