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Rheumatoid arthritis is prevalent in more than 1% of the global population, with the highest occurrence between ages 35 and 50, which places a huge burden on the economy. Drug discovery for the prevention of this chronic disease is; therefore, a priority. It is known that subclinical progression of many chronic non-communicable diseases is exacerbated via accelerated ageing, a pro-inflammatory phenotype shift. However, rheumatoid arthritis additionally has significant humoral immune activation, inflammatory signalling-and thus the accelerated ageing profile-may differ from other chronic inflammatory diseases. The current study simulated inflammatory arthritis onset in a collagen-induced arthritis (CIA) rodent model, to characterise the redox and inflammatory profile at the onset of clinical symptoms, in different tissues, in the presence and absence of preventative antioxidant treatment. The data illustrate that an increased free radical level are evident already very early on in RA disease progression. Furthermore, oxidative stress seems to somewhat precede a significant pro-inflammatory state, perhaps due to humoral immune activation. Our data across different compartments further suggest that the compensatory increase in endogenous antioxidant activity is gradually exhausted at a different pace, with the liver showing the first signs of oxidant damage, even before significant evidence exist in circulation. The current data further suggest that preventative antioxidant intervention may have a sparing effect on endogenous antioxidant mechanisms and preserve telomere length to delay disease progression-or at least the accelerated ageing known to exacerbate RA symptoms-although it did not seem to have a significant direct effect on the autoimmune activity.

Rheumatoid arthritis targets numerous organs in patients, including the skeletal muscle, resulting in rheumatoid cachexia. In the muscle niche, satellite cells, macrophages, and myofibroblasts may be affected and the factors they release altered. This study aimed to assess these cell types, cytokines, and growth factors and their relationships to muscle fiber size and number in a rodent collagen‐induced arthritis (CIA) model, in order to identify new therapeutic targets. Fiber cross‐sectional area (CSA) was 57% lower in CIA than controls (p, Collagen‐induced arthritis in rodents simulate rheumatoid cachexia in humans. Skeletal muscle fibers exhibit decreased size, but not decreased number. Data illustrates that the unresolved inflammatory cellular environment hampers muscle maintenance, but that muscle fibers still have regenerative capacity.

Although rheumatoid arthritis affects 1% of the global population, the role of rheumatoid cachexia, which occurs in up to a third of patients, is relatively neglected as research focus, despite its significant contribution to decreased quality of life in patients. A better understanding of the cellular and molecular processes involved in rheumatoid cachexia, as well as its potential treatment, is dependent on elucidation of the intricate interactions of the cells involved, such as myoblasts, fibroblasts and macrophages. Persistent RA-associated inflammation results in a relative depletion of the capacity for regeneration and repair in the satellite cell niche. The repair that does proceed is suboptimal due to dysregulated communication from the other cellular role players in this multi-cellular environment. This includes the incomplete switch in macrophage phenotype resulting in a lingering pro-inflammatory state within the tissues, as well as fibroblast-associated dysregulation of the dynamic control of the extracellular matrix. Additional to this endogenous dysregulation, some treatment strategies for RA may exacerbate muscle wasting and no multi-cell investigation has been done in this context. This review summarizes the most recent literature characterising clinical RA cachexia and links these features to the roles of and complex communication between multiple cellular contributors in the muscle niche, highlighting the importance of a targeted approach to therapeutic intervention.

Mesenchymal stem cell (MSC) dysfunction is a serious complication in ageing and age-related inflammatory diseases such as type 2 diabetes mellitus. Inflammation and oxidative stress-induced cellular senescence alter the immunomodulatory ability of MSCs and hamper their pro-regenerative function, which in turn leads to an increase in disease severity, maladaptive tissue damage and the development of comorbidities. Targeting stem/progenitor cells to restore their function and/or protect them against impairment could thus improve healing outcomes and significantly enhance the quality of life for diabetic patients. This review discusses the dysregulation of MSCs' immunomodulatory capacity in the context of diabetes mellitus and focuses on intervention strategies aimed at MSC rejuvenation. Research pertaining to the potential therapeutic use of either pharmacological agents (NFкB antagonists), natural products (phytomedicine) or biological agents (exosomes, probiotics) to improve MSC function is discussed and an overview of the most pertinent methodological considerations given. Based on in vitro studies, numerous anti-inflammatory agents, antioxidants and biological agents show tremendous potential to revitalise MSCs. An integrated systems approach and a thorough understanding of complete disease pathology are however required to identify feasible candidates for in vivo targeting of MSCs.

Due to atrophy, muscle weakness is a common occurrence in rheumatoid arthritis (RA). The majority of human studies are conducted on the vastus lateralis muscle—a muscle with mixed fiber type—but little comparative data between multiple muscles in either rodent or human models are available. The current study therefore assessed both muscle ultrastructure and selected redox indicators across various muscles in a model of collagen-induced rheumatoid arthritis in female Sprague-Dawley rats. Only three muscles, the gastrocnemius, extensor digitorum longus (EDL), and soleus, had lower muscle mass (38%, 27%, and 25% loss of muscle mass, respectively; all at least P<0.01), while the vastus lateralis muscle mass was increased by 35% (P<0.01) in RA animals when compared to non-RA controls. However, all four muscles exhibited signs of deterioration indicative of rheumatoid cachexia. Cross-sectional area was similarly reduced in gastrocnemius, EDL, and soleus (60%, 58%, and 64%, respectively; all P<0.001), but vastus lateralis (22% smaller, P<0.05) was less affected, while collagen deposition was significantly increased in muscles. This pathology was associated with significant increases in tissue levels of reactive oxygen species (ROS) in all muscles except the vastus lateralis, while only the gastrocnemius had significantly increased levels of lipid peroxidation (TBARS) and antioxidant activity (FRAP). Current data illustrates the differential responses of different skeletal muscles of the hindlimb to a chronic inflammatory challenge both in terms of redox changes and resistance to cachexia.

Due to a lack of specific or sensitive biomarkers, drug discovery advances have been limited for individuals suffering from irritable bowel syndrome (IBS). While current therapies provide symptomatic relief, inflammation itself is relatively neglected, despite the presence of chronic immune activation and innate immune system dysfunction. Moreover, considering the microgenderome concept, gender is a significant aetiological risk factor. We believe that we have pinpointed a “missing link” that connects gender, dysbiosis, diet, and inflammation in the context of IBS, which may be manipulated as therapeutic target. The trace aminergic system is conveniently positioned at the interface of the gut microbiome, dietary nutrients and by-products, and mucosal immunity. Almost all leukocyte populations express trace amine associated receptors and significant amounts of trace amines originate from both food and the gut microbiota. Additionally, although IBS-specific data are sparse, existing data supports an interpretation in favour of a gender dependence in trace aminergic signalling. As such, trace aminergic signalling may be altered by fluctuations of especially female reproductive hormones. Utilizing a multidisciplinary approach, this review discusses potential mechanisms of actions, which include hyperreactivity of the immune system and aberrant serotonin signalling, and links outcomes to the symptomology clinically prevalent in IBS. Taken together, it is feasible that the additional level of regulation by the trace aminergic system in IBS has been overlooked, until now. As such, we suggest that components of the trace aminergic system be considered targets for future therapeutic action, with the specific focus of reducing oxidative stress and inflammation.

Considering that the phenomenon of accelerated ageing contributes to early onset of various chronic diseases, modelling of the relevant dysregulated systems or responses is vital for research aimed at identification of potential therapeutic targets. Here, we aimed to establish a model capable of simulating the redox and inflammatory changes of accelerated ageing—specifically, the aim was early phase accelerated ageing, which would allow therapeutic intervention in a preventative approach prior to clinical disease manifestation. A secondary aim was to evaluate the sensitivity of the model to reflect preventative treatment efficacy. Daily d-galactose injections (250 mg/kg body mass/day) for 8 weeks in 9-week-old male Wistar rats induced a model of early accelerated ageing (decreased plasma FRAP; P

It is a well-known fact that DHEA declines on ageing and that it is linked to ageing-related neurodegeneration, which is characterised by gradual cognitive decline. Although DHEA is also associated with inflammation in the periphery, the link between DHEA and neuroinflammation in this context is less clear. This review drew from different bodies of literature to provide a more comprehensive picture of peripheral vs central endocrine shifts with advanced age—specifically in terms of DHEA. From this, we have formulated the hypothesis that DHEA decline is also linked to neuroinflammation and that increased localised availability of DHEA may have both therapeutic and preventative benefit to limit neurodegeneration. We provide a comprehensive discussion of literature on the potential for extragonadal DHEA synthesis by neuroglial cells and reflect on the feasibility of therapeutic manipulation of localised, central DHEA synthesis.

Increasing consumer bias toward natural products and the considerable wealth of indigenous knowledge has precipitated an upturn in market-driven research into potentially beneficial medicinal plants. In this context, Aspalathus linearis (Rooibos) has been identified to be a promising candidate which may impact cardiovascular disease (CVD), which is one of the most widely studied chronic diseases of modern times. Despite these efforts, ischemic heart disease remains the number one cause of mortality globally. Apart from genetic predisposition and other aetiological mechanisms specific to particular types of CVD, co-factors from interlinked systems contribute significantly to disease development and the severity of its clinical manifestation. The bioactivity of Rooibos is directed towards multiple therapeutic targets. Experimental data to date include antioxidant, anti-inflammatory and anti-diabetic effects, as well as modulatory effects in terms of the immune system, adrenal steroidogenesis and lipid metabolism. This review integrates relevant literature on the therapeutic potential of Rooibos in the context of CVD, which is currently the most common of non-communicable diseases. The therapeutic value of whole plant extracts versus isolated active ingredients are addressed, together with the potential for overdose or herb-drug interaction. The body of research undertaken to date clearly underlines the benefits of Rooibos as both preventative and complementary therapeutic functional food in the context of CVD.

Staphylococcus aureus is a bacterial pathogen responsible for the majority of skin and soft tissue infections. Antibiotics are losing their efficacy as treatment for skin and soft tissue infections as a result of increased resistance in a variety of pathogens, including S. aureus . It is thus imperative to explore alternative antimicrobial treatments to ensure future treatment options for skin and soft tissue infections. A select few lantibiotics, a group of natural defense peptides produced by bacteria, inhibit the growth of numerous clinical S. aureus isolates, including methicillin-resistant strains. In this study, the antimicrobial activities of nisin, clausin, and amyloliquecidin, separately administered, were compared to that of a mupirocin-based ointment, which is commonly used as treatment for S. aureus- induced skin infections. Full-thickness excisional wounds, generated on the dorsal surfaces of mice, were infected with a bioluminescent strain of S. aureus (strain Xen 36). The infections were monitored in real time using in vivo bioluminescent imaging. Lantibiotic treatments significantly reduced the bioluminescence of S. aureus Xen 36 to a level similar to that recorded with mupirocin treatment. Wound closure, however, was more pronounced during lantibiotic treatment. Lantibiotics thus have the potential to be used as an alternative treatment option for S. aureus- induced skin infections.

With the effectiveness of therapeutic agents ever decreasing and the increased incidence of multi-drug resistant pathogens, there is a clear need for administration of more potent, potentially more toxic, drugs. Alternatively, biopharmaceuticals may hold potential but require specialized protection from premature in vivo degradation. Thus, a paralleled need for specialized drug delivery systems has arisen. Although cell-mediated drug delivery is not a completely novel concept, the few applications described to date are not yet ready for in vivo application, for various reasons such as drug-induced carrier cell death, limited control over the site and timing of drug release and/or drug degradation by the host immune system. Here, we present our hypothesis for a new drug delivery system, which aims to negate these limitations. We propose transport of nanoparticle-encapsulated drugs inside autologous macrophages polarized to M1 phenotype for high mobility and treated to induce transient phagosome maturation arrest. In addition, we propose a significant shift of existing paradigms in the study of host-microbe interactions, in order to study microbial host immune evasion and dissemination patterns for their therapeutic utilization in the context of drug delivery. We describe a system in which microbial strategies may be adopted to facilitate absolute control over drug delivery, and without sacrificing the host carrier cells. We provide a comprehensive summary of the lessons we can learn from microbes in the context of drug delivery and discuss their feasibility for in vivo therapeutic application. We then describe our proposed “synthetic microbe drug delivery system” in detail. In our opinion, this multidisciplinary approach may hold the solution to effective, controlled drug delivery.

The intestinal barrier, consisting of the vascular endothelium, epithelial cell lining, and mucus layer, covers a surface of about 400 m2. The integrity of the gut wall is sustained by transcellular proteins forming tight junctions between the epithelial cells. Protected by three layers of mucin, the gut wall forms a non-permeable barrier, keeping digestive enzymes and microorganisms within the luminal space, separate from the blood stream. Microorganisms colonizing the gut may produce bacteriocins in an attempt to outcompete pathogens. Production of bacteriocins in a harsh and complex environment such as the gastro-intestinal tract (GIT) may be below minimal inhibitory concentration (MIC) levels. At such low levels, the stability of bacteriocins may be compromised. Despite this, most bacteria in the gut have the ability to produce bacteriocins, distributed throughout the GIT. With most antimicrobial studies being performed in vitro, we know little about the migration of bacteriocins across epithelial barriers. The behavior of bacteriocins in the GIT is studied ex vivo, using models, flow cells, or membranes resembling the gut wall. Furthermore, little is known about the effect bacteriocins have on the immune system. It is generally believed that the peptides will be destroyed by macrophages once they cross the gut wall. Studies done on the survival of neurotherapeutic peptides and their crossing of the brain–blood barrier, along with other studies on small peptides intravenously injected, may provide some answers. In this review, the stability of bacteriocins in the GIT, their effect on gut epithelial cells, and their ability to cross epithelial cells are discussed. These are important questions to address in the light of recent papers advocating the use of bacteriocins as possible alternatives to, or used in combination with, antibiotics.

The current treatment options for soft tissue injuries remain suboptimal and often result in delayed/incomplete recovery of damaged muscle. The current study aimed to evaluate the effects of oral Prosopis glandulosa treatment on inflammation and regeneration in skeletal muscle after contusion injury, in comparison to a conventional treatment. The gastrocnemius muscle of rats was subjected to mass-drop injury and muscle samples collected after 1-, 3 h, 1- and 7 days post-injury. Rats were treated with P. glandulosa (100 mg/kg/day) either for 8 weeks prior to injury (up until day 7 post-injury), only post-injury, or with topically applied diclofenac post-injury (0.57 mg/kg). Neutrophil (His48-positive) and macrophage (F4/80-positive) infiltration was assessed by means of immunohistochemistry. Indicators of muscle satellite cell proliferation (ADAM12) and regeneration (desmin) were used to evaluate muscle repair. Chronic P. glandulosa and diclofenac treatment (p &lt, 0.0001) was associated with suppression of the neutrophil response to contusion injury, however only chronic P. glandulosa treatment facilitated more effective muscle recovery (increased ADAM12 (p &lt, 0.05) and desmin (p &lt, 0.001) expression), while diclofenac treatment had inhibitory effects on repair, despite effective inhibition of neutrophil response. Data indicates that P. glandulosa treatment results in more effective muscle repair after contusion.

Ethnopharmacological relevance Sceletium tortuosum, among other Sceletium species, was traditionally used by the Khoisan people of Southern Africa for relief of pain-related ailments. However, the commercial availability of this supplement has greatly expanded due to anecdotal claims of its mood-elevating and anxiolytic properties. Unrelated research has elucidated a significant link between cytokines and the mediation of depression. Therefore, the effect of Sceletium supplementation on immune cell functionality is of interest, since the efficacy of potential depression treatments could, at least in part, rely on downregulation of pro-inflammatory signalling. Aim of the study The current study evaluated the immunomodulatory effects of a Sceletium extract, both basally and in the context of acute endotoxin stimulation. Materials and methods Primary human monocytes were supplemented with either a 0.01 mg/ml or 1 mg/ml Sceletium extract dose, with or without E. coli LPS stimulation in vitro, for 24 h. Mitochondrial viability, as an indirect measure of cytotoxicity, and cytokine release in response to the treatment intervention were assessed. Results Sceletium extract treatment was associated with increased mitochondrial viability, as well as up-regulated IL-10 release under basal conditions. LPS exposure significantly decreased mitochondrial viability, but this was prevented completely under Sceletium-treated conditions. The acute inflammatory response to LPS stimulation was not negatively affected. Sceletium treatment conferred most significant effects at a dose of 0.01 mg/ml. Conclusions Sceletium exerts significant cytoprotective effects in the setting of endotoxin stimulation. Cytokine assessment indicated that Sceletium possesses mild anti-inflammatory properties, but does not hinder the mounting of an adequate immune response to acute immune challenge. These findings indicate that Sceletium may be beneficial for the attenuation of cytokine-induced depression, as well as in systemic low-grade inflammation.

AIMS Very little data are available on the physical requirements for drumming and the potential health benefits of particularly djembe drumming. We hypothesized that djembe drumming constitutes low-to-moderate intensity exercise, and that drumming would simultaneously reduce stress and anxiety levels and benefit cardiovascular health. METHODS Two study populations, middle-aged experienced drummers and a younger novice group participated in 40-min djembe drumming sessions. Measurements of blood pressure, blood lactate and stress and anxiety levels were taken before and after sessions. Also, heart rate was monitored at 5-s intervals throughout each session. RESULTS Participation in drumming significantly decreased the Stress Anxiety Index scores acutely, both in a middle-aged (P

Sutherlandia frutescens is widely used in indigenous medicine for the treatment of stress- and anxiety-related disorders, and although anecdotal evidence has been scientifically confirmed, relatively little data are available on its potential mechanisms of action. We manipulated a rodent model of acute psychological stress by acutely administering a low dose (4 mg/kg body mass) of S. frutescens extract 30 min prior to stress exposure (1 h restraint), to elucidate both its central and peripheral mechanisms of action in the context of acute stress. After 1 h of exposure to stress, acute restraint resulted in a significant increase in plasma corticosterone levels (56 ± 33 versus 499 ± 50 ng/ml; P

Staphylococcus aureus is a virulent pathogen and a major causative agent of superficial and invasive skin and soft tissue infections (SSSTIs). Antibiotic resistance in S. aureus , among other bacterial pathogens, has rapidly increased, and this is placing an enormous burden on the health care sector and has serious implications for infected individuals, especially immunocompromised patients. Alternative treatments thus need to be explored to continue to successfully treat infections caused by S. aureus , including antibiotic-resistant strains of S. aureus . In this study, an antimicrobial nanofiber wound dressing was generated by electrospinning nisin (Nisaplin) into poly(ethylene oxide) and poly( d,l -lactide) (50:50) blend nanofibers. Active nisin diffused from the nanofiber wound dressings for at least 4 days in vitro , as shown by consecutive transfers onto plates seeded with strains of methicillin-resistant S. aureus (MRSA). The nisin-containing nanofiber wound dressings significantly reduced S. aureus Xen 36 bioluminescence in vivo and viable cell numbers in a murine excisional skin infection model. The bacterial burden of wounds treated with nisin-containing nanofiber wound dressings was 4.3 × 10 2 CFU/wound, whereas wounds treated with control nanofiber wound dressings had 2.2 × 10 7 CFU/wound on the last day of the trial (day 7). Furthermore, the wound dressings stimulated wound closure of excisional wounds, and no adverse effects were observed by histological analysis. Nisin-containing nanofiber wound dressings have the potential to treat S. aureus skin infections and to potentially accelerate wound healing of excisional wounds.

Injury of skeletal muscle, and especially mechanically induced damage such as contusion injury, frequently occurs in contact sports, as well as in accidental contact sports, such as hockey and squash. The large variations with regard to injury severity and affected muscle group, as well as non-specificity of reported symptoms, complicate research aimed at finding suitable treatments. Therefore, in order to increase the chances of finding a successful treatment, it is important to understand the underlying mechanisms inherent to this type of skeletal muscle injury and the cellular processes involved in muscle healing following a contusion injury. Arguably the most important of these processes is inflammation since it is a consistent and lasting response. The inflammatory response is dependent on two factors, namely the extent of actual physical damage and the degree of muscle vascularization at the time of injury. However, long-term anti-inflammatory treatment is not necessarily effective in promoting healing, as indicated by various studies on NSAID treatment. Because of the factors named earlier, human studies on the inflammatory response to contusion injury are limited, but several experimental animal models have been designed to study muscle damage and regeneration. The early recovery phase is characterized by the overlapping processes of inflammation and occurrence of secondary damage. Although neutrophil infiltration has been named as a contributor to the latter, no clear evidence exists to support this claim. Macrophages, although forming part of the inflammatory response, have been shown to have a role in recovery, rather than in exacerbating secondary damage. Several probable roles for this cell type in the second phase of recovery, involving resolution processes, have been identified and include the following: (i) phagocytosis to remove cellular debris; (ii) switching from a pro- to anti-inflammatory phenotype in regenerating muscle; (iii) preventing muscle cells from undergoing apoptosis; (iv) releasing factors to promote muscle precursor cell activation and growth; and (v) secretion of cytokines and growth factors to facilitate vascular and muscle fibre repair. These many different roles suggest that a single treatment with one specific target cell population (e.g. neutrophils, macrophages or satellite cells) may not be equally effective in all phases of the post-injury response. To find the optimal targeted, but time-course-dependent, treatments requires substantial further investigations. However, the techniques currently used to induce mechanical injury vary considerably in terms of invasiveness, tools used to induce injury, muscle group selected for injury and contractile status of the muscle, all of which have an influence on the immune and/or cytokine responses. This makes interpretation of the complex responses more difficult. After our review of the literature, we propose that a standardized non-invasive contusion injury is the ideal model for investigations into the immune responses to mechanical skeletal muscle injury. Despite its suitability as a model, the currently available literature with respect to the inflammatory response to injury using contusion models is largely inadequate. Therefore, it may be premature to investigate highly targeted therapies, which may ultimately prove more effective in decreasing athlete recovery time than current therapies that are either not phase-specific, or not administered in a phase-specific fashion.

Advanced age is associated with increased incidence of a variety of chronic disease states which share oxidative stress and inflammation as causative role players. Furthermore, data point to a role for both cumulative oxidative stress and low grade inflammation in the normal ageing process, independently of disease. Therefore, arguably the best route with which to address premature ageing, as well as age-associated diseases such as diabetes, cardiovascular disease, and dementia, is preventative medicine aimed at modulation of these two responses, which are intricately interlinked. In this review, we provide a detailed account of the literature on the communication of these systems in the context of ageing, but with inclusion of relevant data obtained in other models. In doing so, we attempted to more clearly elucidate or identify the most probable cellular or molecular targets for preventative intervention. In addition, given the absence of a clear pharmaceutical solution in this context, together with the ever-increasing consumer bias for natural medicine, we provide an overview of the literature on grape (Vitis vinifera) derived products, for which beneficial effects are consistently reported in the context of both oxidative stress and inflammation.

Background Neuroinflammation is central to the aetiology of HIV-associated neurocognitive disorders (HAND) that are prevalent in late stage AIDS. Anti-retroviral (ARV) treatments are rolled out relatively late in the context of neuroinflammatory changes, so that their usefulness in directly preventing HAND is probably limited. It is common practice for HIV+ individuals in developing countries to make use of traditional medicines. One such medicine is Sutherlandia frutescens - commonly consumed as a water infusion. Here its efficacy as an anti-inflammatory modality in this context was investigated in an in vitro co-culture model of the blood–brain barrier (BBB). Methods Single cultures of human astrocytes (HA), HUVECs and primary human monocytes, as well as co-cultures (BBB), were stimulated with HIV-1 subtype B & C Tat protein and/or HL2/3 cell secretory proteins after pre-treatment with S.frutescens extract. Effects of this pre-treatment on pro-inflammatory cytokine secretion and monocyte migration across the BBB were assessed. Results In accordance with others, B Tat was more pro-inflammatory than C Tat, validating our model. S.frutescens decreased IL-1β secretion significantly (P

The aim of this study was to investigate the endotoxin-induced interleukin-6 (IL-6) release in whole blood cultures from samples taken at rest, 24 h post-exercise, from a control group of recreationally trained individuals (C), a group of highly trained triathletes (TA) and a group of highly trained professional rugby players (RP). Fifteen RP [mean (SD): age 26 (3) years, height 1.90 (0.2) m, body mass 104.5 (12.2 kg)], 13 male TA [age 33 (5) years, height 1.78 (0.1) m, body mass 76.3 (12.6) kg] and eight recreationally active male volunteers [age 28 (6) years, height 1.80 (0.1) m, body mass 72.3 (7.3) kg] participated in the study. Plasma IL-6 concentration and in vitro IL-6 synthesis by whole blood cultures were measured in samples taken at rest. Plasma IL-6 concentration was significantly higher ( P0.01) for the RP and TA groups than for C, as were the in vitro basal and endotoxin activated concentrations. However, after endotoxin stimulation, newly induced IL-6 concentration was significantly lower ( P0.01) in the RP and TA than in the C group. Therefore, professional rugby players have a similar IL-6 release of whole blood cultures in vitro to that of triathletes. Specifically, mononuclear cells appear to be chronically activated to spontaneously release IL-6, but have a decreased capacity to respond to a further stimulus. Amongst possible explanations for this, the most likely is counter-regulation due to already elevated IL-6 release.

AB Introduction: In vivo, daily proanthocyanidolic oligomer (PCO) supplementation before and after experimental skeletal muscle contusion injury has been shown to result in a blunted neutrophil response in tissue, quicker macrophage infiltration into muscle, and faster recovery due to a left shift in time course of inflammation. The current study investigated effects of PCO on circulatory neutrophils and macrophage subpopulations as well as in vitro neutrophil migration. Methods: Primary cultured neutrophils obtained from control animals were incubated in media with 20% conditioned plasma. To obtain conditioned media, male Wistar rats were supplemented with PCO (20 mg[middle dot]kg-1[middle dot]d-1) or placebo (PLA) for 2 wk before a mass-drop contusion injury. Conditioned plasma was prepared from blood collected at different time points after injury (12 h, 1 d, 3 d, and 5 d). Macrophage subpopulation distribution, inflammatory cytokine, and myeloperoxidase levels were assessed for all time points. Results: On day 1 postinjury, circulating neutrophil numbers were significantly lower in PLA than PCO, suggesting that extravasation from the blood was reduced by PCO. Concurrently, neutrophil migration in vitro was blunted in the presence of conditioned plasma from PCO supplemented rats compared with PLA supplemented rats. Plasma M1 and M2c macrophage numbers differed over time and between groups. M1 macrophage numbers peaked on day 3 with PCO supplementation, followed by a rise in M2c macrophages on day 5, when M1 macrophages numbers were still high in PLA. Conclusions: We conclude that PCO supplementation limits neutrophil migration capacity in vitro despite a chemotactic gradient. Furthermore, the earlier appearance of type M2 macrophages suggests a switch to an anti-inflammatory phenotype after injury even in circulation

Chapter described the complexity of simulating physiologically relevant stress levels in rodents

Purpose: Given the major role that oxidants play in cellular damage, and the recent focus on antioxidants as treatment for muscle injuries, the aim of this study was to examine the effect of short-term postinjury grape seed�derived polyphenol supplementation on muscle inflammation and repair processes after contusion injury. Methods: Experimental injury of the right gastrocnemius muscle was achieved by drop-mass method (200 g from a height of 50 cm), after which rats were gavaged with either 0.9% saline (placebo�PLA) or 20 mg·kg-1·d-1 of proanthocyanidolic oligomer (PCO) from 2 h after contusion injury, for up to 14 d after injury. Blood samples and injured muscle were collected at 4 h and at days 1, 3, 5, 7, and 14 after injury. Results: Compared to an uninjured control group, PCO supplementation resulted in an earlier peak in number of activated satellite cells in contusion-injured muscle tissue (4 h for PCO vs day 3 for PLA, n = 4 per time point per group) and fetal myosin heavy chain expression (day 5 for PCO, P < 0.01 with no change in PLA, n = 3 per time point per group), indicative of quicker muscle regeneration. PCO supplementation limited neutrophil infiltration and facilitated earlier macrophage infiltration into the injured area (n = 4 per group). PCO also resulted in an earlier return toward control levels of muscle proinflammatory cytokines on day 3 (P < 0.01 for interleukin 6 and P < 0 05 for tumor necrosis factor a, both n = 3 per group). Conclusions: Data show that short-term postinjury PCO supplementation was able to quicken muscle regeneration by facilitating earlier recruitment of activated satellite cells and to modulate the immune system in favor of an anti-inflammatory status.

The effect of acute pre-surgery dexamethasone treatment on the inflammatory immune and endocrine responses to orthopaedic surgery was investigated. Whole blood samples were obtained before and 5 days after surgery for immune analysis, and serum was obtained before and 6 h, 3 days and 5 days after surgery for endocrine assessment. Dexamethasone did not affect the post-surgery granulocyte response, but inhibited the increase in monocyte count (an average increase of 38.5% was seen in the control group). Peak C-reactive protein concentration (3 days after surgery) was 51.4% lower in the dexamethasone group than in the control group. Dexamethasone had a major effect on cortisol concentrations and the cortisol:testosterone and cortisol: dehydroepiandrosterone ratios, but no effect on anabolic hormone concentrations. In conclusion, acute pre-surgery dexamethasone treatment may have beneficial effects in the post-surgery period, by limiting the extent of systemic inflammation and the cortisol response.

The effects of exercise training on lymphocyte responses, as well as changes in circulating endocrine parameters at rest, were investigated. Seven male cyclists participated in a 4 week high-intensity (HI) cycling training intervention. Training improved performance significantly (peak power output (PPO): 1.4%, p < 0.05; 5 km time trial: 3.8%, p < 0.01; 40 km time trial: 0.4%, p < 0.05). Resting hormone concentrations (testosterone, sex hormone binding globulin (SHBG), cortisol, corticosteroid-binding globulin (CBG), and dehydroepiandrosterone-sulphate (DHEA-S)) were unchanged, with the exception of a 20% decrease in testosterone post-HI training (p < 0.067). Subjects' CD3+ cell counts decreased by 15% (p < 0.05), owing to significantly decreased CD4+ cell counts and slightly lower CD8+ and natural killer (NK) cell counts. Spontaneous in vitro CD69 expression increased in CD4+ cells (mean ± SD, pre: 12 ± 6 cells·µL-1; post: 35 ± 37 cells·µL-1; p < 0.05), but not in CD8+ cells (pre: 20 ± 29 cells·µL-1; post: 33 ± 16 cells·µL-1). Mitogen-induced CD69 expression decreased in both CD4+ (pre: 1570 ± 1258 cells·µL-1; post: 596 ± 597 cells·µL-1; p < 0.05) and CD8+ lymphocytes (pre: 676 ± 434 cells·µL-1; post: 412 ± 235 cells·µL-1; p < 0.05). Testosterone correlated positively with several immune parameters at baseline, whereas cortisol correlated negatively with parameters of the innate immune system post-HI training. We conclude that the stress of unaccustomed exercise is evident in resting lymphocytes, but not in resting endocrine parameters. However, correlations between testosterone and cortisol and immune parameters suggest that these 2 hormones play a role in modulating immune status. Our results indicate the importance of assessing both spontaneous and mitogen-induced aspects of immune-cell activation.Key words: CD69, DHEA, lymphocytes, exercise.

Objective. The impact of a professional cricket match schedule on white blood cell (WBC) distribution and lymphocyte activation (CD69 expression) was investigated. Methods. After a 3-month pre-season training period, physical and immune parameters were determined in 14 male cricketers before (B) and after (A) an intensive 5- week match schedule. Results. Exercise test results were unchanged from B to A. Total WBC counts were similar, but total lymphocyte and lymphocyte subpopulation counts decreased significantly. The CD4:CD8 ratio did not change. After in vitro stimulation, percentage CD4+CD69+ cells increased (B: 54.4 ± 9.7%, A: 64.0 ± 8.5%, p < 0.01), but absolute CD4+CD69+ cell counts did not change from B to A. In contrast, both the %CD8+CD69+ cells and absolute CD8+CD69+ cell count remained similar. Conclusion. A strenuous, interregional, professional cricket match schedule resulted in a decreased number of lymphocytes, but relatively increased in vitro reactivity of CD4+ cells, thus maintaining the absolute capacity of the CD4+ cells to become activated on stimulation. In cricketers who suffered upper respiratory tract symptoms during the match schedule (N = 7), none of the immune parameters investigated differed significantly from the others at B or A. SA Sports Medicine Vol.16(2) 2004: 22-27

Background and Aim: We aimed to determine the incidence of metabolic syndrome risk factors in young and older university campus population. The influence of life-style choices on the physiological risk profile was also assessed. Methods: For this cross-sectional study, 335 volunteers were recruited from the main campus of Stellenbosch University in the Western Cape, South Africa. Complete data sets were available for 200 subjects (older males n = 35; older females n = 53; young males n = 27 and young females n = 85). Venous blood samples were collected and analyzed for fasting levels of glucose, triglycerides (TG) and total cholesterol. In addition, height, body mass, waist and hip circumferences as well as resting pulse rate and blood pressure (BP), were determined and body mass index was calculated. Subjects also completed a questionnaire on life-style choices. Results: Central obesity and high BP was the major risk factors contributing to metabolic risk in the older population, while increased fasting TG level was the most common risk factor in young females. Gender differences in the young population included relatively higher cholesterol in females and higher BP in males. Although younger males consumed fast food more often than older males, the older population consumed significantly more alcohol and exercised significantly less. Conclusion: We conclude that different generations and gender difference may have different etiologies for metabolic risk. Therefore, the preventative education on metabolic risk and monitoring of disease progression should be optimized for individual groups and revised regularly in order to accommodate these differences.