Neuroinflammation is induced by tongue-instilled ZnO nanoparticles via the Ca<Superscript>2+</Superscript>-dependent NF-κB and MAPK pathways

Background

The extensive biological applications of zinc oxide nanoparticles (ZnO NPs) in stomatology have created serious concerns about their biotoxicity. In our previous study, ZnO NPs were confirmed to transfer to the central nervous system (CNS) via the taste nerve pathway and cause neurodegeneration after 30 days of tongue instillation. However, the potential adverse effects on the brain caused by tongue-instilled ZnO NPs are not fully known.

Methods

In this study, the biodistribution of Zn, cerebral histopathology and inflammatory responses were analysed after 30 days of ZnO NPs tongue instillation. Moreover, the molecular mechanisms underlying neuroinflammation in vivo were further elucidated by treating BV2 and PC12 cells with ZnO NPs in vitro.

Results

This analysis indicated that ZnO NPs can transfer into the CNS, activate glial cells and cause neuroinflammation after tongue instillation. Furthermore, exposure to ZnO NPs led to a reduction in cell viability and induction of inflammatory response and calcium influx in BV2 and PC12 cells. The mechanism underlying how ZnO NPs induce neuroinflammation via the Ca²⁺-dependent NF-κB, ERK and p38 activation pathways was verified at the cytological level.

Conclusion

This study provided a new way how NPs, such as ZnO NPs, induce neuroinflammation via the taste nerve translocation pathway, a new mechanism for ZnO NPs-induced neuroinflammation and a new direction for nanomaterial toxicity analysis.

     

Suppression of PTPN6 exacerbates aluminum oxide nanoparticle-induced COPD-like lesions in mice through activation of STAT pathway

Background

Inhaled nanoparticles can deposit in the deep lung where they interact with pulmonary cells. Despite numerous studies on pulmonary nanotoxicity, detailed molecular mechanisms of specific nanomaterial-induced lung injury have yet to be identified.

Results

Using whole-body dynamic inhalation model, we studied the interactions between aluminum oxide nanoparticles (Al₂O₃ NPs) and the pulmonary system in vivo. We found that seven-day-exposure to Al₂O₃ NPs resulted in emphysema and small airway remodeling in murine lungs, accompanied by enhanced inflammation and apoptosis. Al₂O₃ NPs exposure led to suppression of PTPN6 and phosphorylation of STAT3, culminating in increased expression of the apoptotic marker PDCD4. Rescue of PTPN6 expression or application of a STAT3 inhibitor, effectively protected murine lungs from inflammation and apoptosis, as well as, in part, from the induction of chronic obstructive pulmonary disease (COPD)-like effects.

Conclusion

In summary, our studies show that inhibition of PTPN6 plays a critical role in Al₂O₃ NPs-induced COPD-like lesions.

     

Effects of differently shaped TiO<Subscript>2</Subscript>NPs (nanospheres,nanorods and nanowires) on the <Emphasis Type="Italic">in vitro</Emphasis> model (Caco-2/HT29) of the intestinal barrier

Background

The biological effects of nanoparticles depend on several characteristics such as size and shape that must be taken into account in any type of assessment. The increased use of titanium dioxide nanoparticles (TiO₂NPs) for industrial applications, and specifically as a food additive, demands a deep assessment of their potential risk for humans, including their abilities to cross biological barriers.

Methods

We have investigated the interaction of three differently shaped TiO₂NPs (nanospheres, nanorods and nanowires) in an in vitro model of the intestinal barrier, where the coculture of Caco-2/HT29 cells confers inherent intestinal epithelium characteristics to the model (i.e. mucus secretion, brush border, tight junctions, etc.).

Results

Adverse effects in the intestinal epithelium were detected by studying the barrier’s integrity (TEER), permeability (LY) and changes in the gene expression of selected specific markers. Using Laser Scanning Confocal Microscopy, we detected a different behaviour in the bio-adhesion and biodistribution of each of the TiO₂NPs. Moreover, we were able to specifically localize each type of TiO₂NPs inside the cells. Interestingly, general DNA damage, but not oxidative DNA damage effects, were detected by using the FPG version of the comet assay.

Conclusions

Results indicate different interactions and cellular responses related to differently shaped TiO₂NPs, nanowires showing the most harmful effects.

     

Phosphonate coating of SiO<Subscript>2</Subscript> nanoparticles abrogates inflammatory effects and local changes of the lipid composition in the rat lung: a complementary bioimaging study

Background

The well-known inflammatory and fibrogenic changes of the lung upon crystalline silica are accompanied by early changes of the phospholipid composition (PLC) as detected in broncho-alveolar lavage fluid (BALF). Amorphous silica nanoparticles (NPs) evoke transient lung inflammation, but their effect on PLC is unknown. Here, we compared effects of unmodified and phosphonated amorphous silica NP and describe, for the first time, local changes of the PLC with innovative bioimaging tools.

Methods

Unmodified (SiO₂-n), 3-(trihydroxysilyl) propyl methylphosphonate coated SiO₂-n (SiO₂-p) as well as a fluorescent surrogate of SiO₂-n (SiO₂-FITC) nanoparticles were used in this study. In vitro toxicity was tested with NR8383 alveolar macrophages. Rats were intratracheally instilled with SiO₂-n, SiO₂-p, or SiO₂-FITC, and effects on lungs were analyzed after 3 days. BALF from the right lung was analyzed for inflammatory markers. Cryo-sections of the left lung were subjected to fluorescence microscopy and PLC analyses by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MS), Fourier transform infrared microspectroscopy (FT-IR), and tandem mass spectrometry (MS/MS) experiments.

Results

Compared to SiO₂-p, SiO₂-n NPs were more cytotoxic to macrophages in vitro and more inflammatory in the rat lung, as reflected by increased concentration of neutrophils and protein in BALF. Fluorescence microscopy revealed a typical patchy distribution of SiO₂-FITC located within the lung parenchyma and alveolar macrophages. Superimposable to this particle distribution, SiO₂-FITC elicited local increases of phosphatidylglycerol (PG) and phosphatidylinositol (PI), whereas phoshatidylserine (PS) and signals from triacylgyceride (TAG) were decreased in the same areas. No such changes were found in lungs treated with SiO₂-p or particle-free instillation fluid.

Conclusions

Phosphonate coating mitigates effects of silica NP in the lung and abolishes their locally induced changes in PLC pattern. Bioimaging methods based on MALDI-MS may become a useful tool to investigate the mode of action of NPs in tissues.

     

Calcium-dependent cyto- and genotoxicity of nickel metal and nickel oxide nanoparticles in human lung cells

Background

Genotoxicity is an important toxicological endpoint due to the link to diseases such as cancer. Therefore, an increased understanding regarding genotoxicity and underlying mechanisms is needed for assessing the risk with exposure to nanoparticles (NPs). The aim of this study was to perform an in-depth investigation regarding the genotoxicity of well-characterized Ni and NiO NPs in human bronchial epithelial BEAS-2B cells and to discern possible mechanisms. Comparisons were made with NiCl₂ in order to elucidate effects of ionic Ni.

Methods

BEAS-2B cells were exposed to Ni and NiO NPs, as well as NiCl₂, and uptake and cellular dose were investigated by transmission electron microscopy (TEM) and inductively coupled plasma mass spectrometry (ICP-MS). The NPs were characterized in terms of surface composition (X-ray photoelectron spectroscopy), agglomeration (photon cross correlation spectroscopy) and nickel release in cell medium (ICP-MS). Cell death (necrosis/apoptosis) was investigated by Annexin V-FITC/PI staining and genotoxicity by cytokinesis-block micronucleus (cytome) assay (OECD 487), chromosomal aberration (OECD 473) and comet assay. The involvement of intracellular reactive oxygen species (ROS) and calcium was explored using the fluorescent probes, DCFH-DA and Fluo-4.

Results

NPs were efficiently taken up by the BEAS-2B cells. In contrast, no or minor uptake was observed for ionic Ni from NiCl₂. Despite differences in uptake, all exposures (NiO, Ni NPs and NiCl₂) caused chromosomal damage. Furthermore, NiO NPs were most potent in causing DNA strand breaks and generating intracellular ROS. An increase in intracellular calcium was observed and modulation of intracellular calcium by using inhibitors and chelators clearly prevented the chromosomal damage. Chelation of iron also protected against induced damage, particularly for NiO and NiCl₂.

Conclusions

This study has revealed chromosomal damage by Ni and NiO NPs as well as Ni ionic species and provides novel evidence for a calcium-dependent mechanism of cyto- and genotoxicity.

     

Usefulness of myeloperoxidase as a biomarker for the ranking of pulmonary toxicity of nanomaterials

Background

In order to examine whether myeloperoxidase (MPO) can be a useful marker for evaluating the pulmonary toxicity of nanomaterials, we analyzed MPO protein in bronchoalveolar lavage fluid (BALF) samples obtained from previous examinations of a rat model. In those examinations we performed intratracheal instillation exposures (dose: 0.2–1.0 mg) and inhalation exposures (exposure concentration: 0.32–10.4 mg/m³) using 9 and 4 nanomaterials with different toxicities, respectively. Based on those previous studies, we set Nickel oxide nanoparticles (NiO), cerium dioxide nanoparticles (CeO₂), multi wall carbon nanotubes with short or long length (MWCNT (S) and MWCNT (L)), and single wall carbon nanotube (SWCNT) as chemicals with high toxicity; and titanium dioxide nanoparticles (TiO₂ (P90) and TiO₂ (Rutile)), zinc oxide nanoparticles (ZnO), and toner with external additives including nanoparticles as chemicals with low toxicity. We measured the concentration of MPO in BALF samples from rats from 3 days to 6 months following a single intratracheal instillation, and from 3 days to 3 months after the end of inhalation exposure.

Results

Intratracheal instillation of high toxicity NiO, CeO_2, MWCNT (S), MWCNT (L), and SWCNT persistently increased the concentration of MPO, and inhalation of NiO and CeO₂ increased the MPO in BALF. By contrast, intratracheal instillation of low toxicity TiO₂ (P90), TiO₂ (Rutile), ZnO, and toner increased the concentration of MPO in BALF only transiently, and inhalation of TiO₂ (Rutile) and ZnO induced almost no increase of the MPO. The concentration of MPO correlated with the number of total cells and neutrophils, the concentration of chemokines for neutrophils (cytokine-induced neutrophil chemoattractant (CINC)-1 and heme oxygenase (HO)-1), and the activity of released lactate dehydrogenase (LDH) in BALF. The results from the receiver operating characteristics (ROC) for the toxicity of chemicals by the concentration of MPO proteins in the intratracheal instillation and inhalation exposures showed that the largest areas under the curves (AUC) s in both examinations occurred at 1 month after exposure.

Conclusion

These data suggest that MPO can be a useful biomarker for the ranking of the pulmonary toxicity of nanomaterials, especially at 1 month after exposure, in both intratracheal instillation and inhalation exposure.

     

Metabolomic effects of CeO<Subscript>2</Subscript>, SiO<Subscript>2</Subscript> and CuO metal oxide nanomaterials on HepG2 cells

Background

To better assess potential hepatotoxicity of nanomaterials, human liver HepG2 cells were exposed for 3 days to five different CeO₂ (either 30 or 100 μg/ml), 3 SiO₂ based (30 μg/ml) or 1 CuO (3 μg/ml) nanomaterials with dry primary particle sizes ranging from 15 to 213 nm. Metabolomic assessment of exposed cells was then performed using four mass spectroscopy dependent platforms (LC and GC), finding 344 biochemicals.

Results

Four CeO₂, 1 SiO₂ and 1 CuO nanomaterials increased hepatocyte concentrations of many lipids, particularly free fatty acids and monoacylglycerols but only CuO elevated lysolipids and sphingolipids. In respect to structure-activity, we now know that five out of six tested CeO₂, and both SiO₂ and CuO, but zero out of four TiO₂ nanomaterials have caused this elevated lipids effect in HepG2 cells. Observed decreases in UDP-glucuronate (by CeO₂) and S-adenosylmethionine (by CeO₂ and CuO) and increased S-adenosylhomocysteine (by CuO and some CeO₂) suggest that a nanomaterial exposure increases transmethylation reactions and depletes hepatic methylation and glucuronidation capacity. Our metabolomics data suggests increased free radical attack on nucleotides. There was a clear pattern of nanomaterial-induced decreased nucleotide concentrations coupled with increased concentrations of nucleic acid degradation products. Purine and pyrimidine alterations included concentration increases for hypoxanthine, xanthine, allantoin, urate, inosine, adenosine 3′,5′-diphosphate, cytidine and thymidine while decreases were seen for uridine 5′-diphosphate, UDP-glucuronate, uridine 5′-monophosphate, adenosine 5′-diphosphate, adenosine 5′-monophophate, cytidine 5′-monophosphate and cytidine 3′-monophosphate. Observed depletions of both 6-phosphogluconate, NADPH and NADH (all by CeO₂) suggest that the HepG2 cells may be deficient in reducing equivalents and thus in a state of oxidative stress.

Conclusions

Metal oxide nanomaterial exposure may compromise the methylation, glucuronidation and reduced glutathione conjugation systems; thus Phase II conjugational capacity of hepatocytes may be decreased. This metabolomics study of the effects of nine different nanomaterials has not only confirmed some observations of the prior 2014 study (lipid elevations caused by one CeO₂ nanomaterial) but also found some entirely new effects (both SiO₂ and CuO nanomaterials also increased the concentrations of several lipid classes, nanomaterial induced decreases in S-adenosylmethionine, UDP-glucuronate, dipeptides, 6-phosphogluconate, NADPH and NADH).

     

Different degrees of malnutrition and immunological alterations according to the aetiology of cirrhosis: a prospective and sequential study

Objectives

In this work we investigated how immunological dysfunction and malnutrition interact in alcoholic and viral aetiologies of cirrhosis.

Methods

To investigate the matter, 77 cirrhotic patients divided in three aetiologies [Alcohol, HCV and Alcohol + HCV) and 32 controls were prospectivelly and sequentially studied. Parameters of humoral immunity (Components 3 and 4 of seric complement and immunoglobulins A M, G and E) and of cellular immunity (total leukocytes and lymphocytes in peripheral blood, T lymphocytes subpopulations, CD4+ and CD8+, CD4+/CD8+ ratio and intradermic tests of delayed hypersensitivity), as well as nutrititional parameters: anthropometric measures, serum albumin and transferrin were evaluated.

Results

Multiple statistical comparisons showed that IgM was higher in HCV group; IgG was significantly elevated in both HCV and Alcohol + HCV, whereas for the Alcohol group, IgE was found at higher titles. The analysis of T- lymphocytes subpopulations showed no aetiologic differences, but intradermic tests of delayed hypersensitivity did show greater frequency of anergy in the Alcohol group. For anthropometric parameters, the Alcohol +HCV group displayed the lowest triceps skinfold whereas creatinine – height index evaluation was more preserved in the HCV group. Body mass index, arm muscle area and arm fat area showed that differently from alcohol group, the HCV group was similar to control.

Conclusion

Significant differences were found among the main aetiologies of cirrhosis concerning immunological alterations and nutritional status: better nutrition and worse immunology for HCV and vice-versa for alcohol.

     

Group II innate lymphoid cells and microvascular dysfunction from pulmonary titanium dioxide nanoparticle exposure

Background

The cardiovascular effects of pulmonary exposure to engineered nanomaterials (ENM) are poorly understood, and the reproductive consequences are even less understood. Inflammation remains the most frequently explored mechanism of ENM toxicity. However, the key mediators and steps between lung exposure and uterine health remain to be fully defined. The purpose of this study was to determine the uterine inflammatory and vascular effects of pulmonary exposure to titanium dioxide nanoparticles (nano-TiO₂). We hypothesized that pulmonary nano-TiO₂ exposure initiates a Th2 inflammatory response mediated by Group II innate lymphoid cells (ILC2), which may be associated with an impairment in uterine microvascular reactivity.

Methods

Female, virgin, Sprague-Dawley rats (8–12 weeks) were exposed to 100 μg of nano-TiO₂ via intratracheal instillation 24 h prior to microvascular assessments. Serial blood samples were obtained at 0, 1, 2 and 4 h post-exposure for multiplex cytokine analysis. ILC2 numbers in the lungs were determined. ILC2s were isolated and phosphorylated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B) levels were measured. Pressure myography was used to assess vascular reactivity of isolated radial arterioles.

Results

Pulmonary nano-TiO₂ exposure was associated with an increase in IL-1ß, 4, 5 and 13 and TNF- α 4 h post-exposure, indicative of an innate Th2 inflammatory response. ILC2 numbers were significantly increased in lungs from exposed animals (1.66?±?0.19%) compared to controls (0.19?±?0.22%). Phosphorylation of the transactivation domain (Ser-468) of NF-κB in isolated ILC2 and IL-33 in lung epithelial cells were significantly increased (126.8?±?4.3% and 137?±?11% of controls respectively) by nano-TiO₂ exposure. Lastly, radial endothelium-dependent arteriolar reactivity was significantly impaired (27?±?12%), while endothelium-independent dilation (7?±?14%) and α-adrenergic sensitivity (8?±?2%) were not altered compared to control levels. Treatment with an anti- IL-33 antibody (1 mg/kg) 30 min prior to nano-TiO₂ exposure resulted in a significant improvement in endothelium-dependent dilation and a decreased level of IL-33 in both plasma and bronchoalveolar lavage fluid.

Conclusions

These results provide evidence that the uterine microvascular dysfunction that follows pulmonary ENM exposure may be initiated via activation of lung-resident ILC2 and subsequent systemic Th2-dependent inflammation.

     

Soy versus whey protein bars: Effects on exercise training impact on lean body mass and antioxidant status

Background

Although soy protein may have many health benefits derived from its associated antioxidants, many male exercisers avoid soy protein. This is due partly to a popular, but untested notion that in males, soy is inferior to whey in promoting muscle weight gain. This study provided a direct comparison between a soy product and a whey product.

Methods

Lean body mass gain was examined in males from a university weight training class given daily servings of micronutrient-fortified protein bars containing soy or whey protein (33 g protein/day, 9 weeks, n = 9 for each protein treatment group). Training used workouts with fairly low repetition numbers per set. A control group from the class (N = 9) did the training, but did not consume either type protein bar.

Results

Both the soy and whey treatment groups showed a gain in lean body mass, but the training-only group did not. The whey and training only groups, but not the soy group, showed a potentially deleterious post-training effect on two antioxidant-related related parameters.

Conclusions

Soy and whey protein bar products both promoted exercise training-induced lean body mass gain, but the soy had the added benefit of preserving two aspects of antioxidant function.

     

Effect of whey protein supplementation on levels of endocannabinoids and some of metabolic risk factors in obese women on a weight-loss diet: a study protocol for a randomized controlled trial

Background

Besides the effects of dietary long chain PUFA on circulating endocannabinoids concentrations, the impact of other nutrients on these system is not known and, whether changes in plasma endocannabinoids levels correlated with changes in body composition and biochemical metabolic risk factors in obese individuals, however, still remains to be characterized.

Methods

We will conduct a 2 months’ open label, parallel-group, randomized controlled trial to determine the effect of whey protein supplementation on levels of endocannabinoids, glycemic and lipid profile, inflammatory factors, adipocytokines and body composition in 60 premenopausal obese women on a weight-loss diet.

Conclusion

Due to strong relationship between endocannabinoids level and insulin resistance and obesity, in this trial, we will illustrate the other benefits of weight loss diet on health and metabolic risk factors. Also for the first, the effects of simultaneous weight loss diet and whey protein supplementation on these variables will be determined.

Trial registration

Iranian Registry of Clinical Trials IRCT2017021410181N8.

     

The influence of frequently consumed beverages and snacks on dental erosion among preschool children in Saudi Arabia

Background

To determine the prevalence of dental erosion and its association to commonly used beverages and snacks among 3 to 5 year old preschool children in Riyadh, Saudi Arabia.

Methods

Three hundred eighty-eight preschool children between 3 and 5 years old were selected from 10 different schools using a cluster random sample selection; there were 184 (47%) boys and 204 (53%) girls. The surfaces of each tooth were examined for erosion, and the level of tooth wear was recorded. Data on the frequently used beverages and snacks were obtained by questionnaires completed by the parents of the preschool children.

Results

Among the 388 children examined, 47% exhibited low erosion, 10% exhibited moderate erosion and 4% exhibited severe erosion. There was no statistically significant difference between boys and girls in terms of the prevalence of erosion. Sixty percent of the children regularly consumed juice drinks. Among daily consumers, 84% of children showed erosion prevalence with strongly significant association (p?<?0.005). Holding the drink in the mouth also showed a significant association with erosion (p?<?0.02).

Conclusion

It was concluded that an association was found between the prevalence of dental erosion and the frequency of citrus and carbonated juice consumed by the preschool children in Saudi Arabia.

     

Association between eating behaviour and diet quality: eating alone vs. eating with others

Background

To discover the association between eating alone and diet quality among Korean adults who eat alone measured by the mean adequacy ratio (MAR),

Methods

The cross-sectional study in diet quality which was measured by nutrient intakes, indicated as MAR and nutrient adequacy ratio (NAR) with the Korean National Health and Nutrition Examination Survey (KNHANES) VI 2013–2015 data. Study population was 8523 Korean adults. Multiple linear regression was performed to identify the association between eating behaviour and MAR and further study analysed how socioeconomic factors influence the diet quality of those who eat alone.

Results

We found that the diet quality of people who eat alone was lower than that of people who eat together in both male (β: ??0.110, p?=?0.002) and female participants (β: ??0.069, p?=?0.005). Among who eats alone, the socioeconomic factors that negatively influenced MAR with the living arrangement, education level, income levels, and various occupation classifications.

Conclusions

People who eat alone have nutrition intake below the recommended amount. This could lead to serious health problems not only to those who are socially disadvantaged but also those who are in a higher social stratum. Policy-makers should develop strategies to enhance diet quality to prevent potential risk factors.

     

In utero exposure to extra vitamin D from food fortification and the risk of subsequent development of gestational diabetes: the D-tect study

Background

The primary aim of this study was to assess whether exposure during fetal life to extra vitamin D from food fortification was associated with a reduction in the risk of subsequently developing gestational diabetes mellitus (GDM). Furthermore, we examined whether the effect of the vitamin D from fortification differed by women’s season of birth.

Methods

This semi-ecological study is based on the cancellation in 1985 of the mandatory policy to fortify margarine with vitamin D in Denmark, with inclusion of entire national adjacent birth cohorts either exposed or unexposed to extra vitamin D in utero. The identification of GDM cases later in life among both exposure groups was based on the Danish national health registers. Logistic regression analyses generating odds ratios (ORs) and 95% confidence intervals (95% CIs) were performed.

Results

Women who were prenatally exposed to the extra vitamin D from fortification tended to have a lower risk of subsequently developing GDM than unexposed women (OR 0.87, 95%CI 0.74,1.02, P?=?0.08). When analyses were stratified by women’s season of birth, exposed women born in spring had a lower risk of developing GDM compared to unexposed subjects (OR 0.68, 95%CI 0.50,0.94, p?=?0.02).

Conclusion

This study suggests that prenatal exposure to extra vitamin D from mandatory fortification may lower the risk of developing gestational diabetes among spring-born women.

Trial registration

This study is part of the D-tect project, which is registered on clinicaltrials.gov: NCT03330301.

     

Effects of olive oil and its minor phenolic constituents on obesity-induced cardiac metabolic changes

Background

Olive oil and its minor constituents have been recommended as important dietary therapeutic interventions in preventive medicine. However, a question remains to be addressed: what are the effects of olive oil and its phenolic compounds on obesity-induced cardiac metabolic changes?

Methods

Male Wistar rats were divided into two groups (n = 24/group): (C) receiving standard-chow; (Ob) receiving hypercaloric-chow. After 21 days C and Ob groups were divided into four subgroups (n = 6/group):(C) standard-chow and saline; (C-Olive)standard-chow and olive-oil (3.0 g/kg.day); (C-Oleuropein)standard-chow and oleuropein (0.023 mg/kg/day); (C-Cafeic) standard-chow and cafeic-acid (2.66 mg/kg/day); (Ob)receiving hypercaloric-chow and saline;(Ob-Olive) hypercaloric-chow and olive-oil;(Ob-Oleuropein) hypercaloric-chow and oleuropein;(Ob-Cafeic) hypercaloric-chow and cafeic-acid. Treatments were given twice a week during 21 days.

Results

After 42 days, obesity was evidenced in Ob rats from enhanced body-weight, surface-area, and body-mass-index. Energy-expenditure, oxygen consumption(VO₂) and fat-oxidation were lower in Ob-group than in C. Despite no morphometric changes, Ob-Olive, Ob-Oleuropein and Ob-Cafeic groups had higher VO₂, fat-oxidation, myocardial beta-hydroxyacyl coenzyme-A dehydrogenase and lower respiratory-quotient than Ob. Citrate-synthase was highest in Ob-Olive group. Myocardial lipid-hydroperoxide(LH) and antioxidant enzymes were unaffected by olive-oil and its compounds in obesity condition, whereas LH was lower and total-antioxidant-substances were higher in C-Olive and C-Oleuropein than in C.

Conclusions

The present study demonstrated for the first time that olive-oil, oleuropein and cafeic-acid enhanced fat-oxidation and optimized cardiac energy metabolism in obesity conditions. Olive oil and its phenolic compounds improved myocardial oxidative stress in standard-fed conditions.

     

Use of plant stanol ester margarine among persons with and without cardiovascular disease: Early phases of the adoption of a functional food in Finland

Background

The plant stanol ester margarine Benecol^® is a functional food that has been shown to lower effectively serum total and LDL-cholesterol. The purpose of this post-marketing study is to characterize users of plant stanol ester margarine with and without cardiovascular disease.

Methods

A cohort of plant stanol ester margarine users was established based on a compilation of 15 surveys conducted by the National Public Health Institute in Finland between 1996–2000. There were 29 772 subjects aged 35–84 years in the cohort. The users of plant stanol ester margarine were identified by the type of bread spread used.

Results

The plant stanol ester margarine was used as bread spread by 1332 (4.5%) subjects. Almost half (46%) of the users reported a history of cardiovascular disease. Persons with cardiovascular disease were more likely to use plant stanol ester margarine (8%) than persons without cardiovascular disease (3%). Users with and without cardiovascular disease seemed to share similar characteristics.In particular, they were elderly people with otherwise healthy life-styles and diet. They were less likely smokers, more likely physically active and less likely obese than nonusers. The users reported being in good or average health in general and having used cholesterol-lowering drugs.

Conclusion

Plant stanol ester margarine seems to be used by persons for whom it was designed and in a way it was meant: as part of efforts for cardiovascular disease risk reduction.

     

The role of soluble fiber intake in patients under highly effective lipid-lowering therapy

Background

It has been demonstrated that statins can increase intestinal sterol absorption. Augments in phytosterolemia seems related to cardiovascular disease.

Objective

We examined the role of soluble fiber intake in endogenous cholesterol synthesis and in sterol absorption among subjects under highly effective lipid-lowering therapy.

Design

In an open label, randomized, parallel-design study with blinded endpoints, subjects with primary hypercholesterolemia (n = 116) were assigned to receive during 12 weeks, a daily dose of 25 g of fiber (corresponding to 6 g of soluble fibers) plus rosuvastatin 40 mg (n = 28), rosuvastatin 40 mg alone (n = 30), sinvastatin 40 mg plus ezetimibe 10 mg plus 25 g of fiber (n = 28), or sinvastatin 40 mg plus ezetimibe 10 mg (n = 30) alone.

Results

The four assigned therapies produced similar changes in total cholesterol, LDL-cholesterol, and triglycerides (p < 0.001 vs. baseline) and did not change HDL-cholesterol. Fiber intake decreased plasma campesterol (p < 0.001 vs. baseline), particularly among those patients receiving ezetimibe (p < 0.05 vs. other groups), and β-sitosterol (p = 0.03 vs. baseline), with a trend for lower levels in the group receiving fiber plus ezetimibe (p = 0.07). Treatment with rosuvastatin alone or combined with soluble fiber was associated with decreased levels of desmosterol (p = 0.003 vs. other groups). Compared to non-fiber supplemented individuals, those treated with fibers had weight loss (p = 0.04), reduced body mass index (p = 0.002) and blood glucose (p = 0.047).

Conclusion

Among subjects treated with highly effective lipid-lowering therapy, the intake of 25 g of fibers added favorable effects, mainly by reducing phytosterolemia. Additional benefits include improvement in blood glucose and anthropometric parameters.

     

Biodistribution of single and aggregated gold nanoparticles exposed to the human lung epithelial tissue barrier at the air-liquid interface

Background

The lung represents the primary entry route for airborne particles into the human body. Most studies addressed possible adverse effects using single (nano)particles, but aerosolic nanoparticles (NPs) tend to aggregate and form structures of several hundreds nm in diameter, changing the physico-chemical properties and interaction with cells. Our aim was to investigate how aggregation might affect the biodistribution; cellular uptake and translocation over time of aerosolized NPs at the air-blood barrier interface using a multicellular lung system.

Results

Model gold nanoparticles (AuNPs) were engineered and well characterized to compare single NPs with aggregated NPs with hydrodynamic diameter of 32 and 106 nm, respectively. Exposures were performed by aerosolization of the particles onto the air-liquid interface of a three dimensional (3D) lung model. Particle deposition, cellular uptake and translocation kinetics of single and aggregated AuNPs were determined for various concentrations, (30, 60, 150 and 300 ng/cm²) and time points (4, 24 and 48 h) using transmission electron microscopy and inductively coupled plasma optical emission spectroscopy. No apparent harmful effect for single and aggregated AuNPs was observed by lactate dehydrogenase assay, nor pro-inflammation response by tumor necrosis factor α assessment. The cell layer integrity was also not impaired. The bio-distribution revealed that majority of the AuNPs, single or aggregated, were inside the cells, and only a minor fraction, less than 5%, was found on the basolateral side. No significant difference was observed in the translocation rate. However, aggregated AuNPs showed a significantly faster cellular uptake than single AuNPs at the first time point, i.e. 4 h.

Conclusions

Our studies revealed that aggregated AuNPs showed significantly faster cellular uptake than single AuNPs at the first time point, i.e. 4 h, but the uptake rate was similar at later time points. In addition, aggregation did not affect translocation rate across the lung barrier model since similar translocation rates were observed for single as well as aggregated AuNPs.

     

Short-term effects of fine particulate matter and ozone on the cardiac conduction system in patients undergoing cardiac catheterization

Background

Air pollution-induced changes in cardiac electrophysiological properties could be a pathway linking air pollution and cardiovascular events. The evidence of air pollution effects on the cardiac conduction system is incomplete yet. We investigated short-term effects of particulate matter ≤ 2.5 μm in aerodynamic diameter (PM_2.5) and ozone (O₃) on cardiac electrical impulse propagation and repolarization as recorded in surface electrocardiograms (ECG).

Methods

We analyzed repeated 12-lead ECG measurements performed on 5,332 patients between 2001 and 2012. The participants came from the Duke CATHGEN Study who underwent cardiac catheterization and resided in North Carolina, United States (NC, U.S.). Daily concentrations of PM_2.5 and O₃ at each participant’s home address were predicted with a hybrid air quality exposure model. We used generalized additive mixed models to investigate the associations of PM_2.5 and O₃ with the PR interval, QRS interval, heart rate-corrected QT interval (QTc), and heart rate (HR). The temporal lag structures of the associations were examined using distributed-lag models.

Results

Elevated PM_2.5 and O₃ were associated with four-day lagged lengthening of the PR and QRS intervals, and with one-day lagged increases in HR. We observed immediate effects on the lengthening of the QTc interval for both PM_2.5 and O₃, as well as delayed effects for PM_2.5 (lagged by 3 – 4 days). The associations of PM_2.5 and O₃ with the PR interval and the association of O₃ with the QRS interval persisted until up to seven days after exposure.

Conclusions

In patients undergoing cardiac catheterization, short-term exposure to air pollution was associated with increased HR and delays in atrioventricular conduction, ventricular depolarization and repolarization.

     

The effects of EPA and DHA enriched fish oil on nutritional and immunological markers of treatment naïve breast cancer patients: a randomized double-blind controlled trial

Background

We evaluated the effects of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids enriched fish oil (FO) on nutritional and immunological parameters of treatment naïve breast cancer patients.

Methods

In a randomized double blind controlled trial, the FO group (FG) patients were supplemented with 2 g/ day of FO concentrate containing 1.8 g of n-3 fatty acids during 30 days. The placebo group (PG) received 2 g/ day of mineral oil. At baseline and after the intervention, plasma levels of n-3 fatty acids, dietary intake, weight, body composition, biochemical and immunological markers were assessed.

Results

At the end of the intervention period, no between group differences were observed regarding anthropometric parameters. There was a significant increase in the plasma phospholipid EPA (p = 0.004), DHA (p = 0.007) of the FG patients. In FG patients the percentages of peripheral blood CD4⁺ T lymphocytes and serum high sensitivity C-reactive protein (hsCRP) levels were maintained while in PG patients there was a significant increase in hsCRP (p = 0.024). We also observed a significant reduction in the percentage of CD4⁺ T lymphocytes in the peripheral blood (p = 0.042) of PG patients. No changes in serum proinflammatory cytokine and prostaglandin E₂ levels were observed.

Conclusions

Supplementation of newly diagnosed breast cancer patients with EPA and DHA led to a significant change in the composition of plasma fatty acids, maintained the level of CD4⁺ T cells and serum levels of hsCRP, suggestive of a beneficial effect on the immune system and less active inflammatory response.

Trial registration

Brazilian Clinical Trials Registry (REBEC): RBR-2b2hqh. Registered 29 April 2013, retrospectively registered.