Vicenin 2 isolated from Artemisia capillaris exhibited potent anti-glycation properties

Vicenin 2, isolated from a traditionally used medicinal plant Artemisia capillaris, is a 6,8-di-C-glucoside of apigenin which has been previously reported to possess a wide variety of pharmacological activities including antioxidant, anti-inflammatory, anti-cancer, and hepatoprotective. However, there have not been any reports concerning its anti-diabetic potential until now. Therefore, in the present study, we evaluated the anti-diabetic potential of vicenin 2 via α-glucosidase, protein tyrosine phosphatase 1B (PTP1B), rat lens aldose reductase (RLAR), and advanced glycation end products (AGE) formation inhibitory assays. Vicenin 2 strongly inhibited α-glucosidase, PTP1B, and RLAR in the corresponding assays. In addition, vicenin 2 inhibited the formation of both fluorescent AGE and nonfluorescent AGE, e.g., CML, as well as the level of fructosamine in glucose–fructose-induced bovine serum albumin (BSA) glycation. In the test system, vicenin 2 suppressed glycation-induced protein oxidation by attenuating the formation of protein carbonyl groups as well as by inhibiting the modification of protein thiol groups. Moreover, vicenin 2 was found to be a potent inhibitor of glycation-induced formation of amyloid cross-β structures in BSA. Taken together, vicenin 2 might be a useful lead for the development of multiple target-oriented therapeutic modalities for the treatment of diabetes and diabetes-associated complications.     

Statins can induce myasthenia gravis

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, are commonly prescribed for prevention of cardiovascular morbidity. A rare side effect of statin medication is the induction of autoimmune illnesses, including myasthenia gravis (myasthenia). Here we present two patients with seropositive myasthenia that developed 4 weeks after initiation of atorvastatin, increasing the total reported patients to seven. Reviewing recent literature we highlight the connections between statins, auto-immunity and myasthenia. Statins may favour T-cell phenotypes that reduce cell-mediated immunity but could increase antibody-mediated humoral immunity.     

Folate,folic acid and 5-methyltetrahydrofolate are not the same thing

Abstract

1.?Folate, an essential micronutrient, is a critical cofactor in one-carbon metabolism. Mammals cannot synthesize folate and depend on supplementation to maintain normal levels. Low folate status may be caused by low dietary intake, poor absorption of ingested folate and alteration of folate metabolism due to genetic defects or drug interactions.

2.?Folate deficiency has been linked with an increased risk of neural tube defects, cardiovascular disease, cancer and cognitive dysfunction. Most countries have established recommended intakes of folate through folic acid supplements or fortified foods. External supplementation of folate may occur as folic acid, folinic acid or 5-methyltetrahydrofolate (5-MTHF).

3.?Naturally occurring 5-MTHF has important advantages over synthetic folic acid – it is well absorbed even when gastrointestinal pH is altered and its bioavailability is not affected by metabolic defects. Using 5-MTHF instead of folic acid reduces the potential for masking haematological symptoms of vitamin B₁₂ deficiency, reduces interactions with drugs that inhibit dihydrofolate reductase and overcomes metabolic defects caused by methylenetetrahydrofolate reductase polymorphism. Use of 5-MTHF also prevents the potential negative effects of unconverted folic acid in the peripheral circulation.

4.?We review the evidence for the use of 5-MTHF in preventing folate deficiency.     

Persistence of atorvastatin and simvastatin among patients with and without prior cardiovascular diseases: a US managed care study

ABSTRACT

Background: In clinical practice, persistence with statin therapy is poor. While little is known about relative persistence to specific statins, previous studies have observed greater persistence in patients who achieve greater degrees of lipid lowering. Identification of statin therapies which improve patient persistence has the potential to improve the quality of patient care and clinical outcomes. Therefore, we assessed patient persistence with atorvastatin and simvastatin in primary and secondary prevention patients enrolled in managed care.

Methods: New statin users aged ≥18 years, both with and without prior cardiovascular (CV) events within the 12 month pre-treatment period, were identified from a large national database of managed care patients. Patients initiated atorvastatin or simvastatin therapy from January 1, 2003 to September 30, 2005 and were continuously enrolled in a covered plan for at least 12 months before and after initiation of statin therapy. Subanalyses of patients ≥65 years were also conducted. Measures of interest included demographic and clinical characteristics of the study samples and persistence of statin utilization over the 1-year follow-up period. Persistence was defined as the number of days a patient remained on treatment in the first year following their index date, measured from the date of first fill to study end or the date of discontinuation.

Results: A total of 129 764 atorvastatin users and 45 558 simvastatin users without prior CV events were included in the study. For those patients with prior CV events, a total of 6888 atorvastatin users and 4443 simvastatin users were included in the study. Median persistence in patients without prior CV events was 50 days longer for patients initiating therapy with atorvastatin than simvastatin (207 vs. 157 days, p < 0.0001) and after adjusting for confounding factors, those treated with atorvastatin were 15% less likely to discontinue therapy during the first year than those treated with simvastatin (HR = 0.85; 95% CI 0.84, 0.86; p < 0.001). In secondary prevention patients median persistence was 85 days longer in atorvastatin patients than simvastatin patients (266 vs. 181 days, p < 0.0001) and atorvastatin patients were 22% less likely to discontinue therapy (HR = 0.78; 95% CI 0.75, 0.82; p < 0.001). Persistence was worse in the elderly patients, but the relative difference between atorvastatin and simvastatin was similar to the overall patient population.

Conclusions: In patients with and without prior CV disease, persistence is generally poor, even worse in the elderly, but significantly better for atorvastatin patients than simvastatin patients (p < 0.001). Further studies are required to determine whether this is due to differences in cost, effectiveness, side-effects, or other attributes of the statins.

Study limitations: Differences in persistence could be, in part, due to unmeasured confounders although all available variables were adjusted in multivariate analyses. Additionally, the claims database lacks some clinical data such as lipid levels, limiting assessments of statin efficacy, and does not include any reasons for discontinuation of therapy.     

Hyperoxaluria and systemic oxalosis: current therapy and future directions

Excessive urinary oxalate excretion, termed hyperoxaluria, may arise from inherited or acquired diseases. The most severe forms are caused by increased endogenous production of oxalate related to one of several inborn errors of metabolism, termed primary hyperoxaluria. Recurrent kidney stones and progressive medullary nephrocalcinosis lead to the loss of kidney function, requiring dialysis or transplantation, accompanied by systemic oxalate deposition that is termed systemic oxalosis. For most primary hyperoxalurias, accurate diagnosis leads to the use of therapies that include pyridoxine supplementation, urinary crystallisation inhibitors, hydration with enteral fluids and, in the near future, probiotic supplementation or other innovative therapies. These therapies have varying degrees of success, and none represent a cure. Organ transplantation results in reduced patient and organ survival when compared with national statistics. Exciting new approaches under investigation include the restoration of defective enzymatic activity through the use of chemical chaperones and hepatocyte cell transplantation, or recombinant gene therapy for enzyme replacement. Such approaches give hope for a future therapeutic cure for primary hyperoxaluria that includes correction of the underlying genetic defect without exposure to the life-long dangers associated with organ transplantation.     

Chemoprevention of liver cancer by plant polyphenols

Primary liver cancer or hepatocellular carcinoma (HCC) is one of the most frequent tumors representing the fifth commonest malignancy worldwide and the third cause of mortality from cancer. Currently, the treatments for HCC are not so effective and new strategies are needed for its fight. Chemoprevention, the use of natural or synthetic chemical agents to reverse, suppress or prevent carcinogenesis is considered an important way for confronting HCC. Many of the chemopreventive agents are phytochemicals, namely non-nutritive plant chemicals with protective or disease preventive properties. In this review, we focus on plant polyphenols, one of the most important classes of phytochemicals, their chemopreventive properties against HCC and discuss the molecular mechanisms accounting for this activity.     

急性淋巴细胞白血病患儿MTHFR C677T基因多态性与大剂量甲氨蝶呤治疗后肝功能异常的相关性

目的：探讨急性淋巴细胞白血病（ALL）患儿亚甲基四氢叶酸还原酶（MTHFR）C677T基因多态性与大剂量甲氨蝶呤（HD-MTX）治疗后肝功能异常的相关性。方法：收集2017年10月至2020年3月温州医科大学附属第二医院育英儿童医院66例ALL患儿HD-MTX治疗的临床资料,检测MTHFR C677T的基因多态性,根据基因型将患儿分为野生型（CC）和突变型（CT+TT）,比较2组患儿经HD-MTX治疗后不良反应的发生率、肝功能指标PA、ALT、AST、AST/ALT、TP、ALB、LDH、GGT、TBIL、CHE以及48 h、72 h血药浓度的差异。结果：MTHFR C677T突变型与野生型相比肝功能异常的发生率更高（P＜0.05）,其中血清AST、ALT、CHE含量异常的患儿比例显著升高（P＜0.05）,其他肝功能指标差异无统计学意义（P＞0.05）。进一步分析不同基因型患儿HD-MTX血药浓度的差异,结果显示与野生型相比,突变型48 h、72 h血药浓度均升高（P＜0.05）。结论：MTHFR C677T突变型患儿HD-MTX治疗后,血清AST、ALT、CHE含量异常的患儿比例较高,检测MTHFR C677T基因型对预测HD-MTX治疗后肝功能异常有一定的临床应用价值。     

长期染砷致家兔肝脏蛋白巯基水平及巯基代谢相关酶活力下降

目的 探讨长期砷暴露对家兔肝脏蛋白巯基水平及与巯基代谢相关酶活力的影响及机制。方法 家兔以自由饮水方式慢性暴露于无机3价砷（iAs^Ⅲ）及5价砷（iAs^Ⅴ），18周后，测定肝脏组织中蛋白巯基、非蛋白巯基、硫氧还蛋白（TRX）水平，以及硫氧还蛋白还原酶（TR）、谷胱甘肽还原酶（GR）活性，同时检测血、尿及毛发中无机砷及其代谢产物甲基砷（MMAs）和二甲基砷（DMAs）。结果 经过18周的砷暴露，两个染毒组血和尿中iAs、MMAs、DMAs以及毛发中iAs、DMAs均显著高于对照组；iAs^Ⅴ组血中iAs、MMAs及尿中MMAs水平显著低于iAs^Ⅲ组，而尿及毛发中iAs水平显著高于iAs^Ⅲ组。iAs^Ⅴ组总巯基及蛋白巯基水平显著低于对照组。iAs^Ⅵ组TRX水平、TR及GR活力以及iAs^Ⅲ组TR活力与对照组相比亦显著下降。结论 家兔长期砷暴露导致肝脏中蛋白巯基水平及与巯基代谢密切相关的TR、GR活力显著下降，提示慢性无机砷暴露会引起肝脏内氧化及抗氧化失衡从而引发组织氧化损伤。