Plasma Prostaglandin Research Articles

Cannabidiol exerts antipyretic effects by downmodulating inflammatory mediators in LPS-induced fever

Contrasting to tetrahydrocannabinol (THC), cannabidiol (CBD) has virtually no psychoactive effects and thus presents a minor risk for abuse. Furthermore, emerging preclinical and clinical evidence indicates that CBD exerts several beneficial pharmacological effects, including anti-inflammatory and antioxidant properties. Even though fever is one of the responses associated with systemic inflammation, no previous study assessed the putative impact of CBD on lipopolysaccharide (LPS)-induced fever. The present study aimed to evaluate whether CBD exerts effects on febrile responses, by modulating the hypothalamic-pituitary-adrenal (HPA) axis, and the inflammatory reflex, in this response. CBD caused no change in euthermic mice, indicating that it does not alter euthermia. Conversely, CBD blunted all the assessed systemic inflammation parameters including fever (a hallmark of infection), plasma pro-inflammatory cytokines and prostaglandin E2 (PGE2) surges, and hypothalamic PGE2 (the proximal mediator of fever) synthesis. Moreover, CBD also reduced LPS-induced increase in plasma corticosterone levels and spleen TNF-α. These data are consistent with the notion that CBD has antipyretic effects, reducing peripheral febrigenic signaling (plasma pro-inflammatory cytokines levels), and eventually down-modulating hypothalamic PGE2 production, possibly in a corticosterone- and inflammatory reflex-dependent manner.

Prostaglandins suppress neutrophil function after sexual intercourse and may promote urinary tract infections

Sexually active women have an increased risk of urinary tract infections (UTIs), which may be influenced by components in seminal plasma. Prostaglandins in seminal plasma are key modulators of the immune system and maternal-fetal immunological tolerance, influencing cells like platelets and neutrophils. Specifically, prostaglandin I2 (PGI2) inhibits platelet aggregation, while prostaglandin E2 (PGE2) alters neutrophil activity, including the production of reactive oxygen species (ROS) and the formation of neutrophil extracellular traps (NETs). Given that the NET response is associated with UTIs, and PGI2 is known to modulate NETs, these interactions may contribute to the higher incidence of UTIs in sexual activity in women. This study aims to investigate whether UTIs following sexual activity are facilitated by an imbalance in NET formation mediated by prostaglandins. We employed four search strategies: Sex and UTI, NETs and UTIs, Prostaglandins and NETs, and Inflammasome and NETs, alongside a review of original research publications. By understanding this mechanism, we hope to reveal how prostaglandin-mediated immune modulation may increase susceptibility to UTIs after sexual activity.

Hereditary TTP/Upshaw-Schulman syndrome: the ductus arteriosus controls newborn survival.

Hereditary TTP (hTTP), termed Upshaw-Schulman syndrome, is an ultra-rare disorder caused by a severe deficiency of plasma ADAMTS13 activity that allows circulation of ultra-large von Willebrand factor (UL-VWF) multimers. The greatest risk for hTTP is in their first days after birth, when 35-50% of patients will have severe hemolysis, jaundice, and thrombocytopenia. It is often fatal without effective treatment. In utero, fetal blood flowing from the pulmonary artery through the ductus arteriosus (DA) to the aorta is under low-shear-force. At birth, blood flow through the DA reverses to a left-to-right shunt, and the diameter of the DA begins to decrease due to hyper-oxygenated blood and decreased plasma prostaglandin E2. This causes turbulent circulation that unfolds UL-VWF, allowing platelet aggregation. If the DA closes promptly, hTTP newborns survive, but if it remains patent, turbulent circulation persists, triggering microvascular thrombosis. hTTP is commonly diagnosed as hemolytic disease of the fetus and newborn (HDFN) caused by anti-red cell antibodies and treated with exchange blood transfusion, which prevents kernicterus even when the diagnosis of hTTP is missed. The diagnosis of newborn-onset hTTP should be considered because HDFN does not cause severe thrombocytopenia, which might be effectively treated with recombinant ADAMTS13.

Prostaglandin F2α Affects the Cycle of Clock Gene Expression and Mouse Behavior.

Prostaglandins are bioactive compounds, and the activation of their receptors affects the expression of clock genes. However, the prostaglandin F receptor (Ptgfr) has no known relationship with biological rhythms. Here, we first measured the locomotor period lengths of Ptgfr-KO (B6.129-Ptgfrtm1Sna) mice and found that they were longer under constant dark conditions (DD) than those of wild-type (C57BL/6J) mice. We then investigated the clock gene patterns within the suprachiasmatic nucleus in Ptgfr-KO mice under DD and observed a decrease in the expression of the clock gene cryptochrome 1 (Cry1), which is related to the circadian cycle. Moreover, the expression of Cry1, Cry2, and Period2 (Per2) mRNA were significantly altered in the mouse liver in Ptgfr-KO mice under DD. In the wild-type mouse, the plasma prostaglandin F2α (PGF2α) levels showed a circadian rhythm under a 12 h cycle of light-dark conditions. In addition, in vitro experiments showed that the addition of PTGFR agonists altered the amplitude of Per2::luc activity, and this alteration differed with the timing of the agonist addition. These results lead us to hypothesize that the plasma rhythm of PGF2α is important for driving clock genes, thus suggesting the involvement of PGF2α- and Ptgfr-targeting drugs in the biological clock cycle.

Thermotolerance capabilities, blood metabolomics, and mammary gland hemodynamics and transcriptomic profiles of slick-haired Holstein cattle during mid lactation in Puerto Rico

Holstein cattle carrying a prolactin receptor gene mutation (SLICK) exhibit short and sleek hair coats (short-haired Holstein [SLK]) enhancing thermotolerance and productivity compared with wild type-haired Holstein (WT) under tropical conditions. The objectives were to unravel the physiological and molecular mechanisms that confer an advantage to this slick genotype in Puerto Rico and determine potential correlations between metabolites and physiological variables. At 160 ± 3 DIM we compared vaginal temperatures (VT) and voluntary solar radiation exposure (VSRE) during 48 h between 9 SLK and 9 WT Holsteins, whereas a subsample of 7 SLK and 7 WT were used to assess udder skin temperature, mammary gland hemodynamics and transcriptomics, and blood plasma untargeted metabolomics at a single time point. The SLK cattle showed lower VT throughout the day and greater VSRE at 1000 h and 1100 h compared with their WT counterparts. Total mammary blood flow (MBF) was greater in SLK Holsteins compared with WT. The metabolite 9-nitrooctadecenoic acid was identified as a potential biomarker for MBF; moreover, SLK cattle had greater amounts of this metabolite in their plasma. Prostaglandin D2 synthase (PTGS) was upregulated in the slick mammary gland, while plasma prostaglandin D2 was positively correlated with milk yield and increased in SLK Holsteins compared with WT. Interestingly, the arachidonic acid metabolism pathway was enriched in the mammary gland transcriptome and perturbed in the blood metabolome in the SLK Holsteins. In conclusion, SLK Holsteins exhibited lower body temperatures, greater VSRE, enhanced blood supply to the mammary gland, and alterations in genes and metabolites involved in arachidonic acid metabolism at the mammary gland and blood plasma. The usage of the SLK Holstein cattle genetics in dairy operations could be a feasible alternative to mitigate the adverse consequences of heat stress.

Effects of early treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) on the bronchoalveolar lavage proteome and oxylipids during bovine respiratory syncytial virus (BRSV) infection.

Non-steroidal anti-inflammatory drugs (NSAID) are not recommended for use against pneumonia in humans, but are commonly utilised against bovine respiratory disease. This study aimed to determine if the use of NSAIDs in the early phase of bovine respiratory syncytial virus (BRSV)-infection limits pulmonary inflammation. Four to nine-week old calves were infected with BRSV by aerosol and were treated with either meloxicam intravenously on day (D)4 (n = 5, MEL), acetylsalicylat-DL-lysin intravenously on D4 and D5 (n = 5, ASA), or were left untreated as controls (n = 5, CTR). Clinical signs were monitored daily until necropsy on D7, BRSV-RNA was detected in nasal swabs and bronchoalveolar lavage (BAL) by RT-qPCR, inflammatory cells and proteins were identified in BAL by cytology and label-free quantitative mass spectrometry-based proteomics, respectively, and oxylipids were quantified in BAL and plasma by liquid chromatography tandem mass spectrometry with triple quadrupole mass detectors. The calves developed mild to moderate signs of respiratory disease and, with the exception of one MEL-treated and one ASA-treated calf, limited lung lesions. None of the treatments had a significant effect on virus replication, clinical signs or lung lesion extent. Relative to controls, both treatments initially induced a downregulation of proteins in BAL. Immunoglobulin (Ig)-related proteins, such as the Ig kappa and lambda locus and the joining chain of IgA and IgM, were downregulated in MEL-treated calves compared to controls. In addition, meloxicam induced an increased neutrophil influx in BAL in response to BRSV, possibly related to a reduction in plasma prostaglandin, and to a downregulation of The Liver X Receptor/ Retinoid X Receptor (LXR/RXR), the Farnesoid X Receptor (FXR)/RXR and the 24-Dehydrocholesterol Reductase (DHC24) signalling pathways in the lung. The risk of NSAIDs to increase neutrophil activity during stimulation with BRSV or other toll-like receptor 4 agonists needs to be investigated further. Since augmented neutrophil responses can be detrimental, the results of the present study do not support the use of NSAIDs to prevent the clinical expression of BRSV-infection.

Tissue lipidomic profiling supports a mechanistic role of the prostaglandin E2 pathway for albuminuria development in glomerular hyperfiltration.

Background: Glomerular hyperfiltration (GH) is an important mechanism in the development of albuminuria in hypertension. The Munich Wistar Frömter (MWF) rat is a non-diabetic model of chronic kidney disease (CKD) with GH due to inherited low nephron number resulting in spontaneous albuminuria and podocyte injury. In MWF rats, we identified prostaglandin (PG) E2 (PGE2) signaling as a potential causative mechanism of albuminuria in GH. Method: For evaluation of the renal PGE2 metabolic pathway, time-course lipidomic analysis of PGE2 and its downstream metabolites 15-keto-PGE2 and 13-14-dihydro-15-keto-PGE2 was conducted in urine, plasma and kidney tissues of MWF rats and albuminuria-resistant spontaneously hypertensive rats (SHR) by liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS). Results: Lipidomic analysis revealed no dysregulation of plasma PGs over the time course of albuminuria development, while glomerular levels of PGE2 and 15-keto-PGE2 were significantly elevated in MWF compared to albuminuria-resistant SHR. Overall, averaged PGE2 levels in glomeruli were up to ×150 higher than the corresponding 15-keto-PGE2 levels. Glomerular metabolic ratios of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) were significantly lower, while metabolic ratios of prostaglandin reductases (PTGRs) were significantly higher in MWF rats with manifested albuminuria compared to SHR, respectively. Conclusion: Our data reveal glomerular dysregulation of the PGE2 metabolism in the development of albuminuria in GH, resulting at least partly from reduced PGE2 degradation. This study provides first insights into dynamic changes of the PGE2 pathway that support a role of glomerular PGE2 metabolism and signaling for early albuminuria manifestation in GH.

Determination of milk concentrations and pharmacokinetics of salicylic acid following acetylsalicylic acid (aspirin) administration in postpartum dairy cows

The objectives of this descriptive study were to 1) describe the pharmacokinetics of salicylic acid (SA) in the milk and plasma of postpartum dairy cattle following oral administration of ace­tylsalicylic acid (ASA) (aspirin); 2) to estimate a recommended milk withdrawal period for dairy cattle treated with ASA; and 3) to determine the impact of ASA administration on plasma prostaglandin E2 metabolite (PGEM) concentrations. Adminis­tration of non-steroidal anti-inflammatory drugs, such as the widely available drug aspirin, or acetylsalicylic acid (ASA), may improve health and milk production in postpartum dairy cows. However, plasma pharmacokinetic data for salicylic acid (SA), the active metabolite of ASA, are unrepresentative of lactating dairy cows and current treatment regimens, and there are cur­rently no published milk residue and minimal pharmacody­namic data available for ASA or SA in dairy cows.

Measurement of Cyclooxygenase Products in Plasma as Markers for Inhibition of Cyclooxygenase Isoforms by Oral Meloxicam in New Zealand White Rabbits (Oryctolagus cuniculus ).

Pain management in rabbits is a challenging task that is complicated by the rabbit's ability to hide signs of distress and the limited pharmacologic data available for this species. Pharmacokinetic data has shown that in rabbits, meloxicam, a nonsteroidal anti-inflammatory NSAID, reaches plasma concentrations that are known to provide analgesia in dogs and cats; these concentrations could theoretically alleviate pain in rabbits. However, the inhibitory effects of meloxicam on cyclooxygenase (COX) isoforms have not been studied in rabbits. In this study, we measured the products of COX-1 and COX-2 after the oral administration of a single 1 mg/kg dose of meloxicam to New Zealand White rabbits (n = 6). Blood samples were collected before drug administration (T0) and then at predetermined time points over 48 h. Plasma prostaglandin E₂ (PGE₂ ) and thromboxane (TxB₂) concentrations were measured as surrogate markers for COX-1 and COX-2, respectively, by using commercial ELISA kits. After meloxicam administration, both TxB₂ and PGE₂ plasma concentrations fell significantly below baseline, with maximal mean reductions to 80% and 60% of baseline at 8 h, respectively. The reduction in PGE₂ concentrations was followed by a significant increase that moved its mean plasma concentrations toward baseline between 8 and 24 h. Adverse effects such as lethargy, inappetence, or changes in fecal production were not observed in any rabbits. In conclusion, meloxicam appeared to significantly inhibit both COX-1 and COX-2 with a time course similar to previously reported meloxicam plasma concentration-time profiles in rabbits. Our data suggest that a dosage of 1 mg/kg given orally could provide analgesia to rabbits, but a more frequent dosing interval than the currently recommended daily dosing may be required to maintain clinical efficacy.

Dietary supplementation with a complex of cinnamaldehyde, carvacrol, and thymol negatively affects the intestinal function in LPS-challenged piglets.

The effects of cinnamaldehyde, carvacrol and thymol complex (CCT) on the growth performance and intestinal function of piglets challenged with lipopolysaccharide (LPS) were determined. Colistin sulphate (CS) was as a positive control. Piglets (n = 24, 32 days of age) were allocated to four treatments: Control group (fed basal diet), LPS group (fed basal diet), CS+LPS group (fed basal diet + 50 mg/kg CS), and CCT+LPS group (fed basal diet + 50 mg/kg CCT). Results showed that diarrhea rates of piglets were significantly reduced by CCT and CS supplementation respectively. Further research showed that CS supplementation tended to improve the intestinal absorption function in LPS-challenged piglets. Moreover, CS supplementation significantly reduced the contents of cortisol in blood and malondialdehyde in the duodenum and the activities of inducible nitric oxide synthase in the duodenum and ileum and total nitric oxide synthase in the ileum in LPS-challenged piglets. CS supplementation significantly increased the activities of sucrase in the ileum and myeloperoxidase in the jejunum in LPS-challenged piglets. CS supplementation significantly alleviated the reduced mRNA levels of immune-related genes (IL-4, IL-6, IL-8, IL-10) in mesenteric lymph nodes and jejunum and mucosal growth-related genes (IGF-1, mTOR, ALP) in LPS-challenged piglets. These results suggested that CS supplementation improved the intestinal function in LPS-challenged piglets by improving intestinal oxidative stress, immune stress, and absorption and repair function. However, although CCT supplementation improved oxidative stress by reducing (p < 0.05) the content of malondialdehyde and the activity of nitric oxide synthase in the duodenum, CCT supplementation tended to aggravate the intestinal absorption dysfunction in LPS-challenged piglets. Furthermore, compared with the control and LPS groups, CCT supplementation remarkably elevated the content of prostaglandin in plasma and the mRNA levels of pro-inflammatory factor IL-6 in mesenteric lymph nodes and jejunum, and reduced the activity of maltase in the ileum in LPS-challenged piglets. These results suggested that CCT supplementation had a negative effect on intestinal function by altering intestinal immune stress response and reducing disaccharidase activity in LPS-challenged piglets. Compared to CS, CCT supplementation exhibited a negative effect on intestinal function, suggesting whether CCT can be as an effective feed additive still needs further study.

Effects of dietary camelina, flaxseed, and canola oil supplementation on transepidermal water loss, skin and coat health parameters, and plasma prostaglandin E2, glycosaminoglycan, and nitric oxide concentrations in healthy adult horses

Abstract Camelina oil is derived from a low-input, high-yield crop and, in comparison to many other dietary fat sources currently used in equine diets, provides a greater amount of α-linolenic acid [ALA; (n-3)], than linoleic acid [LA; (n-6)]. However, no research exists assessing the effects of feeding camelina oil to horses in contrast to other commonly used oils. The objective of this study was to compare the effect of supplementing camelina oil to that of flaxseed and canola oil supplementation, on outcomes related to skin and coat health in horses. Thirty adult horses [23 mares, 7 geldings; 14.9 years ± 5.3 years; 544 ± 66 kg body weight (BW) (mean ± SD)] underwent a 4-week wash-in period consuming hay and sunflower oil. Following the wash-in period, horses were blocked by location, age, and BW, and assigned to one of three treatment oils for 16 weeks (370 mg oil/kg BW): camelina (CAM), canola (OLA), or flaxseed (FLX) oil. Blood samples were collected and plasma prostaglandin E2 (PGE2; ELISA), nitric oxide (NO; Griess Reaction), and glycosaminoglycan (GAG; DMMB) concentrations were measured on weeks 0 (n = 30), 14 (n = 24), and 16 (n = 30). On weeks 0, 2, 4, 8, and 16, transepidermal water loss (TEWL) was measured pre- and post-acetone application using a VapoMeter (n = 26), and a 5-point-Likert scale was used to assess skin and coat characteristics on the side and rump of the horses (n = 30). All data were analyzed with repeated measures ANOVA using PROC GLIMMIX in SAS. Independent of treatment, coat color, and quality increased from baseline. There were no differences in the outcomes assessed between the horses supplemented camelina oil and those supplemented canola or flaxseed oil. These results suggest that independent of treatment, all oil supplements improved coat color and quality in horses. This provides indication that camelina oil is comparable to existing plant-based oil supplements in supporting skin and coat health and inflammation in horses.

Determination of milk concentrations and pharmacokinetics of salicylic acid following acetylsalicylic acid (aspirin) administration in postpartum dairy cows.

The objectives of this descriptive study were to (1) describe the pharmacokinetics of salicylic acid (SA) in the milk and plasma of postpartum dairy cattle following oral administration of acetylsalicylic acid (ASA; aspirin), (2) to estimate a recommended milk withdrawal period for dairy cattle treated with ASA, and (3) to determine the effect of ASA administration on plasma prostaglandin E2 metabolite (PGEM) concentrations. Primiparous (n = 3) and multiparous (n = 7) postpartum Holstein dairy cows received 2 oral treatments with ASA at 200 mg/kg of body weight, 24 h apart. Concentrations of SA in plasma and milk from 0 h through 120 h after ASA administration were analyzed using ultra performance liquid chromatography triple quadrupole mass spectrometry and a milk withdrawal period was estimated using the United States Food and Drug Administration Milk Discard App in R. Two withdrawal periods were estimated: (1) a whole-herd treatment scenario with no dilution factor and (2) an individual animal treatment scenario with a bulk tank factor included in analysis. Plasma PGEM concentrations in samples from 0 h to 24 h after ASA administration were determined using a commercially available competitive ELISA. Milk SA concentrations were undetected in all cows by 48 h after the last ASA treatment. Secondary peaks were observed in plasma at 58 and 82 h after the last treatment and in milk at 87 h after the last treatment. In the absence of a tolerance for SA in milk, the estimated milk withdrawal periods were (1) 156 h for the whole-herd treatment scenario and (2) 120 h for the individual animal treatment scenario. Plasma PGEM concentrations were reduced compared with baseline for up to 12 h after ASA administration, with the greatest reduction observed at 2 h. Results from this study suggest that the current milk withhold recommendation for dairy cattle administered ASA may need revision to 120 h (5 d) and that ASA administration may mitigate postpartum inflammation through reduction in prostaglandin production for up to 12 h after treatment. Pharmacokinetic and milk withdrawal data from this study will inform future recommendations for extra-label use of aspirin in postpartum dairy cows. Further research is required to determine the basis for the secondary SA peaks and to elucidate the long-term effects of ASA administration on dairy cow health.

Classification of primary dysmenorrhea by brain effective connectivity of the amygdala: a machine learning study.

The amygdala plays a crucial role in the central pathogenesis mechanism of primary dysmenorrhea (PDM). However, the detailed pain modulation principles of the amygdala in PDM remain unclear. Here, we applied the Granger causality analysis (GCA) to investigate the directional effective connectivity (EC) alterations in the amygdala network of PDM patients. Thirty-seven patients with PDM and 38 healthy controls were enrolled in this study and underwent resting-state functional magnetic resonance imaging scans during the pain-free stage. GCA was employed to explore the amygdala-based EC network alteration in PDM. A multivariate pattern analysis (MVPA)-based machine learning approach was used to explore whether the altered amygdala EC could serve as an fMRI-based marker for classifying PDM and HC participants. Compared to the healthy control group, patients with PDM showed significantly decreased EC from the amygdala to the right superior frontal gyrus (SFG), right superior parietal lobe/middle occipital gyrus, and left middle cingulate cortex, whereas increased EC was found from the amygdala to the bilateral medial orbitofrontal cortex. In addition, increased EC was found from the bilateral SFG to the amygdala, and decreased EC was found from the medial orbitofrontal cortex, caudate nucleus to the amygdala. The increased EC from the right SFG to the amygdala was associated with a plasma prostaglandin E2 level in PDM. The MVPA based on an altered amygdala EC pattern yielded a total accuracy of 86.84% for classifying the patients with PDM and HC. Our study is the first to combine MVPA and EC to explore brain function alteration in PDM. The results could advance understanding of the neural theory of PDM in specifying the pain-free period.

Dietary silymarin ameliorating reproductive and lactation performance of sows via regulating body antioxidant and metabolism

ObjectiveThe experiment was conducted to explore the effects of silymarin on reproductive and lactation performance, serum antioxidants, and body metabolism of sows. MethodsSixty pregnant sows (85 d, Large × Landrace) with similar genetic background, body condition, and parity were randomly divided into three groups, and each group has 20 individually housed sows. The sows in the control group (CG) were fed with basal diet, and those in the experimental group A (EGA) and B (EGB) were fed with basal diet containing 250 and 500 mg/kg silymarin, respectively. The experiment lasted 46 days from day 85 of gestation to the end of lactation (weaning on day 17 ).The milk composition and serum biochemical parameters were determined by a milk composition analyzer and a blood biochemical analyzer, respectively. Serum antioxidant indexes and plasma hormone levels were measured using the biochemical kits. The gas chromatograph was applied to detect the fecal short chain fatty acids. ResultsCompared with the CG, the total feed intake (TFI) and average daily feed intake (ADFI) were significantly increased (P < 0.01), and the urea content in regular milk tended to increase (P = 0.095) in the EG. The serum malondialdehyde (MDA) contents were decreased on day 90 of gestation and the day of farrowing (P < 0.01), and the serum contents of total antioxidant capacity (T-AOC) tended to increase on day 17 of lactation (P = 0.099) compared with the CG. Compared with the CG, the serum triglyceride (TG) concentrations in the EG tended to increase on day 90 of gestation (P = 0.062), and the content of serum total protein (TP) and albumin (ALB) reduced on day 17 of lactation (P < 0.01). Compared with the CG, plasm D-lactic acid content was decreased (P < 0.05), and the plasma prostaglandin (PG) level tended to increase (P = 0.088) in the EG on the day of farrowing and day 17 of lactation. Compared with the CG, fecal isobutyric acid concentration in the EG significantly decreased on the day of farrowing ( P < 0.05). ConclusionAdding 250 – 500 mg/kg silymarin to diets from the late gestation to the end of lactation could improve reproductive and lactation performance of sows via the regulation of nutrient metabolism and serum antioxidant.

Systemic and Ocular Anti-Inflammatory Mechanisms of Green Tea Extract on Endotoxin-Induced Ocular Inflammation.

IntroductionGreen tea extract (GTE) alleviated ocular inflammations in endotoxin-induced uveitis (EIU) rat model induced by lipopolysaccharide (LPS) but the underlying mechanism is unclear.ObjectivesTo investigate the systematic and local mechanisms of the alleviation by untargeted metabolomics using liquid chromatography-tandem mass spectrometryMethodsSprague-Dawley rats were divided into control group, LPS treatment group, and LPS treatment group treated with GTE two hours after LPS injection. The eyes were monitored by slip lamp and electroretinography examination after 24 hours. The plasma and retina were collected for metabolomics analysisResultsIn LPS treated rats, the iris showed hyperemia. Plasma prostaglandins, arachidonic acids, corticosteroid metabolites, and bile acid metabolites increased. In the retina, histamine antagonists, corticosteroids, membrane phospholipids, free antioxidants, and sugars also increased but fatty acid metabolites, N-acetylglucosamine-6-sulphate, pyrocatechol, and adipic acid decreased. After GTE treatment, the a- and b- waves of electroretinography increased by 13%. Plasma phosphorylcholine lipids increased but plasma prostaglandin E1, cholanic metabolites, and glutarylglycine decreased. In the retina, tetranor-PGAM, pantothenic derivatives, 2-ethylacylcarinitine, and kynuramine levels decreased but anti-oxidative seleno-peptide level increased. Only phospholipids, fatty acids, and arachidonic acid metabolites in plasma and in the retina had significant correlation (p < 0.05, r > 0.4 or r < -0.4).ConclusionsThe results showed GTE indirectly induced systemic phosphorylcholine lipids to suppress inflammatory responses, hepatic damage, and respiratory mitochondrial stress in EIU rats induced by LPS. Phospholipids may be a therapeutic target of GTE for anterior chamber inflammation

Major clinical findings of maxillary sinus surgery and the use of bio stimulators: a systematic review

Introduction: In the scenario of maxillary sinus surgery, when there is a loss of a dental element in the posterior region of the maxilla, there is natural resorption of the alveolar process and at the same time there will be pneumatization of the maxillary sinus. For this reason, the maxillary sinus floor elevation procedure should be performed. When grafting procedures are needed, our focus is often on the types of biomaterials and their bio stimulating properties, as well as on other types of bio stimulators to be used. Objective: It was to analyze the main clinical findings of maxillary sinus surgery and the use of bio stimulators through a systematic review. Methods: The present study followed a systematic review model, following the rules of systematic review – PRISMA. The search strategy was performed in the PubMed, Cochrane Library, Web of Science and Scopus, and Google Scholar databases. The present study was carried out from January to March 2022. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: After analyzing the main clinical findings on maxillary sinus surgery and the use of bio stimulators, it was concluded that bone regeneration processes using biomaterials and the main molecular and cellular constituents such as mesenchymal stem cells, cytokines, platelet-rich plasma, fibrin-rich plasma, exosomes, microRNAs, TNF-α, IL-1, LIF and IL-6 and prostaglandin E2 (PGE2) are strategic for the solution to large bone defects, leading to tissue or bone regeneration. The main filler biomaterials can be fibrin-rich plasma (FRP), Bio-Oss®. However, it is necessary to understand the chemical, physical and biological processes of both the biological material and the biological niche of the host for successful neovascularization and bone filling.

11 Determination of Milk Concentrations and Pharmacokinetics of Salicylic Acid Following Acetylsalicylic Acid (Aspirin) Administration in Postpartum Dairy Cows

Abstract Administration of non-steroidal anti-inflammatory drugs, such as the widely available drug aspirin, or acetylsalicylic acid (ASA), may improve health and milk production in postpartum dairy cows. However, plasma pharmacokinetic (PK) data for salicylic acid (SA), the active metabolite of ASA, are unrepresentative of lactating dairy cows and current treatment regimens, and there are currently no published milk residue and minimal pharmacodynamic data available for ASA or SA in dairy cows. The objectives of this descriptive study were to (1) describe the pharmacokinetics of SA in the milk and plasma of postpartum dairy cows following oral ASA administration; (2) to estimate a milk withdrawal period for dairy cows treated with ASA; and (3) to determine the impact of ASA on plasma prostaglandin E2 metabolite (PGEM) concentrations. Primiparous (n = 3) and multiparous (n = 7) postpartum Holstein dairy cows received 2 oral treatments with ASA at 200 mg/kg, 24 h apart. Plasma and milk SA concentrations from 0 h through 120 h after ASA administration were analyzed using ultra-performance liquid chromatography triple quadrupole mass spectrometry. Plasma PK analysis was performed using a non-compartmental approach using the free software, PKSolver, in Excel. An estimated milk withdrawal interval of 168 h was determined using the FDA Milk Discard App in R (RStudio, Boston, MA) using a 99th percentile upper tolerance limit with 95% confidence. Plasma PGEM concentrations from 0 h to 24 h after ASA administration were determined in duplicate using ELISA and were reduced compared with baseline for up to 12 h after ASA administration. A mean reduction in PGEM of -49.3% was observed at 2 h. Results from this study suggest that the current milk withhold recommendation of 24 h for dairy cows administered ASA should be revised and that ASA administration may mitigate postpartum inflammation through reduction in prostaglandin production.

Study of Stripping of Membranes at Term Gestation to Reduce Post-Term Pregnancies

Introduction: Any pregnancy which has passed beyond the expected date of delivery is called a prolonged pregnancy &amp; which have passed 42 weeks, 294 days is called postmaturity or post term pregnany [1], these are at an increased risk for fetal postmaturity syndrome, macrosomia, fetal intolerance of labor, oligohydramnios, meconium-stained amniotic fluid, and cesarean delivery [2]. The clinical evidence of an increased potential for these poor perinatal outcomes has triggered a movement toward increased antenatal testing between 37- 42 weeks of gestation, and cervical ripening with labor inductions at or before 42 weeks of gestation. While a ripe cervix is usually suggestive of fetal maturity to find an unripe cervix does not exclude maturity. Induction of labor is one of the most common procedures in obstetrics and is carried out in approximately 20% of pregnancies [3]. Mechanical and biochemical means have been used to affect cervical ripening and to induce labor. Methods of induction include amniotomy, membrane stripping or sweeping, prostaglandins, laminaria and oxytocin. Membrane stripping or sweeping is a commonly use procedure aimed at preventing the post term pregnancy and avoid the application of formal method of induction of labour. Aims and Objectives: 1. to determine the effectiveness &amp; safety of membrane stripping at term pregnancy as a OPD procedure weekly which can reduce the incidence of Post term pregnancy, labour induction and its complication. 2. To determine what factors occurring after digital separation of the chorionic membranes from the lower uterine segment (membrane stripping) are involved in observed clinical changes compared with patients not so treated. Material and Methods: Study Design: This was a prospective study conducted at department of Obstetrics and Gynaecology at our hospital. Study Duration: Study was conducted during the period of duration September 2014 to September 2016. Results: After documenting the confirm gestational dating criteria and obtaining inform consent 200 patients at 37 complete week of gestation were randomly selected for the study. Data were collected from findings at 1,2,3 week and during labour, which is compaired by pearson chi-square and fischer exact test. Conclusion: Stripping of membranes is a very old procedure. This causes the release of plasma prostaglandin F2, Increase in endocervical phospholipase A activity and oxytocin release have also been observed. This will initiate uterine contraction and onset of labour. It is safe, cheap, effective and even an out patient procedure. It is associated with earlier delivery and decreased incidence of posterm gestation and hence maternal and fetal complication related to post maturity.

Eicosanoid profiling in patients with complete form of pachydermoperiostosis carrying SLCO2A1 mutations.

Pachydermoperiostosis (PDP) is a genetic disease characterized by digital clubbing, periostosis, and pachydermia caused by mutated HPGD or SLCO2A1. Plasma prostaglandin (PG)E2 levels are increased in these patients. However, other eicosanoids have not been quantitated. We aimed to quantitate plasma eicosanoid levels in four patients carrying SLCO2A1 mutations by high-performance liquid chromatography-tandem mass spectrometry. PGE2 level was elevated in all patients; PGD2 and 11β-PGF2 α levels were also increased in some patients, whereas eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid levels were decreased in all patients. Our data indicate a dysfunctional eicosanoid homeostasis and varied levels of PG in patients with a complete form of PDP carrying SLCO2A1 mutations. PGE2 levels seem to mostly affect the symptoms, with other eicosanoids possibly having a minor effect.

Protective Effect of Pyrus ussuriensis Maxim. Extract against Ethanol-Induced Gastritis in Rats.

Pyrus ussuriensis Maxim (Korean pear) has been used for hundreds of years as a traditional herbal medicine for asthma, cough, and atopic dermatitis in Korea and China. Although it was originally shown to possess anti-inflammatory, antioxidant, and antiatopic properties, its gastroprotective effects have not been investigated. In the present study, we evaluated the protective effects of Pyrus ussuriensis Maxim extract (PUE) against ethanol-induced gastritis in rats. The bioactive compound profile of PUE was determined by gas chromatography mass spectroscopy (GC-MS) and high-performance liquid chromatography (HPLC). The gastroprotection of PUE at different doses (250 and 500 mg/kg body weight) prior to ethanol ingestion was evaluated using an in vivo gastritis rat model. Several endpoints were evaluated, including gastric mucosal lesions, cellular degeneration, intracellular damage, and immunohistochemical localization of leucocyte common antigen. The gastric mucosal injury and ulcer score were determined by evaluating the inflamed gastric mucosa and by histological examination. To identify the mechanisms of gastroprotection by PUE, antisecretory action and plasma prostaglandin E2 (PGE2), gastric mucosal cyclic adenosine monophosphate (cAMP), and histamine levels were measured. PUE exhibited significant antioxidant effects with IC50 values of 56.18 and 22.49 µg/mL for 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′- azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) inhibition (%), respectively. In addition, GC/MS and HPLC analyses revealed several bioactive compounds of PUE. Pretreatment with PUE significantly (p < 0.05) decreased the ulcer index by preventing gastric mucosal lesions, erosion, and cellular degeneration. An immunohistochemical analysis revealed that PUE markedly attenuated leucocyte infiltration in a dose-dependent manner. The enhancement of PGE2 levels and attenuation of cAMP levels along with the inhibition of histamine release following PUE pretreatment was associated with the cytoprotective and healing effects of PUE. In contrast, the downregulation of the H+/K+ ATPase pathway as well as muscarinic receptor (M3R) and histamine receptor (H2R) inhibition was also involved in the gastroprotective effects of PUE; however, the expression of cholecystokinin-2 receptors (CCK2R) was unchanged. Finally, no signs of toxicity were observed following PUE treatment. Based on our results, we conclude that PUE represents an effective therapeutic option to reduce the risk of gastritis and warrants further study.