Biochemical Markers Of Inflammation Research Articles

Surge in Procalcitonin Levels Post ATG During Stem Cell Transplantation for Aplastic Anemia: A Diagnostic Dilemma with Sepsis?

Allogenic Stem Cell Transplantation (AlloSCT) has paved way for curative therapy in numerous hematologic diseases such as Aplastic Anemia. Anti-Thymocyte Globulin (ATG), a polyclonal T-cell antibody is an integral part of the numerous conditioning regimens. Its purpose is the T-cell depletion of the recipient, which is of utmost importance for the prevention of graft rejection and successful engraftment. Febrile responses after ATG administration pose a diagnostic dilemma in these patients who are frequently neutropenic [1]. During the conditioning phase before AlloSCT, patients undergo substantial immunosuppression and immune-alteration under the effect of pharmacotherapy and total body irradiation. Conditioning with ATG can be associated with febrile episodes, circulatory instability and/or respiratory insufficiency. The severity of this reaction especially in a neutropenic patient can closely resemble sepsis. Since blood cultures can take a few days in reporting, biochemical markers of inflammation, such as C-Reactive Protein (CRP) and Procalcitonin (PCT) levels have a diagnostic value. In contrast to CRP, Procalcitonin is a sensitive and specific marker for systemic bacterial infection and fungal sepsis [2,3]. We observed a surge in procalcitonin levels after ATG administration in a patient suffering from severe aplastic anemia undergoing conditioning for allogenic bone marrow transplantation from a matched sibling donor. The patient weighing 72 kilograms, received rabbit ATG as GVHD prophylaxis at the rate 1.5mg/kg (5 vials of 25mg each) on Day - 3 of conditioning and developed high grade fever with chills, reaching a peak temperature of 103.6 degrees Fahrenheit. Microbiological cultures and procalcitonin levels were sent to rule out sepsis as part of the protocol. First line intravenous antibiotics were started and antipyretics were administered. Fever settled on its own once the ATG therapy was completed. On day -2 and -1, the same dose of ATG was given and the patient did not develop any febrile episodes. The median PCT elevation on day 1 after ATG infusion was 87.68mcg/L, nearly 70 times the baseline level. Patient was clinically stable with no features of sepsis. There was a steady decline in PCT levels over the next 4 days, 58.54, 24.79, 4.38 and 1.13 (mcg/L) respectively. No derangements in liver function tests or renal function tests were observed. Subsequently, the microbiological cultures were sterile ruling out sepsis. Several previous reports suggested limited diagnostic value of PCT and CRP in the presence of anti-T-lymphocyte antibodies. Dornbusch et al. compared 15 consecutive febrile episodes after T cell antibody infusion without clinical signs of infection with nine episodes of Gram-negative sepsis. After T-cell antibody infusion PCT and CRP serum levels increased to a similar extent as in Gramnegative sepsis. They concluded that during T-cell antibody treatment neither PCT nor CRP are adequate for differentiating between fever due to infection or to unspecific cytokine release. The median PCT elevation on day1 after T-cell antibody infusion was nearly 40 times the baseline [4]. In our patient, the levels reached 70 times the baseline value probably related to higher ATG dose according to the weight of the patient. Brodska et al., prospectively evaluated the validity of CRP and PCT to diagnose infection in patients receiving ATG prior to hematopoietic stem cell transplantation. They assessed renal and liver functions and their relationship to PCT and CRP changes. They found no interrelationship between PCT levels and BL markers of renal or liver functions (P > 0.05 for all comparisons) [5]. Similarly in our patient, no derangements in LFT or RFTs were seen. To conclude, febrile episodes during treatment with ATG are associated with markedly elevated levels of PCT directly proportional to the dose of ATG given. This causes a diagnostic dilemma with sepsis and early use of antimicrobials, which may be kept in reserve during actual crisis in the post-transplant period. In such a scenario, detailed clinical assessment of patient’s condition and careful interpretation of biochemical and microbiological investigations is of utmost importance for judicious use of antimicrobials in this era of emerging antibiotic resistance.

Low mortality rates among critically ill adults with COVID-19 at three non-academic intensive care units in south Sweden.

BackgroundThe COVID‐19 pandemic has put an exceptional strain on intensive care units worldwide. During the first year, the survival of patients with acute hypoxaemic respiratory failure appears to have improved. We aimed to describe the mortality rates, management characteristics and two pandemic waves during the first year at three non‐academic rural intensive care units in Sweden.MethodsWe retrospectively analysed all cases of COVID‐19 admitted to intensive care units in Region Jönköping County during 1 year. The primary endpoint was 30‐day mortality.ResultsBetween 14th March 2020 and 13th March 2021, 264 patients were admitted to undergo intensive care with confirmed SARS‐CoV‐2 infection. The 30‐day mortality rate after the initial intensive care admission was 12.9%, and this rate remained unchanged during both pandemic waves. However, we found several distinct differences between the two pandemic waves, including an increase in the use of high‐flow nasal oxygen but a decrease in invasive mechanical ventilation use, biochemical markers of inflammation, continuous renal replacement therapy and length of stay in the intensive care unit.ConclusionOur study showed that critically ill patients with COVID‐19 in Sweden have a low 30‐day mortality rate which compares well with results published from academic centres and national cohorts throughout Scandinavia. During the second pandemic wave, the proportion of patients receiving invasive mechanical ventilation and continuous renal replacement therapy was lower than that in the first wave. This could be the result of increased knowledge and improved therapeutic options.

Bone-related polymorphisms and dental status in older men and women. Results of the longitudinal Pro.V.A. study

Background/purposeGenetics plays a role in the susceptibility to periodontitis and tooth loss. Several studies examined the involvement of polymorphisms in candidate genes. We hypothesize that bone metabolism-related polymorphisms could be associated with the number of remaining teeth. Materials and methodsParticipants in the Pro.V.A. longitudinal Study: 3099 Italians (aged 65+ at baseline), 2196 at follow-up 1 (5yrs), 1641 at follow-up 2 (7yrs) underwent detailed interview and clinical-instrumental examination. Subjects, grouped by remaining teeth number (0, 1–7, 8–19, 20+), were genotyped for six different bone-related polymorphisms: collagen type Iα1 (COL1A1, Sp1, Ss alleles, n = 1068), vitamin D receptor (VDR, Fok I, Ff alleles, n = 300), calcitonin receptor (CALCR, Alu I, CT alleles, n = 1430), estrogen receptor alpha (ESR1, Pvu II and Xba I, Pp and Xx alleles, n = 1335 and n = 1324). ResultsCOL1A1 associated with dental status: ss carriers had reduced incident tooth loss (p < 0.05). The low frequency of this genotype, 3.6% in the whole population, didn't grant sufficient statistical power to other findings, such as the lower prevalence of edentulism, consistent throughout the study. In men, CC genotype of CALCR was associated with higher tooth loss between follow ups (p < 0.05). Biochemical markers of inflammation didn't differ by genotype. Confounders such as diabetes, neoplasms, and smoking hampered the detrimental effect of S allele in the logistic regression analysis (OR = 0.67, 95% CI 0.4–1.0, p = 0.06). ConclusionThe present study, demonstrating an association between tooth loss and COL1A1 and -in men- CALCR, contributes to the identification of genes involved in tooth loss and, possibly, susceptibility to periodontitis.

Inflammatory Potential of Diet Is Associated with Biomarkers Levels of Inflammation and Cognitive Function among Postmenopausal Women.

In postmenopausal women (PW), estrogen depletion may predispose to cognitive decline through an increased risk of chronic inflammation. Unhealthy diets also appear to have an impact on the cognitive health of these women. The aim of this study was to investigate the association between inflammatory potential of the diet, levels of inflammatory biomarkers, and cognitive function in PW. In a population of 222 PW, energy intake-adjusted Dietary Inflammatory Index (E-DII) was used to assess the dietary inflammatory potential. Cognitive function was estimated using the Polish version of Mini-Mental State Examination (MMSE), corrected by age and educational level. Selected biochemical inflammatory markers (C-reactive protein, CRP; interleukin-6, IL-6; and tumor necrosis factor alpha, TNF-α) were measured by ELISA tests. PW with an anti-inflammatory diet (first tercile) had significantly higher MMSE, while BMI, percentage fat mass and TNFα concentration were significantly lower compared to those with the most proinflammatory diets (third tercile). Women with cognitive impairment had significantly higher IL-6 concentrations (4.1 (0.8) pg/mL vs. 2.5 (0.2) pg/mL, p = 0.004), and were less educated (12.7 (0.7) years vs. 14.1 (0.2) years, p = 0.03) and less physically active compared to cognitively normal women. PW with the most proinflammatory diets had increased odds of cognitive impairment compared to those with the most anti-inflammatory diets, even after adjustment (OR = 11.10, 95% confidence level; 95%CI: 2.22; 55.56; p = 0.002). Each one-point increase in E-DII (as a continuous value) was also associated with 1.55-times greater odds of cognitive impairment (95%Cl: 1.19; 2.02 p = 0.003) in this population. Dietary inflammation may increase the risk of cognitive impairment in PW, but future studies should include a more sensitive battery of tests to assess cognitive function in this population. Implementation of an anti-inflammatory dietary pattern in PW may help prevent cognitive decline.

Effects of Bilberry and Oat intake on lipids, inflammation and exercise capacity after Acute Myocardial Infarction (BIOAMI): study protocol for a randomized, double-blind, placebo-controlled trial

BackgroundBilberries from Sweden, rich in polyphenols, have shown cholesterol-lowering effects in small studies, and the cholesterol-lowering properties of oats, with abundant beta-glucans and potentially bioactive phytochemicals, are well established. Both may provide cardiometabolic benefits following acute myocardial infarction (AMI), but large studies of adequate statistical power and appropriate duration are needed to confirm clinically relevant treatment effects. No previous study has evaluated the potential additive or synergistic effects of bilberry combined with oats on cardiometabolic risk factors. Our primary objective is to assess cardioprotective effects of diet supplementation with dried bilberry or with bioprocessed oat bran, with a secondary explorative objective of assessing their combination, compared with a neutral isocaloric reference supplement, initiated within 5 days following percutaneous coronary intervention (PCI) for AMI.MethodsThe effects of Bilberry and Oat intake on lipids, inflammation and exercise capacity after Acute Myocardial Infarction (BIOAMI) trial is a double-blind, randomized, placebo-controlled clinical trial. A total of 900 patients will be randomized post-PCI to one of four dietary intervention arms. After randomization, subjects will receive beverages with bilberry powder (active), beverages with high-fiber bioprocessed oat bran (active), beverages with bilberry and oats combined (active), or reference beverages containing no active bilberry or active oats, for consumption twice daily during a 3-month intervention. The primary endpoint is the difference in LDL cholesterol change between the intervention groups after 3 months. The major secondary endpoint is exercise capacity at 3 months. Other secondary endpoints include plasma concentrations of biochemical markers of inflammation, metabolomics, and gut microbiota composition after 3 months.DiscussionControlling hyperlipidemia and inflammation is critical to preventing new cardiovascular events, but novel pharmacological treatments for these conditions are expensive and associated with negative side effects. If bilberry and/or oat, in addition to standard medical therapy, can lower LDL cholesterol and inflammation more than standard therapy alone, this could be a cost-effective and safe dietary strategy for secondary prevention after AMI.Trial registrationClinicalTrials.gov NCT03620266. Registered on August 8, 2018.

The Effect of Omega-3 Fatty Acid Supplementation on Serum Adipocytokines, Lipid Profile and Biochemical Markers of Inflammation in Recreational Runners.

Background: The study aimed to evaluate the effects of a 3-week ω-3 PUFA supplementation on serum adipocytokines (i.e., adiponectin, leptin), neuregulin-4 (NRG4) and erythrocyte omega-3 (ω-3) fatty acid content, as well as the blood antioxidant defense capacity in non-elite endurance runners. Methods: Twenty-four runners were randomized into two groups: the supplemented group, who received omega free fatty acids extract containing 142 mg of EPA, 267 mg of DHA, 12 mg of vitamin E and 5 µg of vitamin D, each administrated at a dose of six capsules twice a day for three weeks, or the placebo group. Venous blood samples were withdrawn at the start and at the end of the study protocols to estimate serum biochemical variables. Results: A significantly higher ω-3 index and lower AA/EPA ratio was observed after ω-3 PUFA compared to pre-supplementation levels (p < 0.001 and p < 0.001, respectively). An increase in baseline adiponectin and NRG4 levels, as well as a decrease of leptin concentration and lipid profile improvement, were observed in subjects after a ω-3 PUFA diet. The increased ω-3 index had a significant effect on TNFα levels and a serum marker of antioxidant defense. Conclusions: The ω-3 PUFA extract with added vitamin E and D supplementation may have a positive effect on the function of the adipocyte tissue, as well as the ability to prevent cardiovascular complications in athletes.

Tezepelumab as an Emerging Therapeutic Option for the Treatment of Severe Asthma: Evidence to Date.

Asthma is a complex heterogeneous disease defined by chronic inflammation of the airways. Patients present with wheezing, chest tightness, cough and shortness of breath. Bronchial hyperresponsiveness and variable expiratory airflow limitation are hallmark features. About 3.6–6.1% of patients, despite receiving high-dose inhaled corticosteroids (ICS) and a second controller medication, report persistent symptoms referred to as severe asthma. Uncontrolled severe asthma is associated with increased mortality, morbidity, diminished quality of life and increased health expenditures. The development of modern biological therapy has revolutionized severe asthma treatment. By targeting specific chemokines, asthma control has drastically improved, resulting in better quality of life, less emergency department visits and inpatient admissions, and decreased chronic systemic corticosteroid utilization. Despite these advances, there remains a subset of asthma patients who remain symptomatic with poor quality of life and heavy utilization of the healthcare system. Recently attention has been given to pharmaceutical therapy directed at receptors and cytokines on the epithelial layer of the lung referred to as “alarmins”. Thymic stromal lymphopoietin (TSLP) is an interleukin-7-like receptor family found on the epithelial layer of the lung that releases a cytokine cascade inducing eosinophilic inflammation, mucus production and airflow obstruction in asthmatics. Tezepelumab is the first investigational monoclonal antibody that inhibits TSLP. Proof of concept study and phase IIb studies demonstrated reduced asthma exacerbations, improvement in quality of life, less decline in FEV1 and decrease in biochemical inflammatory markers in comparison to placebo. It is presently undergoing three phase III studies and an additional phase II study.

Association between subclinical atherosclerosis, bone mass and biochemical markers of inflammation in postmenopausal women

Background and Aims: to study the association pulse wave velocity (PWV), augmentation index (AI), intima-media thickness (IMT) and the presence of atherosclerotic plaques (ASP) with bone mineral density (BMD) and inflammation markers: high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6).

Acute Cardiovascular Manifestations in 286 Children With Multisystem Inflammatory Syndrome Associated With COVID-19 Infection in Europe.

The aim of the study was to document cardiovascular clinical findings, cardiac imaging, and laboratory markers in children presenting with the novel multisystem inflammatory syndrome associated with coronavirus disease 2019 (COVID-19) infection. This real-time internet-based survey has been endorsed by the Association for European Paediatric and Congenital Cardiologists Working Groups for Cardiac Imaging and Cardiovascular Intensive Care. Children 0 to 18 years of age admitted to a hospital between February 1 and June 6, 2020, with a diagnosis of an inflammatory syndrome and acute cardiovascular complications were included. A total of 286 children from 55 centers in 17 European countries were included. The median age was 8.4 years (interquartile range, 3.8-12.4 years) and 67% were boys. The most common cardiovascular complications were shock, cardiac arrhythmias, pericardial effusion, and coronary artery dilatation. Reduced left ventricular ejection fraction was present in over half of the patients, and a vast majority of children had raised cardiac troponin when checked. The biochemical markers of inflammation were raised in most patients on admission: elevated C-reactive protein, serum ferritin, procalcitonin, N-terminal pro B-type natriuretic peptide, interleukin-6 level, and D-dimers. There was a statistically significant correlation between degree of elevation in cardiac and biochemical parameters and the need for intensive care support (P<0.05). Polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 was positive in 33.6%, whereas immunoglobulin M and immunoglobulin G antibodies were positive in 15.7% cases and immunoglobulin G in 43.6% cases, respectively, when checked. One child in the study cohort died. Cardiac involvement is common in children with multisystem inflammatory syndrome associated with the Covid-19 pandemic. The majority of children have significantly raised levels of N-terminal pro B-type natriuretic peptide, ferritin, D-dimers, and cardiac troponin in addition to high C-reactive protein and procalcitonin levels. In comparison with adults with COVID-19, mortality in children with multisystem inflammatory syndrome associated with COVID-19 is uncommon despite multisystem involvement, very elevated inflammatory markers, and the need for intensive care support.

Comparative nephrotoxic effect on rats of different pathogens

Aim. Compare the nephrotoxicity of different pathogens.Methods. Nephrotoxicity was assessed in rats treated with the following pathogens: hydrazine sulfate, prednisolone, cyclophosphamide, lincomycin and lipopolysaccharide, according to the degree of increase in biochemical markers of inflammation: elastase activity and malondialdehyde (MDA) content.Result. A significant increase in the level of both inflammatory markers in the kidneys was established, the most pronounced under the influence of hydrazine sulfate. The recalculation of the percentage increase in the level of markers per 1 mg of the pathogen (specific pro-inflammatory activity, SPIA) showed the highest SPIA in lipopolysaccharide, especially after oral applications, exceeding SPIA for hydrazine sulfate by a factor of thousands.Conclusion. The pro-inflammatory effect on kidneys of many non-microbial toxicants can be realized through the formation of lipopolysaccharide by lysis of gram-negative bacteria.

Long-term effectiveness and pharmacokinetics of the infliximab biosimilar CT-P13 after switching from the originator during the treatment of inflammatory bowel disease

ObjectiveSwitching patients from the originator infliximab to a biosimilar is a measure to expand access to treatments and counteract its negative impact on healthcare budgets. However, industry-independent long-term studies on...

Acute Cardiovascular Manifestations in 286 Children with Multisystem Inflammatory Syndrome Associated with COVID-19 Infection in Europe

Background: The aim of the study was to document cardiovascular clinical findings, cardiac imaging and laboratory markers in children presenting with the novel multisystemic inflammatory syndrome associated with COVID-19. Methods: A real-time internet based survey was sent via the member mailing database for Association for European Paediatric and Congenital Cardiologists (AEPC) working groups for Cardiac Imaging and Cardiovascular Intensive Care member. Inclusion criteria was children 0-18 years admitted to hospital between March 1 and June 6, 2020 with diagnosis of an inflammatory syndrome and acute cardiovascular complications. Findings: A total of 286 children from 55 centres from 17 European countries were included. The median age was 8·4 years (IQR 3·8-12·4 years) and 67% were males. Most common cardiovascular complications were shock (40%), cardiac arrhythmias (35%), pericardial effusion (28%) and coronary artery dilatation (24%). Reduced left ventricular ejection fraction was present in 52% of patients and 93% had raised cardiac troponin (cTnT). The biochemical markers of inflammation were raised in majority of patients on admission: elevated CRP (99%), ferritin (79%), procalcitonin (96%), NT-proBNP (93%), IL-6 level (88%) and D-dimers (90%). There was a statistically significant correlation between degree of elevation in cardiac and biochemical parameters and need of intensive care support (p Interpretation: Cardiac involvement is common in children with multi-inflammatory syndrome associated with COVID-19 pandemic. A majority of children have significantly raised levels of NT pro-BNP, ferritin, D-dimers and cardiac troponin in addition to high CRP and procalcitonin levels. Compared to adults, mortality in children with PIMS-TS is extremely rare despite multi-system involvement, very elevated inflammatory markers and need of intensive care support.Funding Statement: There was no external funding source for this studyDeclaration of Interests: The authors declare no competing interests.Ethics Approval Statement: Local institutional approval was obtained, where required, by participating centres as collaborative anonymised data, according to the principles of the Declaration of Helsinki.

Drain management after distal pancreatectomy based on a predictive model, including drainage fluid amylase and biochemical inflammatory markers: a preliminary study

Introduction Postoperative pancreatic fistula (POPF) is the Achilles’ heel of distal pancreatectomy. Surgeons use abdominal drains for early prediction, diagnosis, and timely management of POPF. The utility of drainage fluid in the prediction and diagnosis of POPF is a matter of debate. Patients and methods This is a retrospective cohort study of all patients who underwent distal pancreatectomy between January 2018 and January 2020. The present study aims to evaluate the association between drainage fluid amylase (DFA) and systemic inflammatory markers in the prediction of clinically relevant POPF. Results This study included 44 patients with a mean age of 40.3±16.3 years, and the female : male ratio was 2.7 : 1. POPF occurred in 11 (25%) patients. Of them, nine (20.5%) patients were managed by additional ultrasound-guided tube drainage. Higher drainage fluid amount and DFA-D1 were associated with a higher risk of POPF (P=0.036, and 0.009, respectively). The leukocytic count was significantly higher in POPF in the third postoperative day (POD) (P=0.032). POPF group had a significantly higher level of serum lactate dehydrogenase (LDH) on the fourth POD (P=0.001). Patients with high DFA-D1 (>330 IU/l), rising leukocytic count, and high serum LDH were significantly at higher risk of POPF (9/11 developed POPF, P=0.0001). Conclusion DFA-D1, rising leukocytic count, and high serum LDH level compromised a more robust predictive model for POPF. The cutoff value of DFA proposed by the ISGPF is applicable when combined with leukocytic count and serum LDH. Prospective large-scale studies are needed.

PNPLA3 rs738409 associates with alcoholic liver cirrhosis but not with serum levels of IL6, IL10, IL8 or CCL2 in the Russian population

Introduction and aimPolymorphic variant rs738409 within the PNPLA3 gene associates with alcoholic liver cirrhosis (ALC) in heavy drinkers of various ancestry but has not yet been established in the Russian population characterized by high incidence of ALC. PNPLA3 rs738409 involvement in the inflammatory process has been proposed as one of the mechanisms of liver dysfunction. Relationship between the PNPLA3 polymorphism and the biochemical markers of inflammation in patients with ALC remains unclear. The current study revealed the association between the rs738409 polymorphism, liver cirrhosis and serum cytokines in heavy drinkers in the Russian population. Materials and methodsThe serum levels of IL6, IL10, IL8, and CCL2 along with PNPLA3 rs738409 polymorphism were determined in heavy drinkers (AA, n=71) and heavy drinkers with diagnosed liver cirrhosis (ALC, n=110). All of the recruited individuals were Caucasians and belonged to the Russian population. ResultsHeavy drinkers carrying PNPLA3 rs738409 CG or CG+GG genotypes as compared with CC genotype carriers or G allele as compared with C allele carriers had significant risk of ALC. In ALC levels of interleukins and CCL2 increased as compared with AA. PNPLA3 rs738409 CC carriers had lower cirrhosis stage as compared with CG+GG carriers, however there were no differences of IL6, IL10, IL8 or CCL2 levels between G allele carriers and non-carriers in heavy drinkers. ConclusionThus, in the Russian population heavy drinkers carrying PNPLA3 rs738409 G allele are at higher risk of ALC, however the presence of rs738409 allele does not influence the serum cytokine levels.

Papaverine Has Therapeutic Potential for Sepsis-Induced Neuropathy in Rats, Possibly via the Modulation of HMGB1-RAGE Axis and Its Antioxidant Prosperities

Aim Our aim was to investigate the possible neuroprotective properties of papaverine in sepsis-induced critical illness neuropathy (SCIN) through the evaluation of various inflammatory biochemical markers, including interleukin 6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α), and oxidative stress biomarkers, such as malondialdehyde (MDA) and lactic acid. Additionally, evaluation of the HMGB1/RAGE interactions in SCIN was another target of this research. Method To create a sepsis model, a procedure involving intraperitoneal injection of feces was performed on 48 rats. The rats were divided into four equal groups: sham operated, controls and those receiving 20 and 40 mg/kg/day papaverine. After five-day treatments, compound muscle action potential (CMAPs) with electroneuromyography (ENMG) was recorded in all rats. Following ENMG evaluations, the plasma levels of sRAGE, HMGB1, TNF-α, IL-6, CRP, MDA and lactic acid were measured. Results TNF-α, CRP, IL-6, HMGB1, MDA, and lactic acid levels were significantly elevated in the SCIN group, and sRAGE levels were significantly decreased. In recipients of papaverine (20 and 40 mg/kg) treatment, these biochemical findings were improved. Furthermore, electrophysiological findings also showed significant improvement in both 20 and 40 mg/kg papaverine treated groups. Conclusion Papaverine demonstrates neuroprotective effects in a rat model of SCIN. Considering its anti-inflammatory and antioxidant properties, papaverine’s neuroprotective effects possibly stem from the suppression of the RAGE-HMGB1 axis.

RELATIONSHIP OF BONE MINERAL DENSITY AND VASCULAR WALL CONDITION WITH BIOCHEMICAL MARKERS OF INFLAMMATION IN POSTMENOPAUSAL WOMEN

Objective: to investigate the correlation of bone mass, the parameters of vascular stiffness and subclinical atherosclerosis with biochemical markers of inflammation in postmenopausal women. Subjects and methods. The cross-sectional investigation included 98 patients aged 45–82 years who were followed up in the outpatient setting and signed an informed consent. The investigation did not include patients with any clinical manifestations of atherosclerosis, malignant neoplasms, with diseases causing secondary osteoporosis, as well as with the presence of symptoms of acute bacterial or viral infections and an exacerbation of chronic diseases, who took drugs affecting bone metabolism and vascular stiffness. C-reactive protein (CRP) level was determined by a high-sensitive immunoturbidimetric assay using carboxylated polystyrene particles. interleukin (IL)-6 concentration was measured by an enzyme immunoassay. The intima-media thickness (IMT), the presence and number of atherosclerotic plaques (ASP) were studied with duplex scanning. Pulse wave velocity (PWV) and augmentation index (AI) were measured by applanation tonometry using a SphygmoCor device (AtCor Medical Pty. Ltd., Sydney, Australia). Lumbar spine and hip bone mineral density (BMD) was determined using dual energy X-ray absorptiometry. Results and discussion. There was an increase in the parameters of vascular stiffness, subclinical atherosclerosis, and CRP level and a decrease in bone mass with a longer length of menopause. The vascular stiffness parameters, including IMT (r=0.26; p&lt;0.05), AI (r=0.25; p&lt;0.05), the presence of ASP (r=0.24; p&lt;0.05), and PWV (r=0.23; p&lt;0.05), directly correlated with CRP level. A negative correlation was found between LI–IV BMD and CRP (r=-0.31; p&lt;0.05). The probability of detecting increased IMT with a high CRP level was increased by 2.64 times, ASP by 3.18 times, and low BMD by 2.4 times. There was no association of bone mass, and the parameters of subclinical atherosclerosis and vascular stiffness with IL-6. Conclusion. Lower bone mass and the development of osteoporosis in postmenopausal women were associated with increased vascular stiffness and the presence of signs of subclinical atherosclerosis, and with a high level of CRP, which allows one to discuss the common mechanisms for development of osteoporosis and atherosclerosis, as well as the involvement of chronic inflammation in them.

To beer or not to beer: A meta-analysis of the effects of beer consumption on cardiovascular health.

A moderate alcohol consumption is demonstrated to exert a protective action in terms of cardiovascular risk. Although this property seems not to be beverage-specific, the various composition of alcoholic compounds could mediate peculiar effects in vivo. The aim of this study was to evaluate potential beer-mediated effects on the cardiovascular health in humans, using a meta-analytic approach (trial registration number: CRD42018118387). The literature search, comprising all English articles published until November, 30th 2019 in EMBASE, PubMed and Cochrane database included all controlled clinical trials evaluating the cardiovascular effects of beer assumption compared to alcohol-free beer, water, abstinence or placebo. Both sexes and all beer preparations were considered eligible. Outcome parameters were those entering in the cardiovascular risk charts and those related to endothelial dysfunction. Twenty-six trials were included in the analysis. Total cholesterol was significantly higher in beer drinkers compared to controls (14 studies, 3.52 mg/dL, 1.71-5.32 mg/dL). Similar increased levels were observed in high-density lipoprotein (HDL) cholesterol (18 studies, 3.63 mg/dL, 2.00-5.26 mg/dL) and in apolipoprotein A1 (5 studies, 0.16 mg/dL, 0.11-0.21 mg/dL), while no differences were detected in low density lipoprotein (LDL) cholesterol (12 studies, -2.85 mg/dL, -5.96-0.26 mg/dL) and triglycerides (14 studies, 0.40 mg/dL, -5.00-5.80 mg/dL) levels. Flow mediated dilation (FMD) resulted significantly higher in beer-consumers compared to controls (4 studies, 0.65%, 0.07-1.23%), while blood pressure and other biochemical markers of inflammation did not differ. In conclusion, the specific beer effect on human cardiovascular health was meta-analysed for the first time, highlighting an improvement of the vascular elasticity, detected by the increase of FMD (after acute intake), and of the lipid profile with a significant increase of HDL and apolipoprotein A1 serum levels. Although the long-term effects of beer consumption are not still understood, a beneficial effect of beer on endothelial function should be supposed.

Ameliorative Effect of Gum Acacia on Hookah Smoke-Induced Testicular Impairment in Mice.

We investigated some reproductive actions of hookah smoke (HS) exposure (30 min/day, for 30 days) in male mice, and the possible mitigative effect of the prebiotic agent gum acacia (GA) thereon. Control mice were air-exposed (AE). Twenty-four hours after the last exposure, the levels of some plasma reproductive hormones, biochemical markers of inflammation, oxidative and nitrosative stress and testicular histopathology were assessed. The urinary level of cotinine, a major nicotine metabolite, was also measured. HS exposure induced significant decreases in testosterone, estradiol, luteinizing hormone, and androgen binding protein, as well as glutathione reductase activity and levels of nitrite and total nitrite. Plasma inhibin B, alkaline phosphatase, lipopolysaccharide binding protein, uric acid, lactate dehydrogenase, lipid peroxidation, 8-oxo-2’-deoxyguanosine, and cytochrome C were significantly increased following HS exposure. In testicular homogenate, nuclear factor-κB (NF-ĸB), nuclear factor erythroid 2–related factor 2 (Nrf2), interleukin- 6 (IL-6), interleukin-1β (IL-1β), transforming growth factor-β1(TGF- β1), and tumor necrosis factor-α (TNF- α) were all significantly elevated, and the steroidogenic acute regulatory protein (StAR) significantly decreased. Histopathologically, there was slight impairment and disorganization of spermatogenesis. Urinary cotinine concentration was elevated significantly in the HS-exposed group compared with the air-exposed group. GA co-administration mitigated the adverse actions of HS measured. In conclusion, daily exposure to HS at the above dose induced adverse actions on the reproductive system of male mice. GA co-administration significantly mitigated these effects by reducing the inflammation, oxidative and nitrosative stress, via a mechanism involving Nrf2, and reduction of StAR expression.

Ameliorative Effect of Gum Acacia on Water Pipe Smoke ‐ Induced Testicular Impairment in Mice

We investigated some effects of water pipe smoke (WPS) exposure (30 min/day, for 30 days) in male mice, and the possible ameliorative of gum acacia (GA) coadministration thereon. Controls were exposed to air‐only (AE). Twenty‐four hours post last exposure, the levels of some plasma reproductive hormones, biochemical markers of inflammation, oxidative and nitrosative stress and testicular histopathology were assessed. The concentration of cotinine, the predominant metabolite of nicotine, was also measured in urine. WPS exposure induced a significant decreases in testosterone, estradiol, luteinizing hormone, and androgen binding protein. Inhibin B concentration was significantly increased. Plasma alkaline phosphatase, lipopolysaccharide binding protein, uric acid, and lactate dehydrogenase were all significantly increased following WPS exposure. In testicular homogenate, NF‐κB p65, Nrf2, interleukin‐1β, interleukin‐6, tumor necrosis factor –α, and transforming growth factor‐β1 were all significantly elevated after WPS exposure. WPS exposure decreased nitrite and total nitrite, glutathione reductase activity, and increased lipid peroxidation, cytochrome C, and 8‐Oxo‐2′‐deoxyguanosine. Histopathologically, there was slight reduction in the diameter of the seminiferous tubules with disorganized spermatogenesis. Cotinine concentration was significantly increased in the WPS‐exposed group compared with the control group. GA co‐administration mitigated the adverse actions of WPS measured. We conclude that daily exposure to WPS at the above dose induced damaging effects to the reproductive system in male mice, and that GA co‐administration mitigated the adverse actions of WPS measured.Support or Funding InformationSupported by a joint grant from Sultan Qaboos University and United Arab Emirates University (CL/SQU ‐ UAEU/18/01).

A rare type of skeletal dysplasia resembling rheumatoid arthritis

Abstract Progressive pseudorheumatoid dysplasia is a rare type of spondylo-epi-metaphyseal dysplasia that can be confused clinically and radiologically with juvenile idiopathic arthritis. Precise diagnosis is essential to avoid unnecessary investigation and treatment. The disease is characterized by predominant involvement of joints with progressive limitation of movement with absence of clinical and biochemical markers of inflammation. Here we report three children (two boys and one girl) with this rare disease. Their age of presentation ranged from 3-5 years with pain, swelling and deformities of interphalangeal joints of both hands which progressed with time to joint contractures. Other affected joints included elbows and knees. Back was involved in the oldest patient with lumbar lordosis. All three patients had short stature and normal mentality. The patients had several misdiagnoses before referral to the genetics clinic including rheumatoid arthritis and Morquio syndrome which was excluded by proper investigations. In conclusion, Progressive pseudorheumatoid dysplasia can be confused with Juvenile rheumatoid arthritis as well as other MPS diseases, both clinically and radiologically. Early diagnosis is mandatory to avoid associated disabilities and to avoid unnecessary investigations and treatment