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Chloroquine, hydroxystilbamidine, and dapsone inhibit resorption of fetal rat bone in organ culture.

Three potential inhibitors of lysosomal enzyme release, chloroquine, hydroxystilbamidine, and dapsone were tested for their effects on the release of previously incorporated 45Ca and beta (beta)-glucuronidase from fetal rat long bones cultured in a chemically defined medium. At concentrations of 10(-5) to 10(-8)M, all three agents were able to inhibit the stimulation of bone resorption by parathyroid hormone (PTH) or prostaglandin E2 (PGE2). Inhibition was seen at concentrations which did not alter the uptake of (3H)-2-deoxy-glucose or the incorporation of (3H)-thymidine in bone. While the inhibitors blocked the stimulation of beta-glucuronidase release by PTH and PGE2, they could also cause a direct increase in total beta-glucuronidase content and release. Hence the usual strong correlation between the release of beta-glucuronidase and 45Ca was no longer seen in the presence of inhibitors. These data indicate that chloroquine, hydroxystilbamidine, and dapsone are potent inhibitors of bone resorption which may act by blocking the release of lysosomal enzymes in cells stimulated by PTH or PGE2, but may have a different effect on other cell populations.

Animals↗

Intraoperative cyanosis: a case of dapsone-induced methaemoglobinaemia.

Intraoperative cyanosis is most commonly caused by hypoxaemia. The anaesthetist is required to perform a rapid series of diagnostic manoeuvres and take remedial action. Occasionally methaemoglobin, sulfhaemoglobin, or haemoglobin M, undetected preoperatively, is the cause of the cyanosis. We report a case of methaemoglobinaemia secondary to dapsone ingestion that was diagnosed intraoperatively. Dapsone, a sulfone, is used therapeutically to treat leprosy and dermatitis herpetiformis. The differential diagnosis of cyanosis, and the origin and fate of methaemoglobin are discussed. In addition the diagnostic steps and the laboratory investigations required to make the diagnosis are listed.

Adolescent↗

[ANCA-positive lupus erythematodes profundus. Successful therapy with low dosage dapsone].

A 44-year-old male patient with lupus erythematosus profundus (lupus panniculitis) (LEP) of the right cheek/infraorbital region presented as a recurrent swelling. He had only anti-neutrophil-cytoplasmic antibodies (ANCA), which have not been previously described in association with LEP. There was no indication of systemic lupus erythematosus. While chloroquine produced no benefits, the skin lesions promptly cleared with dapsone. Step by step we reduced dapsone to a final dose of 50-75 mg per week. The ANCA titer decreased in parallel to the clinical improvement.

Adult↗

[Henoch-Schönlein purpura: successful treatment with Dapsone].

A 26-year old patient who suffered from purpura for four years evolved into the complete clinical picture of Henoch-Schönlein-purpura in the past two years. A causative agent was never found. Multiple therapeutic approaches including systemic steroids, azathioprine as well as pentoxyfylline failed to control the arthralgias, intestinal symptoms and skin lesions. Therefore dapsone therapy was initiated at a dosage of 100 mg daily after checking the glucose-6-phosphate-dehydrogenase and with regular control of the blood methemoglobin level. Within two weeks, the patient's symptoms completely cleared, he has now been in remission for the past six months. As noted elsewhere, dapsone is an effective therapy for severe cases of Henoch-Schönlein- purpura.

Adult↗

Epidermolysis bullosa acquisita responsive to dapsone therapy.

BACKGROUND: Epidermolysis bullosa acquisita (EBA) is a chronic subepidermal blistering disease that is frequently resistant to therapy. OBJECTIVE: A 58-year-old man who had a one-year history of a bullous eruption involving the hands, forearms, trunk, scalp, and oral mucosa. Histopathology revealed a subepidermal bulla, and direct and indirect immunofluorescence studies were consistent with EBA. The patient failed respond to niacinamide and tetracycline and oral prednisone 40 mg per day. METHODS: Complete control of his blistering was achieved within two months of initiating oral dapsone, 150 mg per day. CONCLUSION: Dapsone may be an effective agent for some patients with EBA.

Anti-Inflammatory Agents, Non-Steroidal↗

Inhibition of tubulin assembly by antileprosy drug dapsone.

The effect of dapsone on assembly-disassembly process of bovine brain tubulin was examined. The drug was found to readily bind tubulin dimer and that in its presence colchicine binding to tubulin was enhanced. Although dapsone associated with tubulin at a site other than the colchicine binding site, distinct inhibition of microtubule assembly was detected.

Animals↗

Oral acantholytic itching disease responding to dapsone. Dermatitis herpetiformis, pemphigus, or a new disease?

A patient had a blistering and severely itching disease confined solely to the oral cavity. The histopathologic findings had the features of both pemphigus and dermatitis herpetiformis. There were no gastrointestinal symptoms, no IgA could be found in uninvolved skin, and no intercellular or basement membrane antibodies were present in the serum or epidermis. The disease responded favorable to dapsone (diaminodiphenylsulfone), which could be discontinued after 2 1/2 years. The literature is briefly reviewed, and there is a discussion of whether the patient was suffering from pemphigus or dermatitis herpetiformis. The conclusion is drawn that the diagnosis cannot be established with certainty and that we are perhaps dealing with a new disease. It is stressed that in such aberrant cases a therapeutic trial with dapsone should be made.

Acantholysis↗

The effect of dapsone-pyrimethamine on immunoglobulin concentrations in malaria chemoprophylaxis.

Immunoglobulins IgG, IgM, IgA were estimated on 3 occasions in 59 male volunteers who were taking dapsone-pyrimethamine once weekly (dapsone: 100 mg + pyrimethamine: 12.5 mg) for malaria chemoprophylaxis. Immunoglobulins IgG and IgM measured at the 7th week of chemoprophylaxis were significantly lower than baseline values (using Students' t-test for paired data), but none of the values were below 700 mg% for IgG or 30 mg% for IgM. Immunoglobulin concentrations estimated in 45 of the 59 men 6 weeks after discontinuation of chemoprophylaxis showed a return to baseline for IgM but not IgG, which remained low. On all 3 occasions there was no significant change in the IgA concentrations. The clinical implication of these findings is not known. Further studies are required to define the effects of antimalarial drugs on the antibody response to infection and immunization.

Adolescent↗

Bilateral pyoderma gangrenosum of the hand: treatment with dapsone.

The first reported case of bilateral pyoderma gangrenosum of the hands is presented. One lesion was treated with wound care only, with spontaneous healing after two months. The contralateral lesion which occurred one month later was treated with wound care and oral dapsone. Healing occurred between four and six weeks after the start of dapsone. It is suggested that this acts by limiting the necrotizing process, thus allowing earlier epithelialization. Pyoderma gangrenosum is rare, and treatment is non-surgical. It is important that it is recognized to avoid extension of the necrotizing process through ill-advised surgery.

Aged↗

Methemoglobinemia from dapsone therapy for a suspected brown spider bite.

Recent reports have suggested the use of dapsone for brown spider bites. This drug, for many years restricted to use in cases of leprosy and rare dermatologic disorders, has significant side effects that must be recognized. A case of methemoglobinemia is reported in one such patient treated with dapsone. The difficulty of making the diagnosis of brown spider bite is discussed.

Adult↗

Crohn's disease and mycobacteria: two cases of Crohn's disease with high anti-mycobacterial antibody levels cured by dapsone therapy.

Five patients with Crohn's colitis or ileocolitis (CD) refractory to conventional therapy were enrolled in an open trial with dapsone (100 mg/day). This therapy was apparently effective in two out of five patients. In these patients we observed a clinical improvement after one month of therapy and, in the first patient, a complete healing of all the cutaneous and rectal ulcers. In the two responders antibody levels to a soluble extract of M. paratuberculosis (MPSE) were significantly greater than in the three non-responders (P = 0.03); in the first patient, moreover, there was a rise of 39% in antibody titres following the treatment. This rise in antibody levels, that might be expected following death of the pathogen and release of antigen, is similar to that observed after treatment of tuberculosis. Our data suggest that a mycobacterial species or another pathogen that cross-react with those of MPSE, sensitive to dapsone, may in a subset of cases be responsible for the development of CD. This is the first report of clinical cure with an agent active against specific bacterial species, associated with immunologic confirmation of a response.

Adult↗

Acute methemoglobinemia following attempted suicide by Dapson.

This report describes the case of an otherwise healthy young adult female, with oral ingestion of 40 unknown tablets. Her clinical course included progressive bluish discoloration of lips and limbs, hemolysis and jaundice. A high PaO2 in the presence of cyanosis and dark blood lead to suspicion of methemoglobinemia. Laboratory results showed methemoglobin level to be 3.8 g/dL (38%). The etiology was traced to dapsone according to patient history; after 3 days it became evident that she had ingested 2 g dapsone in suicidal intent. The therapeutic and diagnostic approach in such patients is discussed. In conclusion, acute methemoglobinemia is an uncommon but potentially treatable disorder.

Acute Disease↗

Presentation of dapsone-induced methemoglobinemia in a patient status post small bowel transplant.

Methemoglobinemia, an uncommon hemoglobinopathy, affects oxygen transport, causing tissue hypoxia. In the perioperative period, methemoglobinemia is often overlooked as a cause of low oxygen saturation, often mistaken for the more common causes of hypoxia, such as atelectasis, pulmonary edema, or pulmonary embolus, among other causes of respiratory failure. Most cases of methemoglobinemia in the perioperative period are precipitated by local anesthetics, especially benzocaine. Dapsone, a sulfone antibiotic, is used for prophylaxis against Pneumocystis carinii pneumonia in immunosuppressed patients. It is commonly used in organ transplant patients, especially those intolerant to sulfa. With the expansion of organ transplantation and improved long-term survival of these patients, presentation of status post organ transplant patients for surgery will inevitably increase. We report a case of dapsone-induced methemoglobinemia observed in a status post small bowel transplant patient in the postanesthesia care unit.

Adolescent↗

Reduction of sulfamethoxazole and dapsone hydroxylamines by a microsomal enzyme system purified from pig liver and pig and human liver microsomes.

Biotransformation involving nitrogen are of pharmacological and toxicological relevance. In principle, nitrogen containing functional groups can undergo all the known biotransformation processes such as oxidation, reduction, hydrolysis and formation of conjugates. For the N-reduction of benzamidoxime an oxygen-insensitive liver microsomal enzyme system that required cytochrome b5, NADH-cytochrome b5 reductase and a cytochrome P450 isoenzyme of the subfamily 2D has been described. In previous studies it was demonstrated that N-hydroxylated derivates of strongly basic functional groups are easily reduced by this enzyme system. The N-hydroxylation of sulfonamides such sulfamethoxazole (SMX) and dapsone (DDS) to sulfamethoxazole-hydroxylamine (SMX-HA) and dapsone-hydroxylamine (DDS-N-OH), respectively is the first step in the formation of reactive metabolites. Therefore it seemed reasonable to study the potential of cytochrome b5, NADH-cytochrome b5 reductase and CYP2D to detoxify these N-hydroxylated metabolites by N-reduction. Metabolites were analysed by HPLC analysis. SMX-HA and DDS-N-OH are reduced by cytochrome b5, NADH-cytochrome b5 reductase and CYP2D but also only by cytochrome b5 and NADH-cytochrome b5 reductase without addition of CYP2D. The reduction rate for SMX-HA by cytochrome b5, NADH-cytochrome b5 reductase and CYP2D was 0,65 +/- 0,1 nmol SMX/min/mg protein. The reduction rate by b5 and b5 reductase was 0,37 +/- 0,15 nmol SMX/min/mg protein. For DDS-N-OH the reduction rate by cytochrome b5, NADH-cytochrome b5 reductase and CYP2D was 1.79 +/- 0.85 nmol DDS/min/mg protein and by cytochrome b5 and NADH-cytochrome b5 reductase 1.25 +/- 0.15 nmol DDS/min/mg protein. Cytochrome b5, NADH-cytochrome b5 reductase are therefore involved in the detoxification of these reactive hydroxylamines and CYP2D increased the N-reduction.

Animals↗

Evidence for prevention of borderline leprosy reactions by dapsone.

68 patients were included in a prospective study of the treatment of borderline leprosy. 34 were treated with dapsone 5 mg daily, and 34 with 50 mg daily. Reversal reactions developed in 11 of those on 5 mg daily and in 3 of those on 50 mg daily. The statistically significant difference between the two treatment groups indicates that, contrary to previous teaching, dapsone given in higher dosage does not predispose patients to reversal reactions and indeed may prevent them.

Adolescent↗

Anticonvulsant activity of dapsone analogs. Electrophysiologic evaluation.

BACKGROUND: In a previous study we reported that 4,4'diaminodiphenylsulfone (dapsone) has anticonvulsant activity using kainic acid (KA) model. This work shows the behavioral and electrophysiologic changes caused by systemic application of several dapsone derivatives. These derivatives include disodium salt of 4,4'-diaminodifenylsulfone N,N'-diformaldehyde sulfoxylate (I), 4,4'-diaminodiphenylsulfone N,N'-didextrose sulfonate (II), sodium dibisulfite 4,4'-biscinamilidenamindiphenyl sulfone (III), and N,N'-dimethyl-4,4'-dimethylphenylsulfone (IV), which were synthesized and purified in our laboratory. METHODS: A KA model was used to provoke limbic seizures. Limbic seizures were provoked by injection, KA, and electrophysiologic recorder at the following concentrations: 6.25 and 12.50 mg/kg of III and 6.25 and 12.50 mg/kg of IV. RESULTS: Compounds III and IV caused decrease of postdischarges; we found percentage of protection of 55.60 and 70.78%, respectively. This showed possible anticonvulsant activity of these compounds (III and IV), while I and II showed no significant changes. We also studied whether there was a dose-dependence relationship, and different doses of compound IV were evaluated (25.00, 12.50, 6.25, 3.12, and 1.62 mg/kg). We found that greatest anticonvulsant effect occurred using doses of 3.12 and 6.25 mg/kg (two of the three lowest doses). CONCLUSIONS: We concluded that IV at doses of 3.25 and 6.25 mg/kg has anticonvulsant effect because it diminished duration of the first limbic seizure induced by KA; latency of first limbic seizure crisis was also increased. Both facts demonstrated possible therapeutic application of compound IV as anticonvulsant.

Analysis of Variance↗

Dapsone in the treatment of erosive lichen planus.

A patient with erosive lichen planus responded to therapy with dapsone after multiple therapeutic modalities had failed. The potential usefulness of dapsone therapy for lymphocyte-mediated inflammatory diseases such as erosive lichen planus is suggested.

Biopsy↗

Bullous lichen planus: diagnosis by indirect immunofluorescence and treatment with dapsone.

Bullous lichen planus may be confused with other subepidermal bullous dermatoses, especially if bullae arise on normal-appearing skin. We present two patients who were originally thought, on the basis of clinical and histopathologic criteria, to have bullous pemphigoid. However, results of standard indirect and direct immunofluorescence assays did not support the diagnosis of bullous pemphigoid. Further investigation using the indirect autologous immunofluorescence assay revealed deposits of immunoglobulins in the stratum granulosum. Moreover, the indirect allogeneic immunofluorescence assay (using papular lichen planus lesional substrates from different patients) was positive for the same pattern, confirming the diagnosis of bullous lichen planus. Bullous lichen planus with bullous pemphigoid-like histologic features can be differentiated from bullous pemphigoid on the basis of the indirect autologous and allogeneic immunofluorescence assays for circulating antigranulosum antibodies. Both patients were treated with systemic corticosteroids. One patient went into remission with this therapy alone; the other patient had a favorable response when dapsone was given with systemic corticosteroids. The suggestion that there is a subset of bullous lichen planus with bullous pemphigoid-like histologic features that responds to dapsone needs to be explored.

Adult↗