Soluble iron modulates iron oxide particle-induced inflammatory responses via prostaglandin E2 synthesis: In vitro and in vivo studies

Background  

Ambient particulate matter (PM)-associated metals have been shown to play an important role in cardiopulmonary health outcomes. To study the modulation of PM-induced inflammation by leached off metals, we investigated intracellular solubility of radio-labeled iron oxide (⁵⁹Fe₂O₃) particles of 0.5 and 1.5 μm geometric mean diameter. Fe₂O₃ particles were examined for the induction of the release of interleukin 6 (IL-6) as pro-inflammatory and prostaglandin E₂ (PGE₂) as anti-inflammatory markers in cultured alveolar macrophages (AM) from Wistar Kyoto (WKY) rats. In addition, we exposed male WKY rats to monodispersed Fe₂O₃ particles by intratracheal instillation (1.3 or 4.0 mg/kg body weight) to examine in vivo inflammation.     

Environmentally persistent free radicals induce airway hyperresponsiveness in neonatal rat lungs

Background  

Increased asthma risk/exacerbation in children and infants is associated with exposure to elevated levels of ultrafine particulate matter (PM). The presence of a newly realized class of pollutants, environmentally persistent free radicals (EPFRs), in PM from combustion sources suggests a potentially unrecognized risk factor for the development and/or exacerbation of asthma.     

Shape matters: effects of silver nanospheres and wires on human alveolar epithelial cells

Background

Ambient particulate matter (PM) exposure is associated with respiratory and cardiovascular morbidity and mortality. To what extent such effects are different for PM obtained from different sources or locations is still unclear. This study investigated the in vitro toxicity of ambient PM collected at different sites in the Netherlands in relation to PM composition and oxidative potential.

Method

PM was sampled at eight sites: three traffic sites, an underground train station, as well as a harbor, farm, steelworks, and urban background location. Coarse (2.5-10 μm), fine (< 2.5 μm) and quasi ultrafine PM (qUF; < 0.18 μm) were sampled at each site. Murine macrophages (RAW 264.7 cells) were exposed to increasing concentrations of PM from these sites (6.25-12.5-25-50-100 μg/ml; corresponding to 3.68-58.8 μg/cm²). Following overnight incubation, MTT-reduction activity (a measure of metabolic activity) and the release of pro-inflammatory markers (Tumor Necrosis Factor-alpha, TNF-α; Interleukin-6, IL-6; Macrophage Inflammatory Protein-2, MIP-2) were measured. The oxidative potential and the endotoxin content of each PM sample were determined in a DTT- and LAL-assay respectively. Multiple linear regression was used to assess the relationship between the cellular responses and PM characteristics: concentration, site, size fraction, oxidative potential and endotoxin content.

Results

Most PM samples induced a concentration-dependent decrease in MTT-reduction activity and an increase in pro-inflammatory markers with the exception of the urban background and stop & go traffic samples. Fine and qUF samples of traffic locations, characterized by a high concentration of elemental and organic carbon, induced the highest pro-inflammatory activity. The pro-inflammatory response to coarse samples was associated with the endotoxin level, which was found to increase dramatically during a three-day sample concentration procedure in the laboratory. The underground samples, characterized by a high content of transition metals, showed the largest decrease in MTT-reduction activity. PM size fraction was not related to MTT-reduction activity, whereas there was a statistically significant difference in pro-inflammatory activity between Fine and qUF PM. Furthermore, there was a statistically significant negative association between PM oxidative potential and MTT-reduction activity.

Conclusion

The response of RAW264.7 cells to ambient PM was markedly different using samples collected at various sites in the Netherlands that differed in their local PM emission sources. Our results are in support of other investigations showing that the chemical composition as well as oxidative potential are determinants of PM induced toxicity in vitro.     

Nanoparticle inhalation augments particle-dependent systemic microvascular dysfunction

Background  

We have shown that pulmonary exposure to fine particulate matter (PM) impairs endothelium dependent dilation in systemic arterioles. Ultrafine PM has been suggested to be inherently more toxic by virtue of its increased surface area. The purpose of this study was to determine if ultrafine PM (or nanoparticle) inhalation produces greater microvascular dysfunction than fine PM. Rats were exposed to fine or ultrafine TiO₂ aerosols (primary particle diameters of ~1 μm and ~21 nm, respectively) at concentrations which do not alter bronchoalveolar lavage markers of pulmonary inflammation or lung damage.     

Long-Term Administration of Cod Liver Oil Ameliorates Cognitive Impairment Induced by Chronic Stress in Rats

Cod liver oil (CLO) is a rich source of omega-3 fatty acids (FA), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The existing data suggest that EPA and DHA are the active agents of fish oil. In this study, we tested a hypothesis that the active constituents of CLO alleviate the negative impact of prolonged restraint stress on cognitive functions of male Wistar rats. Specifically, we attempted to characterize the preventive action of long-lasting treatment with CLO [0.375 ml/100 g body weight (equivalent to a dose of 300 mg/kg DHA and 225 mg/kg EPA), p.o. for 21 days] against an impairment caused by chronic restraint stress (2 h daily for 21 days) on recall as tested in a passive avoidance situation and on the spatial reference and working memory tested in a Barnes maze as well as on locomotor activity and anxiety behavior tested respectively in an open field and elevated plus-maze. We found that CLO administration statistically significantly (p < 0.01, both) prevented the deleterious effects of chronic restraint stress on recall and the spatial memory.     

To treat or not to treat: comparison of different criteria used to determine whether weight loss is to be recommended

Background  

Excess body fat is a major risk factor for disease primarily due to its endocrine activity. In recent years several criteria have been introduced to evaluate this factor. Nevertheless, treatment need is currently assessed only on the basis of an individual's Body Mass Index (BMI), calculated as body weight (in kg) divided by height in m². The aim of our study was to determine whether application of the BMI, compared to adiposity-based criteria, results in underestimation of the number of subjects needing lifestyle intervention.     

Oral Absorption and Disposition of alpha‐Linolenic,Rumenic and Vaccenic Acids After Administration as a Naturally Enriched Goat Dairy Fat to Rats

Although there is extensive information describing the positive biological effects of conjugated linoleic acid and its main isomer rumenic acid (RA; C18:2 cis 9, trans 11), and alpha‐linolenic acid (ALA) and vaccenic acid (TVA), data about their bioavailability are not available. In this work, we investigated the oral absorption and disposition of these fatty acids in Wistar rats. A naturally enriched goat dairy fat (EDF) was obtained by supplementing ruminant diets with oils or oilseeds rich in polyunsaturated fatty acids (PUFA). The EDF was administered orally (single dose of 3000 mg EDF/kg body weight equivalent to 153 mg TVA/kg body weight, 46 mg RA/kg body weight and 31 mg ALA/kg body weight), and serial blood and liver samples were collected and TVA, RA and ALA concentrations determined by GC/MS. The fatty acids TVA, RA and ALA were rapidly absorbed (t_1/2a, 0.36, 0.66 and 0.76 h, respectively, for plasma) and slowly eliminated (t_1/2β, 17.04, 18.40 and 16.52 h, respectively, for plasma). The maximum concentration (C_max) was detected in liver > plasma > erythrocyte. Our study shows that when orally administered EDF, its components TVA, RA and ALA were rapidly absorbed and distributed throughout the body by the blood circulation to exert systemic effects.     

Cytokine release from alveolar macrophages exposed to ambient particulate matter: Heterogeneity in relation to size,city and season

Background  

Several studies have demonstrated an association between exposure to ambient particulate matter (PM) and respiratory and cardiovascular diseases. Inflammation seems to play an important role in the observed health effects. However, the predominant particle component(s) that drives the inflammation is still not fully clarified. In this study representative coarse (2.5–10 μm) and fine (0.1–2.5 μm) particulate samples from a western, an eastern, a northern and a southern European city (Amsterdam, Lodz, Oslo and Rome) were collected during three seasons (spring, summer and winter). All fractions were investigated with respect to cytokine-inducing potential in primary macrophages isolated from rat lung. The results were related to the physical and chemical parameters of the samples in order to disclose possible connections between inflammatory potential and specific characteristics of the particles.     

Composition,anti-inflammatory,and antioxidant activities of avocado oil obtained from Duke and Fuerte cultivars

Avocado (Persea americana Mill.) fruit and oil are traditionally used for their antioxidant, anti-inflammatory and anti-aging properties. We investigated chemical variability between two avocado cultivars (Duke and Fuerte) in relation to their antioxidant and anti-inflammatory activities. Duke cultivar showed higher β-carotene and α-tocopherol content but significantly lower lipid content (36% dry weight) compared to Fuerte (52% dry weight). The ethanolic extract of Duke cultivar showed good antioxidant properties in 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay with IC₅₀ at 27.21 μg/ml, while that of Fuerte showed weak activity. Meanwhile, in rat paw edema anti-inflammatory model, Duke oil (15 mg/kg) was slightly more effective in reducing inflammation by 41.12% after 1 h compared to Fuerte oil (15 mg/kg). However, after 4 h, both oils showed comparable inhibition of edema by 35.39% and 34.14% (15 mg/kg). The study underscores that variability in chemical composition of different avocado cultivars could affect biological activities attributed to the fruit and its oil.     

A method for exposing rodents to resuspended particles using whole-body plethysmography

Background  

Epidemiological studies have reported increased risks of cardiopulmonary-related hospitalization and death in association with exposure to elevated levels of particulate matter (PM) across a wide range of urban areas. In response to these findings, researchers have conducted animal inhalation exposures aimed at reproducing the observed toxicologic effects. However, it is technically difficult to quantitate the actual amount of PM delivered to the lung in such studies, and dose is frequently estimated using default respiration parameters. Consequently, the interpretation of PM-induced effects in rodents exposed via whole-body inhalation is often compromised by the inability to determine deposited dose. To address this problem, we have developed an exposure system that merges the generation of dry, aerosolized particles with whole-body plethysmography (WBP), thus permitting inhalation exposures in the unrestrained rat while simultaneously obtaining data on pulmonary function.     

Kinetics of Enzyme Inhibition and Antihypertensive Effects of Hemp Seed (<Emphasis Type="Italic">Cannabis sativa</Emphasis> L.) Protein Hydrolysates

The aim of this study was to determine the antihypertensive effects of enzymatic hemp seed protein hydrolysate (HPH) and its peptide fractions. Hemp seed protein isolate was digested by the sequential action of pepsin and pancreatin to mimic gastrointestinal digestion in human beings. The resultant HPH was separated by membrane ultrafiltration into peptide fractions with different sizes (<1 and 1–3 kDa). The HPH led to significantly higher (P < 0.05) in vitro inhibition of the activities of angiotensin I-converting enzyme (ACE) and renin, the two main enzymes involved in abnormal blood pressure elevation (hypertension). Kinetic studies showed that HPH and peptide fractions inhibited renin and ACE activities in a mixed-type pattern, indicating binding to areas other than the active site. Oral administration of HPH (200 mg/kg body weight) to spontaneously hypertensive rats led to significant reductions (P < 0.05) in systolic blood pressure (SBP) that reached a maximum of −30 mmHg after 8 h. In contrast, the hypotensive effects of peptide fractions (<1 and 1–3 kDa) had a maximum value of about −15 mmHg after 6–8 h post oral administration. The results suggest a synergistic antihypertensive effect of the peptides present within HPH; this effect was reduced significantly (P < 0.05) upon separation into peptide fractions.     

Comparison of a low carbohydrate and low fat diet for weight maintenance in overweight or obese adults enrolled in a clinical weight management program

Background  

Recent evidence suggests that a low carbohydrate (LC) diet may be equally or more effective for short-term weight loss than a traditional low fat (LF) diet; however, less is known about how they compare for weight maintenance. The purpose of this study was to compare body weight (BW) for participants in a clinical weight management program, consuming a LC or LF weight maintenance diet for 6 months following weight loss.     

Vitamin E supplementation and pneumonia risk in males who initiated smoking at an early age: effect modification by body weight and dietary vitamin C

Background  

We had found a 14% higher incidence of pneumonia with vitamin E supplementation in a subgroup of the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) Study cohort: participants who had initiated smoking by the age of 20 years. In this study, we explored the modification of vitamin E effect by body weight, because the same dose could lead to a greater effect in participants with low body weight.     

Efficacy of a meal replacement diet plan compared to a food-based diet plan after a period of weight loss and weight maintenance: a randomized controlled trial

Background  

Obesity has reached epidemic proportions in the United States. It is implicated in the development of a variety of chronic disease states and is associated with increased levels of inflammation and oxidative stress. The objective of this study is to examine the effect of Medifast's meal replacement program (MD) on body weight, body composition, and biomarkers of inflammation and oxidative stress among obese individuals following a period of weight loss and weight maintenance compared to a an isocaloric, food-based diet (FB).     

Combustion of dried animal dung as biofuel results in the generation of highly redox active fine particulates

Background  

The burning of biomass in the developing world for heating and cooking results in high indoor particle concentrations. Long-term exposure to airborne particulate matter (PM) has been associated with increased rates of acute respiratory infections, chronic obstructive lung disease and cancer. In this study we determined the oxidative activity of combustion particles derived from the biomass fuel dung cake by examining their capacity to deplete antioxidants from a model human respiratory tract lining fluid (RTLF). For comparison, the observed oxidative activity was compared with that of particles derived from industrial and vehicular sources.     

Metabolic Kinetics of <Emphasis Type="Italic">tert</Emphasis>-Butylhydroquinone and Its Metabolites in Rat Serum after Oral Administration by LC/ITMS

Liquid chromatography–ion trap mass spectrometry (LC/ITMS) was employed for a metabolic kinetics study of tert-butylhydroquinone (TBHQ) and its metabolites in rat serum after oral administration. The mean serum concentration–time data of TBHQ and its four metabolites (M1–M4) in both male and female rats after oral administration of TBHQ at dosages of 7, 350 and 700 mg/kg were all best-fitted by a two-compartment model with first-order absorption. TBHQ was rapidly absorbed, distributed and metabolized. The metabolites were also distributed rapidly except M2, but eliminated more slowly than TBHQ. At the doses of 350 and 700 mg/kg, the total concentrations of TBHQ and its metabolites in serum were much higher for male than female rats during the metabolic process (P < 0.01). In addition, the serum concentrations of M1, M3 and M4 were all much higher for males than for females (P < 0.01) during the metabolic process, while no significant differences between male and female rats were found (P > 0.05) for TBHQ and M2, at the doses of 350 and 700 mg/kg. The exploratory assessment of dose proportionality for TBHQ and its metabolites by the power model indicated that the TBHQ exposure increased in a more-than-dose-proportional manner, but the exposures of the metabolites M1–M4 increased in a less-than-dose-proportional manner, across the dose of 7–700 mg/kg.     

Dietary Supplementation with 22-<Emphasis Type="Italic">S</Emphasis>-Hydroxycholesterol to Rats Reduces Body Weight Gain and the Accumulation of Liver Triacylglycerol

This study explores the pharmacokinetics of 22-S-hydroxycholesterol (22SHC) in vivo in rats. We also carried out a metabolic study to explore whether the beneficial effects observed of 22SHC on glucose and lipid metabolism in vitro could be seen in vivo in rats. In the pharmacokinetic study, rats were given 50 mg/kg of [³H]22-S-hydroxycholesterol before absorption, distribution and excretion were monitored. In the metabolic study, the effect of 22SHC (30 mg/kg/day for 3 weeks) in rats on body weight gain [chow and high-fat diet (HFD)], serum lipids triacylglycerol (TAG) content and gene expression in liver and skeletal muscle were examined. Results showed that 22SHC was well absorbed after oral administration and distributed to most organs and mainly excreted in feces. Rats receiving 22SHC gained less body weight than their controls regardless whether the animals received chow diet or HFD. Moreover, we observed that animals receiving HFD had elevated levels of serum TAG while this was not observed for animals on HFD supplemented with 22SHC. The amount of TAG in liver was reduced after 22SHC treatment in animals receiving either chow diet or HFD. Gene expression analysis revealed that two genes (carnitine palmitoyltransferase 2 and uncoupling protein 3) involved in fatty acid oxidation and energy dissipation were increased in liver. Ucp3 expression (both protein and mRNA level) was increased in skeletal muscle, but insulin-stimulated glucose uptake and TAG content were unchanged. In conclusion, 22SHC seems to be an interesting model substance in the search of treatments for disorders involving aberrations in lipid metabolism.     

Lower energy expenditures in infants from obese biological mothers

Background  

Previous studies in adults have found that a lower resting metabolic rate is a predictor of future body weight gain.     

Dose response effects of a caffeine-containing energy drink on muscle performance: a repeated measures design

Background

Energy drinks have become the most used caffeine-containing beverages in the sport setting. The aim of this study was to determine the effects of two doses of a caffeine-containing energy drink on muscle performance during upper- and lower-body power-load tests.

Methods

In a randomized order, twelve active participants ingested 1 and 3?mg of caffeine per kg of body weight using a commercially available energy drink (Fure?, ProEnergetics) or the same drink without caffeine (placebo; 0?mg/kg). After sixty minutes, resting metabolic rate, heart rate and blood pressure were determined. Then, half-squat and bench-press power production with loads from 10 to 100% of 1 repetition maximum was determined using a rotator encoder.

Results

In comparison to the placebo, the ingestion of the caffeinated drink increased mean arterial pressure (82?±?7?P?<?59?±?8?<?62?±?8 beats/min, respectively; P?P?P?Conclusions A caffeine dose of at least 3?mg/kg in the form of an energy drink is necessary to significantly improve half-squat and bench-press maximal muscle power.     

Response of spontaneously hypertensive rats to inhalation of fine and ultrafine particles from traffic: experimental controlled study

Background  

Many epidemiological studies have shown that mass concentrations of ambient particulate matter (PM) are associated with adverse health effects in the human population. Since PM is still a very crude measure, this experimental study has explored the role of two distinct size fractions: ultrafine (<0.15 μm) and fine (0.15- 2.5 μm) PM. In a series of 2-day inhalation studies, spontaneously hypersensitive (SH) rats were exposed to fine, concentrated, ambient PM (fCAP) at a city background location or a combination of ultrafine and fine (u+fCAP) PM at a location dominated by traffic. We examined the effect on inflammation and both pathological and haematological indicators as markers of pulmonary and cardiovascular injury. Exposure concentrations ranged from 399 μg/m³ to 3613 μg/m³ for fCAP and from 269μg/m³ to 556 μg/m³ for u+fCAP.