Toxicological aspects of trans fat consumption over two sequential generations of rats: Oxidative damage and preference for amphetamine

Chronic consumption of processed food causes structural changes in membrane phospholipids, affecting brain neurotransmission. Here we evaluated noxious influences of dietary fats over two generations of rats on amphetamine (AMPH)-conditioned place preference (CPP). Female rats received soybean oil (SO, rich in n-6 fatty acids (FA)), fish oil (FO, rich in n-3 FA) and hydrogenated vegetable fat (HVF, rich in trans fatty acids (TFA)) for two successive generations. Male pups from the 2nd generation were maintained on the same supplementation until 41 days of age, when they were conditioned with AMPH in CPP. While the FO group showed higher incorporation of n-3 polyunsaturated-FA (PUFA) in cortex/hippocampus, the HVF group showed TFA incorporation in these same brain areas. The SO and HVF groups showed AMPH-preference and anxiety-like symptoms during abstinence. Higher levels of protein carbonyl (PC) and lower levels of non-protein thiols (NPSH) were observed in cortex/hippocampus of the HVF group, indicating antioxidant defense system impairment. In contrast, the FO group showed no drug-preference and lower PC levels in cortex. Cortical PC was positively correlated with n-6/n-3 PUFA ratio, locomotion and anxiety-like behavior, and hippocampal PC was positively correlated with AMPH-preference, reinforcing connections between oxidative damage and AMPH-induced preference/abstinence behaviors. As brain incorporation of trans and n-6 PUFA modifies its physiological functions, it may facilitate drug addiction.     

Lipid membranes accelerate amyloid formation in the mouse model of AA amyloidosis

Introduction: AA amyloidosis develops as a result of prolonged inflammation and is characterized by deposits of N-terminal proteolytic fragments of the acute phase reactant serum amyloid A (SAA). Macrophages are usually found adjacent to amyloid, suggesting their involvement in the formation and/or degradation of the amyloid fibrils. Furthermore, accumulating evidence suggests that lipid membranes accelerate the fibrillation of different amyloid proteins.

Methods: Using an experimental mouse model of AA amyloidosis, we compared the amyloidogenic effect of liposomes and/or amyloid-enhancing factor (AEF). Inflammation was induced by subcutaneous injection of silver nitrate followed by intravenous injection of liposomes and/or AEF to accelerate amyloid formation.

Results: We showed that liposomes accelerate amyloid formation in inflamed mice, but the amyloidogenic effect of liposomes was weaker compared with AEF. Regardless of the induction method, amyloid deposits were mainly found in the marginal zones of the spleen and coincided with the depletion of marginal zone macrophages, while red pulp macrophages and metallophilic marginal zone macrophages proved insensitive to amyloid deposition.

Conclusions: We conclude that increased intracellular lipid content facilitates AA amyloid fibril formation and show that the mouse model of AA amyloidosis is a suitable system for further mechanistic studies.     

柱前衍生高效液相色谱法测定复方氨基酸注射液中氨基酸的含量

目的建立以2,4-二硝基氟苯为衍生化试剂,高效液相色谱法(HPLC)测定复方氨基酸注射液(18AA)中各氨基酸含量的方法。方法采用Agilent HC-C 18色谱柱,乙腈-水(60∶40)为流动相A,乙腈-磷酸盐缓冲液(9∶91)流动相B,梯度洗脱,流速1.0 mL·min-1,检测波长360 nm,柱温27℃。结果复方氨基酸注射液中各氨基酸分离度良好,线性相关系数均大于0.9989,平均回收率均在98%~102%之间,RSD%均小于2%。结论本方法可以用于复方氨基酸注射液(18AA)中氨基酸检测。     

Adipose tissue polyunsaturated fatty acids and metabolic syndrome among adult parents and their children

Background and aims

Polyunsaturated fatty acids (PUFA) may play a role in the etiology of the metabolic syndrome (MetS). The aim of the study was to examine the associations of adipose tissue PUFA biomarkers with MetS among parents and children in Mesoamerica.

Effect of intensive glycemic control on platelet reactivity in patients with long-standing uncontrolled diabetes

Background

It has been previously shown that platelets of patients with diabetes are more reactive and less responsive to anti-platelet drugs compared with platelets from subjects without diabetes. Studies examining the effect of glycemic control on platelet reactivity have yielded conflicting data. Thus, in this study, we sought to explore the effect of tight glycemic control on platelet reactivity in patients with long standing uncontrolled diabetes.

Methods

The study included 30 patients with long-standing treated diabetes and a baseline HbA1c level of ≥ 8.5%. All patients were treated with aspirin and statins. Patients were tested at baseline and after 3 months of intensive glycemic and metabolic control. The treatment goal was to achieve a HbA1c level of ≤ 7%. Platelet reactivity was assessed by light transmission aggregation in response to 5 and 10 μM ADP and to 0.5 mg/ml arachidonic acid (AA). Additonally, platelet activation was assessed by plasma levels of soluble P-selectin using an enzyme-linked immunosorbent assay.

Results

The mean duration of diabetes from the time of diagnosis was 20.46 ± 9.31 years. Baseline HbA1c was 9.4 ± 0.8%. Following the intensive glycemic control period, the HbA1C level decreased to 8.1 ± 0.8% (P < 0.0001). Other laboratory parameters did not change significantly except for triglyceride levels, which decreased. None of the platelet aggregation studies nor P-selectin levels differed between baseline and after 3 months of intensive glycemic control.

Conclusions

Intensive glycemic control in patients with longstanding uncontrolled diabetes does not seem to result in a reduction in platelet reactivity.     

Vanilloid-like agents inhibit aggregation of human platelets

Introduction

Plant-derived and endogenous vanilloid-like agents exert their effects on cells through transient receptor potential vanilloid-1 (TRPV1). Little is known about the effects of these agents on platelet aggregation. We investigated the effect of various vanilloid-like agents on in-vitro platelet aggregation and tested whether this action is mediated through TRPV1. Understanding the mechanism of action of these compounds in platelets is important in that these compounds may be developed as novel anti-platelet agents.

Materials and Methods

The effects of plant-derived (capsaicin; dihydrocapsaicin, DHC) and endogenous vanilloid-like agents (N-oleoyldopamine, OLDA; N-arachidonoyl-dopamine, NADA) on platelet aggregation were investigated using ADP (5, 10 μM), collagen (4, 8 μg/mL) and arachidonic acid (AA, 300, 400 μg/mL) as agonists. The direct effects of these agents on platelet viability were also determined using an LDH release assay.

Results

Capsaicin, OLDA and NADA inhibited ADP-induced platelet aggregation in a concentration-dependent manner. OLDA and NADA, but not capsaicin and DHC, inhibited collagen-induced aggregation, whereas AA-induced aggregation was inhibited by capsaicin, DHC and NADA, but not OLDA. Inhibition of aggregation was not due to direct toxicity of these agents towards platelets. The TRPV1 antagonist, SB-452533, did not affect inhibition of ADP-induced platelet aggregation by capsaicin and OLDA.

Conclusions

These results demonstrate that the endovanilloids, OLDA and NADA, and plant-derived vanilloid, capsaicin, inhibit ADP-induced platelet aggregation. Collagen-induced aggregation was inhibited only by endovanilloids, whereas AA-induced aggregation was inhibited by capsaicin, DHC and NADA. This inhibition was not due to direct toxic effects of these agents, nor was inhibition of ADP-induced aggregation TRPV1 mediated.     

Does sponsorship improve outcomes above Alcoholics Anonymous attendance? A latent class growth curve analysis

Aims To construct Alcoholics Anonymous (AA) attendance, sponsorship and abstinence latent class trajectories to test the added benefit of having a sponsor above the benefits of attendance in predicting abstinence over time. Design Prospective with 1‐, 3‐, 5‐ and 7‐year follow‐ups. Setting and participants Alcoholic‐dependent individuals from two probability samples, one from representative public and private treatment programs and another from the general population (n = 495). Findings Individuals in the low attendance class (four classes identified) were less likely than those in the high, descending and medium attendance classes to be in high (versus low) abstinence class (three classes identified). No differences were found between the other attendance classes as related to abstinence class membership. Overall, being in the high sponsor class (three classes identified) predicted better abstinence outcomes than being in either of two other classes (descending and low), independent of attendance class effects. Although declining sponsor involvement was associated with greater likelihood of high abstinence than low sponsor involvement, being in the descending sponsor class also increased the odds of being in the descending abstinence class. Conclusions Any pattern of Alcoholics Anonymous attendance, even if it declines or is never high for a particular 12‐month period, is better than little or no attendance in terms of abstinence. Greater initial attendance carries added value. There is a benefit for maintaining a sponsor over time above that found for attendance.     

Tissue Doppler is a More Reliable Method in Early Detection of Cardiac Dysfunction in Patients with AA Amyloidosis

Objective. Cardiac deposition of AA amyloidosis may result in increasing left ventricular mass and systolic and diastolic dysfunction (DD). The aim of this study was to investigate the left ventricular systolic and diastolic functions by both tissue Doppler imaging (TDI) and pulsed wave Doppler echocardiography (PWD) in patients with AA amyloidosis without congestive heart failure symptoms or arrthymia. Methods and Results. Twenty-four patients with AA amyloidosis without congestive heart failure symptoms or arrthymia (15 men and nine women; mean age 44.3 ± 16.7 years) and 25 healthy subjects (19 men and six women; mean age 43.1 ± 9.2 years) as controls were included in the study. M-mode, two-dimensional, PWD, and TDI were performed. Peak transmitral filling velocity (E wave), peak transmitral atrial filling velocity (A wave), deceleration time, and isovolumic relaxation time were measured by PWD recordings. Peak myocardial systolic velocity (S_m), peak myocardial early (E_m), and late diastolic velocities (A_m) were also recorded by TDI. E/A ratio less than one was accepted as DD for both methods. Ejection fraction (EF) was calculated by Teicholtz method. The subjects were divided into three groups as follows: healthy controls (group 1), patients without DD (group 2), and patients with DD (group 3) according to the PWD findings. PWD echocardiography showed that DD was present in 50% of the patients, whereas TDI showed DD in 66% of such cases. In subgroup analysis, S_m wave as a systolic function index was lower in group 3 than in groups 1 and 2, whereas mean EF values were similar in all groups. Conclusion. Although AA amyloidosis uncommonly causes cardiac symptoms and findings, according to our results, patients with AA amyloidosis may have systolic and diastolic dysfunction eventhough they are asymptomatic. Also, tissue Doppler imaging is a more reliable method in the early detection of cardiac dysfunction in such patients.