Inflammatory Response In Women Research Articles

Maternal serum uric acid concentration is associated with the expression of tumour necrosis factor-α and intercellular adhesion molecule-1 in patients with preeclampsia.

We aimed to investigate whether there is a correlation between elevated serum uric acid (SUA) concentration and endothelial inflammatory response in women with preeclampsia (PE). On the basis of clinical and laboratory findings, patients were assigned to three groups: normal blood pressure (Control (Con)), gestational hypertension (GH) and PE (n=50 in each group). SUA concentration was measured by spectrophotometry, and serum tumour necrosis factor-α (TNF-α) and intercellular adhesion molecule-1 (ICAM-1) levels were measured by enzyme-linked immunosorbent assay. Western blotting and immunohistochemical staining were also used to detect the changes in TNF-α and ICAM-1 expression in subcutaneous fat tissue. PE patients showed significantly higher systolic and diastolic blood pressures compared with Con and GH pregnant women (P=0.02 and P=0.02, respectively). The changes of body mass index (ΔBMI) before and after pregnancy and 24-h urine protein were significantly different among the three groups (P<0.001). Maternal SUA, TNF-α and soluble ICAM-1 (sICAM-1) levels were significantly increased in the patients with PE (P<0.05) compared with the other two groups. Scatterplot analysis revealed that elevated SUA concentration positively correlated with TNF-α and sICAM-1 in pregnant women. Moreover, vessels in subcutaneous fat tissues of preeclamptic patients showed intense TNF-α and ICAM-1 staining compared with Con and GH patients. The results support that, to a certain extent, elevated SUA concentration is significantly associated with inflammation of maternal systemic vasculature as indicated by increased TNF-α and ICAM-1 expression in women with PE.

Sex (always) matters: inflammatory, neuroendocrine, and psychological responses to endotoxin

Depressed mood and increased anxiety represent core symptoms of sickness mediated by pro-inflammatory cytokines. Moreover, inflammation seems to be implicated in the development of mood disorders. Although women are known to mount stronger pro-inflammatory responses and are at higher risk to develop depressive/anxiety disorders, experimental studies on sex differences in sickness-related behavioral symptoms are scarce. Thus, we compared physiological and psychological responses to endotoxin administration in healthy men and women. Subjects were injected with lipopolysaccharide (LPS; 0.4 ng/kg) and plasma concentrations of cytokines and neuroendocrine factors as well as negative state emotions were measured before and until 6h after endotoxin administration. Women exhibited a more profound pro-inflammatory response (TNF-a, IL 6) and higher increases in anti-inflammatory IL-1ra. The LPS-induced increase in IL-10 was higher in men. Cytokine alterations were accompanied by changes in neuroendocrine factors involved in inflammation regulation. Endotoxin administration induced an increase in noradrenaline, without evidence for sex differences. Cortisol responses were significantly higher in woman. LPS administration also increased prolactin secretion, but only in women. Despite these profound sex differences in inflammatory and neuroendocrine responses, men and women did not differ in endotoxin-induced alterations in mood and state anxiety. This suggests that compensatory mechanisms exist that counteract the more pronounced inflammatory response in women, preventing exaggerated sickness responses. Disturbance of these compensatory mechanisms may promote the development of affective disorders in women.

Men and women differ in inflammatory and neuroendocrine responses to endotoxin but not in the severity of sickness symptoms

Impaired mood and increased anxiety represent core symptoms of sickness behavior that are thought to be mediated by pro-inflammatory cytokines. Moreover, excessive inflammation seems to be implicated in the development of mood/affective disorders. Although women are known to mount stronger pro-inflammatory responses during infections and are at higher risk to develop depressive and anxiety disorders compared to men, experimental studies on sex differences in sickness symptoms are scarce. Thus, the present study aimed at comparing physiological and psychological responses to endotoxin administration between men and women. Twenty-eight healthy volunteers (14 men, 14 women) were intravenously injected with a low dose (0.4ng/kg) of lipopolysaccharide (LPS) and plasma concentrations of cytokines and neuroendocrine factors as well as negative state emotions were measured before and until six hours after LPS administration. Women exhibited a more profound pro-inflammatory response with significantly higher increases in tumor necrosis factor (TNF)-α and interleukin (IL)-6. In contrast, the LPS-induced increase in anti-inflammatory IL-10 was significantly higher in men. The cytokine alterations were accompanied by changes in neuroendocrine factors known to be involved in inflammation regulation. Endotoxin injection induced a significant increase in noradrenaline, without evidence for sex differences. The LPS-induced increase in cortisol was significantly higher in woman, whereas changes in dehydroepiandrosterone were largely comparable. LPS administration also increased secretion of prolactin, but only in women. Despite these profound sex differences in inflammatory and neuroendocrine responses, men and women did not differ in endotoxin-induced alterations in mood and state anxiety or non-specific sickness symptoms. This suggests that compensatory mechanisms exist that counteract the more pronounced inflammatory response in women, preventing an exaggerated sickness response. Disturbance of these compensatory mechanisms by environmental factors such as stress may promote the development of affective disorders in women.

Systemic and Local Inflammatory Response in Women with Preterm Prelabor Rupture of Membranes

ObjectiveTo evaluate the inflammatory pattern in maternal circulation, amniotic cavity, cervix and vagina from women with preterm prelabor rupture of membranes (PPROM) considering the occurrence of microbial invasion of the amniotic cavity (MIAC).MethodologyA prospective study was performed in 58 women with PPROM before 34+0 weeks of gestational age. Twenty-six proteins were analyzed by a multiple immunoassay in samples of amniotic fluid, serum, cervix and vagina. Association of an inflammatory response in the invasive and non-invasive samples with MIAC was investigated.ResultsThe rate of MIAC was 36.2% (21/58). Both amniotic fluid IL-6 and cervical C-reactive protein (CRP) showed to be independent predictors of MIAC. A cut-off level of cervical CRP≥1836 pg/mL showed a detection rate of 75%, false positive rate of 19% and positive and negative predictive values to predict MIAC of 67% and 87%, respectively. There were no independent biomarkers of MIAC either in the serum or vaginal compartment.ConclusionA cervical inflammatory response mediated by CRP was observed in PPROM women with MIAC. Evaluation of serum or vaginal samples did not add valuable information regarding the outcome evaluated.

Особенности нарушений коагуляционного потенциала крови в условиях развития системного воспалительного ответа при гнойных тубоовариальных образованиях

Objective: There are no any systemized studies of relationship between the coagulative haemostasis’ disorders and metabolic and cytokine status in patients with septic tuboovarial formations. The aim of the present work was to study the mechanisms of blood coagulation disorders and their relationships with changes of cytokine status and acute phase of inflammatory response in septic tubovarial formations in women. Methods: 32 patients with purulent tubovarial formations and 30 healthy women were examined. Results: Shortening of activated partial thromboplastin, prothrombin and thrombin clotting time, increasing the duration of XIIa-kallikrein-dependent fibrinolysis, as well as the elevation of paracoagulation products in blood plasma were observed. IL-1β (p =0.000023), TNF-α (р &lt;0.001), C-reactive protein (р &lt;0.001), haptoglobin (р &lt;0.001) and fibrinogen (р &lt;0.001) levels were higher in peripheral blood of patients in comparison with healthy women. Accumulation of lipid hydroperoxides (р &lt;0.001) and malonic dialdehyde (р &lt;0.001) occurred in the blood plasma of patients. Serum albumin (р &lt;0.001) and transferring (р &lt;0.001) levels were lesser in patients with purulent tuboovarial formations in comparison with healthy women. Conclusion: The obtained results showing an initiating role of cytokine and oxidative metabolic status changes in blood coagulation potential’s and fibrinolysis activity’s disorders developing. This biochemical signs may be used as objective criteria which may serve to determine the risk of thrombosis in case of acute inflammatory response in women with purulent tubovarial inflammation.

Stress-Induced Inflammatory Responses in Women

African Americans experience preterm birth at nearly twice the rate of whites. Chronic stress associated with minority status is implicated in this disparity. Inflammation is a key biological pathway by which stress may affect birth outcomes. This study examined the effects of race and pregnancy on stress-induced inflammatory responses. Thirty-nine women in the second trimester of pregnancy (19 African American, 20 white) and 39 demographically similar nonpregnant women completed an acute stressor (Trier Social Stress Test). Psychosocial characteristics, health behaviors, and affective responses were assessed. Serum interleukin (IL)-6 was measured at baseline, 45 minutes, and 120 minutes poststressor. IL-6 responses at 120 minutes poststressor were 46% higher in African Americans versus whites (95% confidence interval = 8%-81%, t(72) = 3.51, p = .001). This effect was present in pregnancy and nonpregnancy. IL-6 responses at 120 minutes poststressor tended to be lower (15%) in pregnant versus nonpregnant women (95% confidence interval = -5%-32%, p = .14). Racial differences in inflammatory responses were not accounted for by demographics, psychological characteristics, health behaviors, or differences in salivary cortisol. Pregnant whites showed lower negative affective responses than did nonpregnant women of either race (p values ≤ .007). This study provides novel evidence that stress-induced inflammatory responses are more robust among African American women versus whites during pregnancy and nonpregnancy. The ultimate impact of stress on health is a function of stressor exposure and physiological responses. Individual differences in stress-induced inflammatory responses represent a clear target for continued research efforts in racial disparities in health during pregnancy and nonpregnancy.

PP071. suPAR levels in normal- and preeclamptic pregnancies

Preeclampsia (PE) has been considered to be a maternal inflammatory response to pregnancy and may be hazardous for mother and child. Soluble urokinase Plasminogen Activator receptor (suPAR) is a non-specific marker that reflects overall systemic inflammation and immune activation. We examined the levels of suPAR in first and third trimesters of normal- and preeclamptic pregnancies. Two clinical studies were conducted. The first study included 43 women who subsequently developed PE and 86 control women not developing PE. Blood samples were collected during the first trimester. The two groups were matched with respect to gestational age. In the second study, 13 cases of PE and 8 controls were enrolled and blood samples were collected during the third trimester. Serum suPAR were analyzed by the commercially availably suPARnostic® assay kit (ELISA, Virogates, Copenhagen, Denmark). There were no significant differences in first trimester suPAR level between women who subsequently developed PE and those who completed a normal pregnancy (4.5 [3.7-5.4] ng/mL versus 4.3 [3.8-5.0] ng/mL, p=0.49, median [interquartile range]). In the third trimester, suPAR levels were significantly elevated in the preeclamptic group compared to the control group (2.5 [2.2-3.5] ng/mL versus 1.9 [1.5-2.1] ng/mL, p=0.008). After adjustment for gestational age (38.6 (0.7) and 31 (3.1) weeks in the control- and the PE-group respectively, p<0.001, mean (SD)), the group difference did not remain statistically significant (p=0.064). suPAR is not a suitable marker for detecting the systemic maternal inflammatory response in women with established PE nor a useful pre-clinical marker of the disorder. The observation of the higher suPAR level in first trimester of pregnancy compared to third trimester suPAR level alludes to a possible physiological function that needs to be clarified.

Intra‐amniotic inflammation predicts microbial invasion of the amniotic cavity but not spontaneous preterm delivery in preterm prelabor membrane rupture

To predict microbial invasion of the amniotic cavity (MIAC) and spontaneous preterm delivery within seven days using a panel of selected proteins from amniotic fluid in a Swedish population of preterm prelabor membrane rupture (PPROM). Prospective cohort study. Evaluation of intra-amniotic inflammation in preterm premature rupture of membranes. Sixty-six pregnant women with preterm prelabor membrane rupture at 22(+0) -33(+6) weeks' gestational age. Methods. Twenty-seven amniotic fluid proteins were assayed by a multiple immunoassay. The intra-amniotic inflammatory response was evaluated according to the presence of MIAC and the risk of spontaneous preterm delivery within seven days. A prediction model was constructed using logistic regression. The overall rates of MIAC and spontaneous preterm delivery within seven days were 20 and 50%, respectively. There was a higher inflammatory response in women with MIAC than in those without. Earlier gestational age at delivery and lower birthweight were observed in the presence of microbial invasion of the amniotic cavity. Amniotic fluid interleukin (IL)-6 and IL-10 were the best predictors of MIAC in terms of sensitivity (69%), specificity (81%), positive predictive value (47%), negative predictive value (91%) and a positive likelihood ratio of 3.6. There were no differences in intra-amniotic inflammatory response according to the risk of spontaneous preterm delivery within seven days. Amniotic fluid IL-6 and IL-10 are the best inflammatory biomarkers to predict MIAC in women with PPROM. Intra-amniotic inflammation does not predict the occurrence of spontaneous preterm delivery within seven days of PPROM.

Sex differences in creatine kinase after acute heavy resistance exercise on circulating granulocyte estradiol receptors

Previous research has shown reduced tissue disruption and inflammatory responses in women as compared to men following acute strenuous exercise. While the mechanism of this action is not known, estrogen may reduce the inflammatory response through its interaction with granulocytes. The purpose of this study was to determine if estrogen receptor β expression on granulocytes is related to sex differences in tissue disruption in response to an acute heavy resistance exercise protocol. Seven healthy, resistance-trained, eumenorrheic women (23 ± 3 years, 169 ± 9.1 cm, 66.4 ± 10.5 kg) and 8 healthy, resistance-trained men (25 ± 5 years, 178 ± 6.7 cm, 82.3 ± 9.33 kg) volunteered to participate in the study. Subjects performed an acute resistance exercise test consisting of six sets of five squats at 90% of the subject's one repetition maximum. Blood samples were obtained pre-, mid-, post-, and 1-, 6-, and 24-h postexercise. Blood samples were analyzed for 17-β-estradiol by ELISA, creatine kinase by colorimetric enzyme immunoassay, and estradiol receptors on circulating granulocytes through flow cytometry. Men had higher CK concentrations than women at baseline/control. Men had significantly higher CK concentrations at 24-h postexercise than women. No significant changes in estradiol β receptors were expressed on granulocytes after exercise or between sexes. While sex differences occur in CK activity in response to strenuous eccentric exercise, they may not be related to estradiol receptor β expression on granulocytes. Thus, although there are sex differences in CK expression following acute resistance exercise, the differences may not be attributable to estrogen receptor β expression on granulocytes.

Cardiovascular Disease-Related Lifestyle Factors and Longevity

Cardiovascular disease is one of the leading causes of death in the developed world. Understanding trends in cardiovascular disease prevalence and identifying factors associated with its development are important, since they provide information to define the burden and the mechanisms of the disease, which is the first step before population-based interventions. This special issue is devoted to highlight lifestyle factors and behaviors associated with the development of cardiovascular disease. According to the World Health Organization, sedentary lifestyle, smoking habits, and unhealthy dietary habits, are the most important factors associated with the development of cardiac diseases; and the main reason for classifying these factors as the most significant is because they can be prevented. In their paper, G. S. Metsios et al. presented current scientific evidence about the role of passive smoking in the development of cardiovascular disease in children. The authors identified a total of 42 articles (i.e., 30 reviews and 12 observational), and they revealed that passive smoking may be implicated in deteriorating cardiovascular status in children in terms of unfavorable high-density lipoprotein levels and deteriorated vascular function. In another article based on a middle-aged population of the Ikaria island in Greece, C. Chrysohoou et al. reported that short-term depressive symptoms are related to a worse 30-day prognosis of ACS patients; however, this relationship was mediated by Mediterranean diet adherence. It is well known that depression is an independent risk factor for cardiac diseases. Due to a significant increase of the incidence of depression during the past decades, there has been a growing interest regarding the mechanisms underlying its pathogenesis, including the parameter of nutrition. Y. Ma et al. reported that chronic depression is associated with inflammatory response in women, but not in men. Previous studies have also observed the positive relationship between depression and inflammation. It seems that Mediterranean diet, due to its antioxidant role, may mediate the adverse effect of depression on cardiac system; the majority of studies suggest the beneficial effects of omega-3 PUFAs, a main constituent of Mediterranean diet, in the treatment of clinical depression, with eicosapentaenoic acid (EPA) being more effective than docosahexaenoic (DHA). Another lifestyle factor that has received much attention concerning the prevention of cardiovascular diseases is physical activity status. In the paper by S. A. Kavouras et al., from the ATTICA study, the investigators revealed another mechanism about the protective role of physical activity in atherosclerosis, the improvement in total antioxidant capacity of the study's participants. Moreover, under the context of the IKARIA study, the authors observed that frequent fish intake (i.e., >3 times per week) seems to moderate depressive mood. In addition to the latter, Tyrovolas et al. reported that nutrition services provided in Greek islands played a significant role in modifying dietary habits of older adults. M. M. Pryde and W. B. Kannel resumed that dietary modifications about polyunsaturated fat intake, processed meat consumption, fish choices and preparation, trans fatty acids, low carbohydrate diets, egg consumption, coffee, added sugar, soft drink beverages, glycemic load, chocolate, orange juice, nut consumption, vitamin D supplements, food portion size, and alcohol drinking may preserve cardiovascular health and longevity. In this special issue, the role of lifestyle, mainly represented by diet, smoking, and physical activity, has been extensively studied in relation to cardiovascular disease development. The scientific evidence strongly supports the protective role of healthy diet, abstinence of smoking, and engagement in physical activities for the prevention of cardiovascular disease. Public health policy makers should target on these lifestyle behaviors which seemingly can cost-effectively reduce the burden of the disease at population level. Christina Chrysohoou Christodoulos Stefanadis Christos Pitsavos Demosthenes Panagiotakos Undurti N. Das Dario Giugliano

Polymorphism in Vitamin D-Binding Protein as a Genetic Risk Factor in the Pathogenesis of Endometriosis

Context: Previous studies have implicated a deficiency in the inflammatory response in women who develop endometriosis. The specific immunological deficits have not been completely elucidated. Objective: Our objective was to identify differences in protein expression in serum that might shed light on the pathophysiology of endometriosis. Design and Setting: This cross-sectional study of women undergoing laparoscopy between 2003 and 2005 took place at a university medical center. Patients: Patients included consenting women age 18-49 yr undergoing surgery for pain and/or infertility or elective tubal ligation. Women with acute or chronic medical conditions were excluded. Intervention: Blood was collected preoperatively. Main Outcome Measure: Proteomic analysis of serum was done using two-dimensional difference gel electrophoresis. Results: We found 25 protein spots with a significant difference in abundance between women with endometriosis and controls, including acute-phase proteins and complement components. The abundance of vitamin D-binding protein was higher in all endometriosis pools by a factor of approximately 3 compared with the control pool (P &amp;lt; 0.02). Analysis of specific allele products using nano-LC-ESI-MS indicated that it was the GC*2 allele product that was in greater concentration in serum pools, as well as in single validation samples, in women with endometriosis (P = 0.006). In contrast to the GC*1 allele product, which is readily converted to a potent macrophage factor (Gc protein-derived macrophage-activating factor), the GC*2 allele product undergoes practically no such conversion. Conclusions: We speculate that the inability to sufficiently activate macrophages’ phagocytotic function in those carrying the GC*2 polymorphism (more prevalent in endometriosis) may allow endometriotic tissues to implant in the peritoneal cavity. Future studies evaluating specific vitamin D-binding protein polymorphisms as a risk factor for endometriosis in larger populations of women are warranted.

Polymorphism in Vitamin D-Binding Protein as a Genetic Risk Factor in the Pathogenesis of Endometriosis

Context Previous studies have implicated a deficiency in the inflammatory response in women who develop endometriosis. The specific immunological deficits have not been completely elucidated. Objective Our objective was to identify differences in protein expression in serum that might shed light on the pathophysiology of endometriosis. Design and Setting This cross-sectional study of women undergoing laparoscopy between 2003 and 2005 took place at a university medical center. Patients Patients included consenting women age 18-49 yr undergoing surgery for pain and/or infertility or elective tubal ligation. Women with acute or chronic medical conditions were excluded. Intervention Blood was collected preoperatively. Main Outcome Measure Proteomic analysis of serum was done using two-dimensional difference gel electrophoresis. Results We found 25 protein spots with a significant difference in abundance between women with endometriosis and controls, including acute-phase proteins and complement components. The abundance of vitamin D-binding protein was higher in all endometriosis pools by a factor of approximately 3 compared with the control pool (P &amp;lt; 0.02). Analysis of specific allele products using nano-LC-ESI-MS indicated that it was the GC*2 allele product that was in greater concentration in serum pools, as well as in single validation samples, in women with endometriosis (P = 0.006). In contrast to the GC*1 allele product, which is readily converted to a potent macrophage factor (Gc protein-derived macrophage-activating factor), the GC*2 allele product undergoes practically no such conversion. Conclusions We speculate that the inability to sufficiently activate macrophages’ phagocytotic function in those carrying the GC*2 polymorphism (more prevalent in endometriosis) may allow endometriotic tissues to implant in the peritoneal cavity. Future studies evaluating specific vitamin D-binding protein polymorphisms as a risk factor for endometriosis in larger populations of women are warranted.

Polymorphism in Vitamin D-Binding Protein as a Genetic Risk Factor in the Pathogenesis of Endometriosis

Previous studies have implicated a deficiency in the inflammatory response in women who develop endometriosis. The specific immunological deficits have not been completely elucidated. Our objective was to identify differences in protein expression in serum that might shed light on the pathophysiology of endometriosis. This cross-sectional study of women undergoing laparoscopy between 2003 and 2005 took place at a university medical center. Patients included consenting women age 18-49 yr undergoing surgery for pain and/or infertility or elective tubal ligation. Women with acute or chronic medical conditions were excluded. Blood was collected preoperatively. Proteomic analysis of serum was done using two-dimensional difference gel electrophoresis. We found 25 protein spots with a significant difference in abundance between women with endometriosis and controls, including acute-phase proteins and complement components. The abundance of vitamin D-binding protein was higher in all endometriosis pools by a factor of approximately 3 compared with the control pool (P < 0.02). Analysis of specific allele products using nano-scale liquid chromatography-electrospray ionization-mass spectrometry indicated that it was the GC*2 allele product that was in greater concentration in serum pools, as well as in single validation samples, in women with endometriosis (P = 0.006). In contrast to the GC*1 allele product, which is readily converted to a potent macrophage factor (Gc protein-derived macrophage-activating factor), the GC*2 allele product undergoes practically no such conversion. We speculate that the inability to sufficiently activate macrophages' phagocytotic function in those carrying the GC*2 polymorphism (more prevalent in endometriosis) may allow endometriotic tissues to implant in the peritoneal cavity. Future studies evaluating specific vitamin D-binding protein polymorphisms as a risk factor for endometriosis in larger populations of women are warranted.

M5.2 Down-regulation of SOCS-3 signaling is associated with increased endothelial inflammatory response in women with preeclampsia

Prolactin (PRL) is a hormone that plays a crucial role during pregnancy and lactation. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, which is an important pathway in signal transduction from PRL to target cells, can be modulated by various factors, including suppressor of cytokine signaling-3 (SOCS-3). PRL may increase and decrease SOCS-3 expression, and its actions are mostly dependent on additional factors such as the photoperiod. There is also evidence for a relationship between suckling and SOCS-3 expression in the mammary gland. The aim of this study was to examine the influence of seasonality and physiological status on SOCS-3 expression levels in ovine mammary glands. Mammary gland fragments were obtained from 18 Polish Longwool ewes, and the fine-needle aspiration biopsy technique was used on 4 groups of animals under specific physiological and photoperiodic conditions: non-lactating ewes during long days (LD; n = 6), ewes on day 30 (n = 6) or day 56 of lactation (n = 6) and non-lactating ewes during short days (SD; n = 6). SOCS-3 mRNA levels were measured by real-time PCR. The results of this study confirmed that SOCS-3 mRNA expression in sheep is dependent on the season and stage of lactation. The highest expression of the examined factors was noted in the mammary glands of non-lactating sheep during SD, and the lowest levels were observed in ewes on day 30 of lactation. The transcript levels observed in the tissues collected from non-lactating sheep during SD and LD were higher (74% and 41%, respectively) compared with the expression observed on day 30 of lactation. On day 56 of lactation, the SOCS-3 mRNA level was similar to that observed in the udders of non-lactating sheep during LD. These results indicate that SOCS-3 could play an integrating role between hormones and other factors that are involved in the physiological functions of the mammary gland.

Circuit resistance training in sedentary women: body composition and serum cytokine levels

Exercise can generate alterations in body composition and modulate the immune system. The objective of this study was to verify whether a circuit resistance training (CRT) protocol can increase lean body mass (LM), and reduce fat body mass (FM) and the percent of FM (%FM) of sedentary women, without inducing inflammatory responses, indicated by serum cytokine levels. The initial hypothesis was that CRT would improve body composition, without changing serum cytokine levels. The study consisted of 14 healthy, sedentary women, aged 33-45 years (mean +/- SD, 40.23 +/- 3.98 years), with a normal body mass index. They participated in 3 sessions per week of CRT, which included 2 rounds in 9 stations with 1 set of 8-12 repetition maximum at each station, for 10 weeks. During the 10-week CRT period, participants maintained their pretraining nutritional standard. Body composition was analysed with dual-energy X-ray absorptiometry both pre- and post-training. Blood samples were collected after 96 h of rest pre- and post-training, and 5 min, 24 h, and 48 h after the second and last training sessions to measure serum cytokine levels by flow cytometry. The nutritional standard was accompanied throughout the study period with 24-h dietary recall. Increases in LM (35.937 +/- 4.926 to 39.130 +/- 4.950 kg) and decreases in FM (21.911 +/- 8.150 to 17.824 +/- 4.235 kg) and %FM (37.10 +/- 10.84 to 31.19 +/- 6.06), without concurrent changes in serum cytokine levels, and in the nutritional standard (alpha = 0.05). The proposed CRT improved body composition and did not induce any changes in serum cytokine levels characteristic of the inflammatory response in women.

Inflammatory response in patients undergoing uterine artery embolization as compared to patients undergoing conventional hysterectomy

Uterine fibroids are benign tumors seen in 20-40% of women of childbearing age, and these fibroids are usually treated by hysterectomy. During the last decade, embolization of the uterine arteries with polyvinyl alcohol microparticles has become an alternative treatment. To investigate whether uterine artery embolization generates a reduced inflammatory response as compared with conventional hysterectomy. 40 women, 20 in each group, entered this prospective, non-randomized study. The two groups were comparable concerning age, comorbidity, and body-mass index (BMI). We found a significant difference between the inflammatory responses in women undergoing embolization compared with the inflammatory response in women having an abdominal hysterectomy. Women undergoing embolization were subjected to a much smaller inflammatory burden, their total morphine consumption was lower, and their return to work was faster than women subjected to conventional hysterectomy. Uterine artery embolization generates a reduced inflammatory response compared with conventional hysterectomy.

Effect of combined genetic polymorphisms on lung cancer risk in northern Thai women

Lung cancer is a major cause of cancer-related death in developed countries, and its incidence in developing countries is increasing. In Thailand, cancer incidences differ greatly from region to region, and lung cancer is the most common cancer in the northern Thai population. The polymorphic frequency of 10 genetic susceptibility genes and their association with lung cancer were examined in a northern Thai population: CYP1A1 ( MspI), CYP1A1 (Ile462Val), CYP2E1 ( PstI), CYP2E1 ( DraI), GSTM1, GSTT1, MPO ( AciI), OGG1 (Ser326Cys), TP53 (Arg72Pro), and MMP1( AluI). The 173 subjects were 91 lung cancer patients and 82 healthy volunteers. Although no significant association between any single genetic variant and lung cancer risk was observed, when genetic variants were analyzed in combination, a significant effect on lung cancer risk was found for the variant allele in a combination of five genes involved in oxidative stress and inflammatory response: GSTM1 (null), MPO (—463A), OGG1 (326Cys), TP53 (72Pro) (alias p53), MMP1 (2G). With a reference group of individuals carrying at least two wild-type genotypes of these five genes, it was found that an individual carrying three or more variant genotypes is at significantly higher risk of developing lung cancer with the increasing of odds ratios (OR) in concurrence with the number of variant genes. The OR was 2.41 (95% CI = 0.76–7.64), 3.90 (95% CI = 1.23–12.34), and 5.20 (95% CI = 1.31–20.54) for individuals carrying three, four, and five variants, respectively. After stratifying by sex, the OR was higher for women: OR 4.05 (95% CI = 0.44–36.94), 9.00 (95% CI = 0.95–84.89) and 18.00 (95% CI = 1.49–216.62) for three, four, and five variant genotypes, respectively. This augmented effect on lung cancer risk of variant genes involved in oxidative stress and inflammatory response in women with a low prevalence of smoking indicates their modifying effect on other risk factors, such as environmental cigarette smoke, air pollution, radon radiation, or infection of the airway. Confirmation would require further investigations with larger sample sizes.

Characterization of RAGE, HMGB1, and S100β in Inflammation-Induced Preterm Birth and Fetal Tissue Injury

Immune activation represents an adaptive reaction triggered by both noxious exogenous (microbes) and endogenous [high mobility group box-1 protein (HMGB1), S100 calcium binding proteins] inducers of inflammation. Cell stress or necrosis lead the release of HMGB1 and S100 proteins in the extracellular compartment where they act as damage-associated molecular pattern molecules (or alarmins) by engaging the receptor for advanced glycation end-products (RAGE). Although the biology of RAGE is dictated by the accumulation of damage-associated molecular pattern molecules at sites of tissue injury, the role of RAGE in mediating antenatal fetal injury remains unknown. First, we studied the relationships at birth between the intensity of human fetal inflammation and sRAGE (an endogenous RAGE antagonist), HMGB1, and S100beta protein. We found significantly lower sRAGE in human fetuses that mounted robust inflammatory responses. HMGB1 levels correlated significantly with levels of interleukin-6 and S100beta in fetal circulation. We then evaluated the levels and areas of tissue expression of RAGE, HMGB1, and S100beta in specific organs of mouse fetuses on E16. Using an animal model of endotoxin-induced fetal damage and preterm birth, we determined that inflammation induces a significant change in expression of RAGE and HMGB1, but not S100beta, at sites of tissue damage. Our findings indicate that RAGE and HMGB1 may be important mediators of cellular injury in fetuses delivered in the setting of inflammation-induced preterm birth.

Fetal inflammatory response in women with proteomic biomarkers characteristic of intra-amniotic inflammation and preterm birth.

To determine the relationship between presence of amniotic fluid (AF) biomarkers characteristic of inflammation (defensins 2 and 1 and calgranulins C and A) and fetal inflammatory status at birth. Prospective observational cohort. Tertiary referral University hospital. One hundred and thirty-two consecutive mothers (gestational age, median [interquartile range]: 29.6 [24.1-33.1] weeks) who had a clinically indicated amniocentesis to rule out infection and their newborns. Intra-amniotic inflammation was diagnosed by mass spectrometry surface-enhanced-laser-desorption-ionization time of flight (SELDI-TOF). The AF proteomic fingerprint (mass-restricted [MR] score) ranges from 0-4 (none to all biomarkers present). The intensity of intra-amniotic inflammation was graded based on the number of proteomic biomarkers: MR score 0: 'no' inflammation, MR score 1-2: 'minimal' inflammation and MR score 3-4: 'severe' inflammation. At birth, cord blood was obtained for all women. Severity of histological chorioamnionitis and early-onset neonatal sepsis (EONS) was based on established histological and haematological criteria. Interleukin-6 (IL-6) levels were measured by sensitive immunoassays. The cord blood-to-AF IL-6 ratio was used as an indicator of the differential inflammatory response in the fetal versus the AF compartment. To relate proteomic biomarkers of intra-amniotic infection to cord blood IL-6 and to use the latter as the primary marker of fetal inflammatory response. Women with intra-amniotic inflammation delivered at an earlier gestational age (analysis of variance, P<0.001) and had higher AF IL-6 levels (P<0.001). At birth, neonates of women with severe intra-amniotic inflammation had higher cord blood IL-6 levels (P=0.002) and a higher frequency of EONS (P=0.002). EONS was characterised by significantly elevated cord blood IL-6 levels (P<0.001). Of the 39 neonates delivered by mothers with minimal intra-amniotic inflammation, 15 (39%) neonates had umbilical cord blood IL-6 levels above the mean for the group and 2 neonates had confirmed sepsis. The severity of the neutrophilic infiltrate in the chorionic plate (P<0.001), choriodecidua (P=0.002), umbilical cord (P<0.001) but not in the amnion (P>0.05) was an independent predictor of the cord blood-to-AF IL-6 ratio. Relationships were maintained following correction for gestational age, birthweight, amniocentesis-to-delivery interval, caesarean delivery, status of the membranes, race, MR score and antibiotics and steroid exposure. We provide evidence that presence of proteomic biomarkers characteristic of inflammation in the AF is associated with an increased inflammatory status of the fetus at birth. Neonates mount an increased inflammatory status and have positive blood cultures even in the context of minimal intra-amniotic inflammation.