Estimating the change in pleural pressure using the change in central venous pressure in various clinical scenarios: a pig model study.

BACKGROUND: We have previously reported a simple correction method for estimating pleural pressure (Ppl) using central venous pressure (CVP). However, it remains unclear whether this method is applicable to patients with varying levels of intravascular volumes and/or chest wall compliance. This study aimed to investigate the accuracy of our method under different conditions of intravascular volume and chest wall compliance. RESULTS: Ten anesthetized and paralyzed pigs (43.2 ± 1.8 kg) were mechanically ventilated and subjected to lung injury by saline lung lavage. Each pig was subjected to three different intravascular volumes and two different intraabdominal pressures. For each condition, the changes in the esophageal pressure (ΔPes) and the estimated ΔPpl using ΔCVP (cΔCVP-derived ΔPpl) were compared to the directly measured change in pleural pressure (Δd-Ppl), which was the gold standard estimate in this study. The cΔCVP-derived ΔPpl was calculated as κ × ΔCVP, where "κ" was the ratio of the change in airway pressure to the change in CVP during the occlusion test. The means and standard deviations of the Δd-Ppl, ΔPes, and cΔCVP-derived ΔPpl for all pigs under all conditions were 7.6 ± 4.5, 7.2 ± 3.6, and 8.0 ± 4.8 cmH2O, respectively. The repeated measures correlations showed that both the ΔPes and cΔCVP-derived ΔPpl showed a strong correlation with the Δd-Ppl (ΔPes: r = 0.95, p < 0.0001; cΔCVP-derived ΔPpl: r = 0.97, p < 0.0001, respectively). In the Bland-Altman analysis to test the performance of the cΔCVP-derived ΔPpl to predict the Δd-Ppl, the ΔPes and cΔCVP-derived ΔPpl showed almost the same bias and precision (ΔPes: 0.5 and 1.7 cmH2O; cΔCVP-derived ΔPpl: - 0.3 and 1.9 cmH2O, respectively). No significant difference was found in the bias and precision depending on the intravascular volume and intraabdominal pressure in both comparisons between the ΔPes and Δd-Ppl, and cΔCVP-derived ΔPpl and Δd-Ppl. CONCLUSIONS: The CVP method can estimate the ΔPpl with reasonable accuracy, similar to Pes measurement. The accuracy was not affected by the intravascular volume or chest wall compliance.

Role of Macroautophagy in Mammalian Male Reproductive Physiology.

Physiologically, autophagy is an evolutionarily conserved and self-degradative process in cells. Autophagy carries out normal physiological roles throughout mammalian life. Accumulating evidence shows autophagy as a mechanism for cellular growth, development, differentiation, survival, and homeostasis. In male reproductive systems, normal spermatogenesis and steroidogenesis need a balance between degradation and energy supply to preserve cellular metabolic homeostasis. The main process of autophagy includes the formation and maturation of the phagophore, autophagosome, and autolysosome. Autophagy is controlled by a group of autophagy-related genes that form the core machinery of autophagy. Three types of autophagy mechanisms have been discovered in mammalian cells: macroautophagy, microautophagy, and chaperone-mediated autophagy. Autophagy is classified as non-selective or selective. Non-selective macroautophagy randomly engulfs the cytoplasmic components in autophagosomes that are degraded by lysosomal enzymes. While selective macroautophagy precisely identifies and degrades a specific element, current findings have shown the novel functional roles of autophagy in male reproduction. It has been recognized that dysfunction in the autophagy process can be associated with male infertility. Overall, this review provides an overview of the cellular and molecular basics of autophagy and summarizes the latest findings on the key role of autophagy in mammalian male reproductive physiology.

Decreased Immunoreactivity of Hepatitis E Virus Antigen Following Treatment with Sakhalin Spruce (Picea glehnii) Essential Oil.

The hepatitis E virus (HEV) causes a common infectious disease that infects pigs, wild boars, deer, and humans. In most cases, humans are infected by eating raw meat. Some essential oils have been reported to exhibit antiviral activities. In this study, in order to investigate the anti-HEV properties of essential oils, the immunoreactivities of HEV antigen proteins against the relevant antibodies were analyzed after the HEV antigens underwent treatment with various essential oils. The essential oils extracted from the tea tree, which was previously reported to exhibit antiviral activity, lavender, and lemon had strongly reduced activity. We found that treatment with the essential oil prepared from Sakhalin spruce was associated with the strongest reduction in immunoreactivity of HEV antigen protein(s) among the tested substances. The main volatile constituents of Sakhalin spruce essential oil were found to be bornyl acetate (32.30 %), α-pinene (16.66 %), camphene (11.14 %), camphor (5.52 %), ß-phellandrene (9.09 %), borneol (4.77 %), and limonene (4.57 %). The anti-HEV properties of the various components of the essential oils were examined: treatment with bornyl acetate, the main component of Sakhalin spruce oil, α-pinene, the main component of tea tree oil, and limonene, the main component of lemon oil, resulted in a strong reduction in HEV antigen immunoreactivity. These results indicate that each main component of the essential oils plays an important role in the reduction of the immunoreactivity of HEV antigen protein(s); they also suggest that Sakhalin spruce essential oil exhibits anti-HEV activity. In a formulation with the potential to eliminate the infectivity of HEV in foodborne infections, this essential oil can be applied as an inactivating agent for meat processing and cooking utensils, such as knives and chopping boards.

Diagnostic value of transpulmonary thermodilution measurements for acute respiratory distress syndrome in a pig model of septic shock.

BACKGROUND: No direct approach assessing pulmonary vascular permeability exists in the current therapeutic strategy for patients with acute respiratory distress syndrome (ARDS). Transpulmonary thermodilution measures hemodynamic parameters such as pulmonary vascular permeability index and extravascular lung water, enabling clinicians to assess ARDS severity. The aim of this study is to explore a precise transpulmonary thermodilution-based criteria for quantifying the severity of lung injury using a clinically relevant septic-ARDS pig model. METHODS: Thirteen female pigs (weight: 31 ± 2 kg) were intubated, mechanically ventilated under anesthesia, and either assigned to septic shock-induced ARDS or control group. To confirm the development of ARDS, we performed computed tomography (CT) imaging in randomly selected animals. The pulmonary vascular permeability index, extravascular lung water, and other hemodynamic parameters were consecutively measured during the development of septic lung injury. Lung status was categorized as normal (partial pressure of oxygen/fraction of inspired oxygen ≥ 400), or injured at different degrees: pre-ARDS (300-400), mild-to-moderate ARDS (100-300), or severe ARDS (< 100). We also measured serum inflammatory cytokines and high mobility group box 1 levels during the experiment to explore the relationship of the pulmonary vascular permeability index with these inflammatory markers. RESULTS: Using CT image, we verified that animals subjected to ARDS presented an extent of consolidation in bilateral gravitationally dependent gradient that expands over time, with diffuse ground-glass opacification. Further, the post-mortem histopathological analysis for lung tissue identified the key features of diffuse alveolar damage in all animals subjected to ARDS. Both pulmonary vascular permeability index and extravascular lung water increased significantly, according to disease severity. Receiver operating characteristic analysis demonstrated that a cut-off value of 3.9 for the permeability index provided optimal sensitivity and specificity for predicting severe ARDS (area under the curve: 0.99, 95% confidence interval, 0.98-1.00; sensitivity = 100%, and specificity = 92.5%). The pulmonary vascular permeability index was superior in its diagnostic value than extravascular lung water. Furthermore, the pulmonary vascular permeability index was significantly associated with multiple parameters reflecting clinicopathological changes in animals with ARDS. CONCLUSION: The pulmonary vascular permeability index is an effective indicator to measure septic ARDS severity.

Testicular induced corticosterone synthesis in male rats under fasting stress.

Testicular steroidogenesis is depressed by adrenal-secreted corticosterone (CORT) under stress. However, the mechanisms are not well understood. This study investigated the details of testicular steroidogenesis depression during fasting. Blood levels of adrenocorticotropic hormone secreted from the pituitary glands increased, but blood CORT was not changed in rats that fasted for 96 h, in spite of the rats being severely stressed. CORT in fasting adult male rats increased more than three times in the testis, but reduced testicular testosterone (T) and blood T levels to 5% and 2% of the control, respectively, was observed. The contents of T precursor (except PGN) were drastically reduced in the fasted-rat testes. Testicular CORT levels were elevated, but the enzymatic activity of cytochrome P45011ß, which produces CORT, remained unchanged. The enzymatic activities of 3ß-hydroxysteroid dehydrogenase (3ß-HSD), mediating the conversion of pregnenolone to progesterone, decreased in the fasted-rat testes. Thus, fasting suppressed testicular steroidogenesis by affecting the enzyme activity of 3ß-HSD in the testes and drastically reduced T and increased CORT synthesis. It can be considered that T synthesis involved in cell proliferation is suppressed due to lack of energy during fasting. Conversely, 11ß-hydroxylase enzyme activity was induced and CORT synthesis is increased to cope with the fasting stress. Hence, it can be concluded that CORT synthesis in the testes plays a role in the local defense response.

Early Elevation of Cell-Free DNA After Acute Mesenteric Ischemia in Rats.

BACKGROUND: Acute mesenteric ischemia (AMI) is challenging to diagnose in the early phase. We tested the hypothesis that blood levels of cell-free DNA would increase early after AMI. In addition, proteome analysis was conducted as an exploratory analysis to identify other potential diagnostic biomarkers. METHODS: Mesenteric ischemia, abdominal sepsis, and sham model were compared in Sprague-Dawley rats. The abdominal sepsis model was induced by cecum puncture and mesenteric ischemia model by ligation of the superior mesenteric artery. Blood levels of cell-free DNA were measured 2 h and 6 h after wound closure. Shotgun proteome analysis was performed using plasma samples obtained at the 2 h timepoint; quantitative analysis was conducted for proteins detected exclusively in the AMI models. RESULTS: Blood cell-free DNA levels at 2 h after wound closure were significantly higher in the AMI model than in the sham and the abdominal sepsis models (P < 0.05). Cell-free DNA was positively correlated with the pathologic ischemia severity score (correlation coefficient 0.793-0.834, P < 0.001). Derivative proteome analysis in blood at 2-h time point revealed higher intensity of paraoxonase-1 in the AMI models than in the abdominal sepsis models; the significantly high blood paraoxonase-1 levels in the AMI models were confirmed in a separate quantitative analysis (P = 0.015). CONCLUSIONS: Cell-free DNA was demonstrated to be a promising biomarker for the early diagnosis of mesenteric ischemia in a rat model of AMI. Paraoxonase-1 may also play a role in the differential diagnosis of mesenteric ischemia from abdominal sepsis. The current results warrant further investigation in human studies.

Monitoring the tissue perfusion during hemorrhagic shock and resuscitation: tissue-to-arterial carbon dioxide partial pressure gradient in a pig model.

BACKGROUND: Despite much evidence supporting the monitoring of the divergence of transcutaneous partial pressure of carbon dioxide (tcPCO2) from arterial partial pressure carbon dioxide (artPCO2) as an indicator of the shock status, data are limited on the relationships of the gradient between tcPCO2 and artPCO2 (tc-artPCO2) with the systemic oxygen metabolism and hemodynamic parameters. Our study aimed to test the hypothesis that tc-artPCO2 can detect inadequate tissue perfusion during hemorrhagic shock and resuscitation. METHODS: This prospective animal study was performed using female pigs at a university-based experimental laboratory. Progressive massive hemorrhagic shock was induced in mechanically ventilated pigs by stepwise blood withdrawal. All animals were then resuscitated by transfusing the stored blood in stages. A transcutaneous monitor was attached to their ears to measure tcPCO2. A pulmonary artery catheter (PAC) and pulse index continuous cardiac output (PiCCO) were used to monitor cardiac output (CO) and several hemodynamic parameters. The relationships of tc-artPCO2 with the study parameters and systemic oxygen delivery (DO2) were analyzed. RESULTS: Hemorrhage and blood transfusion precisely impacted hemodynamic and laboratory data as expected. The tc-artPCO2 level markedly increased as CO decreased. There were significant correlations of tc-artPCO2 with DO2 and COs (DO2: r = - 0.83, CO by PAC: r = - 0.79; CO by PiCCO: r = - 0.74; all P < 0.0001). The critical level of oxygen delivery (DO2crit) was 11.72 mL/kg/min according to transcutaneous partial pressure of oxygen (threshold of 30 mmHg). Receiver operating characteristic curve analyses revealed that the value of tc-artPCO2 for discrimination of DO2crit was highest with an area under the curve (AUC) of 0.94, followed by shock index (AUC = 0.78; P < 0.04 vs tc-artPCO2), and lactate (AUC = 0.65; P < 0.001 vs tc-artPCO2). CONCLUSIONS: Our observations suggest the less-invasive tc-artPCO2 monitoring can sensitively detect inadequate systemic oxygen supply during hemorrhagic shock. Further evaluations are required in different forms of shock in other large animal models and in humans to assess its usefulness, safety, and ability to predict outcomes in critical illnesses.

Irisin/FNDC5: A participant in camel metabolism.

The quantification, localization, production, function, and regulation of irisin/FNDC5 in camel species have not been previously studied. The objective of this study was to detect the irisin content in Arabian camel blood and tissues and study the gene expression of FNDC5 and PGC-1α in camel skeletal muscles and white adipose tissue depots under basal conditions. To monitor if exercise influences blood and tissue irisin protein levels as well as FNDC5 and PGC-1α gene expression levels, we analyzed irisin concentrations in the serum, skeletal muscles (soleus and gastrocnemius), and white adipose tissues (hump, subcutaneous, visceral, epididymal, and perirenal) in both control (n = 6) and exercised group (n = 6) using ELISA and determined the cellular localization of irisin/FNDC5 and the mRNA levels of FNDC5 and PGC-1α in skeletal muscles and adipose tissues via immunohistochemistry and real-time PCR, respectively. The possible regulatory roles of exercise on some hormones and metabolites as well as the detection of links between serum irisin and other circulating hormones (insulin, leptin, and cortisol) and metabolites (glucose, free fatty acids, triglycerides, and ATP) were explored for the first time in camels. Our results indicated that exercise induces tissue-specific regulation of the camel irisin, FNDC5, and PGC-1α levels, which subsequently regulates the circulating irisin level. Significant associations were detected between the levels of irisin/FNDC5/PGC-1α in camels and the metabolic and hormonal responses to exercise. Our study suggested that irisin regulates, or is regulated by, glucose, FFA, insulin, leptin, and cortisol in camels. The novel results of the present study will serve as baseline data for camels.

Validation Study of Fibrinogen and Albumin Score in Esophageal Cancer Patients Who Underwent Esophagectomy: Multicenter Prospective Cohort Study.

PURPOSE: To arrange multidisciplinary treatment for esophageal cancer, a simple and accurate predictive marker for prognosis is required. The current multicenter prospective study aims to validate the prognostic significance of fibrinogen and albumin score (FA score) for esophageal cancer patients. PATIENTS AND METHODS: Patients who were planned to undergo surgical resection for esophageal cancer at four participating institutions were enrolled in this study. Patient background, clinicopathological factors, and blood concentration of plasma fibrinogen and albumin were collected. Patients with elevated fibrinogen and decreased albumin levels were allocated a score of 2; those with only one of these abnormalities were allocated a score of 1; and those with neither of these abnormalities were allocated a score of 0. Recurrence-free survival (RFS) and overall survival (OS) were evaluated as a primary endpoint. RESULTS: From four participating institutions, 133 patients were registered for the current analysis. The distribution of FA score of 0/1/2 was 84 (63%)/34 (26%)/15 (11%), respectively. In the analysis of primary endpoint, the preoperative FA score significantly classified RFS (FA score 1/2: HR 2.546, p = 0.013/6.989, p < 0.001) and OS (FA score 1/2: HR 2.756, p = 0.010/6.970, p < 0.001). We further evaluated the prognostic significance of FA score under stratification by pStage. As a result, with increasing FA score, RFS and OS were significantly worse in both pStage 0-I and II-IV groups. CONCLUSIONS: The prognostic impact of preoperative FA score was confirmed for esophageal cancer patients in the current multicenter prospective trial. FA score can be considered to predict postoperative survival and rearrange the treatment strategy before esophagectomy.

Use of perfusion index to detect hemodynamic changes in endotoxemic pigs.

OBJECTIVE: The perfusion index (PI) derived from plethysmographic signals provides a noninvasive indication of peripheral perfusion. This study aimed to investigate changes in PI and other hemodynamic variables in pigs subjected to endotoxemia. DESIGN: Prospective experimental study. SETTING: University teaching hospital. ANIMALS: Twelve healthy pigs weighing a mean (± standard deviation [SD]) of 31.7 ± 2.0 kg. INTERVENTIONS: Pigs were divided into control and endotoxin groups (n = 6 each). Endotoxemia was induced by IV infusion of lipopolysaccharide. Heart rate, mean arterial pressure, cardiac index (CI), central venous pressure, systemic vascular resistance index (SVRI), extravascular lung water index (ELWI), Global end-diastolic volume (GEDV) index, and pulmonary permeability index were measured using a transpulmonary thermodilution monitor in all pigs. PI was measured using a pulse oximeter probe attached to the tail. Pao2 , Paco2 , and plasma lactate concentration were measured by blood gas analysis. Measurements were taken at baseline (T0 ). Saline or lipopolysaccharide was then administered for 30 min to all pigs (control or endotoxemia group, respectively), and each parameter was measured every 30 min up to 270 min. Data were analyzed by analysis of variance and Student's t-tests. MEASUREMENTS AND MAIN RESULTS: There were no significant changes in any variables in the control group, but CI, SVRI, PI, ELWI, blood lactate concentration, and Pao2 changed significantly from baseline in the endotoxin group (P < 0.001, P = 0.0048, P < 0.001, P = 0.0064, P < 0.001, and P = 0.0220, respectively). In the endotoxin group, mean (± SD) %PI increased from T0 to 154 ± 34% at T60 (P = .001) and 135 ± 50% at T90 (P =0 .004), which mirrored significant changes in %CI and %SVRI. CONCLUSION: The PI may be useful to detect changes in CI and SVRI.

Interleukin-6-Mediated Inflammation May Cause Methotrexate-Induced Leukoencephalopathy.

Children with leukemia treated with methotrexate (MTX) may develop MTX-induced leukoencephalopathy, which can present as seizures or focal neurological deficits. However, the precise pathophysiology has not been fully elucidated. Differences in cytokine/chemokine profiles in cerebrospinal fluid (CSF) between children with MTX-induced leukoencephalopathy and those with posterior reversible encephalopathy syndrome (PRES), an acute neurological condition associated with hypertension, were investigated. Interleukin (IL)-1ß, 2, 4, 5, 6, 7, 8, 10, 12, 13, and 17, tumor necrosis factor-alpha, interferon-gamma, granulocyte monocyte colony-stimulating factor, granulocyte colony-stimulating factor, macrophage inflammatory protein-1ß, and monocyte chemoattractant protein-1 concentrations were measured in CSF supernatants from 3 children with acute leukemia with MTX-induced leukoencephalopathy, 3 children with acute leukemia with PRES, 6 children with acute leukemia without neurological complications, and 8 children with acute encephalopathy. CSF IL-6 concentrations were higher in children with MTX-induced leukoencephalopathy than in children with acute leukemia with PRES, with acute leukemia without neurological complications, and with acute encephalopathy. We concluded that IL-6 may be involved in the pathogenesis of MTX-induced leukoencephalopathy.

Clinical significance of preoperative serum concentrations of interleukin-6 as a prognostic marker in patients with esophageal cancer.

BACKGROUND: Although the clinical outcome of esophageal cancer has recently improved, the relapse rate remains high for all disease stages. At present, there is no diagnostic method to predict the long-term outcome for esophageal cancer. In this study, we evaluated serum preoperative proinflammatory cytokine levels and investigated the correlation between preoperative interleukin-6 (IL-6) and IL-8 levels and survival of patients with esophageal cancer. METHODS: Between 2008 and 2015, we evaluated preoperative serum cytokine levels in 122 patients who underwent esophagectomy for esophageal cancer. Serum IL-6 and IL-8 levels were measured by enzyme-linked immunosorbent assays. We investigated the relationship between serum cytokine levels and the response to chemotherapy and survival. RESULTS: The preoperative IL-6 levels were significantly associated with shorter recurrence-free survival (RFS, p = 0.001) and overall survival (OS, p = 0.001) after esophagectomy. Higher IL-8 levels were significantly associated with RFS (p = 0.018). In the multivariate analysis, age, preoperative chemotherapy, lymph node metastasis, serum C-reactive protein (CRP) levels and serum IL-6 levels (hazard ratio (HR), 2.888; p = 0.049) were significantly independent prognostic factors of RFS. Additionally, age, pathological stage, and serum IL-6 levels (HR, 3.247; p = 0.027) were shown to be significantly independent prognostic factors of OS. Serum IL-6 levels were significantly higher in the non-responder group (pathological response pGrade0 and pGrade1) after neoadjuvant therapy. CONCLUSIONS: High preoperative serum IL-6 levels are associated with a poor response to chemotherapy or chemoradiotherapy and poor prognosis after esophagectomy. Preoperative serum IL-6 levels may be a useful independent prognostic marker for esophageal cancer patients.

Rapid prolactin induction in adult male rats after treatment with diethylstilbestrol.

Diethylstilbestrol (DES) is a synthetic oestrogen known to disrupt the endocrine system and to cause reproductive toxicity mediated via the hypothalamic-pituitary-adrenal axis; however, its molecular mechanism of action is poorly understood. In the present study, we found that, after only 1 week of exposure to DES, blood testosterone dramatically decreased and that this decrease was associated with a strong induction of prolactin (PRL). Even with the increase in PRL, the luteinising hormone and follicle-stimulating hormone mRNAs slightly decreased. Our results show that, after 48 hours of a single dose of DES, there was a six-fold increase in PRL expression. After exploring the upstream mechanisms, we determined that dopamine, which inhibits PRL secretion in male rats, did not decrease in the pituitary gland of DES-treated rats, whereas vasoactive intestinal peptide (VIP), which mediates the acute release of PRL, was elevated. Serotonin (5-HT) increased in the brain of male rats 24 hours after a single DES treatment; however, PRL, VIP or 5-HT was not induced by DES in female rats. Our results indicate that DES induces the expression of pituitary PRL in male rats by stimulating VIP in the hypothalamus and 5-HT in the central nervous system.

Deficiency of CRTH2, a Prostaglandin D2 Receptor, Aggravates Bleomycin-induced Pulmonary Inflammation and Fibrosis.

Chemoattractant receptor homologous with T-helper cell type 2 cells (CRTH2), a receptor for prostaglandin D2, is preferentially expressed on T-helper cell type 2 lymphocytes, group 2 innate lymphoid cells, eosinophils, and basophils, and elicits the production of type 2 cytokines, including profibrotic IL-13. We hypothesized that lack of CRTH2 might protect against fibrotic lung disease, and we tested this hypothesis using a bleomycin-induced lung inflammation and fibrosis model in CRTH2-deficient (CRTH2-/-) or wild-type BALB/c mice. Compared with wild-type mice, CRTH2-/- mice treated with bleomycin exhibited significantly higher mortality, enhanced accumulation of inflammatory cells 14-21 days after bleomycin injection, reduced pulmonary compliance, and increased levels of collagen and total protein in the lungs. These phenotypes were associated with decreased levels of IFN-γ, IL-6, IL-10, and IL-17A in BAL fluid. Adoptive transfer of splenocytes from wild-type, but not CRTH2-/-, mice 2 days before injection of bleomycin resolved the sustained inflammation as well as the increased collagen and protein accumulation in the lungs of CRTH2-/- mice. We consider that the disease model is driven by γδT cells that express CRTH2; thus, the adoptive transfer of γδT cells could ameliorate bleomycin-induced alveolar inflammation and fibrosis.

Plethysmography variability index for prediction of fluid responsiveness during graded haemorrhage and transfusion in sevoflurane-anaesthetized mechanically ventilated dogs.

OBJECTIVE: To examine the accuracy of plethysmography variability index (PVI) as a noninvasive indicator of fluid responsiveness in hypovolaemic dogs. STUDY DESIGN: Prospective experimental study. ANIMALS: Six adult healthy sevoflurane-anaesthetized Beagle dogs. METHODS: Dogs were anaesthetized with 1.3-fold their individual minimum alveolar concentration of sevoflurane. The lungs were mechanically ventilated after neuromuscular blockade with vecuronium bromide. Cardiopulmonary variables including mean arterial blood pressure (MAP), central venous pressure (CVP), transpulmonary thermodilution cardiac output (TPTDCO), stroke volume (SV), perfusion index (PI), pulse pressure variation (PPV), stroke volume variation (SVV) and PVI were determined during six stages of graded venous blood withdrawal (5 mL kg-1 increments) and six stages of graded blood infusion (5 mL kg-1 increments). The cardiopulmonary variables were analysed using paired t test or Wilcoxon signed rank test. Correlations between PPV and SVV or PVI were analysed by linear regression. The accuracy of PPV, SVV and PVI for predicting fluid responsiveness was examined by using receiver operating characteristic curve analysis. A value of p < 0.05 was considered statistically significant. RESULTS: Blood withdrawal resulted in significant increases in PPV and PVI and decreases in MAP, CVP, TPTDCO, SV and PI. Blood infusion resulted in significant increases in MAP, CVP, TPTDCO, SV and PI and decreases in PPV and PVI. PPV and PVI showed a relevant correlation (p < 0.001, r2 = 0.62) and threshold values of PPV ≥ 16% (sensitivity 71%, specificity 82%) and PVI ≥ 12% (sensitivity 78%, specificity 72%) for identifying fluid responsiveness. SVV did not change. CONCLUSIONS AND CLINICAL RELEVANCE: Noninvasive measurement of PVI predicted fluid responsiveness with moderate accuracy equal to PPV in sevoflurane-anaesthetized mechanically ventilated dogs. Provisional threshold values for identification of fluid responsiveness were PPV ≥ 16% and PVI ≥ 12%. Clinical trials are needed to confirm these threshold values in dogs.

The alpha-lipoic acid derivative DHLHZn: a new therapeutic agent for acute lung injury in vivo.

OBJECTIVE AND DESIGN: An animal experiment was performed to demonstrate the anti-inflammatory effects of an alpha-lipoic acid (ALA) derivative, dihydrolipoyl histidinate zinc complex (DHLHZn) for acute lung injury (ALI) and to investigate the mechanism of action. MATERIAL: Rats were randomly divided into three experimental groups: control group (n = 17), DHLHZn(-) group (n = 11, ALI model rats), and DHLHZn(+) group (n = 12, ALI model rats treated by DHLHZn). TREATMENT: Lipopolysaccharides (LPS, 10 mg/kg) were administered intratracheally in the DHLHZn(-) group and the DHLHZn(+) group. For the DHLHZn(+) group, DHLHZn (100 mg/kg) was administered intraperitoneally 2 h prior to LPS administration. METHODS: Four hours after LPS administration, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The findings were analyzed using the Mann-Whitney U test. RESULTS: Total number of cells, number of neutrophils and lymphocytes, levels of various inflammatory cytokines, and NF-kB p65 concentration of BALF were significantly lower in the DHLHZn(+) group than in the DHLHZn(-) group (p < 0.05). ALI pathology scores were significantly lower in the DHLHZn(+) group than in the DHLHZn(-) group (p < 0.001). CONCLUSIONS: Anti-inflammatory effects of DHLHZn for ALI were demonstrated by BALF and histopathological findings. The mechanism of action of DHLHZn was considered to be via inhibition of the NF-kB signaling pathway. DHLHZn is thus suggested to be a new prophylactic agent for ALI.

Haptoglobin Reduces Inflammatory Cytokine INF-γ and Facilitates Clot Formation in Acute Severe Burn Rat Model.

Haptoglobin exerts renal protective function by scavenging free hemoglobin from the urine and blood stream in patients with hemolytic disorders. Recent studies elucidate the relationships between haptoglobin and inflammation. In addition, coagulopathy is often induced by systemic inflammation characterized by the presence of vascular endothelial damage. We hypothesize that haptoglobin might have an anti-inflammatory effect and affect hypercoagulability using rat burn model. Thirty anesthetized rats of six-weeks of age received over 30% full-thickness scald burn on the dorsal skin surface. All rats were injected with either haptoglobin (Hpt) or normal saline (NS) intraperitoneally. The rats were divided into three groups: 1) control group (NS 20 mL/kg); 2) low concentration of Hpt group, L-Hpt, (Hpt 4 mL (80 U) /kg+NS 16 mL/kg); and 3) high concentration of Hpt group, H-Hpt, (Hpt 20 mL (400 U) /kg). While under anesthesia, all rats were euthanized by exsanguination at 6 hours (N=5) and 24 hours (N=5). Inflammatory and anti-inflammatory cytokines were measured and whole-blood viscoelastic tests were performed by thromboelastometry (ROTEM). Haptoglobin significantly reduced free hemoglobin 24 hours after the injury. Improvement of hematuria was confirmed in the H-Hpt group. There were no differences in thrombin-antithrombin complex and plasmin-α2 plasmin inhibitor complex. The haptoglobin tended to decrease interferon-gamma (IFN-γ) in H-Hpt group. ROTEM findings of the L-Hpt group showed significantly higher clot firmness and shorter time to maximum clot formation velocity than the control group. Haptoglobin reduced INF-γ, and accelerated speed of clot formation in acute phase of severe burn.

IL-7 and procalcitonin are useful biomarkers in the comprehensive evaluation of the severity of acute cholangitis.

BACKGROUND: The incidence of biliary tract infection (BTI), especially healthcare-associated cholangitis, is increasing. However, there are few reports concerning biomarkers of acute cholangitis. We therefore performed an exhaustive investigation of several biomarkers. METHODS: We retrospectively measured 11 cytokines, six chemokines and procalcitonin (PCT), and endotoxin activity assay (EAA) values (IRB: 110512019) of 61 samples with acute cholangitis. RESULT: The 28-day mortality rate was 9.8%. The levels of most cytokines and chemokines were significantly correlated with each other. A low IL-7 level was found to predict blood culture positivity. Low IL-7 level was also found to predict disseminated intravascular coagulation. Low IL-7 levels and a high PCT level were found to be predictors of severe cholangitis. The 28-day mortality in the group of patients with an IL-7 level of ≤6.0 and a PCT level of >0.5 was 18.2%. It was significantly higher than in the other group. CONCLUSION: The combined use of IL-7 and PCT may be useful for evaluating severe acute cholangitis; these results may suggest that severe acute cholangitis is affected by immunosuppressive changes.