Effects of glycerol on the thermal dependence of the stability of human erythrocytes

Incubation of human blood in saline solution of 0–36% (v/v) ethanol for 30 min produces lysis or stabilization of erythrocytes depending on the ethanol concentration. Under less elevated concentrations of ethanol, erythrocytes are present in expanded shapes (R state) that present lower stability and suffer lysis with increase in the ethanol concentration. Under more elevated concentrations of ethanol, erythrocytes are present in contracted shapes (T state) that have higher stability and suffer lysis at even more elevated ethanol concentrations. This work evaluated the effects of glycerol (0 to 2.0 M) and temperature (7 to 47°C) on the stability of the R erythrocytes, characterized by the ethanol concentration at the mid-transition point (D _50R ) of the hemolysis curve (D _50R ). D _50R declined sigmoidally with increase in the glycerol concentration or temperature, due to transition of the R to the T state erythrocytes. In 1.5 M glycerol, the erythrocytes stability decreased below 32 but increased above 37°C. The combination of temperature, glycerol and ethanol actions generates a critical value of osmotic pressure below which the R state predominates and above which the T state predominates. At 7°C 1.5 M glycerol decreased the erythrocytes stability against ethanol but increased the erythrocytes stability against hypotonic shock. Those conditions favor the R state, which has a lower stability against ethanol; however, in the absence of ethanol, glycerol determines less water entrance in the erythrocytes, making more difficult its lysis by hypotonicity.     

Coenzyme Q10 and statins: Biochemical and clinical implications

Statins are drugs of known and undisputed efficacy in the treatment of hypercholesterolemia, usually well tolerated by most patients. In some cases treatment with statins produces skeletal muscle complaints, and/or mild serum CK elevation; the incidence of rhabdomyolysis is very low. As a result of the common biosynthetic pathway Coenzyme Q (ubiquinone) and dolichol levels are also affected, to a certain degree, by the treatment with these HMG-CoA reductase inhibitors. Plasma levels of CoQ₁₀ are lowered in the course of statin treatment. This could be related to the fact that statins lower plasma LDL levels, and CoQ₁₀ is mainly transported by LDL, but a decrease is also found in platelets and in lymphocytes of statin treated patients, therefore it could truly depend on inhibition of CoQ₁₀ synthesis. There are also some indications that statin treatment affects muscle ubiquinone levels, although it is not yet clear to which extent this depends on some effect on mitochondrial biogenesis. Some papers indicate that CoQ₁₀ depletion during statin therapy might be associated with subclinical cardiomyopathy and this situation is reversed upon CoQ₁₀ treatment. We can reasonably hypothesize that in some conditions where other CoQ₁₀ depleting situations exist treatment with statins may seriously impair plasma and possible tissue levels of coenzyme Q₁₀. While waiting for a large scale clinical trial where patients treated with statins are also monitored for their CoQ₁₀ status, with a group also being given CoQ₁₀, physicians should be aware of this drug-nutrient interaction and be vigilant to the possibility that statin drugs may, in some cases, impair skeletal muscle and myocardial bioenergetics.     

Long-term statin therapy affects the severity of chronic gastritis

Background: Helicobacter pylori (H. pylori) is a major cause of chronic gastritis. Statins have several pleotropic effects and their mechanisms of action could be related to anti‐inflammatory, antioxidants, and immunomodulatory effects. Aim: To determine whether statin therapy affects the severity of chronic gastritis. Materials and Methods: In a retrospective study, we evaluated 516 patients who underwent upper endoscopy. One‐hundred and ninety‐eight patients had chronic gastritis, The 198 patients with chronic gastritis were divided into two groups: group 1 comprised patients with a history of statin therapy and group 2 comprised patients with no history of statin therapy. Both groups were compared for age, gender, body mass index (BMI), underlying diseases, drug therapy, alcohol consumption, smoking and the serum levels of C‐reactive protein (CRP). The presence of H. pylori was determined by gastric biopsy and rapid urease test. The grade and severity of gastritis were assessed using the updated Sydney classification system in two gastric biopsy specimens that were taken from each participant in each group. Results: Of the 198 patients with chronic gastritis, 49% of the patients had mild gastritis and 51% had moderate to severe gastritis. From the results of a multiple logistic regression analysis after adjusting for confounding variables that included age, gender, and BMI, we found that elevated serum CRP levels (odds ratio (OR) 2.33; 95% confidence interval (CI) = 0.8–2.6, p = .02), H. pylori (OR 1.99; CI 0.14–2.4, p = .04), and the use of statin (OR 1.64; CI = 0.71–1.77, p = .05) independently predict the severity of chronic gastritis. Conclusion: Long‐standing statin therapy may reduce the severity of chronic gastritis. Mild increased CRP levels in absence of obvious source can predict the severity of chronic gastritis. Further researches are needed to assess the effect of statin in chronic gastritis.     

Phlorotannins as Radical Scavengers from the Extract of Sargassum ringgoldianum

To screen algal phlorotannins with antioxidative activities, 50% ethanol extracts of 25 Japanese marine algae were evaluated. Scavenging activity against superoxide anion radicals was frequently found with a high content of total phenolic compounds. Among these, the extract from the brown seaweed, Sargassum ringgoldianum, showed the strongest scavenging activity. The active fraction contained a mixture of high molecular weight polyphenols, phlorotannins that were found to be polymerized bifuhalol, as analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The scavenging activity of the fraction against superoxide anion radicals was estimated to be 1.0 μg/ml (IC₅₀), which were approximately five times stronger than that of catechin.     

Use of Fibrates Monotherapy in People with Diabetes and High Cardiovascular Risk in Primary Care: A French Nationwide Cohort Study Based on National Administrative Databases

Background and Aim

According to guidelines, diabetic patients with high cardiovascular risk should receive a statin. Despite this consensus, fibrate monotherapy is commonly used in this population. We assessed the frequency and clinical consequences of the use of fibrates for primary prevention in patients with diabetes and high cardiovascular risk.

Design

Retrospective cohort study based on nationwide data from the medical and administrative databases of French national health insurance systems (07/01/08-12/31/09) with a follow-up of up to 30 months.

Methods

Lipid-lowering drug-naive diabetic patients initiating fibrate or statin monotherapy were identified. Patients at high cardiovascular risk were then selected: patients with a diagnosis of diabetes and hypertension, and >50 (men) or 60 (women), but with no history of cardiovascular events. The composite endpoint comprised myocardial infarction, stroke, amputation, or death.

Results

Of the 31,652 patients enrolled, 4,058 (12.8%) received a fibrate. Age- and gender-adjusted annual event rates were 2.42% (fibrates) and 2.21% (statins). The proportionality assumption required for the Cox model was not met for the fibrate/statin variable. A multivariate model including all predictors was therefore calculated by dividing data into two time periods, allowing Hazard Ratios to be calculated before (HR_<540) and after 540 days (HR_>540) of follow-up. Multivariate analyses showed that fibrates were associated with an increased risk for the endpoint after 540 days: HR_<540 = 0.95 (95% CI: 0.78–1.16) and HR_>540 = 1.73 (1.28–2.32).

Conclusion

Fibrate monotherapy is commonly prescribed in diabetic patients with high cardiovascular risk and is associated with poorer outcomes compared to statin therapy.     

地屈孕酮联合口服黄体酮胶丸对黄体功能不全先兆流产患者血清抑制素A、性激素的影响

摘要 目的：探讨地屈孕酮联合口服黄体酮胶丸对黄体功能不全先兆流产患者血清抑制素A、性激素的影响。方法：选择2018年9月到2020年9月在我院接受治疗的125例黄体功能不全先兆流产患者,采用随机数表法分为试验组（n=63）和对照组（n=62）。对照组给予黄体酮胶丸治疗,试验组在对照组的基础上给予地屈孕酮治疗。比较两组临床疗效、抑制素A、雌二醇（E₂）、孕酮（P）、人绒毛膜促性腺激素（HCG）、临床症状改善情况、妊娠结局及不良反应发生情况。结果：治疗后,两组总有效率比较差异显著（P<0.05）;治疗前,试验组和对照组血清抑制素A、E2、P、HCG比较无显著差异;治疗后试验组和对照组血清抑制素A、E₂、P、HCG随着时间的推移而升高,且试验组均高于对照组,差异显著（P<0.05）;试验组止血时间、腹痛改善时间及腰痛改善时间均显著低于对照组,差异显著（P<0.05）;试验组保胎成功率、新生儿体质量及新生儿Apgar评分均显著高于对照组,差异显著（P<0.05）;两组不良反应总发生率分别为7.94%、9.68%（P>0.05）。结论：在黄体功能不全先兆流产患者中应用地屈孕酮联合口服黄体酮胶丸效果显著,可能与其可有效改善血清抑制素A、性激素水平有关,且不增加不良反应。     

Statin Use Is Not Associated with Improved Progression Free Survival in Cetuximab Treated KRAS Mutant Metastatic Colorectal Cancer Patients: Results from the CAIRO2 Study

Statins may inhibit the expression of the mutant KRAS phenotype by preventing the prenylation and thus the activation of the KRAS protein. This study was aimed at retrospectively evaluating the effect of statin use on outcome in KRAS mutant metastatic colorectal cancer patients (mCRC) treated with cetuximab. Treatment data were obtained from patients who were treated with capecitabine, oxaliplatin bevacizumab ± cetuximab in the phase III CAIRO2 study. A total of 529 patients were included in this study, of whom 78 patients were on statin therapy. In patients with a KRAS wild type tumor (n = 321) the median PFS was 10.3 vs. 11.4 months for non-users compared to statin users and in patients with a KRAS mutant tumor (n = 208) this was 7.6 vs. 6.2 months, respectively. The hazard ratio (HR) for PFS for statin users was 1.12 (95% confidence interval 0.78–1.61) and was not influenced by treatment arm, KRAS mutation status or the KRAS*statin interaction. Statin use adjusted for covariates was not associated with increased PFS (HR = 1.01, 95% confidence interval 0.71–1.54). In patients with a KRAS wild type tumor the median OS for non-users compared to statin users was 22.4 vs. 19.8 months and in the KRAS mutant tumor group the OS was 18.1 vs. 14.5 months. OS was significantly shorter in statin users versus non-users (HR = 1.54; 95% confidence interval 1.06–2.22). However, statin use, adjusted for covariates was not associated with increased OS (HR = 1.41, 95% confidence interval 0.95–2.10). In conclusion, the use of statins at time of diagnosis was not associated with an improved PFS in KRAS mutant mCRC patients treated with chemotherapy and bevacizumab plus cetuximab.     

Preoperative statin therapy and infectious complications in cardiac surgery

AimTo assess whether preoperative statin therapy is associated with the risk of postoperative infection in patients undergoing cardiac surgery.Methods520 patients undergoing cardiac surgery in 2010 were retrospectively examined. Data regarding statin and antibiotic use prior to and after surgery were available from the hospital pharmacy information system. Cultures and clinical data of patients on postoperative antibiotics other than standard prophylactic therapy were studied to identify postoperative infections up to 30 days from day of surgery.Results370 (71.2 %) patients were on preoperative statin therapy. Overall, 82 patients (15.8 %) suffered from postoperative infection of which 11 were surgical site infections. In multivariable regression analysis, statin therapy was associated with a reduced risk of postoperative infection (adjusted odds ratio: 0.329, 95 %: CI 0.19–0.57; P < 0.001).ConclusionsPreoperative statin use was associated with a considerable reduced risk of postoperative infections following cardiac surgery. Randomised controlled trials are required to clarify the role of statin therapy in the prevention of postoperative infections.     

Phytochemical Fingerprints and Bioactivities of Ripe Disseminules (Fruit-Seeds) of Seventeen Gundelia (Kenger-Kereng Dikeni) Species from Anatolia with Chemometric Approach

Gundelia species are known as “Kenger-kereng dikeni” in Anatolia, and their aerial parts are consumed as food. Also, roots and seeds (disseminules) of the Gundelia species are used to prepare gum and coffee. The chemical contents of ethanol and hexane extracts of disseminules of 17 Gundelia species, 13 of them are endemic, were studied using LC/MS/MS and GC/MS. Additionally, their antioxidant potential and enzyme inhibitory capacity against acetyl- and butyryl-cholinesterase, urease, and tyrosinase were determined. The unsaturated fatty acid ratios of Gundelia species were higher than their saturated fatty acid ratio. The highest sum of oleic and linoleic acid was detected in G. tournefortii var. tenuisecta (70.42 %). β-Sitosterol, α-amyrin, 3-acetyllupeol were identified in 17 Gundelia species by GC/MS, while chlorogenic acid and luteolin by LC/MS/MS as major compounds. The ethanol and hexane extracts of G. siirtica, G. rosea, and G. mesopotamica indicated good cholinesterase inhibitory activity. Among all species, ethanol extract of G. colemerikensis exhibited the best activity in ABTS (IC₅₀: 32.30±0.98 μg/mL), DPPH (IC₅₀: 59.91±0.89 μg/mL), and CUPRAC (A_0.5: 57.41±1.03 μg/mL) assays. Ethanol extract of G. colemerikensis also displayed the highest inhibitory activity against butyrylcholinesterase (51.14±0.25 % at 200 μg/mL), urease (51.71±1.75 % at 200 μg/mL), and tyrosinase (39.50±0.85 % at 200 μg/mL) enzymes. According to the chemometric analysis of fatty acids, four groups were observed. Therefore, it is suggested that G. colemerikensis can be used in the pharmaceutical, food, and cosmetic industries due to its antioxidant and enzyme inhibition properties.     

Osteogenesis and osteoclast inhibition in rheumatoid arthritis patients treated with bisphosphonates alone or in combination with pitavastatin over an 18-month follow-up after more than 4 years of treatment with bisphosphonates

Introduction

To investigate the effects of bisphosphonates (Bis) (etidronate, alendronate, and risedronate), alone and in combination with statin, on the BMD (bone mineral density) and bone metabolism of rheumatoid arthritis (RA) patients.

Methods

Seventy-seven RA patients who had been receiving prednisolone (PSL) and Bis for over 4 years were divided into two groups: Bis and Bis + statin (n = 42 and 35; average age, 66.4 and 65.3 years; average disease duration, 24.9 and 20.8 years; average PSL dose, 2.4 and 2.7 mg, respectively). Serum levels of NTX (N-terminal telopeptide of type I collagen), TRACP-5b (tartrate-resistant acid phosphate-5b), PICP (C-terminal propeptide of type I procollagen), and RANKL (receptor activator of NF-κB ligand) were measured over an 18-month period of treatment and follow-up. The BMD levels of the two groups at the radius, lumbar spine, and femoral neck were compared using DXA (dual-energy x-ray absorptiometry).

Results

A significant increase was only observed in the BMD of the lumbar spine at 18-months, but the BMDs of the radius and femoral neck decreased during the follow-up period in the Bis group. Meanwhile, a significant increase was observed in the BMD of the lumbar spine in the Bis + statin group during administration and the BMDs of the radius and femoral neck stayed at baseline. Among the markers of bone metabolism, serum NTX was up-regulated after 6 months in the Bis + statin group. Serum TRACP-5b was significantly increased during the follow-up period in the Bis + statin group, but only at 18 months in the Bis group. Serum PICP recovered to base line in the Bis + statin group, whereas that in the Bis group did not observably recover during the post-administration follow-up, but rather decreased.

Conclusion

Our findings suggest that both bone resorption and bone formation were inhibited by long-term administration of Bis alone, whereas combination therapy with Bis + statin may be associated with a less marked inhibition of bone metabolism. Cardiovascular disease is highly prevalent in RA patients and some patients are prescribed statins and bisphosphonate. Bis + statin may confer more benefit to the bone metabolism of these patients compared to Bis alone.     

Novel Angiotensin I-Converting Enzyme Inhibitory Peptides Found in a Thermolysin-Treated Elastin with Antihypertensive Activity

Angiotensin I-converting enzyme (ACE) inhibitory activity was generated from elastin and collagen by hydrolyzing with thermolysin. The IC₅₀ value of 531.6 µg/mL for ACE inhibition by the elastin hydrolysate was five times less than 2885.1 µg/mL by the collagen hydrolysate. We confirmed the antihypertensive activity of the elastin hydrolysate in vivo by feeding spontaneously hypertensive rats (male) on a diet containing 1% of the elastin hydrolysate for 9 weeks. About 4 week later, the systolic blood pressure of the rats in the elastin hydrolysate group had become significantly lower than that of the control group. We identified novel ACE inhibitory peptides, VGHyp, VVPG and VYPGG, in the elastin hydrolysate by using a protein sequencer and quadrupole linear ion trap (QIT)-LC/MS/MS. VYPGG had the highest IC₅₀ value of 244 µM against ACE and may have potential use as a functional food.     

Effects of Statin Therapy on Clinical Outcomes of Survivors of Acute Myocardial Infarction with Severe Systolic Heart Failure

Objective

Large randomized trials have failed to show a beneficial effect of statin treatment in chronic HF. The investigators tried to evaluate the long-term effects of statin therapy in patients with new onset heart failure (HF) following acute myocardial infarction (AMI).

Methods

Between January 2008 and December 2011, a total of 13,616 AMI patients were enrolled in the Korea Acute Myocardial Infarction Registry (KAMIR) which was a prospective, multi-center, nationwide, web-based database of AMI in Korea. From this database, we studied 1,055 patients with AMI who had newly developed severe acute HF [left ventricular ejection fraction ≤ 40%] and were discharged alive. The patients were divided into two groups, a statin group (n = 756) and a no-statin group (n = 299). We investigated the one-year major adverse cardiovascular events (MACEs), including all-cause mortality, MI, and any revascularization of each group. We then performed a propensity-score matched analysis.

Results

In the original cohort, one-year MACEs were similar between the two groups (16.5% vs. 14.7% in the statin or no-statin groups; p = 0.47). Propensity-score matching yielded 256 pairs, and in that population we observed comparable results in terms of MACEs (18.0% vs. 12.5% in the statin or no-statin groups, p = 0.11) and mortality (5.1% vs. 3.5% in the statin or no-statin groups, p = 0.51). Cox-regression analysis revealed that statin therapy was not an independent predictor for occurrence of a MACE [Hazard ratio (HR) 1.11, 95% CI 0.79–1.57, p = 0.54] or all-cause mortality (HR 1.42, 95% CI 0.75–2.70, p = 0.28).

Conclusion

Statin therapy was not associated with a reduction in the long-term occurrence of MACEs or mortality in survivors of AMI with severe acute HF in this retrospective cohort study.     

Preparation and Evaluation of Dermal Delivery System of Griseofulvin Containing Vitamin E-TPGS as Penetration Enhancer

Griseofulvin, an antifungal agent, is a BCS class II drug slowly, erratically, and incompletely absorbed from the gastrointestinal tract in humans. The clinical failure of the conventional oral therapy of griseofulvin is most likely attributed to its poor solubility and appreciable inter- and intra-subject variation in bioavailability from different commercial products. Moreover, the conventional oral therapy is associated with numerous adverse effects and interactions with other drugs. The purpose of the study was to formulate a topical application of griseofulvin which would deliver the drug locally in a therapeutically effective concentration. Griseofulvin was solubilized in ethanol, d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), and combinations of ethanol with varying amounts of TPGS; then, it was incorporated in the Carbopol (980 NF) base. The formulations were characterized and evaluated ex vivo using Laca mice skin, microbiologically against Microsporum gypseum and Microsporum canis and clinically in a small group of patients. The current study suggested that TPGS and ethanol synergistically enhanced the drug permeation and drug retention in the skin. The selected formulation F VII was found to be effective against M. gypseum and M. canis, non-sensitizing, histopathologically safe, stable at 4°C, 25°C, and 40°C with respect to percent drug content, permeation characteristics, pH, transparency, feel, viscosity, and clinically effective in a small group of subjects. The proposed topical formulation of griseofulvin may be an effective and convenient alternative to the currently available oral therapy for the treatment of superficial fungal infections.     

Comparative analysis of the gut microbiota in distinct statin response patients in East China

Statin response shows great interindividual variations. Recently, emerging studies have shown that gut microbiota is linked to therapeutic responses to drugs, including statins. However, the association between the gut bacteria composition and statin response is still unclear. In this study, gut microbiota of 202 hyperlipidemic patients with statin sensitive (SS) response and statin resistant (SR) response in East China were investigated by high throughput sequencing to compare the gut bacteria composition and biodiversity in distinct statin response patients. Higher biodiversity was detected in Group SS than Group SR. Specifically, group SS showed significantly increased proportion of genera Lactobacillus (P = 0.001), Eubacterium (P = 0.004), Faecalibacterium (P = 0.005), and Bifidobacterium (P = 0.002) and decreased proportion of genus Clostridium (P = 0.001) compared to Group SR. The results indicated that higher gut biodiversity was associated with statin sensitive response. The increased genera Lactobacillus, Eubacterium, Faecalibacterium, Bifidobacterium, and decreased genus Clostridium in patient gut microbiota may predict patient's statin response, and hence may guide statin dosage adjustments.     

Disentangling the Association between Statins,Cholesterol, and Colorectal Cancer: A Nested Case-Control Study

BackgroundSeveral prior studies have found an association between statin use and reduced risk of colorectal cancer. We hypothesized that these findings may be due to systematic bias and examined the independent association of colorectal cancer risk with statin use, serum cholesterol, and change in cholesterol concentration.ConclusionsAlthough the risk of colorectal cancer was lower in statin users versus nonusers, no difference was observed among those who continued versus discontinued statin therapy, suggesting the potential for indication bias. The association between decreased serum cholesterol and colorectal cancer risk suggests a cholesterol-lowering effect of undiagnosed malignancy. Clinical judgment should be used when considering causes of cholesterol reduction in patients, including those on statin therapy.     

Chemodiversity and Antiproliferative Activity of the Essential Oil of Schinus molle Growing in Jordan

The leaves and unripe and fully‐grown fruits of Schinus molle were collected from three geographical regions of Jordan: Amman (the Mediterranean), Madaba (Irano‐Turanean), and Sahab (Saharo‐Arabian). The hydrodistilled volatile oils of fresh and dried leaves and fruits were analyzed by gas chromatography‐mass spectrometry (GC/MS). The actual composition of the emitted volatiles was determined using Solid Phase Micro‐Extraction (SPME). α‐ and β‐Phellandrenes were the major components in all the analyzed samples. Quantitative differences were observed in the obtained essential oils (0.62–5.25 %). Additionally, cluster analysis was performed. Biologically, the antiproliferative activity of the essential oil, ethanol, and water extracts of the fruits and leaves was screened on Caco2, HCT116, MCF7, and T47D cell lines. The essential oil and ethanol extracts exhibited a dose‐dependent inhibition of cell growth with IC₅₀ ranging between 21 and 65 μg/mL. The water extract did not exhibit any antiproliferative activity against the investigated cell lines.     

Development of an LC/MS/MS Method for Simultaneous Detection of 11 Polyphenols in Rat Plasma and Its Pharmacokinetic Application after Oral Administration of Coreopsis tinctoria Extract

Eleven polyphenols, classified as flavonoid glycosides, flavonoid aglycones, and phenolic acids, are important bioactive components in the capitula of Coreopsis tinctoria (CCT). Nevertheless, their full pharmacokinetic profiles have not been demonstrated simultaneously. Therefore, a liquid chromatography – tandem mass spectrometry (LC/MS/MS) method was developed in the present work and used it to study the pharmacokinetics of these 11 compounds. We performed LC/MS/MS with a gradient mobile phase composed of water containing 0.1 % formic acid and acetonitrile containing 0.1 % formic acid on a Proshell 120 SB C18 column (2.1 mm×100 mm, 2.7 μm). We achieved a good chromatographic peak shape, resolution, and mass signal response, and multiple reaction monitoring facilitated the simultaneous detection of 11 analytes. In addition, we validated the selectivity, correlation coefficient, precision, extraction recovery, matrix effects, and stability of the LC/MS/MS method to be acceptable for 11 analytes in rat plasma. Subsequently, rats were orally administered with 50 % ethanol eluent of CCT (ECCT). Nine of 11 polyphenols were absorbed quickly (except for QCD and TCA), and their plasma levels peaked within 40 min. The exposure and C_max values of flavonoid glycosides and phenolic acids were lower than those of flavonoid aglycones. This is the first report to demonstrate the pharmacokinetics of 11 polyphenols in ECCT, which may play an important role in future studies of the bioactive components of ECCT and their bioactive mechanisms.     

Metabolite Profiling by Hyphenated Liquid Chromatographic Mass Spectrometric Technique (HPLC‐DAD‐ESI‐Q‐TOF‐MS/MS) and Neurobiological Potential of Haplophyllum sahinii and H. vulcanicum Extracts

In the current study, the ethanol extracts of flower, stem, and root parts of two endemic Turkish species, e. g., Haplophyllum sahinii O. Tugay & D. Uluku? and H. vulcanicum Boiss . & Heldr ., were screened against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) associated with Alzheimer's disease as well as tyrosinase (TYR) linked to Parkinson's disease using ELISA microplate assay at 200 μg/mL. Among the extracts, the highest inhibition was caused by the stem extract of H. sahinii against BChE (IC₅₀=64.93±1.38 μg/mL). Consistently, all of the extracts were found to exert a selective inhibition towards BChE to some extent. It was only the root extract of H. vulcanicum that could inhibit AChE at low level (IC₅₀=203.18±5.33 μg/mL). None of the extracts displayed an inhibition over 50 % against TYR. Metabolite profiling of the extracts was achieved by a highly hyphenated liquid chromatographic mass spectrometric technique (HPLC‐DAD‐ESI‐Q‐TOF‐MS/MS), which revealed the presence of furoquinoline (β‐fagarine, γ‐fagarine) and amide (tubasenicine, tubacetine) alkaloids; furano‐ (rutamarin), pyrano‐ (xanthyletine), and geranyloxy coumarins; phenylpropanoid (secoisolariciresinol), arylnaphthalene (mono‐O‐acetyldiphyllin apioside), and dibenzylbutyrolactone (kusunokinin, haplomyrfolin) lignans. Several important differences were observed between the extracts analyzed. β‐Fagarine was the major alkaloid in H. vulcanicum, whereas γ‐fagarine was present only in the roots of both Haplophyllum species; moreover, secoisolariciresinol and secoisolariciresinol dimethyl ether were the main lignans in the stems and flowers. This is the first study identifying ChE and TYR inhibitory effect and metabolic profiles of H. vulcanicum and H. sahinii.     

Previous Exposure to Statin May Reduce the Risk of Subsequent Non-Hodgkin Lymphoma: A Nationwide Population-Based Case-Control Study

Background

The purpose of this study was to investigate the association between previous exposure to statins and the risk of non-Hodgkin lymphoma (NHL).

Methods

This nationwide population-based case–control study was conducted using the National Health Insurance Research Database of Taiwan. The NHL group consisted of the patients with a first-time diagnosis of NHL between 2005 and 2008. The cases of the control group were pair-matched to the NHL group according to sex, year of birth and date of NHL diagnosis (index date). The statin administration data from both groups were retrospectively collected from the index date to January 1, 1996. The cumulative defined daily dose (cDDD) was estimated to evaluate the statin exposure. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariate logistic regression.

Results

The study population was composed of 1715 NHL patients and 16942 control subjects. The analysis revealed that previous statin administration was associated with a reduced risk of subsequent NHL with an adjusted OR of 0.52 (95% CI, 0.43–0.62). Additionally, there was a dose-response relationship between statin administration and the risk of NHL. The adjusted ORs were 0.63 (95% CI, 0.46–0.86), 0.58 (95% CI, 0.42–0.79), 0.51 (95% CI, 0.38–0.67), and 0.36 (95% CI, 0.24–0.53) for the subjects with statin administrations of fewer than 28, 28 to 90, 91 to 365, and more than 365 cDDDs, respectively, relative to the subjects without any statin administration.

Conclusions

The results of this study suggest that previous statin administration is associated with a lower risk of subsequent NHL. As statins are widely used medications, the magnitude of the risk reduction may have a substantial influence on public health. Further studies to confirm our findings are warranted.