Do biomarkers of exposure and effect correlate with internal exposure to PAHs in swine?

Humans are commonly exposed to polycyclic aromatic hydrocarbons (PAHs), a family of compounds present as mixtures in the environment. This study exposed swine to PAH mixtures in single and subacute dose regimens and collected liver and ileum tissue to measure cytochrome P450 mRNA expression and enzyme activity as biomarkers of exposure and DNA adducts and oxidized proteins as biomarkers of effect. Micronucleated reticulocytes were measured as systemic biomarkers of effect. Duration of exposure did not influence biomarkers of exposure, though exposure duration produced significant increases in DNA adducts and oxidative stress. Micronucleated reticulocyte numbers were not affected by exposure length.     

Effects of long-term taurine supplementation on age-related changes in skeletal muscle function of Sprague–Dawley rats

Taurine (2-aminoethanesulfonic acid) is a free amino acid found abundantly in mammalian tissues. Increasing evidence suggests that taurine plays a role in the maintenance of skeletal muscle function and increase of exercise capacity. Most energy drinks contain this amino acid; however, there is insufficient research on the effects of long-term, low-dose supplementation of taurine. In this study, we investigated the effects of long-term administration of taurine at low doses on aging in rodents. In Experiment 1, we examined age-related changes in aging Sprague–Dawley (SD) rats (32–92 weeks old) that O₂ consumption and spontaneous activity decreased significantly with aging. In Experiment 2, we examined the effects of long-term (21-week) administration of taurine on healthy aging SD rats. SD rats were stabilized for 32–34 weeks and divided into three groups, administrated water (control), 0.5% taurine (25 mg/kg  body weight (BW)/day), or 1% taurine (50 mg/kg  BW/day) from age 34 to 56 weeks (5 days/week, 5 mL/kg BW). Our findings suggest that long-term administration of taurine at relatively low dose could attenuate the age-related decline in O₂ consumption and spontaneous locomotor activity. Upon intestinal absorption, taurine might modulate age-related changes in respiratory metabolism and skeletal muscle function via peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), succinate dehydrogenase (SDH), cytochrome c (Cycs), myocyte enhancer factor 2A (MEF2A), glucose transporter 4 (GLUT4), and myoglobin, which are regulated by the activation of AMP-activated protein kinase (AMPK). This article examines the mechanism underlying the effects of taurine on age-related changes, which may have potential clinical implications.

     

PGC-1α and FOXO1 mRNA levels and fiber characteristics of the soleus and plantaris muscles in rats after hindlimb unloading

Fifteen-week-old rats were subjected to unloading induced by hindlimb suspension for 3 weeks. The peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and forkhead box-containing protein O1 (FOXO1) mRNA levels and fiber profiles of the soleus and plantaris muscles in rats subjected to unloading (unloaded group) were determined and compared with those of age-matched control rats (control group). The body weight and both the soleus and plantaris muscle weights were lower in the unloaded group than in the control group. The PGC-1α mRNA was downregulated in the soleus, but not in the plantaris muscle of the unloaded group. The FOXO1 mRNA was upregulated in both the soleus and plantaris muscles of the unloaded group. The oxidative enzyme activity was reduced in the soleus, but not in the plantaris muscle of the unloaded group. The percentage of type I fibers was decreased and the percentages of type IIA and IIC fibers were increased in the soleus muscle of the unloaded group, whereas there was no change in fiber type distribution in the plantaris muscle of the unloaded group. Atrophy of all types of fibers was observed in both the soleus and plantaris muscles of the unloaded group. We conclude that decreased oxidative capacity and fiber atrophy in unloaded skeletal muscles are associated with decreased PGC-1α and increased FOXO1 mRNA levels.     

Peak drug levels in linear pharmacokinetic systems—I. Effect of rate of injection

This paper presents three theorems on the peak drug levels that result from injection into a linear pharmacokinetic system. As a preliminary, the “rate of injection” is defined in terms of time expansion or time contraction of the injection function (input). The first theorem then states that the peak drug level will not be greater when the rate of injection is slow than when it is fast, if the impulse response is unimodal. The second theorem sets limits for the time of the maximum drug level, in relation to the time of the maximum of the (unimodal) impulse response and the duration of the input. The third theorem defines conditions which assure a definitely lower peak drug level if the rate of injection is slower. A graphical method is suggested for determining the times and magnitudes of the peak drug levels that result from constant infusions of a fixed dose at different rates. An example is provided to show that if the impulse response is multimodal then the peak drug level may sometimes increase with a decrease in the injection rate. Supported in part by U.S. Public Health Service Research Grant GM 21269 from the National Institute of General Medical Sciences, and in part by Biomedical Research Support Grant S07 RR 05392 from the National Institutes of Health. A portion of this work was presented at the Annual Meeting of the Society for Mathematical Biology at the Medical School of the University of Pennsylvania, Philadelphia, August 1976.     

Content of liver and brain ubiquinol-9 and ubiquinol-10 after chronic ethanol intake in rats subjected to two levels of dietary α-tocopherol

To assess the effect of chronic ethanol ingestion in the content of the reduced forms of coenzymes Q₉ (ubiquinol-9) and Q₁₀ (ubiquinol-10) as a factor contributing to oxidative stress in liver and brain, male Wistar rats were fed ad libitum a basal diet containing either 10 or 2.5 mg α-tocopherol/100 g diet (controls), or the same basal diet plus a 32% ethanol-25% sucrose solution. After three months treatment, ethanol chronically-treated rats showed identical growth rates to the isocalorically pair-fed controls, irrespectively of α-tocopherol dietary level. Lowering dietary α-tocopherol led to a decreased content of this vitamin in the liver and brain of control rats, without changes in that of ubiquinol-9, and increased levels of hepatic ubiquinol-10 and total glutathione (tGSH), accompanied by a decrease in brain tGSH. At the two levels of dietary α-tocopherol, ethanol treatment significantly decreased the content of hepatic α-tocopherol and ubiquinols 9 and 10. This effect was significantly greater at 10 mg α-tocopherol/100 g diet than at 2.5, whereas those of tGSH were significantly elevated by 43% and 9%, respectively. Chronic ethanol intake did not alter the content of brain α-tocopherol and tGSH, whereas those of ubiquinol-9 were significantly lowered by 20% and 14% in rats subjected to 10 and 2.5 mg α-tocopherol/100 g diet, respectively. It is concluded that chronic ethanol intake at two levels of dietary α-tocopherol induces a depletion of hepatic α-tocopherol and ubiquinols 9 and 10, thus contributing to ethanol-induced oxidative stress in the liver tissue. This effect of ethanol is dependent upon the dietary level of α-tocopherol, involves a compensatory enhancement in hepatic tGSH availability, and is not observed in the brain tissue, probably due to its limited capacity for ethanol biotransformation and glutathione synthesis.     

Seasonal changes of water,electrolytes and aldosterone levels in blood serum,brain and kidney of the Egyptian cobra “Naja haje haje”

 

• 1.The levels of water, Na, K, Ca and Mg in blood serum, brain and kidney and aldosterone level in blood of Naja haje haje were studied during the different phases of the annual cycle.
• 2.The water content in the tissues studied displayed only minor changes as the animals passed from one phase to the other.
• 3.A significant increase in Na was recorded in the brain during the different phases indicating a depressed sodium pump, whereas the blood Na level showed a significant decrease during hibernation.
• 4.K increased in blood serum, brain and kidney during hibernation, while a nonsignificant decrease was found in blood serum during arousal. The brain may act as a potassium reservoir.
• 5.An increase in Ca and Mg concentration was recorded in blood serum, brain and kidney during prehibernation and hibernation. The data suggested a homeostatic function in the transport and metabolism of these cations.
• 6.Aldosterone exhibited a highly significant decrease especially during hibernation. The aldosterone regulation of ionic composition is discussed.
• 7.Na/K and Ca/Mg ratios in the brain may explain the decreased excitability during winter torpor.

     

Changes of macromolecular organizations in nonjunctional sarcolemmas after cross—innervation—a study of fast—and slow—twitch muscle fiberes in rats

The purpose of the present study was to analyse the changes of macromolecular organizations in nonjunctional sarcolemmas of different types of skeletal muscle fibres after cross-innervation.In normal rate the mean density of square arrays(6nm particles organized in orthogonal of square arrays(6nm particles organized in othogonal arrays)was 9.02/μm^2 for the nonjunctional sarcolemmas of fast-twitch extensor digitorum longus(control EDL,CE)muscle fibres and 0.34/μm^2 for the nunjunctional sarcolemmas of slow-twitch soleus(control SOL,CS)muscle fibres.After cross-innervation between the fast-twitch EDL and slow-twitch SOL muscle fibres by slow and fast muscle nerves respectively for three months ,the mean density was 0.45/μm^2 for the nonjunctional sarcolemmas of the operated EDL(OE)and 8.3/μm^2 for the nonjunctional sarcolemmas of the operated SOL(OS).This indicates that the cross-innervation causes a reciprocal transformation of the number and distribution of such macromolecular organizations in the electrically excitable nonjunctional sarcolemmas.     

The effects of β-glucan on iron levels and lipid peroxidation in intra-abdominal sepsis in rats

Sepsis is defined as a systemic response of organisms to microorganisms and toxins. Sepsis is associated with the enhanced generation of reactive oxygen metabolites, leading to multiple organ dysfunctions. β-glucan is accepted to be one of the most powerful immune response modifiers. The aim of this study was to investigate the putative protective effect of β-glucan on changes of iron and malondialdehyde (MDA) levels in various tissue and blood after experimental sepsis in rats. Sepsis was induced by cecal ligation and perforation (CLP) in 32 male Wistar albino rat. To evaluate this, rats were divided into four groups as sham operated, β-glucan treated sham operated, CLP and β-glucan treated CLP. Sixteen hours after operation, rats were decapitated and MDA and iron levels were measured in the liver, kidney, heart, diaphragm tissues and blood. Also, whole tissue histopathology was evaluated by a light microscope. The results demonstrate that sepsis significantly decreased iron levels of all tissues and blood. The decrease in tissue iron levels and the increase MDA levels demonstrate the role of trace elements and free radicals in sepsis-induced tissue damage. Our results indicate that the given dose of β-glucan was probably insufficient to prevent sepsis-induced organ injury.     

Surface potential changes in lipid monolayers and the ‘cut-off’ in anaesthetic effects of N-alkanols

The effects of 0.09 saturated solutions of the n-alkanols n-hexanol to n-tridecanol on the surface (compensation) potential of lipid monolayers have been examined. Actions on monolayers spread from pure egg phosphatidylcholine have been compared with effects on a system containing a 2:1 mole ratio of egg phosphatidylcholine and cholesterol. The mean compensation potential for the pure phospholipid system was 475 ± 9 mV; addition of cholesterol increased the potential to 503 ± 10 mV. All n-alkanols tested reduced the surface potential in both systems. The reduction was larger in the pure phospholipid system but the difference in effect between lipid systems declined as the n-alkanol chainlength increased, becoming negligible by n-tridecanol. These results are considered in relation to the ‘cut-off’ in biological activity of n-alkanols around n-tridecanol.     

Evaluating the relationship between biomarkers of potential harm and biomarkers of tobacco exposure among current,past, and nonsmokers: data from the National Health and Nutrition Examination Survey 2007–2012

Potential long-term health effects from tobacco products can be estimated by measuring changes in biochemical indicators of disease mechanisms like inflammation. This study assesses the potential relationships between biomarkers of potential harm (BOPH) and biomarkers of cigarette smoke exposure (BOE) based on data from the NHANES (2007–2012, n?=?17,293 respondents). Statistically significant relationships were observed between white blood cells (WBC) and high-density lipoprotein (HDL) and BOE; between WBC and high-sensitivity C-reactive protein and smoking status; and between WBC and HDL and smoking intensity. This analysis suggests that WBC and HDL are useful BOPH in studies assessing the health risks of cigarette smoking.     

Plasma concentrations of amino acid and nicotinamide metabolites in rheumatoid arthritis – potential biomarkers of disease activity and drug treatment

This study aimed to evaluate changes in plasma amino acid and nicotinamide metabolites concentrations in rheumatoid arthritis (RA) in a search for potential biomarkers of the disease activity and the effect treatment. Analysis of plasma metabolite patterns with liquid chromatography/mass spectrometry revealed specific changes in RA as well as correlations with clinical parameters. Combined concentration parameter calculated as [aspartic acid]?+?[threonine]?+?[tryptophan]???[histidine]???[phenylalanine] offered the strongest correlation (p?<?0.001) with pain joint count, swollen joint count and DAS 28. Such analysis of amino acid and related metabolite pattern offers potential for diagnosis as well as for monitoring disease progression and therapy in RA.     

Short- and long-term effects of temporary early cow–calf separation or restricted suckling on well-being and performance in zebu cattle

Information on weaning techniques in the tropics is scarce, particularly regarding the long-term effect of temporary early cow–calf separation or restricted suckling. Therefore, we studied the effects of these two handling practices on well-being and performance at 150 days postpartum in fifteen zebu cow–calf pairs randomly assigned to three treatments. Continuous suckling (CS) where calves remained with their dams from birth to weaning; restricted suckling (RS) calves were allowed to suckle 30 min/day from Day 34 until weaning at Day 150 and kept separated the rest of the time; temporary separation (TS) calves were separated for 72 h from their dams from Day 33 to 36 but remained with their dams the rest of the time. Blood samples and behavioral data were collected on Days 32–36 (1st period) and 149–153 (2nd period). In the 1st period, a greater percentage of RS and TS calves were observed close to the fence line (< 10 m) that separated them from their dams (P < 0.0001) and vocalized more than CS calves (P < 0.0001), while in the 2nd period, RS calves had the highest cortisol concentration and vocalization rate (P < 0.05). Similarly, during the 1st period, a greater percentage of RS and TS cows were observed close to the fence line than CS cows (P < 0.0001), with TS cows vocalizing the most (P = 0.001). In the 2nd period, RS cows had greater cortisol concentration than TS (P = 0.037) and CS cows (P = 0.003). More TS and CS cows than RS were observed close to the fence line (P = 0.03 and P = 0.05). On Day 150, TS calves and cows vocalized more than RS and CS animals (P < 0.0001). Before calf–cow separation, 27 out of 45 cows were cycling (CS = 10; RS = 6; TS = 11). After separation, 12 of the remaining 18 cows resumed ovarian activity (CS = 3; RS = 5; TS = 4), and all cows were cycling after estrous synchronization treatment. The pregnancy rate was similar between CS, RS, and TS (60, 53, and 60% respectively). In conclusion, temporary separation increased calf distress response to definitive weaning even four months later, while restricted suckling seemed to reduce it.     

β-adrenergic modulation of in vivo long-term potentiation in area CA1 and its role in spatial learning in rats

The hippocampus plays a key role in declarative learning and memory [1]. Hippocampal long-term potentiation (LTP) is a type of synaptic plasticity that has been widely studied as a syn-aptic mechanism underlying learning and memory[27]. It has been reported that in vitro LTP in area CA1 is subjected to b-adrenergic modulation. For example, the theta-pulse stimulation (510 Hz), a neutral frequency not modifying synaptic strength, can elicit a robust LTP in area CA1 in slice when the b-adr…     

Effects of β-adrenergic receptor agonists on drinking and arterial blood pressure in young and old rats

These experiments examined water-drinking and arterial blood pressure responses to β-adrenergic receptor activation in young (4 mo), "middle-aged" adult (12 mo), and old (29 mo) male rats of the Brown-Norway strain. We used isoproterenol to simultaneously activate β(1)- and β(2)-adrenergic receptors, salbutamol to selectively activate β(2)-adrenergic receptors, and the combination of isoproterenol and the β(2)-adrenergic receptor antagonist ICI 118,551 to stimulate only β(1)-adrenergic receptors. Animals received one of the drug treatments, and water drinking was measured for 90 min. About 1 wk later, animals received the same drug treatment for measurement of arterial blood pressure responses for 90 min. In some rats, levels of renin and aldosterone secretion in response to isoproterenol or salbutamol were measured in additional tests. Old and middle-aged rats drank significantly less after isoproterenol than did young rats and also had greater reductions in arterial blood pressure. Old and middle-aged rats drank significantly less after salbutamol than did young rats, although reductions in arterial blood pressure were equivalent across the ages. The β(2)-adrenergic antagonist ICI 118,551 abolished drinking after isoproterenol and prevented most of the observed hypotension. Renin secretion after isoproterenol and salbutamol was greater in young rats than in middle-aged rats, and wholly absent in old rats. Aldosterone secretion was reduced in old rats compared with young and middle-aged rats after treatment with isoproterenol, but not after treatment with salbutamol. In conclusion, there are age-related differences in β-adrenergic receptor-mediated drinking that can be explained only in part by age-related differences in renin secretion after β-adrenergic receptor stimulation.     

Can prenatal exposure to a 900 MHz electromagnetic field affect the morphology of the spleen and thymus,and alter biomarkers of oxidative damage in 21-day-old male rats?

We investigated the effects of a 900 Megahertz (MHz) electromagnetic field (EMF), applied during the prenatal period, on the spleen and thymus of 21-day-old male rat pups. Pregnant Sprague-Dawley rats were divided into control and EMF groups. We applied 900 MHz EMF for 1 h/day to the EMF group of pregnant rats. Newborn male rat pups were removed from their mothers and sacrificed on postnatal day 21. Spleen and thymus tissues were excised and examined. Compared to the control group, thymus tissue malondialdehyde levels were significantly higher in the group exposed to EMF, while glutathione levels were significantly decreased. Increased malondialdehyde and glutathione levels were observed in splenic tissue of rats exposed to EMF, while a significant decrease occurred in superoxide dismutase values compared to controls. Transmission electron microscopy showed pathological changes in cell morphology in the thymic and splenic tissues of newborn rats exposed to EMF. Exposure to 900 MHz EMF during the prenatal period can cause pathological and biochemical changes that may compromise the development of the male rat thymus and spleen.     

Obese state leads to elevated levels of TGF-β and COX isoforms in platelets of Zucker rats

Platelets are rich sources of growth factors and enzymes that are implicated in a number of diseases including obesity, atherosclerosis, heart disease, syndrome X, liver and kidney diseases and certain types of cancers. In this research we investigated, if platelets in Zucker obese rats differ from their lean counterparts with respect to the levels of TGF-β and COX isoforms, implicated in the pathogenesis of chronic diseases. In addition, we investigated if energy intake of the animals affects the platelet physiology. Platelets were isolated from obese and lean rats bearing preneoplastic lesions in their colon. Prior to platelet isolation these rats were fed either ad libitum (Ob or Ln) or energy restricted (Ob-ER or Ln-ER) diets for 8 weeks (n = 8/group). The levels of TGF-β1/-β2 and COX-1/-2 proteins in platelets were analyzed by Western blot. The platelets of the Ob rats had significantly higher levels of TGF-β1, COX-1/-2 (p < 0.001) than did the platelets of the Ln rats and were not affected by moderate energy restriction. There were no significant differences in the protein expression of platelet TGF-β2 among any of the groups. These results demonstrate that cytokines and candidates playing a role in the pathogenesis of chronic diseases, such as TGF-β1 and COX-1/-2, are over-expressed in platelets of Zucker obese rats by comparison to their lean counterparts. These findings also demonstrate that the genotype of the animals exerts a significant effect on the biochemical composition of the platelets and could contribute to the pathogenesis of colon cancer and other metabolic abnormalities associated with obesity.