Functionalizing bioinks for 3D bioprinting applications

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PLASMA PHOSPHOLIPASE A2 ACTIVITY IN CLINICAL ACUTE MYOCARDIAL INFARCTION

1. Phospholipase A2 (PLA2) cleaves phospholipids to produce a lyso-phospholipid and free fatty acid and, in view of the biological activity of the products, PLA2 may play a role in many disease states. Lyso-phospholipids and free arachidonic acid increase in ischaemic myocardium, indicating that ischaemia activates the enzyme. 2. Plasma PLA2 activity was measured in patients with acute myocardial infarction, based on the release of labelled arachidonic acid from Escherichia coli cell membrane. Fourteen males (peak serum creatine phosphokinase (CK) above twice upper normal) were studied on day 1 (within 6 h of chest pain onset), days 2-4, and days 6-9. Normal age matched males (n = 13) were also studied. 3. Plasma PLA2 in patients with uncomplicated myocardial infarction (n = 12) was, initially, 1.14 +/- 0.10 (s.e.m.) nmol/min per mL plasma, similar to that in the normal group (1.52 +/- 0.14). On days 2-4, PLA2 activity increased to 1.94 +/- 0.18 (P less than 0.001) and this activity was correlated with the earlier peak CK level (P less than 0.02). On days 6-9, PLA2 activity was 1.49 +/- 0.13 while in two patients who developed complications and underwent open-heart surgery between the last two measurements, there were further increases to 4.22 and 4.04 nmol/min per mL. 4. The increase in plasma PLA2 in uncomplicated myocardial infarction is likely to be due to release from the damaged myocardium; whether it contributes to pathophysiology is uncertain.     

Acute Cellular Rejection Predominated by Monocytes Is a Severe Form of Rejection in Human Renal Recipients With or Without Campath-1H (Alemtuzumab) Induction Therapy

Campath-1H has been used successfully for induction and has resulted in a low rate of acute cellular rejection (ACR) in renal transplantation in combination with various postoperative immunosuppression regimens. This study was undertaken to investigate the extent of monocyte involvement in ACR, with or without Campath-1H induction. We found that monocytes represented the majority of inflammatory cells in grades Ib or higher ACR, but not with Ia type of ACR, regardless of the status of Campath-1H induction. Cases of ACR, following Campath-1H induction, appear to demonstrate a 'pure form' of monocytic ACR, whereas monocytes were mixed with many other types of inflammatory cells in the cases of ACR in the absence of Campath-1H induction. In addition with Campath-1H induction, the cases of monocyte-predominant ACR were found to uniformly exhibit a good response to corticosteroid treatment. We conclude that monocyte-predominate ACR may represent a severe form of rejection, with or without Campath-1H treatment.     

Mammalian cell cytotoxicity and genotoxicity analysis of drinking water disinfection by-products

Cytotoxicity and genotoxicity assays were used to analyze drinking water disinfection by-products (DBPs) in Chinese hamster ovary (CHO) AS52 cells. The DBPs were chosen because they are common in drinking water, resulting from conventional disinfection using chlorination and chloramination. Data were also available to compare these results with cytotoxicity and mutagenicity studies in Salmonella typhimurium. The rank order in decreasing chronic cytotoxicity measured in a microplate-based assay was bromoacetic acid (BA) > 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX) > dibromoacetic acid (DBA) > chloroacetic acid (CA) > KBrO(3) > tribromoacetic acid (TBA) > EMS (ethylmethanesulfonate, positive control) > dichloroacetic acid (DCA) > trichloroacetic acid (TCA). The induction of DNA strand breaks by these agents was measured by alkaline single-cell gel electrophoresis (SCGE, comet assay) and the rank order in decreasing genotoxicity was BA > MX > CA > DBA > TBA > EMS > KBrO(3), while DCA and TCA were refractory. BA was more cytotoxic (31x) and genotoxic (14x) than MX in CHO cells. BA was over 400x more genotoxic than potassium bromate. The brominated haloacetic acids (HAAs) were more cytotoxic and genotoxic than their chlorinated analogs. The HAAs expressed a statistically significant inverse relationship in CHO cell cytotoxicity and genotoxicity as a function of increased numbers of halogen atoms per molecule. A quantitative comparison was conducted with results from a previous study with cytotoxicity and mutagenicity in S. typhimurium. There was no correlation between chronic CHO cell and bacterial cell cytotoxicity. DBP-induced CHO cell cytotoxicity was not related to mutagenic potency in S. typhimurium. Cytotoxicity in CHO cells was statistically significant and highly correlated to CHO cell genotoxicity. Finally, we determined that the DBP genotoxic potency in CHO cells and the mutagenic potency in S. typhimurium were not related. This suggests that toxicity data in S. typhimurium did not quantitatively predict the toxic effects of DBPs in mammalian cell systems. The microplate CHO cell cytotoxicity and genotoxicity assays were well suited for the analysis of DBPs, especially when the quantity of test material is limited.     

The release profiles of intact and enzymatically digested hyaluronic acid from semisolid formulations using multi-layer membrane system.

A multi-layer membrane system was used to measure in vitro release of hydrophilic macromolecules such as hyaluronic acid (HA) from semisolid formulations. One enzymatically digested HA-derivative with molecular mass of 22 kDa (HA-D) and 1200 kDa intact HA (HA) were incorporated into three semisolid formulations: water-containing hydrophilic ointment (WHO), amphiphilic cream (AC) and water-containing wool wax alcohol ointment (WWO). Because of the high hydrophilic properties of HA-D and HA, the artificial model membranes consisted of collodion as the matrix and glycerol as the hydrophilic acceptor phase. The area under the concentration-time curve and the mean dissolution time were used as a quantitative parameter to characterise the rate and extent of release in vitro. This study showed that the HA-D and HA release as hydrophilic substances from WHO was higher than both from AC and WWO. It was observed that 83% of HA-D1 was released from WHO after 2 h; in contrast, only 10% was released from 2% HA from the same vehicle during the same time. In conclusion, the in vitro availability of enzymatically digested HA-D was higher for WHO than for the other formulations, AC and WWO. Similarly, the availability of HA-D was higher than that of HA from the same formulations.     

Improvement of lipophilicity and membrane transport of cefuroxime using in vitro models.

Most beta-lactam antibiotics cannot be absorbed orally and, therefore, must be administered intravenously (i.v.) or intramuscularly (i.m.). Because of the obvious drawbacks of drug delivery by injection, the development of alternatives with enhanced oral bioavailability is receiving much attention in pharmaceutical research. Cefuroxime exhibiting significant advantages in the parental treatment of common infections, was used as model drug in the present study. The effect of the cationic absorption enhancers (four quaternary ammonium salts) on the lipophilicity of cefuroxime was investigated by means of the n-octanol/water system. The results on partitioning coefficients in the n-octanol/buffer system were confirmed using an in vitro transport model with artificial (dodecanol collodium membrane) and biological membranes (Charles-River guinea pig).     

Fermeture percutanée des communications interventriculaires congénitales par la prothèse Amplatzer Duct OccluderII: données préliminaire d’une étude Tunisienne monocentrique

Introduction . Percutaneous closure of congenital ventricular septal defects (VSDs) represents a promising alternative to surgery with lower rate of complications and shorter hospital stay. Its main limitation is the choice of the appropriate device for each type of defect. Aim. To report the experience of the service of cardiology (Sahloul hospital, Sousse, Tunisia) in percutaneous closure of congenital VSDs with Amplatzer Duct Occluder II (ADOII). Methods. This was a retrospective, monocentric study, conducted from January 2013 to December 2017. The study included patients treated by percutaneous closure of congenital VSDs with the ADOII device. Results. Twelve patients (6 boys; 6 girls) were included. The mean±SD of patients’ age and weight were 65±41 months and 23±10 kg, respectively. VSDs were peri-membranous (n=9) and muscular (n=3), and defects were restrictive (n=11) and non-restrictive (n=1). The mean (minimum-maximum) size of VSDs was 4.72 (3-6) mm. Eleven ADOII prostheses were successfully implanted. One failure procedure was noted with migration of the device into the pulmonary artery. A second child with perimembranous defect developed transient atrioventricular block. No deaths occurred. Conclusion. The present early experience shows that percutaneous closure with ADOII device of perimembranous and trabecular VSDs is safe and effective.     

Determination of etiology in patients admitted due to isolated leukopenia

Patients with isolated leukopenia pose difficulties in diagnosis because there is no related guideline in the literature. In this study, our aim was to evaluate the clinical and laboratory associations of isolated, nonspecific (not related to neutropenia) leukopenia.In this retrospective data review study, patients who were admitted to Hacettepe University Hematology Outpatient Clinic between 2014 and 2019 due to leukopenia were evaluated. The patients with anemia (other than iron deficiency) or thrombocytopenia were excluded. Clinical and laboratory data and the final diagnoses (if present) of the remaining cases and especially of those without neutropenia (the most difficult group to diagnose) were evaluated.One hundred sixty-nine patients were included in the study. One hundred forty-four (85.2%) patients were female and 25 (14.8%) were male. One hundred ten of them had 1500/µL or higher neutrophil count. In these nonneutropenic cases, the etiological factors contributing to leukopenia were as follows: iron deficiency anemia (21.8%), other autoimmune/autoinflammatory diseases (17.3%), autoimmune thyroid disease (21.8%), autoimmune laboratory tests (2.7%), drugs (12.7%), infection (5.5%), hematopoietic disorder (2.7%), hypersplenism (2.7%), radiotherapy sequel (1.8%), and B₁₂ deficiency (1.8%). No etiology was recognized in 44 patients. On the other hand, the etiological factors in patients with neutrophil count <1500/µL were as follows; iron deficiency anemia (10.2%), other autoimmune/autoinflammatory diseases (17%), autoimmune thyroid disease (5.1%), autoimmune laboratory tests (8.5%), drugs (8.5%), infection (6.8%), hematopoietic disorder (11.9%), hypersplenism (1.7%), radiotherapy sequel (1.7%), and B₁₂ deficiency (1.7%). No etiology was recognized in 25 patients. Physicians ordered bone marrow examination more frequently in patients with neutropenia. If isolated antinuclear antibody positivity was also considered in favor of autoimmunity, 91/169 (53.8%) cases had an autoimmune diagnosis or laboratory finding.In the present study, the most frequent reasons of isolated leukopenia in nonneutropenic patients are found as iron deficiency anemia, other autoimmune/autoinflammatory diseases, and autoimmune thyroid disease. In neutropenic patients, the most frequent reasons of isolated leukopenia are found as iron deficiency anemia, autoimmune/autoinflammatory diseases, and hematopoietic disorders. Therefore, autoimmunity is detected as an important factor leading to isolated leukopenia.     

Hepatotoxic effects caused by simultaneous exposure to noise and toluene in New Zealand white rabbits: a biochemical and histopathological study

The aim of this experimental study was to investigate hepatotoxicity effects of noise and toluene, and in particular, to study hepatotoxicity effects of simultaneous exposure to noise and toluene by histopathological and biochemical experiments. To experiment hepatotoxicity effects of noise and toluene, 100 dB white noise and 1000 ppm toluene vapors were generated during two consecutive weeks in healthy male New Zealand White rabbits. Non-simultaneous exposure to noise and toluene increased liver enzymes and the serum levels of superoxide dismutase, malondialdehyde, and total antioxidant capacity, and also decreased serum level of glutathione peroxidase. Alanine transaminase, aspartate transaminase, gamma-glutamyl transferase, malondialdehyde, total antioxidant capacity, and superoxide dismutase levels increased by simultaneous exposure to noise and toluene. Furthermore, catalase and alkaline phosphatase level decreased by simultaneous exposure to noise and toluene. The hematoxylin and eosin stain (H&E) experiments indicated significant swelling, lipidosis, eosinophilic cytoplasm, pyknosis, karyorrhexis, and disruption of the cytoplasmic membrane in the liver tissue due to exposure to noise, toluene and simultaneous exposure to them.