Ergotism and factitious hypotension associated with interaction of ergotamine with CYP3A4 inhibitors

Background. Although uncommon, severe ergotism continues to occur. The purpose of this study is to describe causes and clinical effects of ergotism in recent years. Methods. This is an observational case series with data obtained retrospectively from all patients with ergotism referred to Ramathibodi Poison Center in Bangkok, Thailand from January 2006 to August 2013. Result. Twelve cases of ergotism were identified. All cases involved ergotamine 1 mg/caffeine 100 mg combination tablets. Nine cases (75%) were precipitated by drug–drug interactions with CYP3A4 inhibitors. The other cases involved suicidal attempt (2 cases) and pediatric unsupervised ingestion (1 case). Ten patients (83%) had signs of peripheral vascular insufficiency. Five of these patients initially had factitiously low or unmeasurable blood pressure using non-invasive technique and had paradoxical increase following intravenous vasodilator administration. Two patients required partial foot amputations due to gangrene. Two patients, including a 15-month-old boy with an unsupervised ingestion, died. Discussion. In this series, most cases of severe ergotism were associated with interaction with CYP3A4 inhibitors, which increase ergotamine bioavailability. Factitious low blood pressure in these cases was likely caused by severe vasospasm. Conclusion. Critical ergotism continues to occur in Thailand, most commonly associated with the drug–drug interactions.     

Multiple variants in UGT1A1 gene are factors to develop indirect hyper-bilirubinemia

Most Taiwanese patients with hyper-bilirubinemia have genetic abnormalities in the uridine diphosphoglucuronate-glucuronosyltransferase 1A1 (UGT1A1) gene beyond the variants in the TATA box upstream of UGT1A1 associated with Gilbert’s syndrome. To investigate the role of UGT1A1 in the pathogenesis of indirect hyper-bilirubinemia, we prospectively studied 97 consecutive patients with indirect hyper-bilirubinemia for genotypes of promoter [(TA)₆TAA6, (TA)₇TAA7] and coding region [nucleotide (nt)-211, nt-686, nt-1,091 and nt-1,456] of UGT1A1. Thirty-six of the patients (45.6%) were found to have Gilbert’s syndrome with 7/7 genotype; among them, 14 also carried variants at nt-686. Forty-two patients (43.3%) had the 6/7 genotype; among them, 36 patients were found to have one or more variants in the coding region. Patients with higher serum total bilirubin are associated with higher likelihood of carrying Gilbert’s syndrome genotype: 60.0% (P=0.007) patients with serum total bilirubin level ≥2.5 mg/dL carried the Gilbert’s syndrome genotype, while only 23.9% of patients with serum total bilirubin level <2.5 mg/dL carry the same genotype (P=0.0006). Forty-one of the 61 non-Gilbert’s patients had one homogenous variants or two or more heterozygous variants in UGT1A1. Further studies are necessary to confirm the role of one homo-zygous variant or two or more hetero-zygous variants in UGT1A1 gene as factors for indirect hyper-bilirubinemia.     

Nesfatin‐1: a novel inhibitory regulator of food intake and body weight

The protein nucleobindin 2 (NUCB2) or NEFA (DNA binding/EF‐hand/acidic amino acid rich region) was identified over a decade ago and implicated in intracellular processes. New developments came with the report that post‐translational processing of hypothalamic NUCB2 may result in nesfatin‐1, nesfatin‐2 and nesfatin‐3 and convergent studies showing that nesfatin‐1 and full length NUCB2 injected in the brain potently inhibit the dark phase food intake in rodents including leptin receptor deficient Zucker rats. Nesfatin‐1 also reduces body weight gain, suggesting a role as a new anorexigenic factor and modulator of energy balance. In light of the obesity epidemic and its associated diseases, underlying new mechanisms regulating food intake may be promising targets in the drug treatment of obese patients particularly as the vast majority of them display reduced leptin sensitivity or leptin resistance while nesfatin‐1's mechanism of action is leptin independent. Although much progress on the localization of NUCB2/nesfatin‐1 in the brain and periphery as well as on the understanding of nesfatin‐1's anorexic effect have been achieved during the past three years, several important mechanisms have yet to be unraveled such as the identification of the nesfatin‐1 receptor and the regulation of NUCB2 processing and nesfatin‐1 release.     

Assessment of intracellular cytokines and regulatory cells in patients with autoimmune diseases and primary immunodeficiencies — Novel tool for diagnostics and patient follow-up

Serum and intracytoplasmic cytokines are mandatory in host defense against microbes, but also play a pivotal role in the pathogenesis of autoimmune diseases by initiating and perpetuating various cellular and humoral autoimmune processes.     

阿维A在银屑病中的应用

银屑病是皮肤科常见病、多发病,目前认为是在多基因遗传背景下由炎症细胞和炎症介质共同介导的一种慢性炎症性皮肤病。本病治疗困难,容易复发,美国FDA将阿维A作为其一线治疗药物。因其发病率的增高和阿维A应用的不断普及,本文对阿维A在银屑病中的应用剂量、疗程、适应症、不良反应等做一简单综述。     

Comparative effect of ochratoxin A on inflammation and oxidative stress parameters in gut and kidney of piglets

Ochratoxin A (OTA) is a secondary metabolite produced by fungi of Aspergillus and Penicillium genra. OTA is mainly nephrotoxic but can also cause hepatotoxicity, mutagenicity, teratogenicity, neurotoxicity and immunotoxicity. As recent studies have highlighted the close relationship between gastrointestinal tract and kidney, as principal organs involved in absorption and respective excretion of xenobiotics, the aim of the present study was to analyze the effect of a subchronic exposure (30 days) to 0.05 mg/kg OTA on immune response and oxidative stress parameters at the level of intestine and kidney of young swine. The experiment was realised on twelve crossbred weaned piglets randomly allotted to both control group or toxin group fed 0.050 mg OTA/kg feed. Our results have shown that a subchronic intoxication with a low dose of OTA for 30 days affected the immune response and the anti-oxidant self-defense at gut and kidney level. The gene expression of both markers of signaling pathways involved in inflammation and inflammatory cytokines were affected in a much higher extent in the gut than in the kidney Of OTA intoxicated piglets.     

Blood glucose monitoring (BGM) still matters for many: Associations of BGM frequency and glycemic control in youth with type 1 diabetes

AimsThis study aimed to compare three approaches of blood glucose monitoring (BGM) frequency attainment and to examine their associations with glycemic control in youth with type 1 diabetes (T1D).MethodsCross-sectional data was derived from the baseline assessment in three clinical trials. Clinical and demographic characteristics of youth with T1D was obtained by chart review. BGM frequency was assessed by parent-youth interview, chart review, and meter downloads. To examine the relationship between A1c and frequency of BGM we performed analysis of variance.ResultsIn youth with T1D (N = 385, 50% female, age 13.6 ± 2.5 years, 74% pump users), the 3 methods of assessing BGM frequency were significantly correlated. Frequency by self-report (6.4 ± 2.3 times/day) was significantly higher than both meter download (5.6 ± 2.4 times/day, p < 0.0001) and clinician report (5.7 ± 2.4 times/day, p < 0.0001). For all methods, more frequent BGM was associated with lower A1c and lower mean glucose (p < 0.0001). For each additional daily blood glucose check, there was a 0.2% decrease in A1c (p < 0.0001).ConclusionBGM remains a potent predictor of glycemic control, warranting continued targeting in clinical efforts to improve glycemic management in youth with T1D.     

Human Cytochrome P450 Family 4 Enzymes: Function,Genetic Variation and Regulation

The microsomal cytochrome P450 (CYP) family 4 monooxygenases are the major fatty acid ω-hydroxylases. These enzymes remove excess free fatty acids to prevent lipotoxicity, catabolize leukotrienes and prostanoids, and also produce bioactive metabolites from arachidonic acid ω-hydroxylation. In addition to endogenous substrates, recent evidence indicates that CYP4 monooxygenases can also metabolize xenobiotics, including therapeutic drugs. This review focuses on human CYP4 enzymes and updates current knowledge concerning catalytic activity profiles, genetic variation and regulation of expression. Comparative differences between the human and rodent CYP4 enzymes regarding catalytic function and conditional expression are also discussed.     

Recent advances with a virosomal hepatitis A vaccine

Background: Epaxal^®, a virosomal vaccine against hepatitis A virus (HAV) infection, has been in use for nearly 15 years, especially among at-risk adults. Recent studies have shown that it is also a potent vaccine for children. Objective: To summarise recent advances of Epaxal^® Junior (0.25 ml, paediatric formulation). Methods: Published papers reporting results on the virosomal HAV vaccine were abstracted and reviewed. Results/conclusion: In a comparative randomised trial, the paediatric dose was found to be highly immunogenic and non-inferior to the standard dose with respect to seroprotection rates. The concomitant administration of virosomal HAV vaccine with routine childhood vaccines was investigated in another trial. The virosomal HAV vaccine did not interact with the antibody response of routine childhood vaccines which in turn did not reduce the antibody response to HAV. In countries that recommend immunisation against hepatitis A, this virosomal vaccine is an excellent candidate with few side effects at the site of injection.