Concentrations Of Inflammatory Markers Research Articles

PSXI-18 Effects of different fiber levels on rumination and inflammatory markers in feedlot cattle

Abstract Adding fiber to feedlot diets is essential to maximize performance, optimize feed conversion and maintain animal health. Monitoring blood inflammatory markers and rumination behavior can help to identify fiber levels that maximize performance and animal well-being. We aimed to evaluate the effect of fiber levels on inflammatory markers, lactate dehydrogenase and haptoglobin and rumination of Nellore cattle in confinement fed with diets containing 12% and 7% forage NDF, over a period of 50 d. Diets included corn silage as the source of forage fiber with 23.3% and 13.6% corn silage in the dry matter 64% and 73.5% ground corn, and 0.2 and 0.5% potassium chloride, respectively for the 12% and 7% fNDF. Soybean meal (1.5%); cottonseed (7%), urea (1.2%), and mineral mixture (2.7%) containing 25 ppm of monensin were present in both treatments. Average initial body weight (BW) was 460 ± 38 kg and average age was 20 mo. Bulls (n = 20) were randomly distributed for each treatment with animal being the experimental unit. The feeding behavior was monitored on d 21 and 42, with observations at each 10-min interval, over 24 h and data obtained were averaged for analysis and blood samples were collected immediately after behavior analysis. Blood samples were obtained by puncturing the jugular vein, centrifuged to separate the serum, stored at -20°C and subsequently analyzed. Lactate dehydrogenase was analyzed in an automatic biochemistry system using cattle specific cattle kits (LABTEST Diagnóstica SA). Haptoglobin analyses were carried out by ELISA (Vidavet-Veterinary Lab). Data were evaluated by PROC GLIMMIX from SAS. A significant interaction was observed between minutes of rumination and fNDF levels in relation to the concentration of lactate dehydrogenase (P < 0.0001), expressed by the solution: Lactate = 1,272.12 + 908.86 * (tract = 7) + 1,1427 -3.3170 * (treat = 7) * rumination. For animals receiving the 7% fNDF diet, the concentration of lactate dehydrogenase decreased as the minutes of rumination increased, with a significant linear effect (P < 0.001). On the other hand, for animals treated with 12% fNDF, no significant correlation was observed (P = 0.34) with increasing rumination time. There was also an interaction between minutes of rumination and fNDF levels for haptoglobin concentration (P < 0.01), expressed by the solution: Haptoglobin = 0.1901 + 0.4865 * (treat = 7) + 0.000828 - 0.00163 * (treat = 7) * rumination. In animals treated with 7% fNDF, haptoglobin concentration decreased with increasing minutes of rumination, with a significant linear effect (P = 0.02). Our data demonstrates that, for the low forage diet, as bulls increased rumination time there was an improvement (a decrease) in inflammatory markers concentrations.

Associations between bioaerosols, lung function work-shift changes and inflammatory markers: A study of recycling workers.

We investigated associations between bioaerosol exposures and work-shift changes in lung function and inflammatory markers among recycling workers. Inhalable dust was measured with personal samplers and analyzed for endotoxin, bacteria, and fungi (incubated at 25 °C and 37 °C) levels. Lung function (FEV1, FVC) was measured before and after work-shifts and serum concentrations of inflammatory markers (CRP, SAA, CC16, IL1B, IL2, IL4, IL5, IL6, IL8, IL10, IL13, and TNF) after the shift. Associations were explored by linear mixed-effects models. We included 170 measurements from 88 production workers exposed to inhalable dust, endotoxin, bacteria, and fungi (25 °C and 37 °C) at geometric mean levels of 0.6 mg/m3, 10.7 EU/m3, 1.6×104 CFU/m3, 4.4×104 CFU/m3, and 103 CFU/m3, respectively, and 14 administrative workers exposed at 7-fold lower levels. No associations were observed between bioaerosol exposures and work-shift change in lung function. IL2, IL6, IL10, and TNF concentrations were positively associated with inhalable dust levels, SAA and IL6 with bacteria, CRP, SAA, IL8, and TNF with fungi (25 °C or 37 °C), with the latter being the only statistically significant finding (exp(β) 1.40, 95% confidence interval 1.01-1.96). This study of recycling workers exposed to bioaerosol levels generally below those of farmers and compost workers and above background levels did not indicate any acute effect on lung function. Several inflammatory markers tended to increase with exposure, suggesting a systemic effect. Future research should combine data from bioaerosol-exposed workers to uncover health risks that may form the basis for health-based occupational exposure limits.

Immune checkpoints are suppressed during pregnancy following influenza A virus infection.

Influenza A virus (IAV) infection is a major health risk during pregnancy. Whilst vaccination and antiviral agents are widely employed and reduce IAV-induced symptoms, they are not sufficient to control IAV infections in pregnancy, especially during pandemics. Respiratory viruses like IAV, exploit immune alterations that occur during pregnancy, including the upregulation of immune checkpoint proteins (ICPs) like PDL1, PD1 and CTLA4. We hypothesize that blocking expression of PDL1 on innate immune cells will improve maternal immunity following IAV infection. We utilized murine models of IAV infection during pregnancy with and without treatment with the immune checkpoint inhibitor (ICI), a-PDL1. Pregnant and non-pregnant mice were infected with mouse adapted IAV (A/PR/8) and assessed at 3 days post infection (3dpi). Lung cells were analyzed using flow cytometry. Lung mRNA expression of inflammatory and antiviral markers and histology was measured. Protein concentrations of inflammatory and antiviral markers, as well as viral titers was measured from lung bronchiolar lavage fluid (BALF). Lung function was also assessed. Following IAV infection, immune cells from pregnant mice had significant increases in the ICPs, PDL1, PD1 and CTLA4. a-PDL1 treatment effectively suppressed these ICPs and increased the activation marker, CD86. A-PDL1 treatment also reduced lung inflammatory cell infiltration and viral titres, increased antiviral responses, and improved lung function. Overall, IAV infection in pregnancy activates key inhibitory ICPs, leading to worsened disease outcomes. a-PDL1 treatment during IAV infection in pregnancy is an effective method to reduce ICP expression and improve overall immune cell responses.

Relationship of inflammatory mediators (interleukin and cortisol concentrations) with corneal epithelial quantifiable metrics

PurposeTo investigate the relationship of inflammatory biomarkers with corneal epithelial quantifiable metrics in patients with keratoconus and in healthy eyes. DesignProspective observational comparative study. ParticipantsThis study included 100 eyes of 100 patients, 48 eyes of 48 patients with KC, and 52 healthy eyes of 52 healthy controls. MethodsThe concentrations of tear cytokines were investigated in both groups: interleukin (IL) 1B, IL6, IL8, IL10, IL12p70 and TNFα were obtained by capillary flow and measured using flow cytometer. Cortisol concentrations were determined in both groups from the most proximal hair segment as an index of cumulative secretion and measured by liquid chromatography mass spectrometry. Epithelial variables were obtained with optical coherence tomography (OCT). Pearson correlation (r) was used to measure linear dependence between two different variables. Main Outcome MeasuresInvestigating the existence, strength, and significance of any correlation between inflammatory biomarkers (IL1B, IL6, IL8, IL10, IL12p70, TNFα and hair cortisol concentration) and OCT corneal epithelial quantifiable variables such as minimum and maximum epithelial thickness of the map, difference between the minimum and maximum (Epithelial Min-Max) and standard deviation of the epithelial thickness of the map (Epithelial Std Dev) and average epithelial thickness of the superior and inferior regions of the map. ResultsEyes with keratoconus presented statistically significantly higher levels of IL1b (p=0.02), IL6 (p <0.0001), IL8 (p <0.0001), and TNFα (p <0.0001) and hair cortisol concentration (p=0.01) compared to healthy controls.There was a significant correlation between IL6 and measurement Epithelium Min-Max [Pearson= -0.59 (-0.69, -0.47); p<0.0001] and Epithelial standard deviation (Std Dev) [Pearson= +0.56 (0.44, 0.67); p<0.0001]. There was a significant correlation between hair cortisol concentration and Epithelium Min-Max [Pearson=-0.27 (-0.42, -0.1); p<0.0001] and Epithelium Std Dev groups [Pearson= +0.2 (0.03, 0.36); p=0.021]. There was also a significant correlation between TNFα and Epithelial Max. [Pearson= -0.37 (-0.55, 0.17); p<0.0001]. We found no significant correlation between the concentration of IL1b, IL8, IL10 and IL2p70 with any epithelium parameters. ConclusionsThe higher concentration of inflammatory markers (IL6 and hair cortisol) in eyes with keratoconus present a significant correlation with OCT metrics identifying epithelial variability, such as Epithelial Min-Max and Std Dev. These findings demonstrate the role of chronic inflammation in eyes with keratoconus, and that these epithelial changes detectable with OCT are sensitive to this inflammatory process.

Inflammation and Tumor Progression: The Differential Impact of SAA in Breast Cancer Models

Background: Previous research has shown that the Serum Amyloid A (SAA) protein family is intricately involved in inflammatory signaling and various disease pathologies. We have previously demonstrated that SAA is associated with increased colitis disease severity and the promotion of tumorigenesis. However, the specific role of SAA proteins in breast cancer pathology remains unclear. Therefore, we investigated the role of systemic SAA1 and SAA2 (SAA1/2) in a triple-negative breast cancer mouse model. Methods: Syngeneic breast tumors were established in wild-type mice, and mice lacking the SAA1/2 (SAADKO). Subsequently, tumor volume was monitored, species survival determined, the inflammatory profiles of mice assessed with a multiplex assay, and tumor molecular biology and histology characterized with Western blotting and H&amp;E histological staining. Results: WT tumor-bearing mice had increased levels of plasma SAA compared to wild-type control mice, while SAADKO control and tumor-bearing mice presented with lower levels of SAA in their plasma. SAADKO tumor-bearing mice also displayed significantly lower concentrations of systemic inflammatory markers. Tumors from SAADKO mice overall had lower levels of SAA compared to tumors from wild-type mice, decreased apoptosis and inflammasome signaling, and little to no tumor necrosis. Conclusions: We demonstrated that systemic SAA1/2 stimulates the activation of the NLRP3 inflammasome in breast tumors, leading to the production of pro-inflammatory cytokines. This, in turn, promoted apoptosis and tumor necrosis but did not significantly impact tumor growth or histological grading.

Clinical characteristics, anti-SARS-CoV-2 IgG titers, and inflammatory markers in individuals with post-COVID-19 condition in Kenya: a cross-sectional study.

Post-coronavirus disease 2019 (post-COVID-19) is associated with considerable morbidity and reduced quality of life. However, studies characterizing the post-COVID-19 condition in Kenya are limited. This study aimed to determine the prevalence of post-COVID-19 condition and determine the clinical characteristics, anti-SARS-CoV-2 IgG titers, and concentrations of inflammatory markers of individuals with post-COVID-19 condition in Kenya. This descriptive cross-sectional study was conducted at the Kenyatta University Health Unit, Kenya. Demographic and clinical data were collected using a questionnaire. The serum levels of anti-SARS-CoV-2 antibodies, interleukin 6 (IL-6), and C-reactive protein (CRP) were quantified by enzyme-linked immunosorbent assays. Independent samples t-test was used to compare the anti-SARS-CoV-2 IgG, IL-6, and CRP levels between the participants with and without post-COVID-19 symptoms. The case definition for post-COVID-19 condition was persistence of acute COVID-19 symptoms or emergence of new symptoms 3 months after COVID-19 diagnosis, symptoms lasting for ≥2 months, and absence of any other etiological basis to explain the symptoms. A total of 189 volunteers were recruited in this study (median age: 21 years, range: 18-71 years; male, 49.2%). Forty participants reported having had at least one COVID-19 positive diagnosis in the past, of which 12 (30%) complained of post-COVID-19 symptoms. Significant differences in the number and duration of symptoms were observed between the individuals with and without post-COVID-19 symptoms (t-statistic = 2.87, p = 0.01; t-statistic = 2.39, p = 0.02, respectively). However, no significant differences in serum levels of anti-SARS-CoV-2 IgG, IL-6, and CRP were observed between the two groups (P = 0.08, 0.9, and 0.28, respectively). These findings suggest that post-COVID-19 condition is a health concern even for a relatively young population in Kenya and globally. This condition requires more attention and well-designed studies to better define it and identify clinical chemistry markers that can be used for its diagnosis.

Inflammatory markers in relation to maternal lifestyle and adverse pregnancy outcomes in twin pregnancies

It is well known that inflammatory markers play an important role in the development and maintenance of healthy pregnancies. However, the literature regarding inflammation in relation to lifestyle and adverse pregnancy outcomes in twin pregnancies is remarkably uncovered. Therefore, this study aimed at evaluating the concentration of inflammatory markers in dried capillary blood spot samples from 523 women with twin pregnancies, included at a median gestational age of 21+1 weeks. The relationship between inflammatory markers and maternal lifestyle (current smoking status and pre-pregnancy body mass index) in addition to adverse pregnancy outcomes (preeclampsia, gestational diabetes mellitus, and small for gestational age) was analyzed. The study showed that active smoking at inclusion was associated with an elevated concentration of interleukin-8. Furthermore, maternal obesity was associated with an elevated concentration of C-reactive protein and monocyte chemoattractant protein-1. Analysis of the data showed no statistically significant variations in the concentration of the assessed inflammatory markers for neither preeclampsia, gestational diabetes mellitus, nor small for gestational age. The current study promotes future research on the pathophysiology of twin pregnancies in relation to adverse pregnancy outcomes, as the literature within the area remains scarce.

Association of KLF14 rs4731702 gene polymorphism with metabolic phenotype in young patients with type 1 diabetes.

To explore the potential association between the KLF14 rs4731702 polymorphism and metabolic syndrome traits among patients diagnosed with type 1 diabetes (T1D). The study group included 350 patients with T1D and 250 healthy control subjects. The analysis focused on the genotyping of KLF14 rs4731702 single nucleotide polymorphism (SNP), as well as evaluating serum concentrations of inflammatory markers, blood pressure, lipid profiles, and the quantitative status of CD4 + CD25highFOXP3+ T cells. Patients with T1D carrying the T allele of KLF14 rs4731702 SNP had higher high-density lipoprotein cholesterol, lower low-density lipoprotein cholesterol, as well as lower glycated haemoglobin and serum concentration of proinflammatory markers than C allele carriers. They also developed hypertension less often than carriers of the C allele. The analysis of CD4 + CD25highFOXP3+ regulatory T-cell status based on KLF14 genotype showed that, in T1D patients, those with the TT genotype had the highest frequency of these cells compared to carriers of the CC and CT genotypes. Our study suggests that the T allele of the KLF14 rs4731702 SNP might confer a protective effect against the development of obesity, hypertension, dyslipidaemia, and chronic inflammatory state in patients diagnosed with T1D.

Complexity and Diversity of the Neurological Spectrum of SARS-CoV-2 over Three Waves of COVID-19.

Background/Objectives: SARS-CoV-2 continually mutates, with five identified variants. Many neurological manifestations were observed during the COVID-19 pandemic, with differences between virus variants. The aim of this study is to assess the frequency and characteristics of neurological manifestations during COVID-19 in hospitalized patients over three waves in Poland with comparison and analysis correlation with the course of infection. Methods: This retrospective single-center study included 600 consecutive adults with confirmed COVID-19, hospitalized during 3 waves (pre-Delta, Delta and Omicron) in Poland. Demographic and clinical information and neurological manifestations were collected and compared across three periods. Results: The median age of the study group was 68, lower during the Delta wave. In the Omicron period, the disease severity at admission and inflammatory markers concentration were the lowest. Neurological manifestations were observed in 49%. The most common were altered mentation, headache, myalgia, mood disorder, ischemic stroke and encephalopathy. Smell and taste disturbances (STDs) were less frequent in the Omicron period. Neurological complications were predominant in the pre-Delta and Omicron periods. Ischemic stroke was observed more often in pre-Delta period. Altered mentation was related to higher severity at admission, worse lab test results, higher admission to ICU and mortality, while headache reduced mortality. Pre-existing dementia was related to higher mortality. Conclusions: Neurological manifestations of COVID-19 are frequent, with a lower rate of STDs in the Omicron period and more often cerebrovascular diseases in the pre-Delta period. Headache improves the course of COVID-19, while altered mentation, stroke and neurological comorbidities increase severity and mortality.

The effectiveness of rehabilitation in vulvovaginal atrophy

Objective: to evaluate the effectiveness and safety of rehabilitation programmes in patients with vulvovaginal atrophy (VVA).Material and methods. The study involved 350 patients with VVA in surgical (n=140) and natural (n=140) menopause, the control group included 70 women without VVA. Patients with VVA were distributed into groups receiving complex “active” rehabilitation (surgical menopause: group 1A, natural menopause: group 2A) and “passive” rehabilitation (surgical menopause: group 1B, natural menopause: group 2B). Body mass index (BMI), vaginal pH, carbohydrate profile with calculation of insulin resistance index (HOMA-IR), inflammatory markers leptin, interleukin-6, tumour necrosis factor alpha, serum magnesium, and safety profile with evaluation of adverse events related to rehabilitation measures were assessed over 24 months.Results. BMI decreased significantly in groups 1A and 2A. Vaginal pH at 1-year follow-up decreased in groups 1A and 2A, but increased in groups 2A and 2B. BMI was higher than normal in all patients with VVA, as well as in the control group, demonstrating preobesity (groups 1A, 2A, control group) or first-degree obesity (initially in group 1B and throughout follow-up in group 2B). HOMA-IR initially reflected postoperative insulin resistance in groups 1A and 2A, but in those receiving complex “active” rehabilitation the dynamics of its reduction was the most pronounced. The concentration of inflammatory markers was initially increased compared to the control group and decreased over time in groups 1A and 1B, but only leptin levels reached the control group values by the end of the study. Serum concentration of magnesium levels was 0.71±0.12 mmol/l in group 1A, 0.71±0.10 mmol/l in group 2A, 0.76±0.08 mmol/l in group 1B, 0.72±0.17 mmol/l in group 2B (magnesium deficiency). When organic magnesium salts in combination with pyridoxine were supplemented in groups 1A and 1B, serum magnesium levels were restored to normal from the 3rd month of follow-up. No adverse events were registered.Conclusion. The personalised programme of complex “active” rehabilitation in patients with VVA is more effective than “passive” rehabilitation with comparable safety profile. Its implementation into routine practice will contribute to the improvement of the quality of health care for such patients.

Combined coagulation and inflammation markers as predictors of venous thrombo-embolism and death in COVID-19.

The COVID-19 pandemic related to SARS-CoV-2 virus was responsible for global pandemic. The severe form of the disease was linked to excessive activation of immune pathways together with a systemic cytokine storm response and thrombotic venous or arterial complications. Factors predicting severe outcomes including venous and/or pulmonary thrombosis (VT) and death were identified, but the prognostic role of their combination was not addressed extensively. We investigated the role of prognostic factors from the coagulation or inflammatory pathways to better understand the outcome of the disease. For this, we prospectively studied 167 SARS-CoV-2-positive patients from admission in intensive care units (ICU) or emergency departments from four academic hospitals over a 14-month period. Besides standard biology, we assessed serum concentrations of inflammatory markers, coagulation factors and peripheral blood cells immunophenotyping. Thirty-nine patients (23.3%) developed VT and 30 patients (18%) died. By univariate analysis, C-reactive protein (CRP) level > 150 mg/L, interleukin-6 (IL-6) ≥ 20 pg/mL, D-dimers > 1,500 μg/L, ADAMTS13 activity ≤ 50%, Von. A combination of coagulation and inflammatory markers can refine the prognostication of severe outcome in COVID-19, and could be useful for the initial evaluation of other types of viral infection.

The Impact of Opium Consumption on Inflammatory Factors in Umbilical Cord Blood and Maternal Blood Postpartum: A Potential Contributor to Neonatal Complications

Opium addiction during pregnancy can have significant effects on the activity of the immune system as well as on pregnancy outcomes. A study was conducted comparing opium-addicted pregnant women to healthy pregnant women. Blood samples were taken from the maternal vein and umbilical cord immediately after delivery to measure concentrations of inflammatory markers. The results showed that the opium-addicted group had significantly higher levels of IL-6, IL-10, CRP, C3, and C4 in both maternal and cord blood samples compared to the control group. Additionally, adverse pregnancy outcomes such as NICU admissions, neonatal deaths, and low Apgar scores were more prevalent in the opium-addicted group. These findings suggest that opium addiction during pregnancy can lead to postpartum inflammation and negatively impact pregnancy outcomes. It is important to address opium addiction and provide appropriate support and treatment to pregnant women to improve pregnancy outcomes and reduce the risk of complications.

Phentolamine and B vitamins for feeding intolerance in late preterm infants: a randomised trial.

Feeding intolerance (FI) is a common problem in late preterm infants (34 weeks ≤ gestational age < 37 weeks). This study aimed to evaluate the efficacy and safety of phentolamine combined with B vitamins in treating FI in late preterm infants and to explore its effects on gastrointestinal symptoms, inflammation and complications. We randomly assigned 118 late preterm infants with FI to a treatment group (n = 56) or a control group (n = 62). The treatment group received intravenous phentolamine and intramuscular B vitamins, whereas the control group received basic treatment only. We measured the time of disappearance of gastrointestinal symptoms, the time of basal at-tainment, the time of hospitalisation, the incidence of complications, the concentrations of inflammatory markers and the overall effective rate of treatment. The treatment group had a shorter duration of gastrointestinal symptoms than did the control group (p < 0.01). The treatment group also had lower concentrations of inflammatory markers and a higher overall effective rate than did the control group (p < 0.05). There was no difference between the two groups in the time of hospitalisation, basal attainment, weight re-covery and the incidence of complications (p > 0.05). Phentolamine and B vitamins can reduce gastrointestinal symptoms and inflammation in late preterm infants with FI but do not affect the occurrence of complications.

Increased TMEM166 Level in Patients with Postoperative Stroke after Carotid Endarterectomy

Postoperative stroke is a challenging and potentially devastating complication after elective carotid endarterectomy (CEA). We previously demonstrated that transmembrane protein 166 (TMEM166) levels were directly related to neuronal damage after cerebral ischemia–reperfusion injury in rats. In this subsequent clinical study, we aimed to evaluate the prognostic value of TMEM166 in patients suffering from post-CEA strokes. Thirty-five patients undergoing uncomplicated elective CEA and 8 patients who suffered ischemic strokes after CEA were recruited. We evaluated the protein level and expression of TMEM166 in patients diagnosed with postoperative strokes and compared it to those in patients who underwent uncomplicated elective CEA. Blood samples and carotid artery plaques were collected and analyzed. High expressions of TMEM166 were detected by immunofluorescence staining and Western Blot in carotid artery plaques of all patients who underwent CEA. Furthermore, circulating TMEM166 concentrations were statistically higher in post-CEA stroke patients than in patients allocated to the control group. Mean plasma concentrations of inflammatory markers, including interleukin 6 (IL-6) and C-reactive protein (CRP), were also elevated in patients with postoperative strokes. Therefore, based on these findings, we hypothesize that elevated TMEM166 levels, accompanied by a strong inflammatory response, serve as a useful biomarker for risk assessment of postoperative stroke following CEA.

Association between vaginal microbiota and vaginal inflammatory immune markers in postmenopausal women.

In premenopausal individuals, vaginal microbiota diversity and lack of Lactobacillus dominance are associated with greater mucosal inflammation, which is linked to a higher risk of cervical dysplasia and infections. It is not known if the association between the vaginal microbiota and inflammation is present after menopause, when the vaginal microbiota is generally higher-diversity and fewer people have Lactobacillus dominance. This is a post hoc analysis of a subset of postmenopausal individuals enrolled in a randomized trial for treatment of moderate-severe vulvovaginal discomfort that compared vaginal moisturizer, estradiol, or placebo. Vaginal fluid samples from 0, 4, and 12 weeks were characterized using 16S rRNA gene sequencing (microbiota) and MesoScale Discovery (vaginal fluid immune markers: IL-1b, IL-1a, IL-2, IL-6, IL-18, IL-10, IL-9, IL-13, IL-8, IP10, MIP1a, MIP1b, MIP3a). Global associations between cytokines and microbiota (assessed by relative abundance of individual taxa and Shannon index for alpha, or community, diversity) were explored, adjusting for treatment arm, using linear mixed models, principal component analysis, and Generalized Linear Mixed Model + Microbiome Regression-based Kernel Association Test (GLMM-MiRKAT). A total of 119 individuals with mean age of 61 years were included. At baseline, 29.5% of participants had a Lactobacillus -dominant vaginal microbiota. Across all timepoints, alpha diversity (Shannon index, P = 0.003) was highly associated with immune markers. Individual markers that were associated with Lactobacillus dominance were similar to those observed in premenopausal people: IL-10, IL-1b, IL-6, IL-8 (false discovery rate [FDR] < 0.01), IL-13 (FDR = 0.02), and IL-2 (FDR = 0.09). Over 12 weeks, change in alpha diversity was associated with change in cytokine concentration (Shannon, P = 0.018), with decreased proinflammatory cytokine concentrations observed with decreasing alpha diversity. In this cohort of postmenopausal individuals, Lactobacillus dominance and lower alpha diversity were associated with lower concentrations of inflammatory immune markers, as has been reported in premenopausal people. This suggests that after menopause lactobacilli continue to have beneficial effects on vaginal immune homeostasis, despite lower prevalence.

Are shortened aPTT values always to be attributed only to preanalytical problems?

It has been recognized that shortened activated partial thromboplastin time (aPTT) may be caused by various preanalytical conditions. As coagulation Factor VIII is included in the invitro intrinsic coagulation cascade measured by aPTT, we hypothesized that the shortened aPTT could be a result of elevated FVIII activity. We aimed to inspect the connection of elevated FVIII with shortened aPTT, and the possible effect inflammation has on routine laboratory parameters. 40 patients from various hospital departments with aPTT measurement below the lower limit of the reference interval (<23.0 s) were included in the study. To compare the obtained results with aPTT measurements in the non-inflammatory state, samples from 25 volunteers (laboratory personnel) were collected. White blood cell count, C-reactive protein, aPTT, and FVIII values were measured in the control group. Only two samples among 40 patients with shortened aPTT (5 %) were clotted. Out of the remaining 38, 26 had FVIII activity above 150 % (upper limit of a reference interval), median value of 194 % (IQR: 143-243 %). Seven samples in the control group had shortened aPTT results (36 %). However, all coagulation samples were clot and hemolysis-free. Multiple regression identified only FVIII activity as an independent variable in predicting aPTT values (p=0.001). Our results support the thesis that shortened aPTT is rarely a consequence of preanalytical problems. Elevated FVIII activity causes shortened aPTT, not only in theinflammatory state but also in individuals with concentration of inflammatory markers within reference intervals.

Passive heat therapy to improve cardiometabolic health in persons with a spinal cord injury — a pilot study

Objective: To test the effect of repeated heat therapy on markers of inflammation, glucose metabolism and vascular health in persons with a spinal cord injury (SCI). It was hypothesized that the heat therapy intervention would lead to a reduction in the fasting concentration of inflammatory markers as well as an improvement in glucose tolerance and microvascular function.Methods: Five adults with thoracic SCI ((1 female, age: 43 (27 – 60) yrs, BMI: 29 (23 to 30) kg/m2, years since injury: 7 (1 – 11) yrs)) enrolled in an 8-week passive heat therapy intervention consisting of 24 session during which the oral temperature was elevated by 1°C by means of a water-perfused suit and heating blankets. The number of completed sessions, time to reach the desired oral temperature and adverse events were reported. Thermoregulatory and perceptual responses to a single passive heat therapy session were assessed during the first session of the intervention. Fasting interleukin-6 (IL-6), C-reactive protein (CRP) and glucose concentration were measured in plasma before and after the chronic intervention. Additionally, thermal hyperemia in sensate (i.e., arm) and insensate (i.e., leg) skin through laser Doppler flowmetry were determined at 39°C and 45°C pre- and post-intervention. Descriptive data are expressed as median (range).Results: The median time to reach a 1°C increase in oral temperature during passive heating was 53 (49 – 75) min, which was accompanied by a final mean skin temperature of 38.6 (36.5 – 38.9)°C, a thermal comfort of 2 (0 – 4) on a 0 to 5 ratings scale and a basic affect of +3 (+1 - +4) on a -5 to +5 rating scale. Four out of the five participants completed all prescribed passive heating sessions. However, in two participants a number of sessions (N = 10 and 2 out of 24 sessions) were stopped at 0.8°C due to thermal discomfort. There were no skin burns or signs of autonomic dysreflexia. All participants remained hemodynamically stable throughout the sessions. Resting IL-6 and CRP changed from 3.2 (2.7 – 10.5) pg/ml to 8.1 (7.6 – 11.1) pg/ml and 0.40 (0.14 – 1.16) to 1.11 (0.51 – 1.26) pg/ml, respectively. Fasting glucose concentration changed from 90.0 (85.5 – 206.0) mg/dl to 94.5 (69 – 266) mg/dl. Cutaneous vascular conductance at 39°C as a percentage of maximal vasodilation at the arm and leg changed from 23.2 (11.2 – 36.0)% to 30.4 (13.8 – 46.1)% and 34.3 (30.4 – 49.4)% to 47.4 (6.7 – 52.8)%, respectively. Conclusion: These preliminary findings suggest that it is feasible, well-tolerated and safe for persons with SCI to engage in repeated heat therapy. A full data set of this ongoing study is needed to provide more conclusive insight into its effects on cardiometabolic health outcomes. VA Rehabilitation R&amp;D (I21RX003724-01A1). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The Role of Leu-Enkephalin Synthetic Analogue in Regulation of Systemic Inflammatory Response and Prevention of ARDS in Severe Combined Injury

The aim of the study. To study the effect of ley-enkephalin synthetic analogue on the dynamics of inflammatory response markers and organ dysfunction in patients with severe combined trauma.Materials and methods. A prospective clinical study with historical control from two clinical centers — N. I. Pirogov State Clinical Hospital No. 1 and N.V. Sklifosovsky Clinical and Research Institute for Emergency Medicine — included men and women with severe combined trauma and the ISS scores values of 18–44, aged 18 to 70 years. Diagnostic and therapeutic approaches in all patients followed current international, national&amp; local protocols and 2022 clinical recommendations of the Russian Society of Surgeons «Combined and multiple trauma in combination with shock (Polytrauma)». In the study group, treatment was supplemented with extended (72 hours from the admission) infusion of the test drug through a syringe dispenser following the study protocol. Effects of the test drug prolonged infusion were evaluated for the following laboratory parameters: levels of cortisol, procalcitonin, interleukin 6, NTproBNP and leukocyte count. Laboratory tests were performed at 4 time points: prior to test drug infusion, 24 hours and 72 hours after initiation of infusion, and on Day 7. The study evaluated patient’s dynamics using APACHE II, SOFA and SAPS II scales and percentage of patients developing organ dysfunction (renal, respiratory, cardiovascular), rates of sepsis complications and mortality.Results. Patients who received the test drug had significantly lower concentrations of systemic inflammatory response markers, i. e. PCT (P=0.001) and IL-6 (P=0.010) after 24 hours of follow-up vs the control group patients. The incidence of ARDS has also decreased in the study group (P=0.011 vs control). Acute kidney injury (AKI) rate was insignificantly higher in the control group (P=0.349). The duration of hospital stay in the control group was 35 (17; 51) days vs 18 (14; 30) days in the study group (P=0.140)Conclusion. The use of ley-enkephalin synthetic analogue inhibits production of such key systemic inflammatory response markers as PCT and IL-6, and reduces PCT concentrations within 24 hours in patients with severe combined trauma. ARDS developed less frequently in the study group, but there was no significant difference in the incidence of AKI, AHF and infectious complications between the groups.

Sinomenine attenuates bleomycin-induced pulmonary fibrosis, inflammation, and oxidative stress by inhibiting TLR4/NLRP3/TGFβ signaling

Objective The present work concentrated on validating whether sinomenine alleviates bleomycin (BLM)-induced pulmonary fibrosis, inflammation, and oxidative stress. Methods A rat model of pulmonary fibrosis was constructed through intratracheal injection with 5 mg/kg BLM, and the effects of 30 mg/kg sinomenine on pulmonary inflammation, fibrosis, apoptosis, and 4-hydroxynonenal density were evaluated by hematoxylin and eosin staining, Masson’s trichrome staining, TUNEL staining, and immunohistochemistry. Hydroxyproline content and concentrations of inflammatory cytokines and oxidative stress markers were detected using corresponding kits. MRC-5 cells were treated with 10 ng/ml PDGF, and the effects of 1 mM sinomenine on cell proliferation were assessed by EdU assays. The mRNA expression of inflammatory cytokines and the protein levels of collagens, fibrosis markers, and key markers involved in the TLR4/NLRP3/TGFβ signaling were tested with RT-qPCR and immunoblotting analysis. Results Sinomenine attenuated pulmonary fibrosis and inflammation while reducing hydroxyproline content and the protein expression of collagens and fibrosis markers in BLM-induced pulmonary fibrosis rats. Sinomenine reduced apoptosis in lung samples of BLM-challenged rats by increasing Bcl-2 and reducing Bax and cleaved caspase-3 protein expression. In addition, sinomenine alleviated inflammatory response and oxidative stress in rats with pulmonary fibrosis induced by BLM. Moreover, sinomenine inhibited the TLR4/NLRP3/TGFβ signaling pathway in lung tissues of BLM-stimulated rats. Furthermore, TLR4 inhibitor, TAK-242, attenuated PDGF-induced fibroblast proliferation and collagen synthesis in MRC-5 cells. Conclusion Sinomenine attenuates BLM-caused pulmonary fibrosis, inflammation, and oxidative stress by inhibiting the TLR4/NLRP3/TGFβ signaling, indicating that sinomenine might become a therapeutic candidate to treat pulmonary fibrosis.

Triterpenes G-A and G-E from Galphimia glauca with anti-inflammatory and anti-arthritic activity in mice

Ethnopharmacological relevanceGalphimia glauca is a medicinal plant that treats inflammatory and anti-rheumatic problems. Its anti-inflammatory capacity has been reported pharmacologically, attributed to the triterpenes G-A and G-E. AimThe objective of the present work was to measure the anti-inflammatory and immunomodulatory effect of the methanolic extract (GgMeOH) of Galphimia glauca and the isolated galphimines G-A and G-E, first in an acute test of plantar edema with carrageenan, and later in the model of experimental-induced arthritis with CFA. The effect was measured by quantifying joint inflammation, the concentration of pro- (TNF-α, IL-6, IL-17) and anti-inflammatory (IL-10, and IL-4) cytokines, and the ADA enzyme in joints, kidneys, and spleen from mice with experimental arthritis. MethodThe extract and the active triterpenes were obtained according to established methods using different chromatographic techniques. Female ICR strain mice were subjected to intraplantar administration with carrageenan and treated with different doses of GgMeOH, G-A, and G-E; edema was monitored at different times. Subsequently, the concentration of TNF-a and IL-10 in the spleen and swollen paw was quantified. Meloxicam (MEL) was used as an anti-inflammatory control drug. The most effective doses of each treatment were analyzed using a complete Freunds adjuvant (CFA)-induced experimental arthritis model. Joint inflammation was followed throughout the experiment. Ultimately, the concentration of inflammation markers, oxidant stress, and ADA activity was quantified. In this experimental stage, methotrexate (MTX) was used as an antiarthritic drug. ResultsTreatments derived from G. glauca, GgMeOH (DE50 = 158 mg/kg), G-A (DE50 = 2 mg/kg), and G-E (DE50 = 1.5 mg/kg) caused an anti-inflammatory effect in the plantar edema test with carrageenan. In the CFA model, joint inflammation decreased with all natural treatments; GgMeOH and G-A inhibited the ADA enzyme in all organs analyzed (joints, serum, spleen, left and right kidneys), while G-E inhibited the enzyme in joints, serum, and left kidney. CFA caused an increase in the weight index of the organs, an effect that was counteracted by the administration of G. glauca treatments, which also modulate the response to the cytokines analyzed in the different organs (IL-4, IL-10, IL-17, IL-6, and TNF- α). ConclusionIt is shown, for the first time, that the GgMeOH extract and the triterpenes G-A and G-E of Galphimia glauca have an anti-arthritic effect (anti-inflammatory, immunomodulatory, antioxidant, and ADA inhibitor), using an experimental arthritis model with CFA. Therefore, knowledge of the plant as a possible therapeutic agent for this rheumatic condition is expanding.