Pro-inflammatory cytokines have been implicated in the pathophysiology and maintenance of depression. This study investigated the effects of a short mindfulness intervention on pro-inflammatory correlates of depression (IL-6 and TNF-α) and selfreported psychological health. Sixty-four college females were assigned to a four-week mindfulness training group or a contact-control group. Cytokines and psychological health were assessed at baseline, post-treatment, and 3-month follow-up (mindfulness group only). IL-6 and TNF-α significantly decreased from baseline to post-treatment in the mindfulness group only; these changes were sustained at 3-month follow-up. No between-group differences in psychological health emerged. Although reductions in proinflammatory cytokines in the mindfulness condition were not attributable to psychological changes, they may serve to protect against the development of future depressive episodes.

The concept of sickness behavior offers a framework to view both the neurovegetative and psychological symptoms that accompany illness as a common entity that results from increased inflammatory activation. Despite the prevalence of sickness behavior in medical populations, to our knowledge this study provides the first attempt to develop a standardized measure to assess sickness behavior using standard self-report questionnaires commonly used with cancer patients. The set of items included in the measure match theoretical conceptualizations of sickness behavior and target symptoms that comprise anhedonia, depressed mood, cognitive dysfunction, social disinterest, fatigue, low libido, poor appetite, somnolence, sensitivity to pain, and malaise. The measure showed high internal consistency, adequate test-retest reliability, and good convergent validity with both psychological and biological correlates. A confirmatory factor analysis also determined that a two-factor, rather than a single-factor measurement model, encompassing a physical and a psychological sickness symptom dimension, accounted for sickness behavior. Future psychometric work is still needed to further validate this new practical assessment tool. Descriptive analyses revealed relatively low levels of sickness behavior symptoms in the sample as a whole with both physical and psychological sickness behavior symptoms exhibiting a significant linear decrease over time. As expected, both physical and psychological sickness behavior symptoms showed associations with two pro-inflammatory cytokine markers, IL6 and TNF-alpha and a neuroendocrine marker, cortisol. Longitudinal associations suggest that higher levels of the pro-inflammatory cytokine TNF-alpha may impact the progressive decline of physical sickness symptoms over time with symptoms taking longer to disappear. Because cortisol was associated with more rather than less physical sickness symptoms, results raise the question of whether the anti-inflammatory neuroendocrine activity may be dysregulated in breast cancer survivors. The mechanistic basis for these associations requires further examination. In this study it was also evaluated whether a cognitive behavioral stress management intervention and relaxation training intervention could reduce sickness symptoms over time. Breast cancer survivors were assessed at baseline and then randomly assigned to a 10-week cognitive behavioral stress management intervention (N = 70) or a 1-day control condition (N = 55). Psychosocial measures, urine, and blood were obtained from participants at 3 months, 6 months, and 12 months post-intervention to assess relevant behavioral, endocrine and immune variables. Relative to the control group, the experimental group showed marginally more prevalence of physical sickness behavior symptoms in the short term (post-intervention, 3-months; p = .08) and a steadier decline of symptoms in the long-term (15-month follow-up period). The adaptive nature of sickness behavior as a motivational strategy that helps restore homeostatic balance in the long run may be one possible interpretation of these results. Whether these intervention effects on sickness behavior were mediated by changes in pro-inflammatory cytokines or cortisol was examined but not supported by these data and needs to be further examined in future studies.

The circadian system provides living organisms a means to adapt their internal physiology to constantly changing environmental conditions that exists on our rotating planet, Earth. Clocks in peripheral tissues are referred to as peripheral which may participate in tissue-specific functions. The first step to investigating the circadian regulation in the peripheral tissues of avians was to examine for the presence of avian orthologs of core components of the molecular clock using Quantitative real time (qRTPCR) assays. We investigated the avian spleen for daily and circadian control of core clock genes and regulation of the inflammatory response by the spleen clock. The core clock genes, bmal1, bmal2, per2, per3 and clock displayed both daily and circadian rhythms. Proinflammatory cytokines TNFα, IL-1β, IL-6 and IL-18 exhibited daily and circadian rhythmic oscillations. A differential expression of proinflammatory cytokine induction was observed in the spleen undergoing lipopolysaccharide (LPS)-induced acute inflammation. Exogenous melatonin administration during inflammation seems to enhance some and repress a few inflammatory cytokines, implying that melatonin is pleiotropic molecule. To compare and contrast the role of peripheral clocks in regulating energy balance and reproduction in layer vs. broiler chicken, the visceral adipose tissue (VAT), ovary and hypothalamus were examined for the presence of core clock genes were investigated in these two lines of poultry birds. Quantitative RT-PCR was employed to examine daily control of core clock genes in these three peripheral tissues over a 24hr period. The layer hens exhibit rhythmic oscillations in the mRNA abundance of the core clock genes in the VAT, ovary and the hypothalamus. The hypothalamus and VAT of the broiler hens exhibit rhythmic mRNA abundance of the core clock genes. However, the clock genes in the ovary of the broiler pullets exhibit marked reduction in their amplitude and rhythms over a 24hr period. The broiler hens are prone to poor energy balance, obesity and reproductive capacity. In summary, these data provide evidence for a functional link between the circadian clock and the ovary by determining clock gene regulation under conditions of disrupted or eliminated reproductive function vs. normal reproductive output.

No description available.

No description available.

A number of investigators have examined psychological stress-induced endothelial dysfunction, however, the underlying mechanisms for these responses have not been clearly elucidated. The purpose of this study was to compare the effects of mental challenge on forearm blood flow, total antioxidant capacity (a measure of oxidative stress), the release of norepinephrine (NE; stress induced neurotransmitter), and pro-inflammatory cytokine responses [both lipopolysaccharide (LPS)-stimulated TNF-α and IL-6 cytokine and mRNA] in lean and obese individuals. Twelve subjects who had a BMI above 30 kg/m2 and were above 30% body fat were categorized as obese and twelve subjects with a BMI below 25 kg/m2 and were below 25% body fat were categorized as lean subjects. Blood samples were drawn and forearm blood flow was assessed prior to and following subjects’ participation in a mental challenge protocol consisting of a computer-based Stroop Color-Word task and mental arithmetic task, for a total of 20 minutes. The mental challenge elicited an elevation in HR and NE in both the lean and obese groups. Furthermore, both lean and obese groups demonstrated an increase in FBF following the mental challenge, whereas no changes in total antioxidant capacity were observed. In addition, the lean group exhibited an increase in LPS-stimulated TNF-α cytokine production from baseline to following the mental challenge, whereas the obese group demonstrated a decrease in LPS-stimulated TNF-α cytokines. This corresponded with a decrease in LPS-stimulated TNF-α mRNA expression in the obese group, although the obese subjects maintained higher levels of both measurements (LPS-stimulated TNF-α cytokine and mRNA expression) compared with the lean group. Furthermore, in the LPS-stimulated IL-6 cytokine response, the obese group demonstrated a greater increase than the lean group following the mental challenge, even though both groups showed an increase in LPS-stimulated IL-6 mRNA expression. These findings suggest that the magnitude and direction of LPS-stimulated TNF-α cytokine response and mRNA expression and LPS-stimulated IL-6 cytokine response to acute stress may be dependent upon the effects of the additional percentage of body fat seen in obese individuals.

Orientador: Márcia Guimarães da Silva / Banca: Rodrigo Paupéro de Camargo Soares / Banca: Vera Lúcia Mores Rall / Não disponível / Abstract: Microbial invasion of the amniotic cavity has been described in term deliveries and its role on the immune modulation is of interest to the better understanding of the underlying labor processes. The aim of this study was to determine the prevalence of Mycoplasma hominis and Ureaplasma urealyticum in the amniotic fluid of term pregnancies and to evaluate its influence on cytokines production at the end of pregnancy. A cross sectional study was conducted with fifty five pregnant women out of labor with intact membranes and gestational age between 37 and 41 weeks seen at the Bom Jesus hospital in Ariquemes, Rondônia, between June 2009 and May 2010. Amniotic fluid samples and fragments of chorioamniotic membranes were collected at cesarean section. M. hominis and U. urealyticum detection was performed by PCR and Interleukin (IL)-1β, IL-6, IL-8, IL-10 and Tumor Necrosis Factor (TNF)- levels were determined by ELISA. Chorioamniotic membranes were submitted to histopatological analyses. Presence of M. hominis was detected in 36.4% of amniotic fluid samples and any of them was positive for U. urealyticum. Regarding cytokines levels, 63.6% and 90.9% of samples have not shown detectable concentrations of TNF- and IL-1β. The median concentration of IL-6 and IL-8 were 107.9 pg/mL (0-517.1) and 208.1 pg/mL (0-1897.4), respectively. Interleukin-1, IL-6, IL-8 and TNF- concentrations were not associated with the presence of M. hominis in amniotic fluid, regardless the gestational age. No sample had detectable IL-10 levels. The histopatological analyses have shown no chorioamnionitis in any of the membranes, only a discreet mononuclear infiltration in the decidua could be observed in 40.4% of the samples. Presence of M. hominis was detected in 36.4% of amniotic fluid samples and any of them was positive for U. urealyticum. Regarding cytokines levels, 63.6% and 90.9% of samples have not... (Complete abstact click electronic access below) / Mestre

Mucositis refers to the widespread damage of mucosal surfaces throughout the length of the alimentary tract (AT) that can occur during cancer treatment. Its development is an important clinical problem that complicates and limits treatment options as well as adversely affecting the quality of life and treatment outcomes for patients. Recent studies directed at determining the pathobiology of mucositis have indicated increasing evidence for the role of transcription factors, such as nuclear factor-κB (NF-κB), and certain pro-inflammatory cytokines, for example tumour necrosis factor (TNF), interleukin-1β (IL-1β) and interleukin- 6 (IL-6), in its development. This thesis developed from an initial clinical investigation in which the expression of NF-κB and COX-2 in oral mucosa was investigated in patients undergoing chemotherapy. Increased levels of NF-κB were demonstrated in the buccal mucosa following chemotherapy. It is well established that mucositis occurs in different sites of the AT. The aims of this research, therefore, were to compare and contrast the changes that do occur at different sites of the AT following chemotherapy in an established animal model (Dark Agouti (DA) rat). Furthermore, the studies were conducted to determine whether changes in tissue and serum levels of NF-κB and pro-inflammatory cytokines occurred following chemotherapy and, with respect to tissue levels, identify whether there were differences in expression at different sites throughout the AT. The final aim was to examine whether the histological changes and changes in pro-inflammatory cytokines were affected by the type of chemotherapy drug used. The effects of three chemotherapy drugs with different mechanisms of action (irinotecan, methotrexate and 5-fluorouracil) were investigated, all of which can cause mucositis in the clinical setting. The thesis is divided into a Literature Review (Chapter 1) followed by 4 research papers: Chapter 2 – “Nuclear factor- κB (NF- κB) and cyclooxygenase-2 (COX-2) expression in the oral mucosa following cancer chemotherapy” Chapter 3 -“Characterisation of mucosal changes in the alimentary tract following administration of irinotecan: Implications for the pathobiology of mucositis” Chapter 4 – “Is the pathobiology of chemotherapy-induced alimentary tract mucositis influenced by the type of mucotoxic drug administered?”, Chapter 5 – “Serum levels of NF-κB and pro-inflammatory cytokines following administration of mucotoxic drugs”. Chapter 6 provides an overall summary and discussion of the results. Previous research has indicated that following administration of chemotherapeutic agents there may be subclinical changes occurring in the mucosa prior to obvious clinical manifestations. The results presented in this thesis also demonstrate this in both humans and animals following administration of chemotherapy. Immunohistochemical analysis of tissue taken from the oral cavity, jejunum and colon from the DA rats following chemotherapy demonstrated that changes in NF-κB and the pro-inflammatory cytokines, TNF, IL-1β and IL- 6, occurred at all sites over a 72 hour time period. This was evident before severe histological evidence of mucositis were observed such as epithelial atrophy in the oral mucosa, atrophy, blunting and fusion of the villi in the jejunum and crypt ablation in the jejunum and colon. Furthermore, each of the three drugs caused different patterns of NF-κB and pro-inflammatory cytokine expression in the tissues; in spite of this, however, histological features of damage were similar. With respect to serum levels of NF-κB and pro-inflammatory cytokines, differences were observed between the serum and tissue levels. Generally, serum changes followed initial histological changes in the tissues, or occurred simultaneously with histological changes. The mechanisms behind this are unclear; however it may be that elevated cytokines in the tissues “overflow” into the serum as tissue damage increases. Furthermore, the use of serum cytokine level measurement to predict mucosal damage is limited because of the differences in timing and short time intervals between changes in the serum and tissues. This thesis has provided additional important information on mucositis pathobiology and highlights its complexity. In particular, it has provided new evidence supporting the notion that mucositis is not restricted to the oral cavity and that other sites of the AT are also affected. Furthermore, these results confirm previous data indicating that subclinical changes occur in the mucosa prior to the development of obvious histological damage or clinical manifestations of mucositis. Contrary to previous reports, these studies have indicated that, although the clinical and histological changes may be similar, the alterations in NF-κB and pro-inflammatory cytokines in the tissues are affected by the type of drug used. This has important implications in the management and prevention of mucositis in the clinical setting particularly when multi-drug or chemotherapy-radiotherapy regimens are used. A common pathway that leads to mucosal damage is yet to be determined. The fact that serum levels appear to reflect the “global” nature of the effects of chemotherapy, highlights the fact that ongoing research needs to be directed, not necessarily at specific side effects, but rather how side effects of chemotherapy are interrelated so that better patient management can be achieved and ultimately provide optimum treatment and better survival for patients with cancer. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1321557 / Thesis (Ph.D.) -- University of Adelaide, School of Dentistry, 2008

Made available in DSpace on 2014-06-11T19:27:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-28Bitstream added on 2014-06-13T20:57:18Z : No. of bitstreams: 1 ramos_bra_me_botfm.pdf: 447116 bytes, checksum: 446e118d63a97d1a69658b7e651b69aa (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Microbial invasion of the amniotic cavity has been described in term deliveries and its role on the immune modulation is of interest to the better understanding of the underlying labor processes. The aim of this study was to determine the prevalence of Mycoplasma hominis and Ureaplasma urealyticum in the amniotic fluid of term pregnancies and to evaluate its influence on cytokines production at the end of pregnancy. A cross sectional study was conducted with fifty five pregnant women out of labor with intact membranes and gestational age between 37 and 41 weeks seen at the Bom Jesus hospital in Ariquemes, Rondônia, between June 2009 and May 2010. Amniotic fluid samples and fragments of chorioamniotic membranes were collected at cesarean section. M. hominis and U. urealyticum detection was performed by PCR and Interleukin (IL)-1β, IL-6, IL-8, IL-10 and Tumor Necrosis Factor (TNF)- levels were determined by ELISA. Chorioamniotic membranes were submitted to histopatological analyses. Presence of M. hominis was detected in 36.4% of amniotic fluid samples and any of them was positive for U. urealyticum. Regarding cytokines levels, 63.6% and 90.9% of samples have not shown detectable concentrations of TNF- and IL-1β. The median concentration of IL-6 and IL-8 were 107.9 pg/mL (0-517.1) and 208.1 pg/mL (0-1897.4), respectively. Interleukin-1, IL-6, IL-8 and TNF- concentrations were not associated with the presence of M. hominis in amniotic fluid, regardless the gestational age. No sample had detectable IL-10 levels. The histopatological analyses have shown no chorioamnionitis in any of the membranes, only a discreet mononuclear infiltration in the decidua could be observed in 40.4% of the samples. Presence of M. hominis was detected in 36.4% of amniotic fluid samples and any of them was positive for U. urealyticum. Regarding cytokines levels, 63.6% and 90.9% of samples have not... (Complete abstact click electronic access below)

The aim of the study was to investigate the association between depression and low bone mineral density (BMD) in premenopausal females. The rationale for the study was that depression is often characterized by cortisol hypersecretion. The role of cortisol includes effects on bone metabolism and the immune system: cortisol is a bone resorption agonist through its support of osteoclastogenesis. The release of pro-inflammatory cytokines, (especially IL-1, IL-6 and TNF-alpha) which induce cortisol secretion, also pushes the balance of bone remodelling in favour of resorption, consequently causing loss of bone mineral density. Significant results have been reported in studies of various groups across the USA, Europe and Asia, indicating a causal role for depression in osteoporosis. However, some studies could not support this association. With both osteoporosis and depression representing growing public health concerns in South Africa, the aim of this study was to examine the association between depression and loss of BMD in a South African sample with varying levels of depression. The study was approached from two starting points: the first used low BMD as the departure point and the second was undertaken from the diagnosis of depression. This was achieved by first investigating women where the primary concern was possible low BMD (referred to as Study 1) and secondly by assessing women whose primary diagnosis was clinically confirmed major depression (Study 2). Study 1 involved investigation of BMD in a volunteer-based sample of 40 premenopausal women drawn from three different sources. All volunteers underwent a DEXA scan, were assessed for depression and supplied saliva for cortisol analysis. Study 2 examined the BMD of five psychiatric patients diagnosed with severe, recurrent major depression and four healthy controls. These volunteers were required to undergo the same testing as subjects in Study 1. In addition, blood and urine samples were taken to examine bone turnover markers (bone specific alkaline phosphate, osteocalcin, urine pyridinoline cross-linked C-telopeptide and deoxypyridinoline). The pro-inflammatory status of the psychiatric patients was compared to reference ranges. The latter served as a small exploratory study and an introduction to further avenues of research. Study 1 revealed no clear general association between depression and bone density on DEXA scores. However, a correlation was found between left femoral neck BMD and depression in those women with low BMD only. Significant differences were found though between subjects with normal and low BMD in terms of body mass index (BMI) and contraception use. Study 2 on the other hand, indicated a trend of association between depression and low BMD: subjects suffering with severe major depression were noted to have lower bone density (on DEXA) and higher bone turnover (as measured by markers of bone turnover) as well as higher cortisol levels than healthy controls. In addition, depressed subjects exhibited elevated IL-1-alpha levels but normal TNF-alpha levels when compared to normative data. In conclusion, the study indicated that the effect of depression on bone density is dependent on the intensity and duration of depression. IL-1-alpha and cortisol may be instrumental in this loss of BMD. / Dissertation (MSc)--University of Pretoria, 2008. / Physiology / unrestricted