Browsing by Author "Smith, C."

Now showing 1 - 9 of 9
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    Anti-inflammatory cellular targets on neutrophils elucidated using a novel cell migration model and confocal microscopy : a clinical supplementation study
    (BioMed Central, 2018-01-05) Smith, T.; Engelbrecht, L.; Smith, C.
    Background In vivo studies have shown grape seed-derived polyphenols (GSP) to benefit in recovery from muscle injury by modulation of neutrophil infiltration into damaged tissue, thereby reducing secondary damage, as well as by facilitating an early anti-inflammatory macrophage phenotype shift. The current study aimed to provide data in this context from human models and to elucidate specific molecular targets of GSP. Using a placebo-controlled, double-blind study design, eighteen normally healthy volunteers between the ages of 18–35 years old (13 female and 5 male) were orally supplemented with 140 mg/day of GSP for 2 weeks. Blood samples (days 0 and 14) were comprehensively analysed for in vitro neutrophil chemokinetic capacity towards a chemotaxin (fMLP) using a novel neutrophil migration assay, in combination with live cell tracking, as well as immunostaining for neutrophil polarisation factors (ROCK, PI3K) at migration endpoint. Macrophage phenotype marker expression was assessed using flow cytometry. Results fMLP induced significant chemokinesis (P < 0.01), validating our model. GSP did not exert a significant effect on neutrophil chemokinesis in this non-compromised population, but tended to decrease overall ROCK expression in fMLP-stimulated neutrophils (P = 0.06). Macrophage phenotype markers CD274 and MPO – indicators of a pro-inflammatory M1 phenotype – seemed to be normalised relative to baseline expression levels after GSP treatment. Conclusions Current data suggest that GSP may have a modulatory effect on the ROCK-PI3K-PTEN system, but results in this normal population is not conclusive and should be confirmed in a larger, more inflamed population. Potential modulation of macrophage phenotype by GSP should be investigated further.
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    Assessment of endocrine stress status in athletes – new twists to the tale
    (Health and Medical Publishing Group, 2005) Smith, C.; Myburgh, Kathryn H.
    Objective. Cortisol concentration at rest seems to be an insensitive marker for endocrine stress status in athletes. Therefore, the aim of this review was to identify potentially more sensitive parameters which could be used to monitor endocrine stress status during chronic exercise training. In order to gain more insight from studies not directly related to exercise science, this review also includes findings from studies investigating responses to psychological stress in healthy individuals and in patients suffering from chronic disease. Data sources. Medline. Study selection and data extraction. Key words (e.g. exercise stress, psychological stress, overtraining, chronic fatigue, dehydroepiandrosterone (DHEA), chronic inflammation). Only studies published in peer-reviewed journals included in the International Science Index were used. Care was specifically taken not to over-represent any particular research group’s articles. Data synthesis. A qualitative synthesis was done, based on all papers included in the review. Conclusions. Four main conclusions were drawn: (i) instead of considering changes in mean cortisol concentration over time for a group of athletes, high- and low-responders should be identified at baseline and their responses considered separately; (ii) it may be more useful to express cortisol concentration as a ratio to either testosterone or DHEA-sulphate (DHEAs) concentration than assessing either the catabolic or anti-catabolic variable on its own; (iii) in response to stress, cortisol binding globulin (CBG) and sex hormone binding globulin (SHBG) do not seem to play major roles in the regulation of circulating concentrations of bioactive cortisol and testosterone respectively; and (iv) it is crucial to allow sufficient recovery from the most recent exercise session to ensure that proper resting blood samples are obtained for assessment of chronic effects of training on endocrine status.
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    Central intracrine DHEA synthesis in ageing-related neuroinflammation and neurodegeneration : therapeutic potential?
    (BMC (part of Springer Nature), 2018-10-16) Powrie, Y. S. L.; Smith, C.
    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.
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    Chronic gestational inflammation : transfer of maternal adaptation over two generations of progeny
    (Hindawi, 2019-08-25) Adams, R. C. M.; Smith, C.; Pritchard, Michele T.
    Changes in the in utero environment result in generational transfer of maladapted physiology in the context of conditions such as stress, obesity, and anxiety. Given the significant contribution of noncommunicable diseases—which are characterised by chronic inflammation—to population mortality, the potential for chronic maternal inflammation mediating foetal programming is a growing concern. The extent of generational transfer in terms of immune functionality and leukocyte glucocorticoid sensitivity was investigated over two generations of offspring (F1 and F2) in a model of chronic LPS-induced maternal inflammation in C57/BL/6 mice. Maternal inflammation resulted in glucocorticoid hypersensitivity (increased glucocorticoid receptor expression levels) in the majority of leukocyte subpopulations in both F1 and F2 offspring. Furthermore, splenocytes stimulated with LPS in vitro exhibited exacerbated inflammatory cytokine responses, which were even more prominent in F2 than F1; this effect could be ascribed to NLRP3 inflammasome hyperactivity in F1 but not F2. Current data illustrates that parental chronic inflammation may mediate the inflammatory profile in offspring, potentially propagating a maladapted proinflammatory phenotype in subsequent generations.
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    Effects of redox disturbances on motility, contractility and muscle tissue pathogenesis
    (Hindawi, 2019-06-16) Karatzaferi, C.; Sandri, M.; Sakkas, G. K.; Smith, C.
    Whether in health or disease, reactive oxygen and nitrogen species (ROS/RNS) affect smooth and striated muscle status and function in ways not always discernible or appreciated. Despite the technological and methodological advancements, some key challenges still exist. On the one hand, one challenge is to appreciate acute effects on contractility and/or bioenergetics within a realistic functional context, effectively linking in vitro observations to in vivo conditions. On the other hand, chronic effects on indices of clinical significance are more difficult to clarify given the interplay of redox status variations with systemic inflammation and autophagy but also with lifestyle factors such as nutrition and physical activity—which impact on systemic health indices, as well as directly on smooth and striated muscles.
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    Illuminating the interrelated immune and endocrine adaptations after multiple exposures to short immobilization stress by in vivo blocking of IL-6
    (American Physiological Society, 2006-12) Smith, C.; Wilson, N. W.; Louw, Ann; Myburgh, K. H.
    ACUTE PSYCHOLOGICAL STRESS is known to activate the hypothalamic- pituitary-adrenal (HPA) axis, resulting in transiently increased release of inflammatory cytokines (28) and glucocorticoids (45). In contrast, multiple exposures to stress lead to adaptive responses in target tissues such as liver, skeletal muscle, and immune cells. These responses may be influenced by the severity of the stressor and the duration of the stress exposure. The endocrine and cytokine responses are known to be interrelated but are complex and still incompletely understood.
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    Redox status and muscle pathology in rheumatoid arthritis : insights from various rat hindlimb muscles
    (Hindawi, 2019-03-26) Oyenihi, A. B.; Ollewagen, T.; Myburgh, K. H.; Powrie, Y. S. L.; Smith, C.; Peluso, Ilaria
    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.
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    Rheumatoid cachexia : the underappreciated role of myoblast, macrophage and fibroblast interplay in the skeletal muscle niche
    (BioMed Central, 2021-03-03) Ollewagen, T.; Myburgh, K. H.; van de Vyver, M.; Smith, C.
    ENGLISH ABSTRACT: 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.
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    Safety assessment of antibiotic and probiotic feed additives for Gallus gallus domesticus
    (Nature Research, 2017) Neveling, D. P.; Van Emmenes, L.; Ahire, J. J.; Pieterse, E.; Smith, C.; Dicks, L. M. T.
    Antibiotics in feed select for resistant strains and is thus a threat to human health. In this study, the effect of a multi-strain probiotic and antibiotics on the growth and health of broilers was studied. Equal numbers of broilers received on a daily basis either a multi-strain probiotic or a combination of sulphadiazine, colistin and trimethoprim, whereas the control group received standard feed. The villi of immature broilers (19 days old) administered antibiotics had a larger surface area and their lymphocyte and basophil counts were higher compared to broilers from the probiotic and control groups. The cecal microbiomes of mature broilers (29 days old) that received probiotics had higher levels of Enterobacteriaceae, but lower numbers of Clostridiales, Brucellaceae, Synergistaceae, Erysipelotrichaceae and Coriobacteriaceae compared to the antibiotic-treated group. A decline in the bioluminescence of Listeria monocytogenes observed for broilers on probiotics suggested that the probiotic may be used to control bacterial infections. No significant differences in total red blood cell, haemoglobin and haematocrit content, and mean values for corpuscular volume, corpuscular haemoglobin and corpuscular haemoglobin numbers were recorded amongst broilers from the different treatment groups. This study provides valuable information on the health and performance of broilers when administered probiotics and antibiotics as additives.