PLA Levels Research Articles

Lead exposure affects inflammatory mediators, total and differential white blood cells in sensitized guinea pigs during and after sensitization

Background: Serum inflammatory mediators and white blood cells (WBC) counts in the blood of sensitized and lead exposed guinea pigs were evaluated. Methods: Guinea pigs were randomly allocated into control (C), sensitized (S) and sensitized groups exposed to three lead concentrations (0.1, 0.2 and 0.4 M) during (DS) and after sensitization (PS), (n = 6 for each group). Animals were sensitized by intra-peritoneal injection and aerosol inhalation of ovalbumin (OA). Serum total protein, PLA2, IgE, histamine, total and differential WBC counts of blood were evaluated. Results: Serum PLA2, total protein, IgE, histamine, total and differential WBC counts in all three sensitized groups were significantly increased, but the percentage of lymphocyte was decreased compared to control group (p < 0.05 to p < 0.001). Serum total protein and total WBC number in all animals exposed to lead as well as the eosinophil and histamine in animals exposed to highest lead concentration and IgE in sensitized groups exposed to lead after sensitization were significantly higher, but the lymphocyte in animals exposed to two higher lead concentrations was lower than non exposed sensitized group (p < 0.05 to p < 0.001). The changes in all parameters in lead exposed animals after sensitization were higher than those during sensitization which was statistically significant for total WBC count in the animals exposed to low lead concentration (p < 0.05). Conclusion: Inhaled lead can increase serum total protein, PLA2, IgE and histamine levels, total and most differential WBC counts in sensitized animal which was more pronounced in animals exposed to lead after compared to those during sensitization.

Anti-phospholipase A2 receptor antibody in idiopathic membranous nephropathy: A report from Iranian population.

Idiopathic Membranous Nephropathy (iMN) is the most common cause of nephrotic syndrome in adults. Approximately one third of patients with iMN progress to end-stage renal disease. Anti-phospholipase A2-receptor (anti-PLA2R) antibodies are present in patients with iMN and appear to play a role in the pathogenesis of iMN. In this study, we explored the prevalence of anti-PLA2R antibodies in a cohort of patients with iMN in Iran. We also sought to determine circulating levels of anti-secretory PLA2 (anti-sPLA2) antibodies in those with anti-PLA2R antibodies. Using an indirect immunofluorescence assay, we measured anti-PLA2R antibodies in a group of patients with iMN in Iran. The serum levels of anti-sPLA2 antibodies were also measured in those with positive results for anti-PLA2R antibodies. We studied 23 patients with iMN (M/F 12/11, 34±9.8 year), two patients with secondary MN and five patients with the nephrotic syndrome of other causes.Anti-PLA2R antibodies were detected in 17/23 (74%) of patients with iMN, but not in those with secondary MN or other forms of primary glomerular diseases. We found no correlation between anti-PLA2R antibody titer and the degree of proteinuria. We found high titers of anti-sPLA2 antibodies in a subset of patients with high levels of anti-PLA2R antibodies. Anti-PLA2R antibodies are specific for iMN. Proteinuria may also reflect glomerular structural damage rather than immunological activity of the disease. The preliminary idea of any presumptive role of anti-sPLA2antibodies in iMN needs further investigation.

Long-term treatment with cholinesterase inhibitors restores homeostatic levels of calcium-independent PLA2: Evidence of disease-modification in Alzheimer's disease

both size and color represented percent differences in metabolite levels were easily distinguished across study groups. Edges were directional and displayed as arrows where size represented percent difference in flux and color the difference in expression level across study groups. Colors ranged from green for decreases to brown for zero and orange to red for increases. Pathways had to be mapped separately and some split in order to allow visual analyses. Figure 1 shows the cholesterol pathway comparing the aged with youngest group; note how easily one can assess the extent of decrease in all metabolites and fluxes. Also note how even in cases of increased gene expression (red arrows) flux was low because the substrates were low. Export of maps into image files allowed assembly of Powerpoint slides for film-strip inspections of pathway changes. Conclusions: These results demonstrate the value of flux and metabolite pathway mapping, especially with integrating gene expression changes. Such complete pathway mapping is only.

Rice PLASTOCHRON genes regulate leaf maturation downstream of the gibberellin signal transduction pathway

Rice PLASTOCHRON 1 (PLA1) and PLA2 genes regulate leaf maturation and plastochron, and their loss-of-function mutants exhibit small organs and rapid leaf emergence. They encode a cytochrome P450 protein CYP78A11 and an RNA-binding protein, respectively. Their homologs in Arabidopsis and maize are also associated with plant development/organ size. Despite the importance of PLA genes in plant development, their molecular functions remain unknown. Here, we investigated how PLA1 and PLA2 genes are related to phytohormones. We found that gibberellin (GA) is the major phytohormone that promotes PLA1 and PLA2 expression. GA induced PLA1 and PLA2 expression, and conversely the GA-inhibitor uniconazole suppressed PLA1 and PLA2 expression. In pla1-4 and pla2-1 seedlings, expression levels of GA biosynthesis genes and the signal transduction gene were similar to those in wild-type seedlings. GA treatment slightly down-regulated the GA biosynthesis gene GA20ox2 and up-regulated the GA-catabolizing gene GA2ox4, whereas the GA biosynthesis inhibitor uniconazole up-regulated GA20ox2 and down-regulated GA2ox4 both in wild-type and pla mutants, suggesting that the GA feedback mechanism is not impaired in pla1 and pla2. To reveal how GA signal transduction affects the expression of PLA1 and PLA2, PLA expression in GA-signaling mutants was examined. In GA-insensitive mutant, gid1 and less-sensitive mutant, Slr1-d1, PLA1 and PLA2 expression was down-regulated. On the other hand, the expression levels of PLA1 and PLA2 were highly enhanced in a GA-constitutive-active mutant, slr1-1, causing ectopic overexpression. These results indicate that both PLA1 and PLA2 act downstream of the GA signal transduction pathway to regulate leaf development.

Curcumin and enalapril ameliorate renal failure by antagonizing inflammation in ⅚ nephrectomized rats: role of phospholipase and cyclooxygenase

Previously, we showed that curcumin prevents chronic kidney disease (CKD) development in &frac56; nephrectomized (Nx) rats when given within 1 wk after Nx (Ghosh SS, Massey HD, Krieg R, Fazelbhoy ZA, Ghosh S, Sica DA, Fakhry I, Gehr TW. Am J Physiol Renal Physiol 296: F1146-F1157, 2009). To better mimic the scenario for renal disease in humans, we began curcumin and enalapril therapy when proteinuria was already established. We hypothesized that curcumin, by blocking the inflammatory mediators TNF-α and IL-1β, could also reduce cyclooxygenase (COX) and phospholipase expression in the kidney. Nx animals were divided into untreated Nx, curcumin-treated, and enalapril-treated groups. Curcumin (75 mg/kg) and enalapril (10 mg/kg) were administered for 10 wk. Renal dysfunction in the Nx group, as evidenced by elevated blood urea nitrogen, plasma creatinine, proteinuria, segmental sclerosis, and tubular dilatation, was comparably reduced by curcumin and enalapril, with only enalapril significantly lowering blood pressure. Compared with controls, Nx animals had higher plasma/kidney TNF-α and IL-1β, which were reduced by curcumin and enalapril treatment. Nx animals had significantly elevated kidney levels of cytosolic PLA(2), calcium-independent intracellular PLA(2), COX 1, and COX 2, which were comparably reduced by curcumin and enalapril. Studies in mesangial cells and macrophages were carried out to establish that the in vivo increase in PLA(2) and COX were mediated by TNF-α and IL-1β and that curcumin, by antagonizing the cytokines, could significantly reduce both PLA(2) and COX. We conclude that curcumin ameliorates CKD by blocking inflammatory signals even if it is given at a later stage of the disease.

P.1.027 Modulation of the neurotrophin brain-derived neurotrophic factor in serotonin transporter mutant rats

Decreased levels of Brain-Derived Neurotrophic Factor (BDNF) are a common finding in schizophrenia. Another well-documented protein linked to schizophrenia is intracellular Ca2+-independent Phospholipase (PLA2). However, the potential association between PLA2 and BDNF with regard to schizophrenia has yet to be examined.In the present study, male and female BDNF knockout mice, a possible genetic model of schizophrenia, were exposed to prenatal stress and tested in the nest test, open field test and T-maze. Following behavioral tests, whole brain and plasma samples were harvested to measure the activity of PLA2. BDNF knockout mice showed cognitive deficits in the T-maze. Furthermore, there was a quadratic association of PLA2 with performance in the open field test. Moreover, BDNF deficiency and female sex were associated with elevated plasma PLA2 levels. The cognitive impairment of BDNF heterozygous mice as well as their increased PLA2 activity in plasma is consistent with findings in schizophrenia patients. The particular elevation of PLA2 activity in females may partly explain sex differences of clinical symptoms in schizophrenia (e.g. age of onset, severity of symptoms). Additionally, PLA2 was significantly correlated with body and adrenal weight after weaning, whereby the latter emphasizes the possible connection of PLA2 with steroidogenesis.

High cholesterol impairs water and gas transport in red blood cells and is ameliorated by the PLA2 inhibitor ONO-RS-082

Elevated levels of plasma cholesterol pose significant health risks and are causal to diseases including angina, cardiovascular disorders and diabetes. Although the long-term effect of elevated plasma cholesterol is known for its accretion in arterial walls, little is understood of its immediate effects. Since cholesterol levels in red blood cell (RBC) membranes are inversely associated with O 2 transport, and the RBC water channel AQP1 is also capable of transporting CO 2 , the detrimental effect of cholesterol on active water transport, and likely on the CO 2 and O 2 transport in RBC, was hypothesized and tested in the present study. The rapid gating of water into isolated rat RBC and the corresponding increase in their volume and surface area was determined using dynamic light scattering. Similarly, the entry of CO 2 into the RBC was determined using zeta potential measurements, as increase in intracellular acidity reduces the negative charge at the RBC membrane. Results from our study demonstrate for the first time that the immediate effect of elevated plasma cholesterol is dysfunction of active water and CO 2 transport, possibly via the AQP1 channel at the RBC membrane. Since there is growing evidence that PLA2 may play a key role in atherogenesis, and statins significantly reduce blood PLA2 levels, the effect of the PLA2 inhibitor on ameliorating the detrimental effects of cholesterol was investigated. Interestingly, the PLA2 inhibitor ONO-RS-082 was found to reverse the cholesterol effect on RBC function.

Changes of Cervical Dorsal Root Ganglia Induced by Compression Injury and Decompression Procedure: A Novel Rat Model of Cervical Radiculoneuropathy

Our study aimed to establish a model of compression injury of cervical dorsal root ganglia (DRG) in the rat and to investigate the pathological changes following compression injury and decompression procedures. Thirty rats were divided into three groups: control group receiving sham surgery, compression group undergoing surgery to place a micro-silica gel on C6 DRG, and decompression group with subsequent decompression procedure. The samples harvested from the different groups were examined with light microscopy, ultrastructural analysis, and horseradish peroxidase (HRP) retrograde tracing techniques. Apoptosis of DRG neurons was demonstrated with TUNEL staining. Changes in PGE2 and PLA2 in DRG neurons were detected with enzyme-linked immunosorbent assay (ELISA). Local expression of vascular endothelial growth factor (VEGF) was monitored with immunohistochemistry. DRG neurons in the compression group became swollen with vacuolar changes in cytoplasm. Decompression procedure partially ameliorated the resultant compression pathology. Ultrastructural examination showed a large number of swollen vacuoles, demyelinated nerve root fibers, absence of Schwann cells, and proliferation in the surrounding connective tissues in the compression group. Compared to the control group, the compression group showed a significant decrease in the number of the HRP-labeled cells and a significant increase in levels of PGE2 and PLA2, in the expression of VEGF protein, and in the number of apoptotic DRG neurons. These findings demonstrate that compression results in local inflammation, followed by increased apoptosis and upregulation of VEGF. We conclude that such a model provides a tool to study the pathogenesis and treatment of cervical radiculoneuropathy.

A Catalytically Independent Physiological Function for Human Acute Phase Protein Group IIA Phospholipase A2: CELLULAR UPTAKE FACILITATES CELL DEBRIS REMOVAL

Human group IIA phospholipase A2 (IIA PLA2) is an acute phase protein first identified at high concentrations in synovial fluid from patients with rheumatoid arthritis. Its physiological role has since been debated; the enzyme has a very high affinity for anionic phospholipid interfaces but expresses almost zero activity with zwitterionic phospholipid substrates, because of a lack of interfacial binding. We have prepared the cysteine-containing mutant (S74C) to allow the covalent attachment of fluorescent reporter groups. We show that fluorescently labeled IIA was taken up by phorbol 12-myristate 13-acetate-activated THP-1 cells in an energy-dependent process involving cell surface heparan sulfate proteoglycans. Uptake concurrently involved significant cell swelling, characteristic of macropinocytosis and the fluorescent enzyme localized to the nucleus. The endocytic process did not necessitate enzyme catalysis, ruling out membrane phospholipid hydrolysis as an essential requirement. The enzyme produced supramolecular aggregates with anionic phospholipid vesicles as a result of bridging between particles, a property that is unique to this globally cationic IIA PLA2. Uptake of such aggregates labeled with fluorescent anionic phospholipid was dramatically enhanced by the IIA protein, and uptake involved binding to heparan sulfate proteoglycans on activated THP-1 cells. A physiological role for this protein is proposed that involves the removal of anionic extracellular cell debris, including anionic microparticles generated as a result of trauma, infection, and the inflammatory response, and under such conditions serum levels of IIA PLA2 can increase approximately 1000-fold. A similar pathway may be significant in the uptake into cells of anionic vector DNA involving cationic lipid transfection protocols.

Intratumoral mRNA levels predict clinical outcome in patients with metastatic colorectal cancer treated in a prospective clinical trial with 5-FU and oxaliplatin

10010 Background: 5-flurouracil (5-FU) and Oxaliplatin-based therapy is one of the most frequently used combinations in the treatment of advanced colorectal cancer (CRC). There are no validated and established predictive factors for clinical outcome following 5-FU/Oxaliplatin treatment. We had shown an association between intratumoral mRNA levels of TS and ERCC1 involved in 5-FU metabolism and DNA repair, respectively, and survival to 5-FU/Oxaliplatin chemotherapy in advanced CRC in a retrospective study. Now we investigated whether intratumoral mRNA levels of these two genes and others involved in 5-FU metabolism (DPD, TP, dUTPase), DNA repair (ERCC2, XRCC1), angiogenesis (COX-2, EGFR, IL-8, PLA2), and drug detoxification (GSTP-1) predict the clinical outcome of patients with CRC in a prospectively designed biomarker study. Methods: 85 patients with metastatic CRC treated with second-line 5-FU/Oxaliplatin from the prospective trial were included. mRNA levels of 12 genes were assessed from paraffin- embedded tissue samples using laser capture microdissection and quantitative Real-time PCR. Overall survival (OS) was the primary endpoint. Progression-free survival (PFS), response, and toxicity were the secondary endpoints. Results: There were 40 women and 45 men (median age 60 years; range 29–87), median survival of 9.7 ms, median PFS of 4.2 ms, CR in 1 (1%) patient, PR in 15 (18%), SD in 36 (43%) and PD in 32 (38%) patients. High intratumoral mRNA levels of PLA2, TP, GSPTP-1 and low mRNA levels of COX-2 were each significantly associated with shorter OS (P≤0.05, log-rank test). There was a trend in the association between high mRNA levels of PLA2 and shorter PFS (P=0.08). In addition, high mRNA levels of XRCC1 and IL-8 were each significantly associated with high risk of cumulative grade 3+ toxicity (P≤0.05). No significant association was found between mRNA levels and response to 5-FU/Oxaliplatin. Conclusions: This study suggests that mRNA levels of PLA2, TP, GSTP-1, COX-2, XRCC1, and IL-8 may be useful to predict the outcome of patients with metastatic CRC with second-line 5-FU/Oxaliplatin chemotherapy. These findings should be validated with future basic sciences studies and prospective clinical trials. [Table: see text]

Human Calcium-independent Phospholipase A2 Mediates Lymphocyte Proliferation

Activation of lymphocytes induces blastogenesis and cell division which is accompanied by membrane lipid metabolism such as increased fatty acid turnover. To date little is known about the enzymatic mechanism(s) regulating this process. Release of fatty acids such as arachidonic acid requires sn-2-deacylation catalyzed by a class of enzymes known as phospholipases A(2) (PLA(2), EC ). Herein, we confirm that human peripheral blood B or T lymphocytes (PBL) do not possess measurable levels of 85-kDa PLA(2) as assessed by Western immunoblot. Low levels of 14-kDa PLA(2) protein and activity were detectable in the particulate fraction of PBL and Jurkat cells. Western immunoblot analysis indicates that PBLs possess the calcium-independent PLA(2) (iPLA(2)) protein. Calcium-independent sn-2-acylhydrolytic activity was measurable in PBL cytosols and could be inhibited by the selective iPLA(2) inhibitor bromoenol lactone. Mitogen activation of PBLs resulted in maintenance of activity levels which remained constant over 72 h suggesting an important role for iPLA(2) in this proliferative process. Indeed, evaluation of iPLA(2) activity in cell cycle-arrested Jurkat T cell fractions revealed the highest iPLA(2) levels occurring at the G(2)/M phase. Addition of the iPLA(2) inhibitors, bromoenol lactone, or arachidonyl trifluoromethyl ketone (AAOCF(3)), inhibited both mitogen-induced PBL as well as Jurkat T cell proliferation. Moreover, specific depletion of iPLA(2) protein by antisense treatment also resulted in marked suppression of cell division. Inhibition of Jurkat cell proliferation was not associated with arrest at a particular phase of the cell cycle nor was it associated with apoptosis as assessed by flow cytometry. These findings provide the first evidence that iPLA(2) plays a key role in the lymphocyte proliferative response.

Biochemical Alterations in Rat Thiry?Vella Fistulas

In order to obtain baseline information on the secretory function of normal rat bowel for our work on intestinal graft ischemia, we studied several biochemical parameters in rat Thiry?Vella fistulas (TVF). TVFs were created in 200-g male Lewis rats (n=11) using the 25-cm segment of jejunum normally used as a graft in our intestinal transplant model. The stomas were matured primarily and the animals were allowed to recover. The TVFs were flushed at 0, 6, and 24 h and then daily for up to 21 days with 12 mL normal saline solution. The effluent was collected and analyzed for total protein (TP), secretory phospholipase A (sPLA), intestinal fatty acid binding protein (I-FABP), lactate dehydrogenase (LDH), and N-acetylglucosamine (NAGA). TP content was 0.12 0.01 mg/mL up to 48 h, then gradually increased and stabilized at 0.39 0.05 mg/mL at day 21. By sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), one major protein band was identified in the low-molecular-mass range (15 kD), consistent with I-FABP and sPLA2. Secretory PLA2 levels decreased over the first 4 days to a low of 115 24.8% hydrolysis/min/fraction, then gradually rose to a plateau at approximately 529.76 88.36% hydrolysis/min/fraction by day 18. I-FABP levels rose rapidly from 0 ng/mL at 2 h to 900 250.0 ng/mL at 6 h and approximately 3000 304.9 ng/mL by day 14. LDH levels at 2 h and 48 h did not differ, with 0.03 0.004 and 0.03 0.005 optical density units (OD)/min/mL, respectively. NAGA levels were 0.07 0.05 OD/h/mL at 2 h and rose to 0.14 0.04 OD/h/mL at 48 h. These data suggest that after an early equilibration period, biochemical secretion into the lumen of normal rat bowel reaches a state of equilibrium, and therefore appears to reflect the baseline biochemical status of the bowel. Some of these levels are not negligible as one would expect in ?normal? bowel. This information should prove extremely helpful as a baseline study of abnormal conditions of the intestine, such as ischemia or rejection.

Oxidative Stress as an Early Prognostic Factor in Acute Pancreatitis (AP)

The role of oxidative stress as an important pathogenetic factor in experimental AP is commonly accepted, but its role in human AP has still not been evaluated satisfactorily. In the present study we compared the parameters of oxidative stress to the level of PLA2 and PMN-E in patients with AP. The study was performed in 77 patients with mild (n = 31), moderate (n = 20), and severe (n = 26) AP (alcoholic and biliary) as assessed according to Ranson's and Balthazar's criteria. Serum and urine malondialdehyde (MDA) concentrations, as an index of oxidant-mediated lipid peroxidation, and sulfhydryl (SH) groups, a major nonenzymatic antioxidant, were measured along with serum PLA2 and plasma PMN-E at admission (day 0) and on days 2, 5, and 10 of the disease. The Serum MDA level in severe AP was elevated by 267% on day 0 and 230% after 10 days, in comparison to the control, by 104 and 105% in comparison to mild AP, and by 50 and 76% in comparison to moderate AP, respectively. This was accompanied by a decrease in serum SH groups by 23% on day 0 and 36% after 10 days, in comparison to the control, by 31 and 32% in comparison to mild AP, and by 20 and 11% (ns) in comparison to moderate AP, respectively. In all severity forms of AP, oxidative stress was proportionally accompanied by increased levels of PLA2 and plasma PMN-E. In conclusion, oxidative stress is an early phenomenon in patients with AP, and at the time of admission it is detectable in the serum and urine. The intensity of oxidative stress correlates with the severity of AP. Because of the significant correlation between MDA and PLA2 or PMN-E, we suppose that the parameters of oxidative stress may be useful as another early prognostic factor in human AP.

IL-13 increases the cPLA2 gene and protein expression and the mobilization of arachidonic acid during an inflammatory process in mouse peritoneal macrophages

Pretreatment of mouse peritoneal macrophages with interleukin-13 (IL-13) potentiates the mobilization of arachidonic acid (AA) and the production of HETEs but does not affect the production of cyclooxygenase metabolites triggered by the suboptimal concentration of an inflammatory agonist (opsonized-zymosan). Cycloheximide suppresses these effects of IL-13 suggesting that de novo protein synthesis is involved. Indeed, IL-13 induces a time-dependent increase in the levels of cytolosic PLA2 (cPLA2) protein and mRNA. This study demonstrates a new pathway for IL-13 to modulate the inflammatory process in macrophages via modifications of cPLA2 expression and subsequent AA mobilization.

Torsional Injury Resulting in Disc Degeneration

Torsional injuries may be a precursor to intervertebral disc degeneration, but published rabbit models indicate a latent time of 6 months. We describe a rabbit model in which instability and disc degeneration appear within 3 months. Sixty-five male New Zealand rabbits underwent presurgical irradiation to inhibit heterotopic bone formation. Control animals then underwent either a soft-tissue release or facetectomy and capsulotomy, whereas experimental animals received surgery and an acute 30 degrees torsional lumbar injury. Capsulotomy, as well as facetectomy without torsion, failed to effect disc degeneration. However, the rabbits that received torsion exhibited clear indications of degenerative disc changes (thinning, increased PLA2 levels, and decreased nucleus pulposus volume) within 60-90 days. The observations associate disc degeneration with a destabilizing acute torsional injury.

Elevated levels of synovial fluid PLA2, stromelysin (MMP-3) and TIMP in early osteoarthrosis after tibial valgus osteotomy in young beagle dogs.

We determined the concentration of markers in cartilage and synovium metabolism in the synovial fluid (SF) of the knee of young beagle dogs with slowly progressive osteoarthrosis. Osteoarthrosis (OA) was induced by a tibial 30 degrees valgus osteotomy to the right hindlimb of 16 dogs. The contralateral knee served as control. The animals were killed 7 (group I) and 18 months (group II) after operation. The levels in SF of chondroitin sulfate (CS), tissue inhibitor of metalloproteinases (TIMP-1), stromelysin (MMP-3), hyaluronan (HA), and the activity of phospholipase A2 enzyme (PLA2) were assayed. The first microscopic signs of cartilage degeneration were observed 7 months postoperatively and the lesions became more severe, including osteophyte formation during the following 11 months. The synovial fluid level of MMP-3 was higher (p = 0.04) at both time-points in the knee joint of the operated hindlimb than in the contralateral joint. On the operated side, 7 months postoperatively, synovial fluid PLA2 activity was higher (p = 0.02) than in the contralateral knee joint, but not 18 months postoperatively. The SF level of TIMP-1 was higher (p = 0.04) in the operated joint than in the contralateral joint 18 months after operation. The molar ratio of MMP-3 to TIMP-1 was higher (p = 0.001) in group II than in group I. The changes observed in the concentration of synovial fluid markers in this slowly progressive canine OA model suggest that activation of an inflammation-related process occurs at an early stage of the OA disease induced by unilateral tibial valgus osteotomy.

The determination of phospholipase A2 enzyme activity in the vaginal secretions of pregnant and non-pregnant women with bacterial vaginosis-and in culture exudates of its causative organisms

Summary Bacterial vaginosis (BV) is presently being cited as a probable cause of premature labour, where it is thought that an abnormal excess of phospholipase A2 enzyme (PLA2 ), generated by infecting organisms, prematurely liberates prostaglandins, which trigger-off the labour process. PLA levels of pregnant and non-pregnant women, with and without BV infection were compared. The in vitro concentrations of PLA2 in broth cultures of infecting organisms were also measured. Mean PLA2 level in non-infected pregnant women was 777 units per mg but was raised to 1226 U/mg in those with BV ( P=0.001). Mean level in non-infected normal women was 21 U/mg, but was raised to 97 U/mg in those having BV ( P=0.001). PLA2 concentrations in broth cultures of the causative organisms showed that most Bacteroides strains produced the enzyme, having a mean concentration of 95 U/mg, but that it was generated by only 34% of Gardnerella vaginalis strains, their mean concentration being 32 U/mg.

PHGPx and phospholipase A 2/GPx: Comparative importance on the reduction of hydroperoxides in rat liver mitochondria

The comparative importance of phospholipid hydroperoxide glutathione peroxidase (PHGPx) and of “classic” glutathione peroxidase (GPx) in the reduction of phospholipid hydroperoxides is unclear. Although GPx activity is 500-fold higher than that of PHGPx in rat liver 1, the reduction of phospholipid hydroperoxides by glutathione (GSH) through GPx may be strongly limited by a low PLA2 activity. We address this issue using a moderately detailed kinetic model of mitochondrial lipid peroxidation in rat liver. The model was based on published data and was subjected to validation as reported in the references. 2 It is analysed by computer simulation and sensitivity analysis. Results suggest that in rat liver mitochondria PHGPx is responsible for almost all phospholipid hydroperoxide reduction. Under physiological conditions, the estimated flux of phospholipid hydroperoxides reduction through PHGPx is about four orders of magnitude higher than the estimated hydrolysis flux through PLA2. On the other hand, virtually all hydrogen peroxide is reduced through GPx. Therefore, a functional complementarity between PHGPx and GPx is suggested. Because the results are qualitatively robust to changes of several orders of magnitude in PLA2 and PHGPx levels, the conclusions may not be limited to mitochondria.

Pancreatic and Catalytic Phospholipase A&lt;sub&gt;2&lt;/sub&gt; in Relation to Pregnancy, Labor and Fetal Outcome

The serum pancreatic and catalytic phospholipase A2 level (PLA2) in human pregnancy is normal, and the increase of pancreatic enzyme before delivery is small. In patients with pruritus associated with obstetric hepatosis maternal serum had a slightly lower pancreatic PLA2 level if the cholic acid level was higher. Umbilical cord blood has twice as much pancreatic PLA2 as maternal blood. If the enzyme concentration was very high, pregnancies were postterm and the newborns had low Apgar scores. Amniotic fluid contains these enzymes, but there is no change in the enzymes during the course of pregnancy. The amount of pancreatic enzyme was not reflected in catalytic activity. A very high PLA2 activity was observed in 1 patient with suspected amniotic fluid embolism and in the meconium, but low in the first urine of neonates.