Insulin resistance in hidradenitis suppurativa: a case-control study

Background: The association between chronic inflammatory diseases, such as rheumatoid arthritis and psoriasis, and insulin resistance (IR) has been well established. Hidradenitis suppurativa (HS) is a chronic inflammatory cutaneous disease that affects the apocrine glandbearing areas of the body. Objective: We aimed to determine the prevalence of IR in patients with HS. Methods: This cross-sectional, case-control study enrolled 137 subjects, 76 patients with HS and 61 age- and gender-matched controls. Demographic data, clinical examination of HS patients, anthropometric measures, cardiovascular risk factors and laboratory studies were recorded. The homeostasis model assessment of IR (HOMA-IR) was calculated in all participants by measuring fasting plasma glucose and insulin levels. Results: The median (IQR) HOMA-IR value in HS patients was significantly higher [2.0 (1.0-3.6)] than in controls [1.5(0.9-2.3)] (p=0.01). The prevalence of IR was significantly higher in cases (43.4%) compared with controls (16.4%) (p=0.001). In the linear regression multivariable analysis after adjusting for age, sex and body mass index (BMI), HS remained as a significant factor for a higher HOMA-IR [2.51(0.18) vs 1.92(0.21); p=0.04]. The HOMA-IR value and the prevalence of IR did not differ significantly among HS patients grouped by severity of the disease. Conclusion: Our results show an increased frequency of IR in HS. Thus, we suggest HS patients to be evaluated for IR and managed accordingly

Carotid ultrasound is useful for the cardiovascular risk stratification in patients with hidradenitis suppurativa

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic inflammatory cutaneous disease which has been associated with an increased risk of adverse cardiovascular (CV) outcomes. Adequate stratification of the CV risk is an issue of major importance in patients with HS. To analyze the usefulness of carotid ultrasound (US) assessment for the CV disease risk stratification compared with a traditional score, the Framingham risk score (FRS), in a series of patients with HS. METHODS: Cross-sectional study of 60 patients with HS without history of CV events, diabetes mellitus or chronic kidney disease. Information on CV risk factors was collected and the FRS was calculated. Thus, the patients were classified into low, intermediate and high-CV disease risk categories based on FRS. Carotid US was performed in all participants, and the presence of atherosclerotic plaques was considered as a marker of high CV risk. RESULTS: HS patients had a mean age of 45.1±10.2 years, and 55% were female. The median FRS was 5.7 (IQR: 3.1-14.7). Twenty-four (40%) of the patients were classified into the low risk group, 28 (46.7%) in the intermediate risk group, and 8 (13.3%) into the FRS-high risk category. Noteworthy, carotid US revealed that about one-third of the patients (17/52; 32.6%) in the FRS-based low and intermediate risk categories had carotid plaques, and, therefore, they were reclassified into a high-risk category. CONCLUSION: CV risk in HS patients may be underestimated by using the FRS. Carotid US may be useful to improve the CV risk stratification of patients with HS.This study was funded through an unrestricted grant provided by AbbVie to MGL. AbbVie has not played any role in study design, data collection and analysis, decision to publish or preparation of the manuscript

Intrinsic mutagenicity and electrophilicity of 1-sulfooxy-3-methylcholanthrene: Implications for metabolic activation of the carcinogen 3-methylcholanthrene

Hydroxylation of a meso-anthracenic carbon atom with subsequent formation of a reactive ester bearing a good leaving group (e.g., sulfate) has been proposed as a possible biochemical mechanism responsible for DNA binding, mutagenicity and tumorigenicity of 3-methylcholanthrene, one of the most potent carcinogenic polycyclic aromatic hydrocarbons in experimental animals. In support of this supposition, the chemically synthesized sulfuric acid ester, 1-sulfooxy-3-methylcholanthrene (1-SMC) was directly mutagenic in bacteria and covalently bound to DNA without metabolic activation. The intrinsic mutagenicity of this reactive ester was significantly potentiated by addition of extra acetate or chloride anions to the media. Reduced glutathione and ascorbic acid protected against 1-SMC-induced mutagenesis. These findings suggest 1-SMC as a potential ultimate electrophilic and tumorigenic metabolite of 3-methylcholanthrene

Inhibition of covalent DNA binding and mutagenicity of benzo[a]pyrene by isopropyl-2-(1,3-dithietane-2-ylidene)-2-[N-(4-methylthiazol-2-yl) carbamoyl]acetate (YH439), a novel hepatoprotective agent

Isopropyl-2-(1,3-dithietane-2-ylidene)-2[N-(4-methyl-2-thiazol-2-yl)carbamoyl]acetate (YH439) was synthesized as a hepatoprotective drug for the treatment of chronic hepatitis and liver cirrhosis. In the present investigation, we have tested YH439 for its chemoprotective activity against the carcinogen benzo[n]pyrene. The drug exhibited dose-dependent protection against bacterial mutagenesis induced by benzo[n]pyrene and its covalent binding to DNA in vitro mediated by rat hepatic postmitochondrial supernatant enriched with NADPH. The direct mutagenicity of benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide, the ultimate electrophilic and carcinogenic metabolite of benzo[a]pyrene, was also ameliorated by YH439 in a dose-dependent manner. The results of this study suggest that YH439 has a potential as a chemopreventive agent

Bioactivation of 5-Hydroxymethyl-2-Furaldehyde to an Electrophilic and Mutagenic Allylic Sulfuric Acid Ester

5-Hydroxymethyl-2-furaldehyde (HMF), a ubiquitous food contaminant, has been proposed to be metabolically activated through sulfonation of its allylic hydroxyl functional group. In support of this idea, we have found the strong direct mutagenicity of chemically synthesized sulfuric acid ester, 5-sulfooxymethylfurfural (SMF), in Salmonella typhimurium TA104. The intrinsic mutagenicity of this reactive ester was significantly inhibited by glutathione and glutathione S-transferase activity in dialyzed rat liver cytosol. The metabolic formation of SMF was elucidated by enhanced mutagenicity of HMF in the presence of rat hepatic cytosol enriched with the sulfogroup donor, 3'-phosphoadenosine-5'-phosphosulfate (PAPS). The PAPS- and cytosol-dependent mutagenicity of HMF was markedly lessened by sulfotransferase inhibitors such as 2,6-dichloro-4-nitrophenol and dehydroepiandrosterone. These results suggest that HMF can be metabolically activated to an allylic sulfuric acid ester which may play a role as an ultimate electrophilic metabolite in toxification of the parent compound in vivo. (C) 1995 Academic Press, Inc