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Pneumocystis carinii
Published in Peter D. Walzer, Robert M. Genta, Parasitic Infections in the Compromised Host, 2020
Peter D. Walzer, C. Kurtis Kim, Melanie T. Cushion
Prophylactic TMP-SMX is well tolerated in non-AIDS patients but has found little application in persons with AIDS. The fixed combination of pyrimethamine and sulfadoxine (Fansidar), which was first used in prophylaxis in the epidemic form of pneumocystosis (504), has been used in limited numbers of AIDS patients with mixed results (448-452). Toxicity considerations with this drug and other sulfonamides or sulfones are the same as those discussed under treatment. Pentamidine, administered intravenously or via aerosol, is currently receiving a lot of attention, but controlled studies have not yet been performed. Immunological approaches to P. carinii prophylaxis have attracted little interest. The results of active immunization in the rat model or the administration of immune plasma or serum globulin preparations in small numbers of humans have been discouraging (27,505,506).
Serodiagnostic Tests in Dermatitis Herpetiformis
Published in Tadeusz P. Chorzelski, Ernst H. Beutner, Vijay Kumar, Tadeusz K. Zalewski, Serologic Diagnosis of Celiac Disease, 2020
Tadeusz P. Chorzelski, Ernst H. Beutner, Ewa Maciejowska, Vijay Kumar, Danuta Rosinska, Jadwiga Sulej
Dermatitis herpetiformis is a pruritic, vesicular skin disease. The skin lesions have a characteristic symmetrical distribution on the extensor surfaces of the extremities, upper back, buttocks, and other areas. They respond to treatment with sulfones. The histopathological finding of neutrophilic microabscesses in the dermal papillae served as a diagnostic aid for this disease prior to the adoption of the direct immunofluorescence (DIF) method as the most reliable diagnostic criterion.3,37
Substrates of Human CYP2D6
Published in Shufeng Zhou, Cytochrome P450 2D6, 2018
Spirosulfonamide, a selective inhibitor of COX-2, is metabolized by CYP2D6, with contribution from CYP3A4 (Guengerich et al. 2002). When incubated with human liver microsomes, spirosulfonamide is converted into monohy-droxylated syn and anti OH-spirosulfonamides (M1 and M2, respectively) and a keto metabolite, M3 (Figure 3.99) (Guengerich et al. 2002). Spirosulfonamide is an atypical substrate for CYP2D6 as it lacks the basic nitrogen atom despite a high affinity with a Km of 7 µM. The phenylsulfonamide of spirosulfonamide contains the only nitrogen in the molecule, and at physiologically relevant pH, this moiety is not positively charged. The sulfonamide moiety is not basic owing to the strong electron-withdrawing properties of the sulfone group. Mutation of Asp301 of CYP2D6 to a neutral amino acid (Asn, Ser, or Gly) does not substantially affect the binding affinity to spirosulfonamide but reduced the metabolic turnover to the same extent as for the classical substrate such as bufuralol (90%) (Guengerich et al. 2002).
The importance of sulfur-containing motifs in drug design and discovery
Published in Expert Opinion on Drug Discovery, 2022
Muhamad Mustafa, Jean-Yves Winum
Among the different sulfur-containing functions exploited in drug design, some are of great importance and have been used extensively, such as sulfides, thiols, sulfoxides, sulfones, sulfonamide, sulfamate, sulfamide, sulfoximine, and sulfur-related heterocycles (Figure 1). Sulfur-containing compounds are described to depict large activity profiles through diverse mechanisms of action and the nature of the targets and is related to the special characteristics and polarity of the carbon-sulfur, oxygen-sulfur, and nitrogen-sulfur bonds [3]. In addition, sulfur-containing natural products (e.g. penicillin, quinupristin, and dalfopristin) are of growing significance in medicinal chemistry. Interestingly, over one thousand sulfur-containing natural compounds were isolated from various organisms [4].
In vitro sulfonation of 7-hydroxycoumarin derivatives in liver cytosol of human and six animal species
Published in Xenobiotica, 2020
Risto O. Juvonen, Olli Pentikäinen, Juhani Huuskonen, Juri Timonen, Olli Kärkkäinen, Aki Heikkinen, Muluneh Fashe, Hannu Raunio
The rate of sulfonation can be measured by assays based on radiometric, absorbance, fluorescence and HPLC-MS detection. In radiometric assay the sulfur atom of transferred sulfone is labeled with 35S, which can be measured precisely and at high sensitivity from the isolated metabolite in an endpoint experimental setup (Paul et al., 2012). The absorbance and fluorescence assays are based on indirect measurement of sulfonation in which the actual substrates and p-nitrophenol sulfate or 4-methyl-7-hydroxycoumarin sulfate are tightly coupled to the regeneration of PAP to PAPS by aryl sulfotransferase IV enzyme. In this coupling reaction sulfates are transformed to absorbing p-nitrophenol or fluorescent 4-methyl-7-hydroxycoumarin. The increase in absorbance or fluorescence can be measured by continuous or endpoint assays; measurement of fluorescence is more sensitive than of absorbance (Chen et al., 2005; Lu et al., 2010). The decrease of fluorescence of 7-hydroxycoumarin or resorufin during sulfonation has also been measured directly. In HPLC-MS assays substrates and the formed metabolites are separated by HPLC and then detected and analyzed by different kinds of MS approaches (Paul et al., 2012).
Development and evaluation of dapsone tablets coated for specific colon release
Published in Drug Development and Industrial Pharmacy, 2020
Priscila Debastiani Barros, Isabela Fernanda Teixeira Dias, Giovane Douglas Zanin, Élcio José Bunhak
The dosage of 100 mg of the drug was based on the multidrug therapy treatment of leprosy, where the patient administers 100 mg per day of the drug dapsone. This same dose is related to the incidence of adverse effects of sulfone, the most common being methemoglobinemia, which can lead the patient to cyanosis, coma, convulsions, and even death [27]. Therefore, the development of dapsone 100 mg coated tablets for colonic delivery becomes extremely interesting, given the high absorption capacity of the colon and release of the drug by the action of microbiota. The form of the tablet chosen for development was circular, as it is the most suitable for coating application since there is less possibility of adhesion between the tablets during the process [28].