Effect of high-frequency resistance exercise on adaptive responses in skeletal muscle

PURPOSE: Regulation of skeletal muscle mass is highly dependent on contractile loading. The purpose of this study was to examine changes in growth factor and inflammatory pathways following high-frequency resistance training. METHODS: Using a novel design in which male Sprague-Dawley rats undertook a "stacked" resistance training protocol designed to generate a summation of transient exercise-induced signaling responses (four bouts of three sets × 10 repetitions of squat exercise, separated by 3 h of recovery), we determined the effects of high training frequency on signaling pathways and transcriptional activity regulating muscle mass. RESULTS: The stacked training regimen resulted in acute suppression of insulin-like growth factor 1 mRNA abundance (P < 0.05) and Akt phosphorylation (P < 0.05), an effect that persisted 48 h after the final training bout. Conversely, stacked training elicited a coordinated increase in the expression of tumor necrosis factor alpha, inhibitor kappa B kinase alpha/beta activity (P < 0.05), and p38 mitogen-activated protein kinase phosphorylation (P < 0.05) at 3 h after each training bout. In addition, the stacked series of resistance exercise bouts induced an increase in p70 S6 kinase phosphorylation 3 h after bouts ×3 and ×4, independent of the phosphorylation state of Akt. CONCLUSIONS: Our results indicate that high resistance training frequency extends the transient activation of inflammatory signaling cascades, concomitant with persistent suppression of key mediators of anabolic responses. We provide novel insights into the effects of the timing of exercise-induced overload and recovery on signal transduction pathways and transcriptional activity regulating skeletal muscle mass in vivo.

Stored blood products augment inflammation in a two-event model of Transfusion Related Acute Lung Injury (TRALI)

Aim/Background TRALI is hypothesised to develop via a two-event mechanism involving both the patieint's underlying morbidity and blood product factors. The storage of cellular products has been implicated in cases of non-antibody mediated TRALI, however the pathophysiological mechanisms are undefined. We investigated blood product storage-related modulation of inflmmatory cells and medicators involved in TRALI. Methods In an in vitro mode, fresh human whole blood was mixed with culture media (control) or LPS as a 1st event and "transfused" with 10% (v/v) pooled supernatant (SN) from Day 1 (d1, n=75) or Day 42 (D42, n=113) packed red blood cells (PRBCs) as a 2nd event. Following 6hrs, culture SN was used to assess the overall inflammatory response (cytometric bead array) and a duplicate assay containing protein transport inhibitor was used to assess neutrophil- and monocyte-specific inflmamatory responses using multi-colour flow cytometry. Panels: IL-6, IL-8, IL-10, IL-12, IL-1, TNF, MCP-1, IP-10, MIP-1. One-way ANOVA 95% CI. Results In the absence of LPS, exposure to D1 or D42 PRBC-SN reduced monocyte expression of IL-6, IL-8 and Il-10. D42 PRBC-SN also reduced monocyte IP-10, and the overall IL-8 production was increased. In the presence of LPS, D1-PRBC SN only modified overall IP-10 levels which were reduced. However, cf LPS alone, the combination of LPS and D42 PRBC-SN resulted in increased neutrophil and monocyte productionof IL-1 and IL-8 as well as reduced monocyte TNF production. Additionally, LPS and D42 PRBC-SN resulted in overall inflmmatory changes: elevated IL-8, responses in non-antibody mediated TRALI.

Plasma lipid and lipoprotein responses during exercise

The purpose of this study was to examine the effect of prolonged exercise oil plasma lipid and lipoprotein concentrations and to identify caloric time-points where changes occurred. Eleven active male Subjects ran oil a treadmill at 70%,, of maximal fitness (VO2max) and expended 6 278.7 kilojoules (Kj) energy (1500 kcal). Blood samples were obtained at the 4185.8 Kj (1000 kcal) time-point during exercise and at each additional 418.6 Kj (100 kcal) expenditure until 6278.7 Kj was expended. After correcting for plasma volume changes, decreases in low-density lipoprotein cholesterol (LDL-C) were observed during exercise at time-points corresponding to 4604.4 and 5441.5 Kj (1100 and 1300 kcal) of energy expenditure, and immediately after exercise. Total cholesterol concentrations decreased significantly at exercise kilojoule expenditures of 4604.4, 5441.5 and 5860.1 (1100, 1300 and 1400 kcal). There were also exercise induced increases in high-density lipoprotein cholesterol (HDL-C) and HDL2-C concentrations immediately after exercise. Although acute lipid and lipoprotein changes are typically reported in the days following exercise, the Current data indicate that some lipoprotein concentrations change during acute exercise. Our data suggest that a threshold of exercise may be necessary to change lipoproteins during exercise. Future work Should identify potential mechanisms (lipoprotein lipase, cholesterol ester transport protein, LDL uptake) that alter lipoprotein concentrations during prolonged exercise.

In vitro investigations on the effect of dermal fibroblasts on keratinocyte responses to ultraviolet B radiation

Exposure to ultraviolet radiation is closely linked to the development of skin cancers in humans. The ultraviolet B (UVB) radiation wavelength (280-320 nm), in particular, causes DNA damage in epidermal keratinocytes, which are linked to the generation of signature premalignant mutations. Interactions between dermal fibroblasts and keratinocytes play a role in epidermal repair and regeneration after UVB-induced damage. To investigate these processes, established two and three-dimensional culture models were utilized to study the impact of fibroblast-keratinocyte crosstalk during the acute UVB response. Using a coculture system it was observed that fibroblasts enhanced keratinocyte survival and the repair of cyclobutane pyrimidine dimers (CPDs) after UVB radiation exposure. These findings were also mirrored in irradiated human skin coculture models employed in this study. Fibroblast coculture was shown to play a role in the expression and activation of members of the apoptotic cascade, including caspase-3 and Bad. Interestingly, the expression and phosphorylation of p53, a key player in the regulation of keratinocyte cell fate postirradiation, was also shown to be influenced by fibroblast-produced factors. This study highlights the importance of synergistic interactions between fibroblasts and keratinocytes in maintaining a functional epidermis while promoting repair and regeneration following UVB radiation-induced damage.

Effect of moderate- and high-intensity acute exercise on appetite in obese individuals

Purpose The effect of acute exercise, and exercise intensity, on appetite control in obese individuals requires further study. The aim of this study was to compare the effects of acute isocaloric bouts (250 kcal) of high-intensity intermittent cycling (HIIC) and moderate-intensity continuous cycling (MICC) or short-duration HIIC (S-HIIC) (125 kcal) and a resting control condition on the appetite hormone responses, subjective feelings of appetite, energy intake (EI), and food reward in overweight/obese individuals. Methods This study is a randomized crossover study on 12 overweight/obese volunteers. Participants were assigned to the control, MICC, HIIC, and S-HIIC conditions, 1 wk apart, in a counterbalanced order. Exercise was performed 1 h after a standard breakfast. An ad libitum test lunch was served 3 h after breakfast. Fasting/postprandial plasma samples of insulin, acylated ghrelin, polypeptide YY3–36, and glucagon-like peptide 1 and subjective feelings of appetite were measured every 30 min for 3 h. Nutrient and taste preferences were measured at the beginning and end of each condition using the Leeds Food Preference Questionnaire. Results Insulin levels were significantly reduced, and glucagon-like peptide 1 levels significantly increased during all exercise bouts compared with those during rest. Acylated ghrelin plasma levels were lower in the MICC and HIIC, but not in S-HIIC, compared with those in control. There were no significant differences for polypeptide YY3–36 plasma levels, hunger or fullness ratings, EI, or food reward. Conclusions Our findings suggest that, in overweight/obese individuals, isocaloric bouts of moderate- or high-intensity exercise lead to a similar appetite response. This strengthens previous findings in normal-weight individuals that acute exercise, even at high intensity, does not induce any known physiological adaptation that would lead to increased EI.

Reduced intensity conditioning for allogeneic hematopoietic stem cell transplant determines the kinetics of acute Graft-Versus-Host Disease

Background Preparative myeloablative conditioning regimens for allogeneic hematopoietic stem-cell transplantation (HSCT) may control malignancy and facilitate engraftment but also contribute to transplant related mortality, cytokine release, and acute graft-versus-host disease (GVHD). Reduced intensity conditioning (RIC) regimens have decreased transplant related mortality but the incidence of acute GVHD, while delayed, remains unchanged. There are currently no in vivo allogeneic models of RIC HSCT, limiting studies into the mechanism behind RIC-associated GVHD. Methods We developed two RIC HSCT models that result in delayed onset GVHD (major histocompatibility complex mismatched (UBI-GFP/BL6 [H-2b]→BALB/c [H-2d]) and major histocompatibility complex matched, minor histocompatibility mismatched (UBI-GFP/BL6 [H-2b]→BALB.B [H-2b])) enabling the effect of RIC on chimerism, dendritic cell (DC) chimerism, and GVHD to be investigated. Results In contrast with myeloablative conditioning, we observed that RIC-associated delayed-onset GVHD is characterized by low production of tumor necrosis factor-α, maintenance of host DC, phenotypic DC activation, increased T-regulatory cell numbers, and a delayed emergence of activated donor DC. Furthermore, changes to the peritransplant milieu in the recipient after RIC lead to the altered activation of DC and the induction of T-regulatory responses. Reduced intensity conditioning recipients suffer less early damage to GVHD target organs. However, as donor cells engraft, activated donor DC and rising levels of tumor necrosis factor-α are associated with a later onset of severe GVHD. Conclusions Delineating the mechanisms underlying delayed onset GVHD in RIC HSCT recipients is vital to improve the prediction of disease onset and allow more targeted interventions for acute GVHD.

Proteogenomics of selective susceptibility to endotoxin using circulating acute phase biomarkers and bioassay development in sheep: a review

Scientists have injected endotoxin into animals to investigate and understand various pathologies and novel therapies for several decades. Recent observations have shown that there is selective susceptibility to Escherichia coli lipopolysaccharide (LPS) endotoxin in sheep, despite having similar breed characteristics. The reason behind this difference is unknown, and has prompted studies aiming to explain the variation by proteogenomic characterisation of circulating acute phase biomarkers. It is hypothesised that genetic trait, biochemical, immunological and inflammation marker patterns contribute in defining and predicting mammalian response to LPS. This review discusses the effects of endotoxin and host responses, genetic basis of innate defences, activation of the acute phase response (APR) following experimental LPS challenge, and the current approaches employed in detecting novel biomarkers including acute phase proteins (APP) and micro-ribonucleic acids (miRNAs) in serum or plasma. miRNAs are novel targets for elucidating molecular mechanisms of disease because of their differential expression during pathological, and in healthy states. Changes in miRNA profiles during a disease challenge may be reflected in plasma. Studies show that gel-based two-dimensional electrophoresis (2-DE) coupled with either matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) or liquid chromatography-mass spectrometry (LC-MS/MS) are currently the most used methods for proteome characterisation. Further evidence suggests that proteomic investigations are preferentially shifting from 2-DE to non-gel based LC-MS/MS coupled with data extraction by sequential window acquisition of all theoretical fragment-ion spectra (SWATH) approaches that are able to identify a wider range of proteins. Enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), and most recently proteomic methods have been used to quantify low abundance proteins such as cytokines. qRT-PCR and next generation sequencing (NGS) are used for the characterisation of miRNA. Proteogenomic approaches for detecting APP and novel miRNA profiling are essential in understanding the selective resistance to endotoxin in sheep. The results of these methods could help in understanding similar pathology in humans. It might also be helpful in the development of physiological and diagnostic screening assays for determining experimental inclusion and endpoints, and in clinical trials in future

Photosynthetic responses of seven tropical seagrasses to elevated seawater temperature

This study uses chlorophyll a fluorescence to examine the effect of environmentally relevant (1-4 h) exposures of thermal stress (35-45 [deg]C) on seagrass photosynthetic yield in seven tropical species of seagrasses. Acute response of each tropical seagrass species to thermal stress was characterised, and the capacity of each species to tolerate and recover from thermal stress was assessed. Two fundamental characteristics of heat stress were observed. The first effect was a decrease in photosynthetic yield (Fv / Fm) characterised by reductions in F and Fm'. The dramatic decline in Fv / Fm ratio, due to chronic inhibition of photosynthesis, indicates an intolerance of Halophila ovalis, Zostera capricorni and Syringodium isoetifolium to ecologically relevant exposures of thermal stress and structural alterations to the PhotoSystem II (PSII) reaction centres. The decline in Fm' represents heat-induced photoinhibition related to closure of PSII reaction centres and chloroplast dysfunction. The key finding was that Cymodocea rotundata, Cymodocea serrulata, Halodule uninervis and Thalassia hemprichii were more tolerant to thermal stress than H. ovalis, Z. capricorni and S. isoetifolium. After 3 days of 4 h temperature treatments ranging from 25 to 40 [deg]C, C. rotundata, C. serrulata and H. uninervis demonstrated a wide tolerance to temperature with no detrimental effect on Fv / Fm' qN or qP responses. These three species are restricted to subtropical and tropical waters and their tolerance to seawater temperatures up to 40 [deg]C is likely to be an adaptive response to high temperatures commonly occurring at low tides and peak solar irradiance. The results of temperature experiments suggest that the photosynthetic condition of all seagrass species tested are likely to suffer irreparable effects from short-term or episodic changes in seawater temperatures as high as 40-45 [deg]C. Acute stress responses of seagrasses to elevated seawater temperatures are consistent with observed reductions in above-ground biomass during a recent El Nino event.

Chronic and acute stress in atherosclerosis : the role of endothelial function and arterial elasticity

Atherosclerosis is the main underlying pathology of coronary heart disease. Coronary heart disease is a serious health problem in Finland, and it is the leading cause of morbidity and mortality in industrialized countries. Psychological stress correlates with coronary heart disease events – myocardial infarction and sudden death, which are the most common clinical syndromes of atherosclerotic narrowing of arteries. The present series of studies examines the interaction between stress and endothelial function in relation to atherosclerosis. The study also aims to give new information on the mechanisms through which stress has its effect on atherosclerosis progression, focusing on possible relations between psychological stress and the functioning of the endothelium. Our project is based on data from one of the largest national epidemiological studies, the Cardiovascular Risk in Young Finns study, which has monitored the development of risk factors for coronary heart disease in 3596 young adults since 1980. The present study combines experimental stress research with epidemiology and uses an advanced method for examining atherosclerosis development in healthy subjects (intima-media thickness ultrasound measurement). The physiological parameters used were heart rate, respiratory sinus arrhythmia and pre-ejection period. Chronic stress was assessed by vital exhaustion. The ultrasound measurements that served as the indexes of preclinical atherosclerosis were carotid intima-media thickness, brachial flow-mediated dilatation and carotid artery compliance. The effects of cardiovascular risk factors found to be important were taken into account: serum cholesterols level, triglyceride level, serum insulin level and systolic and diastolic blood pressure. There were 69, 1596, 81 and 1721 participants in studies I-IV, respectively. The results showed that both chronic and acute stress may exert an effect on atherosclerosis in subjects with impaired endothelial responses. The findings are consistent with the idea that risk factors are more harmful if the endothelium is not working properly. Chronic stress was found to be a risk if it has resulted in ineffective cardiac stress reactivity or delayed recovery. Men were shown to be at increased risk for atherosclerotic progression in early life, which suggests men’s decreased stress coping ability in relation to stressful psychosocial coronary risk factors. Autonomic imbalance may be the common mechanism of the stress influence on atherosclerosis development. The results of the present study contain background information for the identification the first stages of atherosclerosis, and they may be useful for preventive medicine programs for young adults and could help to improve cardiovascular health in Finland as well as in other countries.

Uropathogenic Escherichia Coli engages CD14-dependent signaling to enable bladder-macrophage-dependent control of acute urinary tract infection

Background CD14, a coreceptor for several pattern recognition receptors and a widely used monocyte/macrophage marker, plays a key role in host responses to gram-negative bacteria. Despite the central role of CD14 in the inflammatory response to lipopolysaccharide and other microbial products and in the dissemination of bacteria in some infections, the signaling networks controlled by CD14 during urinary tract infection (UTI) are unknown. Methods We used uropathogenic Escherichia coli (UPEC) infection of wild-type (WT) C57BL/6 and Cd14−/− mice and RNA sequencing to define the CD14-dependent transcriptional signature and the role of CD14 in host defense against UTI in the bladder. Results UPEC induced the upregulation of Cd14 and the monocyte/macrophage-related genes Emr1/F4/80 and Csf1r/c-fms, which was associated with lower UPEC burdens in WT mice, compared with Cd14−/− mice. Exacerbation of infection in Cd14−/− mice was associated with the absence of a 491-gene transcriptional signature in the bladder that encompassed multiple host networks not previously associated with this receptor. CD14-dependent pathways included immune cell trafficking, differential cytokine production in macrophages, and interleukin 17 signaling. Depletion of monocytes/macrophages in the bladder by administration of liposomal clodronate led to higher UPEC burdens. Conclusions This study identifies new host protective and signaling roles for CD14 in the bladder during UPEC UTI.

A comparison of welfare outcomes for weaner and mature Bos indicus bulls surgically or tension band castrated with or without analgesia: 2. Responses related to stress, health and productivity

Tension banding castration of cattle is gaining favour because it is relatively simple to perform and is promoted by retailers of the banders as a humane castration method. Two experiments were conducted, under tropical conditions using Bos indicus bulls comparing tension banding (Band) and surgical (Surgical) castration of weaner (7–10 months old) and mature (22–25 months old) bulls with and without pain management (NSAID (ketoprofen) or saline injected intramuscularly immediately prior to castration). Welfare outcomes were assessed using a range of measures; this paper reports on some physiological, morbidity and productivity-related responses to augment the behavioural responses reported in an accompanying paper. Blood samples were taken on the day of castration (day 0) at the time of restraint (0 min) and 30 min (weaners) or 40 min (mature bulls), 2 h, and 7 h; and days 1, 2, 3, 7, 14, 21 and 28 post-castration. Plasmas from day 0 were assayed for cortisol, creatine kinase, total protein and packed cell volume. Plasmas from the other samples were assayed for cortisol and haptoglobin (plus the 0 min sample). Liveweights were recorded approximately weekly to 6 weeks and at 2 and 3 months post-castration. Castration sites were checked at these same times to 2 months post-castration to score the extent of healing and presence of sepsis. Cortisol concentrations (mean ± s.e. nmol/L) were significantly (P < 0.05) higher in the Band (67 ± 4.5) compared with Surgical weaners (42 ± 4.5) at 2 h post-castration, but at 24 h post-castration were greater in the Surgical (43 ± 3.2) compared with the Band weaners (30 ± 3.2). The main effect of ketoprofen was on the cortisol concentrations of the mature Surgical bulls; concentrations were significantly reduced at 40 min (47 ± 7.2 vs. 71 ± 7.2 nmol/L for saline) and 2 h post-castration (24 ± 7.2, vs. 87 ± 7.2 nmol/L for saline). Ketoprofen, however, had no effect on the Band mature bulls, with their cortisol concentrations averaging 54 ± 5.1 nmol/L at 40 min and 92 ± 5.1 nmol/L at 2 h. Cortisol concentrations were also significantly elevated in the Band (83 ± 3.0 nmol/L) compared with Surgical mature bulls (57 ± 3.0 nmol/L) at weeks 2–4 post-castration. The timing of this elevation coincided with significantly elevated haptoglobin concentrations (mg/mL) in the Band bulls (2.97 ± 0.102 for mature bulls and 1.71 ± 0.025 for weaners, vs. 2.10 ± 0.102 and 1.45 ± 0.025 respectively for the Surgical treatment) and evidence of slow wound healing and sepsis in both the weaner (0.81 ± 0.089 not healed at week 4 for Band, 0.13 ± 0.078 for Surgical) and mature bulls (0.81 ± 0.090 at week 4 for Band, 0.38 ± 0.104 for Surgical). Overall, liveweight gains of both age groups were not affected by castration method. The findings of acute pain, chronic inflammation and possibly chronic pain in the mature bulls at least, together with poor wound healing in the Band bulls support behavioural findings reported in the accompanying paper and demonstrate that tension banding produces inferior welfare outcomes for weaner and mature bulls compared with surgical castration.

Patient perspectives of factors contributing to inadequate dietary intake in acute care patients in hospital

Up to 30% of acute care patients consume less than half of the food provided in hospital. Inadequate dietary intake can have adverse clinical outcomes, including a higher risk of in-hospital mortality. This study aimed to investigate the reasons for poor intake among acute care patients in hospital. Patients with an observed intake of ≤50% of the food provided at lunch were approached to participate in the study. Thirty-two patients participated in semi-structured interviews over a three week period, to provide their perspective of food and mealtimes in hospital and discuss the reasons and factors influencing inadequate intake. Responses were coded and analysed thematically using the framework method. Patients reported both individual and organisational factors contribute to their inadequate intake. Half the patients reported the size of the meals were too large, with some patients reporting that large meal sizes puts them off their food and reduced their intake. ‘Not important to eat all the food provided’, and ‘do not need to eat much food in hospital’ were common attitudes among the patients. Half the patients reported that nurses did not observe their intake and were not concerned if all the food was not eaten. Identifying the reasons for poor intake can assist with the development of suitable interventions to improve dietary intake and reduce the risk of adverse clinical outcomes. Further investigation of suitable interventions to reduce portion sizes and improve both staff and patient perceptions of the importance of food in hospital is recommended.

Immune responses to hemagglutinin-neuraminidase protein of peste des petits ruminants virus expressed in transgenic peanut plants in sheep

Peste des petits ruminants (PPR) is an acute, highly contagious disease of small ruminants caused by a morbillivirus, Peste des petits ruminants virus (PPRV). The disease is prevalent in equatorial Africa, the Middle East, and the Indian subcontinent. A live attenuated vaccine is in use in some of the countries and has been shown to provide protection for at least three years against PPR. However, the live attenuated vaccine is not robust in terms of thermotolerance. As a step towards development of a heat stable subunit vaccine, we have expressed a hemagglutinin-neuraminidase (HN) protein of PPRV in peanut plants (Arachis hypogea) in a biologically active form, possessing neuraminidase activity. Importantly. HN protein expressed in peanut plants retained its immunodominant epitopes in their natural conformation. The immunogenicity of the plant derived HN protein was analyzed in sheep upon oral immunization. Virus neutralizing antibody responses were elicited upon oral immunization of sheep in the absence of any mucosal adjuvant. In addition, anti-PPRV-HN specific cell-mediated immune responses were also detected in mucosally immunized sheep. (C) 2010 Elsevier B.V. All rights reserved.

Acute toxicities of Basudine and Gammalin 20 to Aphyosemin gairdneri

Effects of Basudine and Gammalin 20 on the fingerlings of Aphyosemin gairdneri were investigated using static bioassays and continuous aeration over a period of 48 hours. The 48 hours LC sub(50) of the exposed fish to Basudine and Gammalin 20 were determined to be 194.99 mu g dm super(3) and 95.50 mu g dm super(3) respectively. Gammalin 20 was more toxic than Basudine. The behavioural responses observed include agitation, erratic swimming, loss of equilibrium, period of quiescence and death. It is concluded that repeated applications of these herbicides should be avoided before stocking ponds with fish

Effect of Neonatal Asphyxia on the Impairment of the Auditory Pathway by Recording Auditory Brainstem Responses in Newborn Piglets: A New Experimentation Model to Study the Perinatal Hypoxic-Ischemic Damage on the Auditory Syste

Introduction Hypoxia-ischemia (HI) is a major perinatal problem that results in severe damage to the brain impairing the normal development of the auditory system. The purpose of the present study is to study the effect of perinatal asphyxia on the auditory pathway by recording auditory brain responses in a novel animal experimentation model in newborn piglets. Method Hypoxia-ischemia was induced to 1.3 day-old piglets by clamping 30 minutes both carotid arteries by vascular occluders and lowering the fraction of inspired oxygen. We compared the Auditory Brain Responses (ABRs) of newborn piglets exposed to acute hypoxia/ischemia (n = 6) and a control group with no such exposure (n = 10). ABRs were recorded for both ears before the start of the experiment (baseline), after 30 minutes of HI injury, and every 30 minutes during 6 h after the HI injury. Results Auditory brain responses were altered during the hypoxic-ischemic insult but recovered 30-60 minutes later. Hypoxia/ischemia seemed to induce auditory functional damage by increasing I-V latencies and decreasing wave I, III and V amplitudes, although differences were not significant. Conclusion The described experimental model of hypoxia-ischemia in newborn piglets may be useful for studying the effect of perinatal asphyxia on the impairment of the auditory pathway.