Inflammatory Mediators In Blood Research Articles

Alleviating iatrogenic effects of paclitaxel via antiinflammatory treatment.

Paclitaxel (PTX) is touted as an essential medicine due to its extensive use as a chemotherapeutic agent for various cancers and an antiproliferative agent for endovascular applications. Emerging studies in cardio-oncology implicate various vascular complications of chemotherapeutic agents. We evaluated the inflammatory response induced by the systemic administration of PTX. The investigation included RNAseq analysis of primary human endothelial cells (ECs) treated with PTX to identify transcriptional changes in pro-inflammatory mediators. Additionally, we used dexamethasone (DEX), a well-known antiinflammatory compound, to assess its effectiveness in counteracting these PTX-induced changes. Further, we studied the effects of PTX on monocyte chemoattractant protein-1 (MCP-1) levels in the media of ECs. The study also extended to in vivo analysis, where a group of mice was injected with PTX and subsequently harvested at different times to assess the immediate and delayed effects of PTX on inflammatory mediators in blood and aortic ECs. Our RNAseq analysis revealed that PTX treatment led to significant transcriptional perturbations in pro-inflammatory mediators such as MCP-1 and CD137 within primary human ECs. These changes were effectively abrogated when DEX was administered. In vitro experiments showed a marked increase in MCP-1 levels in EC media following PTX treatment, which returned to baseline upon treatment with DEX. In vivo, we observed a threefold increase in MCP-1 levels in blood and aortic ECs 12 h post-PTX administration. Similar trends were noted for CD137 and other downstream mediators like tissue factor, vascular cell adhesion molecule 1, and E-selectin in aortic ECs. Our findings illustrate that PTX exposure induces an upregulation of atherothrombotic mediators, which can be alleviated with concurrent administration of DEX. Considering these observations, further long-term investigations should focus on understanding the systemic implications associated with PTX-based therapies and explore the clinical relevance of DEX in mitigating such risks.

A review on Yuvanpitika with special reference to Acne Vulgaris

Acne vulgaris is a chronic inflammatory condition of skin in youth. In Ayurveda, acne has been elaborated as one of the Kshudra Rogas (minor ailments). It is manifested in adolescence thus called as Yuvanpidika or Tarunyapitika. Symptoms of Mukhadushika show close resemblance with bacterial infection and inflammatory factors of acne. According to Ayurveda, vitiation of Kapha dosha, Vata dosha and Rakta dhatu lead to acne development. Kapha vitiation may resemble with excess sebum production, Vata vitiation may resemble with hyperkeratinization and Rakta vitiation may resemble with inflammatory mediators in blood, play an important role in pathogenesis of acne. Both modernand Ayurvedic sciences have considered the use of topica Dr. Rahul Ishwalal Desai l as well as oral medications and their combinations for the treatment of acne. Modern medications provide relief from acne vulgaris but causenoticeable side effects. In Ayurveda, acne has been treated mainly by Shodhana (purification of body) and Shamana (conservative treatment) Chikitsa or combination of both. Though, several Ayurveda texts such as Sushruta Samhita, Ashtanga Hrudaya etc., have elaborated the pathophysiology and treatment of acne, the available references are scattered. Thus, there is need of in-depth review and compilation of Ayurvedic texts and literatures. This review may be helpful in better understanding ofcomparative pathophysiology and management of acne vulgaris.

Host-microbiome interactions in apical periodontitis: The endodontic microbiome in relation to circulatory immunologic markers.

To explore microbial differences in the endodontic infection of teeth with primary or secondary apical periodontitis (AP), with or without symptomatology. Additionally, to investigate if these differences are depicted in immunologic markers in blood. Twenty-nine teeth with primary or secondary AP were extracted and cryo-pulverized. Blood was drawn from the subjects at three different time-points before and three time-points after the extraction in a time period of four months. The V4 hypervariable region of the 16S rRNA gene was sequenced using Illumina MiSeq. The microbial profiles were ordinated using principal component analysis and tested for differences between groups with permutational multivariate analysis of variance using the Bray-Curtis distance. If significantly different, the microbial profiles were further analysed using the LDA effect size (LEfSe) biomarker discovery tool. A broad panel of inflammatory mediators in blood was examined longitudinally in all subjects during the six visits with mixed models. The Spearman correlation between these mediators and the zOTUs was calculated, and significant correlations (p < .05) were used as input for significant analysis of microarrays (SAM) using MeV. After subsampling, the 467 zOTUs were classified into 9 phyla and 99 genera or higher level taxa. The predominant genus in the entire sample set was Fusobacterium with a relative abundance of 12.3%, followed by Prevotella (9.9%), Actinomyces (7.7%) and Streptococcus (6.7%). The microbiomes of the endodontic infections were significantly associated with endodontic status (primary/secondary infection; p=.015) as well as with the presence or absence of pain (p=.011). There was also a difference in the concentration of inflammatory mediators, namely, C-reactive protein, Interleukin (IL)-8, IL-10, IL-12p70, RANKL and TNF-α, depending on the existence of pain. In addition, the presence of specific bacteria (zOTUs) was correlated, positively or negatively, with the expression of several circulating inflammatory markers. The microbial profiles and the concentration-time relationship of systemic inflammatory mediators of primary endodontic infection differed from those of secondary, and of symptomatic from those of asymptomatic cases. The fingerprint of associations between the immunological and microbiological profiles differed between asymptomatic and symptomatic patients.

CytoSorb in patients with coronavirus disease 2019: A rapid evidence review and meta-analysis.

After its approval by the European Union in 2011, CytoSorb therapy has been applied to control cytokine storm and lower the increased levels of cytokines and other inflammatory mediators in blood. However, the efficiency of this CytoSorb treatment in patients with coronavirus disease (COVID-19) still remains unclear. To elucidate the Cytosorb efficiency, we conducted a systematic review and single-arm proportion meta-analysis to combine all evidence available in the published literature to date, so that this comprehensive knowledge can guide clinical decision-making and future research. The literature published within the period 1 December 2019 to 31 December 2021 and stored in the Cochrane Library, Embase, PubMed, and International Clinical Trials Registry Platform (ICTRP) was searched for all relevant studies including the cases where COVID-19 patients were treated with CytoSorb. We performed random-effects meta-analyses by R software (3.6.1) and used the Joanna Briggs Institute checklist to assess the risk of bias. Both categorical and continuous variables were presented with 95% confidence intervals (CIs) as pooled proportions for categorical variables and pooled means for continuous outcomes. We included 14 studies with 241 COVID-19 patients treated with CytoSorb hemadsorption. Our findings reveal that for COVID-19 patients receiving CytoSorb treatment, the combined in-hospital mortality was 42.1% (95% CI 29.5-54.6%, I2 = 74%). The pooled incidence of adjunctive extracorporeal membrane oxygenation (ECMO) support was 73.2%. Both the C-reactive protein (CRP) and interleukin-6 (IL-6) levels decreased after CytoSorb treatment. The pooled mean of the CRP level decreased from 147.55 (95% CI 91.14-203.96) to 92.36 mg/L (95% CI 46.74-137.98), while that of IL-6 decreased from 339.49 (95% CI 164.35-514.63) to 168.83 pg/mL (95% CI 82.22-255.45). The majority of the COVID-19 patients treated with CytoSorb received ECMO support. In-hospital mortality was 42.1% for the COVID-19 patients who had CytoSorb treatment. Both CRP and IL-6 levels decreased after Cytosorb treatment.

CCL2 (C-C Motif Chemokine Ligand 2) Biomarker Responses in Central Versus Peripheral Compartments After Focal Cerebral Ischemia.

Inflammatory mediators in blood have been proposed as potential biomarkers in stroke. However, a direct relationship between these circulating factors and brain-specific ischemic injury remains to be fully defined. An unbiased screen in a nonhuman primate model of stroke was used to find out the most responsive circulating biomarker flowing ischemic stroke. Then this phenomenon was checked in human beings and mice. Finally, we observed the temporospatial responsive characteristics of this biomarker after ischemic brain injury in mice to evaluate the direct relationship between this circulating factor and central nervous system–specific ischemic injury. In a nonhuman primate model, an unbiased screen revealed CCL2 (C-C motif chemokine ligand 2) as a major response factor in plasma after stroke. In mouse models of focal cerebral ischemia, plasma levels of CCL2 showed a transient response, that is, rapidly elevated by 2 to 3 hours postischemia but then renormalized back to baseline levels by 24 hours. However, a different CCL2 temporal profile was observed in whole brain homogenate, cerebrospinal fluid, and isolated brain microvessels, with a progressive increase over 24 hours, demonstrating a mismatch between brain versus plasma responses. In contrast to the lack of correlation with central nervous system responses, 2 peripheral compartments showed transient profiles that matched circulating plasma signatures. CCL2 protein in lymph nodes and adipose tissue was significantly increased at 2 hours and renormalized by 24 hours. These findings may provide a cautionary tale for biomarker pursuits in plasma. Besides a direct central nervous system response, peripheral organs may also contribute to blood signatures in complex and indirect ways.

Melatonin Moderates the Triangle of Chronic Pain, Sleep Architecture and Immunometabolic Traffic.

Preclinical as well as human studies indicate that melatonin is essential for a physiological sleep state, promotes analgesia and is involved in immunometabolic signaling by regulating neuroinflammatory pathways. Experimental and clinical neuromodulation studies for chronic pain treatment suggest that neurostimulation therapies such as spinal cord stimulation, vagus nerve stimulation and dorsal root ganglion stimulation have an impact on circulating inflammatory mediators in blood, cerebrospinal fluid and saliva. Herein, we provide an overview of current literature relevant for the shared pathways of sleep, pain and immunometabolism and elaborate the impact of melatonin on the crossroad of sleep, chronic pain and immunometabolism. Furthermore, we discuss the potential of melatonin as an adjunct to neurostimulation therapies. In this narrative review, we addressed these questions using the following search terms: melatonin, sleep, immunometabolism, obesity, chronic pain, neuromodulation, neurostimulation, neuroinflammation, molecular inflammatory phenotyping. So far, the majority of the published literature is derived from experimental studies and studies specifically assessing these relationships in context to neurostimulation are sparse. Thus, the adjunct potential of melatonin in clinical neurostimulation has not been evaluated under the umbrella of randomized-controlled trials and deserves increased attention as melatonin interacts and shares pathways relevant for noninvasive and invasive neurostimulation therapies.

Gene transcripts expressed in equine white blood cells are potential biomarkers of extracorporeal shock wave therapy.

Extracorporeal shockwave therapy (ESWT) is a treatment applied to musculoskeletal injuries in equine athletes to alleviate pain and accelerate healing. ESWT also causes acute tissue damage. Therefore, its ability to act as an analgesic and cause tissue damage potentially increases the risk of a catastrophic event if used shortly before a strenuous competition such as horseracing. While ESWT is prohibited by many racing jurisdictions within 10days prior to competition, a test to detect whether a horse has received ESWT is needed. ESWT changes the protein levels of inflammatory mediators in blood, and white blood cells (WBC) typically produce these proteins. Changes in gene expression precede changes in protein production; thus, it was hypothesized that WBC gene transcripts might serve as biomarkers of ESWT. To test this hypothesis, six thoroughbred horses received a single administration of ESWT to the distal limb, and WBC RNA was extracted from blood samples collected before (0h) and after ESWT (2, 4, 6, 24, 48, and 72 h). Targeted and untargeted analyses evaluated the transcriptome using quantitative PCR (qPCR) and microarray. The expression of IL-1α, IL-1β, TNF-α, IL-1Ra1, IL-1Ra2 and TGF-β1, and BMPR1A in circulating WBCs was significantly up-regulated, while IFN-γ, ZNF483, TMEM80, CAH6, ENPP, and S8723 were significantly down-regulated at various time points following ESWT. These data support the hypothesis that changes in WBC gene transcripts could serve as biomarkers for ESWT.

Randomized, phase 1/2, double-blind pioglitazone repositioning trial combined with antifungals for the treatment of cryptococcal meningitis – PIO study

BackgroundCryptococcosis affects more than 220,000 patients/year, with high mortality even when the standard treatment [amphotericin B (AMB), 5-flucytosin (5-FC) and fluconazole] is used. AMB presents high toxicity and 5-FC is not currently available in Brazil. In a pre-clinical study, pioglitazone (PIO - an antidiabetic drug) decreased AMB toxicity and lead to an increased mice survival, reduced morbidity and fungal burden in brain and lungs. The aim of this trial is to evaluate the efficacy and safety of PIO combined with standard antifungal treatment for human cryptococcosis. MethodsA phase 1/2, randomized, double blind, placebo-controlled trial will be performed with patients from Belo Horizonte, Brazil. They will be divided into three groups (placebo, PIO 15 mg/day or PIO 45 mg/day) and will receive an additional pill during the induction phase of cryptococcosis’ treatment. Our hypothesis is that treated patients will have increased survival, so the primary outcome will be the mortality rate. Patients will be monitored for survival, side effects, fungal burden and inflammatory mediators in blood and cerebrospinal fluid. The follow up will occur for up 60 days. ConclusionsWe expect that PIO will be an adequate adjuvant to the standard cryptococcosis’ treatment. Trial registrationICTRP/WHO (and International Clinical Trial Registry Plataform (ICTRP/WHO) (http://apps.who.int/trialsearch/Trial2.aspx?TrialID=RBR-9fv3f4), RBR-9fv3f4 (http://www.ensaiosclinicos.gov.br/rg/RBR-9fv3f4). UTN Number: U1111-1226-1535. Ethical approvement number: CAAE 17377019.0.0000.5149.

A COMPARATIVE STUDY OF SHALMALYADILEPA AND GUDUCHYADIVATI IN THE MANAGEMENT OF YAUVANAPIDIKA W.S.R.TO ACNE VULGARIS – A RESEARCH ARTICLE

Acne vulgaris is a chronic inflammatory condition of skin in youth. In Ayurveda, acne has been elaborated as one of the KshudraRogas (minor ailments). It is manifested in adolescence thus called as Yuvanpidika or Tarunyapitika. Symptoms of Mukhadushika show close resemblance with bacterial infection and inflam-matory factors of acne. According to Ayurveda, vitiation of Kaphadosha, VataDosha and RaktaDhatu lead to acne development. Kapha vitiation may resemble with excess sebum production, Vata vitiation may re-semble with hyperkeratinization and Rakta vitiation may resemble with inflammatory mediators in blood, play an important role in pathogenesis of acne. Both modern and Ayurvedic sciences have considered the use of topical as well as oral medications and their combinations for the treatment of acne. Modern medi-cations provide relief from acne vulgaris but cause noticeable side effects. In this study, 50 patients with symptoms of Yauvanapidika were treated in two groups. In Group A, patients were given local application of Shalmalyadilepa twice a day with milk, while in Group B patients were given 2 gm of Guduchyadivati thrice along with local application of Shalmalyadilepa. At the end of treatment, Group B showed better im-provement in comparison to Group A.

Early application of continuous high-volume haemofiltration can reduce sepsis and improve the prognosis of patients with severe burns

BackgroundIn the early stage of severe burn, patients often exhibit a high level of inflammatory mediators in blood and are likely to develop sepsis. High-volume haemofiltration (HVHF) can eliminate these inflammatory mediators. We hypothesised that early application of HVHF may be beneficial in reducing sepsis and improving the prognosis of patients with severe burns.MethodsAdults patients with burns ≥ 50% total burn surface area (TBSA) and in whom the sum of deep partial and full-thickness burn areas was ≥ 30% were enrolled in this randomised prospective study, and they were divided into control (41 cases) and HVHF (41 cases) groups. Patients in the control group received standard management for major burns, whereas the HVHF group additionally received HVHF treatment (65 ml/kg/h for 3 consecutive days) within 3 days after burn. The incidence of sepsis and mortality, some laboratory data, levels of inflammatory cytokines in the blood, HLA-DR expression on CD14+ peripheral blood monocytes, the proportion of CD25+Foxp3+ in CD4+ T lymphocytes, and the counts of CD3+, CD4+ and CD8+ T lymphocytes were recorded within 28 days post-burn.ResultsThe incidence of sepsis, septic shock and duration of vasopressor treatment were decreased significantly in the HVHF group. In addition, in the subgroup of patients with burns ≥ 80% TBSA, the 90-day mortality showed significant decreases in the HVHF group. The ratio of arterial oxygen partial pressure to the fraction of inspiration oxygen was improved after HVHF treatment. In the patients who received HVHF treatment, the blood levels of inflammatory cytokines, including tumour necrosis factor-α, interleukin (IL)-1β, IL-6 and IL-8, as well as the blood level of procalcitonin were found to be lower than in the control group. Moreover, higher HLA-DR expression on CD14+ monocytes and a lower proportion of CD25+Foxp3+ in CD4+ T lymphocytes were observed in the patients in the HVHF group.ConclusionsEarly application of HVHF benefits patients with severe burns, especially for those with a greater burn area (≥ 80% TBSA), decreasing the incidence of sepsis and mortality. This effect may be attributed to its early clearance of inflammatory mediators and the recovery of the patient’s immune status.Trial registrationChinese Clinical Trial Register, ChiCTR-TRC-12002616. Registered on 24 October 2012.

Do measurements of inflammatory mediators in blood predict recurrence in patients with bisphosphonate-related osteonecrosis of the jaws?

Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is well-recognised, difficult to manage, and often recurs. The aim of this study was to examine the value of preoperative measurements of inflammatory mediators in blood in 212 patients with BRONJ who were studied prospectively. Multiple logistic regression analysis was used to assess the importance of the amounts of substances in the blood that are independently associated with the dependent variable “recurrence of BRONJ”. The only factor that significantly influenced the development of recurrent BRONJ was reduction in the white cell count (p<0.0001; hazard ratio 5.324; 95% CI 2.373 to 11.945). Neither white cell counts nor C-reactive protein concentrations within or above the reference ranges were significantly associated with recurrent BRONJ. Patients whose white cell counts were lower than the reference range were at increased risk of recurrent BRONJ. This may be a marker of reduced immunocompetence, and additional prophylactic measures or treatment should be considered for these patients.

Experimental rhinovirus infection as a human model of chronic obstructive pulmonary disease exacerbation.

Respiratory virus infections are associated with chronic obstructive pulmonary disease (COPD) exacerbations, but a causative relationship has not been proven. Studies of naturally occurring exacerbations are difficult and the mechanisms linking virus infection to exacerbations are poorly understood. We hypothesized that experimental rhinovirus infection in subjects with COPD would reproduce the features of naturally occurring COPD exacerbations and is a valid model of COPD exacerbations. To evaluate experimental rhinovirus infection as a model of COPD exacerbation and to investigate the mechanisms of virus-induced exacerbations. We used experimental rhinovirus infection in 13 subjects with COPD and 13 nonobstructed control subjects to investigate clinical, physiologic, pathologic, and antiviral responses and relationships between virus load and these outcomes. Clinical data; inflammatory mediators in blood, sputum, and bronchoalveolar lavage; and viral load in nasal lavage, sputum, and bronchoalveolar lavage were measured at baseline and after infection with rhinovirus 16. After rhinovirus infection subjects with COPD developed lower respiratory symptoms, airflow obstruction, and systemic and airway inflammation that were greater and more prolonged compared with the control group. Neutrophil markers in sputum related to clinical outcomes and virus load correlated with inflammatory markers. Virus load was higher and IFN production by bronchoalveolar lavage cells was impaired in the subjects with COPD. We have developed a new model of COPD exacerbation that strongly supports a causal relationship between rhinovirus infection and COPD exacerbations. Impaired IFN production and neutrophilic inflammation may be important mechanisms in virus-induced COPD exacerbations.

Protecting effects of a large dose of dexamethasone on spleen injury of rats with severe acute pancreatitis

To explore the protecting effects and mechanisms of dexamethasone on spleen injury in rats with severe acute pancreatitis (SAP). The rats were randomly divided into a model control group, treated group and sham-operated group. The contents of plasma endotoxin, serum NO, phospholipase A(2) enzyme (PLA(2)) and endothelin-1 (ET-1) were determined. The mortality rate, pathological changes and changes of Bax and Bcl-2 protein expression levels and apoptotic indexes in the spleen of rats were observed in all groups, respectively, at 3, 6 and 12 h after operation. Although the survival rate was significantly higher in the treated group than in the model control group, there was no significantly different between them (P > 0.05). The expression levels of Bax and Bcl-2 proteins and apoptotic indexes were significantly higher in the treated group than in the model control group at different time points (P < 0.05 or P < 0.01) while other blood indexes contents and pathological severity scores of spleen were significantly lower in the treated group than in the model control group (P < 0.05, P < 0.01 or P < 0.001). Dexamethasone can protect spleen from injury during SAP mainly by reducing the content of inflammatory mediators in blood.

Effect of Baicalin on Inflammatory Mediator Levels and Microcirculation Disturbance in Rats With Severe Acute Pancreatitis

To investigate the effect of bacailin on inflammatory mediators and microcirculation disturbance in severe acute pancreatitis (SAP) rats and explore its therapeutic mechanism. The rats were randomly divided into SAP group, baicalin-treated group and sham operated group. At 3, 6, and 12 hours after operation, we examined the mortality rate of rats, ascites volume, and pancreatic pathological changes in each group and determined the contents of inflammatory mediators in blood as well as the changes in blood viscosity. Compared with SAP group, treatment with baicalin is able to improve the pathological damage of the pancreas, reduce the contents of multiple inflammatory mediators in blood, decrease the amount of ascitic fluid, and reduce the mortality rates of SAP rats. The low-shear whole blood viscosity in baicalin-treated group (at 3 hours) as well as the high-shear and low-shear whole blood viscosity in baicalin-treated group (at 12 hours) were significantly lower than that in SAP group. Baicalin has good prospects in the treatment for SAP because it can exert therapeutic effects on this disease through inhibiting the production of inflammatory mediators, decreasing blood viscosity, improving microcirculation, and mitigating the pathological damage of the pancreas.

Of Mice and Men (and Effects of Gene Silencing)

In this issue of Circulation , Zheng and coworkers1 demonstrate the efficacy of specific small interfering RNAs (siRNAs) added to University of Wisconsin solution in protecting donor hearts against cold ischemic injury during storage and subsequent reperfusion. siRNAs targeted tumor necrosis factor-α, C3, and Fas. The study design was well rationalized and performed systematically to confirm the efficacy of these siRNA constructs in silencing their respective targets, first in cell culture and subsequently in whole mouse hearts. Quantitative polymerase chain reaction was used to demonstrate knockdown of each of these proteins after ischemia and reperfusion in contrast to their strong upregulation in control hearts. Beneficial effects were confirmed by enhanced function, decreased apoptosis, diminished neutrophil activation and infiltration, and less histological evidence of tissue damage in the treated hearts. Article see p 1099 First discovered as a method for gene silencing in plants, siRNA effectively silences or reduces posttranscriptional efficacy of …

Biomarkers for Infants at Risk for Necrotizing Enterocolitis: Clues to Prevention?

Necrotizing enterocolitis (NEC) is the most common severe gastrointestinal emergency that affects premature newborns. This disease often has a rapid onset with few, if any, antecedent signs that can be used to reliably predict its occurrence. Its rapid onset and progression to death, as well as its severe morbidity when the infant survives, begs for early diagnostic tools that may be used in determining those infants who would be at greatest risk for development of the disease and for whom early preventative measures could be targeted. Although studies have suggested efficacy of several techniques such as breath hydrogen, inflammatory mediators in blood, urine or stool, and genetic markers, these all have drawbacks limiting their use. The application of newly developed "omic" approaches may provide biomarkers for early diagnosis and targeted prevention of this disease.

Influence ofSalvia miltiorrhizaeon the Mesenteric Lymph Node of Rats with Severe Acute Pancreatitis or Obstructive Jaundice

Objective. To observe the effect of salvia miltiorrhizae injection on inflammatory mediator levels and mesenteric lymph nodes in severe acute pancreatitis (SAP) and obstructive jaundice (OJ) rats and explore the protective mechanism of salvia miltiorrhizae on the lymph nodes of these rats. Methods. A total of 288 rats were used in SAP-associated and OJ-associated experiments. The rats were randomly divided into sham-operated group, model control group, and treated group. At various time points after operation, the pathological changes in mesenteric lymph nodes of rats in each group were observed, respectively. Results. The pathological severity scores in lymph nodes of SAP rats in treated group were significantly lower than those in model control group (P < .05) while the pathological changes in lymph nodes of OJ rats in treated group also showed varying degrees of mitigation. Conclusion. Salvia miltiorrhizae can exert protective effects on the lymph nodes of SAP or OJ rats via a mechanism that is associated with reducing the contents of inflammatory mediators in blood.

Comparison of Blood Activation in the Wound, Active Vent, and Cardiopulmonary Bypass Circuit

During cardiopulmonary bypass, aspirated blood exhibits strong activation features, but the triggering event remains unclear. Contact of blood with the pericardial cavity and surgical wound has been advocated as the main trigger, but suction forces are also considered as a possible contributor. We thus designed a study to identify the possible causes involved in this activation. In 10 patients, we analyzed hemostasis activation markers and inflammatory mediators in blood collected in the pericardial cavity and in blood actively aspirated from the left ventricle without any contact with the pericardial cavity. In addition, the same variables were determined in blood sampled in the cardiopulmonary bypass circuit. Markers of tissue factor pathway activation and of thrombin generation, microparticles, free hemoglobin, interleukin 6, and tumor necrosis factor-alpha were significantly increased in pericardial samples as compared with the left ventricle and cardiopulmonary bypass circuit samples. All measured variables were similar between left ventricle and cardiopulmonary bypass samples, except free hemoglobin, interleukin 6, and microparticle levels, which were significantly higher in the left ventricle. Blood contact with the pericardial cavity induces strong hemolysis, inflammatory mediator release, and coagulation activation, driven by tissue factor pathway activation. By contrast, suction forces applied to left ventricular blood poorly contribute to blood trauma and activation. Comparison of pericardial and left ventricular blood shows that contact with the pericardial cavity, and not suction forces, is the leading cause of blood activation. The specific trigger for blood trauma and activation present in the pericardial cavity remains to be identified.

Effect of Baicalin on inflammatory mediator levels and microcirculation disturbance in rats with severe acute pancreatitis

Abstract Objective: To investigate the effect of Bacailin on inflammatory mediator levels and microcirculation disturbance in severe acute pancreatitis (SAP) rats and explore its therapeutic mechanism on this disease. Methods: SAP model rats were randomly divided into model control group and Baicalin treated group, 45 rats in each group. The same number of normal rats were included in sham-operated group. These groups were further subdivided into 3 h, 6 h and 12 h subgroups, respectively (15 rats in each subgroup). At 3, 6 and 12 hours after operation, rats were killed to conduct the following experiments: (1) to examine the mortality rates of rats, the ascites volume and pancreatic pathological changes in each group; (2) to determine the contents of amylase, PLA~2~, TXB~2~, PGE~2~, PAF and IL-1[beta]; in blood as well as the changes in blood viscosity. Results: (1) Compared to model control group, treatment with Baicalin is able to improve the pathological damage of the pancreas, lower the contents of amylase and multiple inflammatory mediators in blood, decrease the amount of ascitic fluid and reduce the mortality rates of SAP rats; (2) at 3 hours after operation, the low-shear whole blood viscosity in Baicalin treated group was significantly lower than that in model control group;at 12 hours after operation, both the high-shear and low-shear whole blood viscosity in Baicalin treated group were also significantly lower than those in model control group. Conclusion: Baicalin, as a new drug, has good prospects in the treatment of SAP since it can exert therapeutic effects on this disease through inhibiting the production of inflammatory mediators, lowering blood viscosity, improving microcirculation and mitigating the pathological damage of the pancreas.

The microcirculation: a motor for the systemic inflammatory response and large vessel disease induced by hypercholesterolaemia?

There is abundant evidence that links hypercholesterolaemia to both vascular inflammation and atherogenesis. While atherosclerosis is a large vessel disease that is characterized by leucocyte infiltration and lipid deposition in the wall of lesion-prone arteries, the inflammatory response does not appear to be confined to these locations. There is evidence supporting a systemic inflammatory response that is characterized by endothelial cell activation in multiple vascular beds and the appearance of activated immune cells and a wide range of inflammatory mediators in blood. The mechanism(s) responsible for initiating this systemic response remain poorly defined, although several inciting factors have been proposed, including infectious agents and oxidative stress resulting from one or more of the cardiovascular risk factors (e.g. hypercholesterolaemia, hypertension). While cells within lesion-prone arteries are often inferred as the source of circulating inflammatory mediators during atherogenesis, the fact that endothelial cells throughout the vasculature are activated raises the possibility that the microvasculature (which encompasses a vast endothelial surface area) may contribute to creating the systemic inflammatory milieu that is linked to atherogenesis. This review addresses evidence that links the microvasculature to the inflammatory responses induced by hypercholesterolaemia and offers the hypothesis that inflammatory events initiated within the microcirculation may contribute to initiation and/or progression of large vessel disease.