Secretory Phospholipase A2 Levels in Patients with Sickle Cell Disease and Acute Chest Syndrome

In a multicenter study (eight centers), we determined secretory phospholipase A₂ (sPLA₂) levels in patients with sickle cell disease and acute chest syndrome (ACS). The diagnosis of ACS was made according to established criteria. The sPLA₂ levels were determined in blood samples collected at baseline (time of diagnosis) and serially thereafter up to day 22–35 follow-up visits. Thirty-four of 43 (80%) patients with ACS had enzyme levels ≥1.00 AU at baseline. The enzyme levels decreased significantly on Days 2 through Days 25–35 after baseline. Nine of 43 (20%) patients had baseline sPLA₂ values of <1.00 AU with six of them never exceeding 1.00 AU at any point in time during follow-up. The data indicate that the reliability of sPLA₂ for predicting the development of ACS is not perfect (100%) as was previously reported but occurs in about 80% of the patients.     

Protease Inhibitors in Plasma and Faecal Extracts from Patients with Active Inflammatory Bowel Disease

The level and functional activity of the major protease inhibitors in plasma and faecal extracts were analysed in 26 consecutive patients admitted during their first attack of acute severe colitis. The patients were retrospectively divided into two groups: one with total colitis and another with distal colitis. The patients with total colitis had a significantly lower alpha₂-macroglobulin level in plasma than normal individuals and patients with distal disease, whereas no difference in the levels of alpha₁-protease inhibitor, antichymotrypsin, antithrombin III, and alpha₂-antiplasmin was noted between the two groups. The protease-inhibiting capacity was saturated, and free proteolytic activity was present in the faecal extracts. In the extracts complex formation was demonstrated between leukocyte proteases and the antiproteases alpha-protease inhibitor and alpha₂-macroglobulin. It is concluded that the low plasma level of alpha₂-macroglobulin in patients with severe total colitis is mainly due to a consumption caused by complex formation with proteases, as earlier demonstrated in patients with acute pancreatitis and sepsis.     

Phospholipase Activation and Arachidonic Acid Release in Intestinal Epithelial Cells from Patients with Crohn's Disease

A method for studying the mobilization of free arachidonic acid (AA) in viable isolated human intestinal epithelial cells has been developed and applied to the study of patients with Crohn's disease. Cells were isolated from morphologically unaffected parts of the distal ileum and incubated with ¹⁴C-AA; most of the incorporated ¹⁴C-AA was then found in phospholipids (mainly phosphatidylcholine) and in a pool of neutral lipids (mainly triacylglycerols). Cells from patients with Crohn's disease incorporated more ¹⁴C-AA into their neutral lipids than did cells from control patients. When the labeled cells were stimulated with phospholipase C from Clos-tridium perfringens or with the calcium ionophore A23187, they released significant amounts of AA, mainly from phosphatidylcholine. There was no difference between cells from Crohn patients and controls in the ¹⁴C-AA amounts released, but unstimu-lated and phospholipase C-stimulated cells from prednisolone-treated Crohn patients released less AA than cells from control patients. The A23187-stimuiated AA release was completely inhibited by the phospholipase A₂ inhibitor 4-bromophenacyl bromide, whereas the phospholipase C-stimulated release was not. These findings suggest that AA release in human small-intestinal epithelial cells may be caused by calcium-mediated phospholipase A₂ activation or by products of microbial phospholipase C activity and that prednisolone reduces the mobilization of free AA in intestinal epithelial cells. They also illustrate the potential use of isolated epithelial cells for revealing mechanisms underlying AA release in the intestinal mucosa in different disease states.     

Changes of gastric and intestinal blood flow, serum phospholipase A2 and interleukin-1β in rats with acute necrotizing pancreatitis

AIM: To explore the relationship between gastric and intestinal microcirculatory impairment and inflammatory mediators released in rats with acute necrotizing pancreatitis (ANP). METHODS: A total of 64 rats were randomized into control group and ANP group. ANP model was induced by injection of 5% sodium taurocholate under the pancreatic membrane. Radioactive biomicrosphere technique was used to measure the gastric and intestinal tissue blood flow at 2 and 12 h after the induction of ANP, meanwhile serum phospholipase A2 (PLA2) activities and interleukin-lβ levels were determined. Pathologic changes in pancreas, gastric and intestinal mucosae were studied. RESULTS: The gastric blood flow in ANP group (0.62&#177;0.06and 0.35&#177;0.05) mL/(min&#183;g) was significantly lower than that in control group (0.86&#177;0.11 and 0.85&#177;0.06) mL/(min&#183;g) (P&lt;0.01) at 2 and 12 h after induction of ANP. The intestinal blood flow in ANP group (0.80&#177;0.07 and 0.50&#177;0.06) mL/(min&#183;g) was significantly lower than that in control group (1.56&#177;0.18 and 1.61&#177;0.11) mL/(min&#183;g) (P&lt;0.01). Serum PLA2 activities (94.29&#177;9.96 and 103.71&#177;14.40) U/L and IL-Iβ levels (0.78&#177;0.13 and 0.83&#177;0.20) μg/Lin ANP group were higher than those in control group (65.27&#177;10.52 and 66.63&#177;9.81) U/L, (0.32&#177;0.06 and 0.33&#177;0.07)μg/L (P&lt;0.01). At 2 and 12 h after introduction of the model, typical pathologic changes were found in ANP. Compared with control group, the gastric and intestinal mucosal pathologic changes were aggravated significantly (P&lt;0.01) at 12 h after induction of ANP. Gastric and intestinal mucosal necrosis, multiple ulcer and hemorrhage occurred. CONCLUSION: Decrease of gastric and intestinal blood flow and increase of inflammatory mediators occur simultaneously early in ANP, both of them are importantpat hogenic factors for gastric and intestinal mucosal injury in ANP.     

The role of combination therapy with corticosteroids and long-acting ��2-agonists in the prevention of exacerbations in COPD

Acute exacerbations of COPD can complicate the course of the disease in patients with severe airway obstruction. Reduction of exacerbations is an important clinical outcome in evaluating new therapies in COPD. Combination therapies with long-acting β-agonists and inhaled corticosteroids have now been approved for use. Three 1-year randomized clinical trials, which studied the effect of combining a long-acting β₂-agonist with an inhaled corticosteroid in COPD, documented that exacerbation frequency was lower with therapy than placebo. Combination therapy had a similar effect to its monocomponents in the trial evaluating salmeterol/fluticasone combination. However, when patients with more severe COPD were studied using a combination of budesonide and formoterol, a clear improvement was seen in the overall exacerbation rates compared with the use of a long-acting β₂-agonist alone.     

Impact of Sulphate Ions Content on Performance of Maleic and Acrylic Superplasticizers in Cement Paste

The paper presents test results of the impact of sulphate ions from calcium sulphates: Hemihydrate, dihydrate and anhydrite, on rheological properties and hydration heat of cement pastes with, and without, superplasticizers, derivatives of maleic (SP-2) and acrylic (SP-1) acids. It is demonstrated that cement pastes fluidity depends on superplasticizer chemical structure, and its effect is expressed by a hydrophilic coefficient. As maleic superplasticizers have flexible comb-like structure composed of a shorter backbone chain containing COO⁻ carboxylate groups and very long side chains, cement pastes showed higher fluidity than with acrylic superplasticizer with ladder-like structure, longer backbone chains with shorter side chains. SP-1 showing lower hydrophilicity coefficient and fewer COO⁻ groups was found to be less sensitive to increased sulphate ion content in pastes. However, with SP-2 with higher hydrophilicity, a gradual fluidity loss (increased paste viscosity) was observed. Plastic viscosity was approximately at the same level in SP-1-containing pastes. Tests showed that sulphates definitely changed polycarboxylate superplasticizers performance. A high concentration of sulphate ions reduced maleic superplasticizer efficiency. Under these conditions, SP-1 is more effective and therefore more suitable for fluidity of pastes containing higher SO₄²⁻ ions content. Thus, sulphate ions concentration in the paste should be considered when selecting superplasticizer.     

Evaluation of the pharmacokinetics and pharmacodynamics of ticagrelor co-administered with aspirin in healthy volunteers

The results of two independent, randomized, two-period crossover, single-center studies, conducted to assess the pharmacokinetics of ticagrelor?±?aspirin, inhibition of platelet aggregation (IPA) with ticagrelor/aspirin vs. clopidogrel/aspirin, and safety, tolerability, and bleeding times are reported here. In Study A (open-label), 16 volunteers received ticagrelor (50?mg bid Days 1–5; 200?mg bid Days 6–9; one 200?mg dose on Day 10)?±?300?mg qd aspirin (Days 1–10). In Study B (double-blind, double-dummy), 16 volunteers received aspirin (300?mg loading dose/75?mg qd Days 2–9) with either ticagrelor (200?mg bid Days 4–8, one 200?mg dose on Day 9) or clopidogrel (300?mg loading dose Day 4, 75?mg qd Days 5–9). At steady-state ticagrelor (50?mg bid, or 200?mg bid), concomitant aspirin (300?mg qd) had no effect on mean maximum plasma concentration (C_max), median time to C_max (t_max), or mean area under the plasma concentration-time curve for the dosing interval (AUC_0–τ) for ticagrelor and its primary metabolite, AR-C124910XX. Following 200?mg bid ticagrelor, mean C_max and AUC_0–τ for both parent and metabolite were comparable with co-administration of aspirin at 75?mg and 300?mg qd. Aspirin (300?mg qd) had no effect on IPA (ADP-induced) by ticagrelor. However, aspirin and ticagrelor had an additive effect on IPA (collagen-induced). Ticagrelor/aspirin increased bleeding times vs. baseline. Ticagrelor/aspirin co-administration was well tolerated at all dose combinations evaluated. In summary, the findings of this study demonstrate that co-administration of aspirin (300?mg qd) with ticagrelor (50?mg bid, or 200?mg bid) had no effect on ticagrelor pharmacokinetics or IPA (ADP-induced) by ticagrelor.     

Study on the predictive ability of emergency CHADS2 score and CHA2DS2-VASc score for coronary artery disease and prognosis in patients with acute ST-segment elevation myocardial infarction

BackgroundAcute ST-segment elevation myocardial infarction (STEMI) has a high morbidity and mortality rate. The congestive heart failure, hypertension, age, diabetes, previous stroke/transient ischemic attack (2 points) (CHADS₂) and CHADS₂ score with 2 points assigned for age >75 years-vascular disease (CHA₂DS₂-VASc) scores are widely used for risk stratification management of non-valvular atrial fibrillation stroke and have high prognostic value in cardiovascular disease. This study aims to investigate the predictive value of the emergency CHADS₂ and CHA₂DS₂-VASc score on coronary artery lesions and prognosis in patients with acute STEMI.MethodsA total of 524 patients with STEMI from May 2018 to October 2021 were selected for emergency CHADS₂ and CHA₂DS₂-VASc. Clinical data and laboratory indicators were collected. Patients were evaluated for coronary artery disease (CAD) and prognosis. Logistic regression and the receiver operating characteristic (ROC) curve were used to analyze the data.ResultsIn severe group, CysC levels, CHADS₂, CHA₂DS₂-VASc score and the proportion of diabetes, stroke or transient ischemic attack (TIA), congestive heart failure, smoking history, Killip class ≥2 was higher than that in mild and moderate group. In poor prognosis group, levels of serum creatinine (Crea), CysC, hemoglobin (Hb), CHADS₂, CHA₂DS₂-VASc score and the proportion of hypertension, diabetes, stroke or TIA, congestive heart failure, smoking history, and Killip class ≥2 was higher than that in good prognosis group. Diabetes (OR, 3.678; 95% CI: 2.876–5.872, 0.008), CHADS₂ (OR, 3.829; 95% CI: 2.310–5.832, 0.003) and CHA₂DS₂-VASc score (OR, 4.671; 95% CI: 3.125–6.187, 0.000) were independent risk factors for the severity of CAD (P<0.05). Diabetes (OR, 3.287; 95% CI: 2.231–5.123, 0.012), Killip class ≥2 (OR, 2.212; 95% CI: 1.023–2.987, 0.045), LVEF (OR, 3.110; 95% CI: 2.124–5.031, 0.023), CHADS₂ (OR, 3.228; 95% CI: 2.133–5.886, 0.005) and CHA₂DS₂-VASc score (OR, 3.988; 95% CI: 2.987–5.873, 0.001) were independent risk factors for prognosis of acute STEMI patients. Area under curve (AUC) value of CHA₂DS₂-VASc score in evaluating CAD and prognosis was 0.947, 0.931, higher than that of the CHADS₂ score (0.836, 0.812) (P<0.05).ConclusionsMultiple factors jointly affect the severity and prognosis of CAD in patients with acute STEMI. The CHA₂DS₂-VASc score is better than the CHADS₂ score in predicting the severity of coronary artery lesions and prognosis of patients, providing theoretical support for clinical practice.     

Acid and Pepsin Secretion in Patients with Esophagitis Refractory to Treatment with H2 Antagonists

The basis for treatment of esophagitis is suppression of gastric acid secretion. To determine whether lack of healing with standard treatment with H₂ antagonists might be due to abnormal gastric secretion, 30 patients who remained unhealed after 12 weeks' therapy with histamine H₂ antagonists were compared with 20 patients who healed after 6 or 12 weeks' therapy. The groups were matched with regard to age, weight, sex, and presence of hiatal hernia or duodenal ulcer. There were no significant differences in fasting gastric juice volume, pH, or acid or pepsin concentrations. All 30 refractory patients had basal acid output (BAO) <10 meq/h, and 16 of 30 had BAO <2 meq/h—that is, there was no evidence of hypersecretion in any refractory patients. Moreover, basal and maximal acid and pepsin outputs were not higher in non-healing patients. Refractory patients had a higher prevalence of initial severe (grade 3 or 4) esophagitis (80% versus 35% in those who healed, p < 0.01) and of strictures (73 versus 15%, p < 0.001), both of which serve as markers for refractoriness to treatment. Thus 77% of patients who presented with severe esophagitis failed to heal versus 32% of those with mild or moderate esophagitis (p < 0.01). Refractoriness of esophagitis is not related to gastric acid or pepsin hypersecretion but represents a constitutional susceptibility to esophagitis and requires both short- and long-term treatment strategies that are not yet well defined.     

Outcome of Pulmonary Vascular Disease in Pregnancy: A Systematic Overview From 1978 Through 1996

Objectives. Published reports were reviewed to evaluate the characteristics of peripartal management and the late pregnancy outcome in women with pulmonary vascular disease (PVD).

Background. Pulmonary hypertension poses one of the highest risks for maternal mortality, but actual data on the maternal and neonatal prognosis in this group are lacking.

Methods. Reports published from 1978 through 1996 of Eisenmenger’s syndrome (n = 73), primary pulmonary hypertension (PPH) (n = 27) and secondary vascular pulmonary hypertension (SVPH) (n = 25) complicating late pregnancy were included and analyzed using logistic regression analysis.

Results. Maternal mortality was 36% in Eisenmenger’s syndrome, 30% in PPH and 56% (p < 0.08 vs. other two groups) in SVPH. Except for three prepartal deaths due to Eisenmenger’s syndrome, all fatalities occurred within 35 days after delivery. Neonatal survival ranging from 87% to 89% was similar in the three groups. Previous pregnancies, timing of the diagnosis and hospital admission, operative delivery and diastolic pulmonary artery pressure were significant univariate (p < 0.05) maternal risk factors. Late diagnosis (p = 0.002, odds ratio 5.4) and late hospital admission (p = 0.01, odds ratio 1.1 per week of pregnancy) were independent predictive risk factors of maternal mortality.

Conclusions. In the last two decades maternal mortality was comparable in patients with Eisenmenger’s syndrome and PPH; however, it was relevantly higher in SVPH. Maternal prognosis depends on the early diagnosis of PVD, early hospital admission, individually tailored treatment during pregnancy and medical therapy and care focused on the postpartal period.     

Analysis of Tribological Properties of Powdered Tool Steels M390 and M398 in Contact with Al2O3

The present article examines special steels used for the production of injection screws in the plastic industry, with a glass fiber content of up to 30%. Experimental materials, M390 and M398, are classified as tool steels, which are produced by powder metallurgy-HIP methods (hot isostatic pressing). The main goal of the presented paper is to propose the optimal tempered temperature of M398 steel and also to compare the tribological properties of both materials and to determine the degree of their wear depending on their final heat treatment. Partial results refer to the analysis of hardness, roughness, the overall wear mechanism, the change in the volume of retained austenite due to the tempering temperature, and the EDS analysis of the worn surfaces in individual contact pairs. A ceramic ball Al₂O₃ in the α phase was used as the contact material, which had a diameter of 6.35 mm. The ceramic ball performed a rotational movement on the experimental material surface at an elevated temperature of 200 °C using the dry ball-on-disk method. It was experimentally shown that the new M398 material can fully replace the M390 material because it exhibits significantly better tribological properties. The M398 material showed more than a 400% reduction in wear compared to the M390 material. The ideal heat treatment consisted of cryogenic quenching to −78 °C and a tempering temperature of 400 °C. At tempering temperatures of 200 and 400 °C, adhesive wear occurred, which was combined with abrasive wear at a tempered temperature of 600 °C. The averaged coefficient of friction (COF) results show that the M398 material presents less resistance in the friction process and its values are approximately 0.25, while the M390 material showed a COF value of 0.3 after the cryogenic hardening process. The friction surface roughness of the M398 materials also showed lower values compared to the M390 material by approximately 35%. Both of these results are related to the content of M₇C₃ and MC carbide particles based on Cr and V in the bulk of the material, which are in favor of the M398 material.