Inhibition Of Prostaglandin Synthesis Research Articles

Pharmacological mechanism of antiulcer activity of chromatographic Fraction B obtained from <i>Acacia nilotica</i> seedpods in experimental rats

Acacia nilotica (Lam) is an important multipurpose tree with many indigenous uses. It is most widely found in Northern Nigeria, tropical and sub-tropical countries. It is used therapeutically to alleviate and manage many illnesses. Acacia nilotica seedpod is used in local traditional medicine to treat gastric-related disorders. The present study was aimed at evaluating the possible mechanism of gastroprotection of chromatographic fraction B derived from Acacia nilotica n-butanol partitioned extract using ethanol for ulcer induction. Chromatographic fractionation of the n-butanol solvent partitioned extract yielded three different fractions (FA, FB, and FC). The possible mechanism of action of FB was assessed by investigating the involvement of endogenous nitric oxide, non-protein sulfhydryl group, and prostaglandin. The ulcer index of ulcerated rats pre-treated with NG-nitro-L-arginine methyl ester (L-NAME) which is a nitric oxide synthase inhibitor and subsequently administered with Fraction B was not significantly higher (p>0.05) from rats in the ulcerated group. Similarly, Pre-treatment with N-ethylmaleimide (NEM), a blocker of endogenous sulfhydryl to ethanol-induced ulcerated rats that were treated with chromatographic FB gave an ulcer index that was not significantly different (p>0.05) from the ulcerated control group. However, prostaglandin synthesis inhibition by pretreatment with indomethacin did not affect the gastroprotective activity of FB. The study concludes that the observed anti-ulcerogenic activity exhibited by chromatographic Fraction B of Acacia nilotica n-butanol partitioned extract is possibly due to the increase in nitric oxide (NO) synthesis and endogenous sulfhydryl group.

BRIDGING GAPS: ADDRESSING TREATMENT CHALLENGES WITH ORAL PGE2 IN DUCTUS-DEPENDENT CONGENITAL HEART DEFECTS

circulation. During fetal development, it diverts approximately 90% of the right ventricular output from the high-resistance pulmonary circulation to the umbilical-placental circulation for gas exchange with maternal blood. After birth, the ductus arteriosus usually shuts within 72 hours to help with lung circulation. Failure to close leads to a persistent left-to-right shunt known as patent ductus arteriosus (PDA). PDA affects up to 80% of premature infants and constitutes 5–10% of all congenital cardiac abnormalities in term infants. Hemodynamically significant PDA is associated with various morbidities, including neurodevelopmental impairment and respiratory distress syndrome (Slaughter et al., 2019). Conversely, in ductus-dependent heart lesions, which account for 20–25% of all congenital heart defects, it is crucial to maintain patency of the neonatal DA to uphold life-saving pulmonary or systemic circulation before corrective surgery (Subramaniam and Solomon, 2013). Treatment for closing patent ductus arteriosus (PDA) mostly involves nonsteroidal anti-inflammatory medicines (NSAIDs) such as indomethacin and ibuprofen, which block cyclooxygenase enzymes necessary for prostaglandin production. Although effective, NSAIDs carry dangers such as renal impairment and intestinal problems. Acetaminophen is considered a safer option, although its effectiveness in premature infants is unclear because it may not fully inhibit prostaglandin synthesis. However, few medications exist for preserving ductus arteriosus (DA) patency, with prostaglandin E1 (PGE1) being the sole pharmacological option despite its associated side effects, such as peripheral vasodilation, apnea, fever, and physiological disturbances (Sear, 2019). Furthermore, the shortage of PGE1 in certain countries like Pakistan highlights the urgent need for alternate solutions. In such situations, adopting other available choices like PGE2, which is accessible in Pakistan as an oral drug, becomes crucial for the efficient management of ductus-dependent congenital heart anomalies. Prostaglandin E2 (PGE2) has been successfully utilized orally in newborns with ductus-dependent cyanotic congenital heart disease. In research by Silove et al., PGE2 was supplied orally in doses ranging from 12 to 65 micrograms/kg at 1 to 4 hours intervals. This treatment regimen resulted in consistent increases in oxygen saturation (SaO2) and plasma PGE2 concentrations within 15-30 minutes after administration, equivalent to those achieved with intravenous infusions. Treatment lasted for durations ranging from 5 days to 4 months, during which the ductus remained open for extended periods, allowing for delayed surgical intervention to support the growth of the infants and their pulmonary arteries. While adverse effects during oral medication were similar to those found with intravenous administration, they were generally less severe in this series, underlining the effectiveness and simplicity of oral PGE2 administration for long-term treatment (Nabavi et al., 2019). Furthermore, a 1987 study by B.D. Thanopoulos et al. supported the effectiveness of oral PGE2 in the treatment of neonates with cyanotic congenital heart disease, which primarily depends on the ductus. The data from this investigation revealed that oral PGE2 treatment, while less productive than intravenous infusions, nonetheless proved useful for long-term therapy, affording more convenience and lower morbidity (Fernández-Francos et al., 2021). It is crucial to highlight that side effects such as apnea and hypotension may occur in newborns following PGE2 therapy and require close monitoring during treatment. In conclusion, oral PGE2 offers a viable alternative for addressing congenital heart defects in resource-limited countries like Pakistan. Its effectiveness and convenience make it a viable choice, especially if access to injectable drugs is limited. This underlines the necessity to investigate alternative treatments for appropriate care in such circumstances.

PREPARATION AND EVALUATION OF MELOXICAM CHEWABLE TABLETS FOR BETTER ORAL DELIVERY

In the current study, meloxicam (MXM) chewable tablets were formulated and evaluated with an aim of improving its solubility, bioavailability and masking its bitter taste in order to create an effective oral drug delivery system. Meloxicam (BCS class II drug), non steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties, acts by inhibition of prostaglandin synthetase leading to inhibition of prostaglandin synthesis. MXM chewable tablets were made by three different techniques: AG (aqueous granulation), NAG (non-aqueous granulation) and DC (direct compression). The chewable tablets of MXM so prepared were assessed for various parameters, namely, palatability test, hardness, weight variation, mechanical strength, disintegration, friability, percent assay and in vitro testing for dissolution profile. The variation found in dissolution profile for all prepared batches was in the order: DC>NAG>AG. The percent assay was found within the range (90-110%). Observations from palatability study showed good overall tolerance levels for DC and AG and moderate tolerance levels for NAG.

Urinary Prostaglandin E2 Excretion and the Risk of Cardiovascular and Kidney Disease.

Inhibition of prostaglandin synthesis by nonsteroidal anti-inflammatory drugs is associated with cardiovascular mortality and kidney disease. This study hypothesizes that urinary prostaglandin E2 (PGE2) and PGE2 metabolite (PGEM) excretions are markers of cardiovascular and kidney health, because they reflect both systemic and kidney-derived PGE2 production. PGE2 and PGEM were measured in spot urine samples from 2291 participants (≥55 years old)of the population-based Rotterdam Study. Urinary PGE2 and PGEM excretions were analyzed using linear regression analyses to identify cross-sectional associations with cardiovascular risk factors and baseline estimated glomerular filtration rate (eGFR). Longitudinal associations with cardiovascular mortality and kidney outcomes (eGFR <60 or <45 mL/min per 1.73 m2 and the composite outcome 40% eGFR loss or kidney failure) were assessed with Cox regression. Urinary PGE2 and PGEM excretions were higher with increasing age, lower eGFR, smoking, diabetes, and albuminuria. A 2-fold higher urinary PGE2 and PGEM excretion was associated with a higher risk of cardiovascular mortality (28 825 patient-years; 160 events; PGE2 hazard ratio [HR], 1.27, [95% CI, 1.06-1.54]; PGEM HR, 1.36 [95% CI, 1.10-1.67]). Higher PGE2 excretions were also associated with a higher risk of incident eGFR <60 mL/min per 1.73 m2 (31 530 person-years; 691 events; HR, 1.13 [95% CI, 1.02-1.25]) with similar HRs for the other kidney outcomes. Urinary PGE2 and PGEM excretions are novel markers for the presence and progression of cardiovascular and kidney disease. Future studies should address whether these associations are causal and can be targeted to improve cardiovascular and kidney outcomes.

Ethnomedicinal uses, phytochemistry, and pharmacology of the genus Sarcophyte: a review.

Although medicinal plants have been used by ethnic communities since ancient times to prevent and treat various diseases, only a few have been scientifically documented. Therefore, due to their rare availability and lack of comprehensive scientific information, we reviewed the ethnomedicinal uses, phytochemistry, and pharmacological activities of plants within the genus Sarcophyte. To do this, we used specific search terms and phrases to retrieve relevant information from online sources published in English from 2000 to July 2023. The results showed that there are only two plants in the genus Sarcophyte (Sarcophyte sanguinea Sparrm. and Sarcophyte piriei Hutch.), which are traditionally used to treat a wide range of diseases, especially cancer, and skin, gastrointestinal, and urinogenital tract ailments in humans, and to cure animals in ethnoveterinary practices. It was noted that 13 secondary metabolites have been isolated from the two plants, the most prominent of which are flavonoids (diinsininol, diinsinin, and naringenin). The antioxidant activity of S. piriei is reported based on the scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH) (IC50: 4.26 ± 0.22μg/mL) and 2 -2'-Azino-di-[3-ethylbenzthiazoline sulfonate (ABTS) radicals (IC50: 4.62 ± 0.14μg/mL), chelating iron (IC50: 1.82 ± 0.01μg/mL, 3.50 ± 0.09μg/mL), and nitric oxide (IC50: 9.97 ± 0.88μg/mL, 9.09 ± 0.11μg/mL). The methanolic stem extracts of S. piriei possess antimicrobial activity against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Vibrio fluvialis, and Enterococcus avium, with minimum inhibitory concentration (MIC) values ranging from 0.16 to 0.625mg/mL, and a minimum bactericidal concentration (MBC) of 1.25 to 5mg/mL. Cytotoxic effects of the extracts from the two plant species were also demonstrated. Sarcophyte piriei possesses therapeutic potential as evidenced by the inhibitory effects of the aqueous rhizome extract on edema (1,000mg/kg) and prostaglandin synthesis (IC50 = 0.2mg/mL). In addition, diinsininol and diinsinin were isolated from S. sanguinea inhibited prostaglandin synthesis (IC50: 9.20µM, 13.14µM) and platelet-activating factor-induced exocytosis. Therefore, based on this review, further scientific research is needed to demystify the links between traditional medicinal uses, various secondary metabolites, and the pharmacology of the two plants.

Protective Effects of Hibiscetin on Ethanol-Induced Ulcers in Rats through Inhibition of Prostaglandin Synthesis/ Oxidative Stress/Caspase-3 and 9 Pathways

Protective Effects of Hibiscetin on Ethanol-Induced Ulcers in Rats through Inhibition of Prostaglandin Synthesis/ Oxidative Stress/Caspase-3 and 9 Pathways

Anti-Inflammatory and Anti-oxidant Activity of Lippia Alba Leaf

Inflammation is part of the body’s defence mechanism which the immune system recognise and removes harmful and foreign stimuli and begins the healing process. The human body’s oxidation process harm DNA, protein, lipids, and other components in addition to cell membranes. As oxygen is metabolized, it produces “free radicals,” which are unstable chemicals that harm DNA and other cells by stealing electrons from other molecules. In this study, anti-inflammatory and Anti-oxidant activity of Lippia alba leaf extracts was investigated to overcome oxidation and inflammation. Lippia alba is a species of flowering plant in the Verbeanceae family having extensive properties like Anti-bacterial, Antiseptic, Anti-depressant, Anti-spasmodic, Anti-bronchitic etc,. Phytochemical Analysis of extract LEE (T1) revealed the presence of phytosterol, alkaloids, flavonoid, phenolic compounds, carbohydrates, whereas the extract of LAE (T2) revealed the presence of alkaloids, flavoniods, carbohydrates, saponins. Anti-inflammatory effect was estimated by inducing carrageenan in four group of rats i.e., control, standard, T1 and T2. Inflammation is caused by chemical mediators such as Histamine/Serotinin, Bradykinin, Prostaglandin, Lysosomes, Inhibition of carrageenan induced inflammation by leaf extracts could be due to inhibition of cyclooxygenase and prostaglandin synthesis. The LEE extract of Lippia alba leaf has shown significant anti-inflammatory activity. Anti-oxidant activity was estimated by mixing the sample with H2SO4, Ammonium molybdate , Na3PO4 and incubated at 95°C for 10min and absorbance was measured at 695 nm .The LEE extract of Lippia alba leaf shown more anti-oxidant activity than LAE. This study has shown that LEE of Lippia alba has shown significant Anti-inflammatory and Anti-oxidant activity. These studies justify the traditional use of plants in some inflammatory and oxidant condition.

Docking for EP4R antagonists active against inflammatory pain

The lipid prostaglandin E2 (PGE2) mediates inflammatory pain by activating G protein-coupled receptors, including the prostaglandin E2 receptor 4 (EP4R). Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce nociception by inhibiting prostaglandin synthesis, however, the disruption of upstream prostanoid biosynthesis can lead to pleiotropic effects including gastrointestinal bleeding and cardiac complications. In contrast, by acting downstream, EP4R antagonists may act specifically as anti-inflammatory agents and, to date, no selective EP4R antagonists have been approved for human use. In this work, seeking to diversify EP4R antagonist scaffolds, we computationally dock over 400 million compounds against an EP4R crystal structure and experimentally validate 71 highly ranked, de novo synthesized molecules. Further, we show how structure-based optimization of initial docking hits identifies a potent and selective antagonist with 16 nanomolar potency. Finally, we demonstrate favorable pharmacokinetics for the discovered compound as well as anti-allodynic and anti-inflammatory activity in several preclinical pain models in mice.

Cytosolic phospholipase A2 regulates lipid homeostasis under osmotic stress through PPARγ.

Physiologically, renal medullary cells are surrounded by a hyperosmolar interstitium. However, different pathological situations can induce abrupt changes in environmental osmolality, causing cell stress. Therefore, renal cells must adapt to survive in this new condition. We previously demonstrated that, among the mechanisms involved in osmoprotection, renal cells upregulate triglyceride biosynthesis (which helps preserve glycerophospholipid synthesis and membrane homeostasis) and cyclooxygenase-2 (which generates prostaglandins from arachidonic acid) to maintain lipid metabolism in renal tissue. Herein, we evaluated whether hyperosmolality modulates phospholipase A2 (PLA2 ) activity, leading to arachidonic acid release from membrane glycerophospholipid, and investigated its possible role in hyperosmolality-induced triglyceride synthesis and accumulation. We found that hyperosmolality induced PLA2 expression and activity in Madin-Darby canine kidney cells. Cytosolic PLA2 (cPLA2) inhibition, but not secreted or calcium-independent PLA2 (sPLA2 or iPLA2 , respectively), prevented triglyceride synthesis and reduced cell survival. Inhibition of prostaglandin synthesis with indomethacin not only failed to prevent hyperosmolality-induced triglyceride synthesis but also exacerbated it. Similar results were observed with the peroxisomal proliferator activated receptor gamma (PPARγ) agonist rosiglitazone. Furthermore, hyperosmolality increased free intracellular arachidonic acid levels, which were even higher when prostaglandin synthesis was inhibited by indomethacin. Blocking PPARγ with GW-9662 prevented the effects of both indomethacin and rosiglitazone on triglyceride synthesis and even reduced hyperosmolality-induced triglyceride synthesis, suggesting that arachidonic acid may stimulate triglyceride synthesis through PPARγ activation. These results highlight the role of cPLA2 in osmoprotection, since it is essential to provide arachidonic acid, which is involved in PPARγ-regulated triglyceride synthesis, thus guaranteeing cell survival.

Paracetamol and ibuprofen in the treatment of pain and fever in children: modern views on the choice of a drug

Paracetamol (acetaminophen) and ibuprofen are commonly used to relieve fever and pain in children. Their effects are similar, but differ in strength and mechanisms of action on the body. Acetaminophen, a para-aminophenol derivative, has antipyretic and analgesic properties. Despite the fact that paracetamol has been officially used as a drug for more than 75 years, its mechanism of biological action has not been sufficiently studied. In paediatric practice, paracetamol is more often used as an antipyretic, but in recent years, with the development of technology and emergence of new dosage forms on the market, it came into common use as an analgesic in many diseases, including oncological, rheumatological, etc. Ibuprofen is the most commonly used non-steroidal anti-inflammatory drug with pronounced analgesic and antipyretic properties. Ibuprofen, a non-selective inhibitor of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), affects the hypothalamic thermoregulatory center via inhibition of prostaglandin synthesis. In the paediatric population, the most common indications for the use of ibuprofen are fever, sore throat, ear pain, headache and toothache, post-traumatic and musculoskeletal pain, and inflammatory joint diseases. Paracetamol and ibuprofen are safe for use in paediatric practice, if dosing rules are observed, and are approved for use by the World Health Organization, FDA and other expert organizations. In addition, the emergence of new presentation forms of these drugs is most important in paediatrics.

FUNCTIONAL STATE OF THE PINEAL GLAND IN WOMEN WITH THREATENED ABORTION IN THE FIRST TRIMESTER – FURTHER PROSPECTS OF PREGNANCY

Melatonin is an important hormone for normal pregnancy development, but the infl uence of serotonin remains poorlyunderstood. Low melatonin production can lead to spontaneous abortion by stimulating progesterone secretion and inhibiting prostaglandin synthesis. Melatonin has an eff ect on the induction and blocking of apoptosis of the villous cytotrophoblast and promotes the development of the syncytiotrophoblast. Analysis of the frequency of positive pregnancy showed a signifi cant impact on the course of pregnancy and childbirth, compliance with sleep and rest also contribute to a positive eff ect, but there is no general concept, which makes the subject relevant.The aim of the study. To evaluate the functional state of the pineal gland, in particular, the amount of melatonin and serotonin in the blood of pregnant women at 10-12 weeks of gestation with a threat of abortion, which was manifested by bloody discharge or formation of retrochorionic hematoma, and the consequences of pregnancy.Materials and methods. Two groups were formed: I main group – 40 pregnant women with a threat of abortion and formation of retrochorionic hematoma, II control group – 44 healthy pregnant women. Obstetric examination, enzyme- linked immunosorbent assay for determination of melatonin, serotonin, chorionic gonadotropin, and ultrasound were performed. Informed consent of pregnant women was obtained with adequate explanation of the purpose, objectives, methods and scope of laboratory and instrumental research methods. The study protocol was approved by the Commission on Biomedical Ethics of the Bukovinian State Medical University, 2015 (minutes of the Commission meeting No 2 from the 19.10.2023 year). The study was conducted in accordance with the basic provisions of GCP (1996), the Convention of the Council of Europe on Human Rights and Biomedicine (April 4, 1997), the Declaration of Helsinki of the World Medical Association for the Ethical Principles of Scientifi c Medical Research Involving Human Subjects (1964-2008), the Order of the Ministry of Health of Ukraine 690 of September 23, 2009 (as amended by the Order of the Ministry of Health of Ukraine 523 of July 12, 2012). Statistical analysis was performed using generally accepted methods of variance statistics. Reliability was assessed by Student’s t-test. Diff erences were considered signifi cant if the signifi cance level was p≤0.05. We also performed correlation analysis in Microsoft Excel, using the method of squares (Pearson’s method) to determine the correlation coeffi cient. The work is a fragment of the research work of the Department of Obstetrics and Gynecology, UDC 618.1-053.34 + 618.1-0536 /.8]. –07-084-08 «Prevention, diagnosis and treatment of disorders of the perinatal period and reproductive system of women and adolescent girls» (No. 201110Н, state registration number 0111U006499. The term of implementation is 02.2011-12.2015).Results of the study. According to the obtained results, retrochorionic hematoma up to 1 cm is detected three times more often than over 1 cm, while the level of melatonin is not signifi cantly lower, but with retrochorionic hematoma over 1 cm a signifi cant decrease is observed in cases of further normal pregnancy and childbirth. With further complications of pregnancy in retrochoroidal hematoma up to 1 cm, there is a signifi cant signifi cant decrease in melatonin (p ˂ 0.001), in contrast to retrochoroidal hematoma over 1 cm, where no signifi cant diff erence was found in the complicated course of pregnancy (p &gt; 0.05). Serotonin levels were elevated in all subgroups regardless of hematoma size and subsequent pregnancy outcome. Conclusions. In case of threatened abortion in the fi rst trimester with formation of retrochorionic hematoma, the risk ofcomplicated pregnancy remains in 60.87 % of cases. Determination of pineal hormones revealed a signifi cant increase inserotonin with a simultaneous signifi cant decrease in melatonin, while maintaining a positive relationship between the hormones, indicating a disruption of melatonin synthesis in the central nervous system. This is confi rmed by the normal level of chorionic gonadotropin and the preservation of embryonic viability. Since the disruption of hormone formation in the pineal gland has been established, adherence to the recommendations for adequate rest may positively aff ect the further outcome of pregnancy and childbirth.

Differential effects of purines and prostaglandins on hypoxia induced dilatation of porcine retinal vessels at different branching level ex vivo

The metabolic pathways leading from hypoxia to retinal vasodilatation can involve effects of both purines and prostaglandins, but the effects of these compounds at different vascular branching levels are unknown. The purpose of the present study was to investigate differential effects of purines and prostaglandins in hypoxia-induced dilatation of retinal arterioles, precapillary arterioles and capillaries ex vivo.Porcine hemiretinas were mounted in a tissue chamber while monitoring temperature, pH, and oxygen tension. The effect of hypoxia on the diameter of larger arterioles, precapillary arterioles and capillaries was studied in the presence of the ecto-nucleotidase inhibitor AOPCP, the nonselective P2 purinoreceptor antagonist PPADS, the A2B adenosine receptor antagonist MRS 1754, the A3 adenosine receptor antagonist MRS 1523, the EP1 receptor antagonist SC-19220, the EP2 receptor antagonist PF-04418948, the EP3 receptor antagonist L-798,106, the EP4 receptor antagonist L-161-982, the prostaglandin synthesis inhibitor ibuprofen, and ibuprofen combined with AOPCP or ATP.Hypoxia-induced dilatation in arterioles was reduced by the A2B adenosine receptor antagonist (p < 0.01) and increased by the EP2 and the EP3 receptor antagonists (p < 0.01 for both comparisons). In precapillary arterioles the dilatation was reduced by the EP2 receptor antagonist (p < 0.04) and increased by the EP1 receptor antagonist (p < 0.03), whereas in capillaries the dilatation was increased by both the A3 adenosine receptor antagonist (p < 0.01), by ibuprofen in combination with the unspecific ecto-nucleotidase inhibitor AOPCP (p = 0.04) and by the prostaglandin EP3 receptor antagonist.Hypoxia-induced dilatation of retinal vessels is influenced by adenosine A2B and A3 receptors, and by the prostaglandin EP1, EP2 and EP3 receptors. The effects mediated by these receptors differ at different branching levels of the resistance vessels.

Low-Intensity Pulsed Ultrasound Promotes BMP9 Induced Osteoblastic Differentiation in Rat Dedifferentiated Fat Cells.

Dedifferentiated fat cells (DFATs) isolated from mature adipocytes have a multilineage differentiation capacity similar to mesenchymal stem cells and are considered as promising source of cells for tissue engineering. Bone morphogenetic protein 9 (BMP9) and low-intensity pulsed ultrasound (LIPUS) have been reported to stimulate bone formation both in vitro and in vivo. However, the combined effect of BMP9 and LIPUS on osteoblastic differentiation of DFATs has not been studied. After preparing DFATs from mature adipose tissue from rats, DFATs were treated with different doses of BMP9 and/or LIPUS. The effects on osteoblastic differentiation were assessed by changes in alkaline phosphatase (ALP) activity, mineralization/calcium deposition, and expression of bone related genes; Runx2, osterix, osteopontin. No significant differences for ALP activity, mineralization deposition, as well as expression for bone related genes were observed by LIPUS treatment alone while treatment with BMP9 induced osteoblastic differentiation of DFATs in a dose dependent manner. Further, co-treatment with BMP9 and LIPUS significantly increased osteoblastic differentiation of DFATs compared to those treated with BMP9 alone. In addition, upregulation for BMP9-receptor genes was observed by LIPUS treatment. Indomethacin, an inhibitor of prostaglandin synthesis, significantly inhibited the synergistic effect of BMP9 and LIPUS co-stimulation on osteoblastic differentiation of DFATs. LIPUS promotes BMP9 induced osteoblastic differentiation of DFATs in vitro and prostaglandins may be involved in this mechanism.

Cyclooxygenase inhibition attenuates peripheral venous distension reflex in healthy humans

Background: Venous distension in limbs evokes a pressor reflex (venous distension reflex, VDR). Group III and IV nerves, innervating peripheral veins, are suggested as the afferent arm of the VDR. Prostaglandins stimulate/sensitize group III/IV nerves. The purpose of this study was to evaluate the effect of cyclooxygenase (COX) blockade on muscle sympathetic nerve activity (MSNA) and blood pressure (BP) responses to venous distension. Hypothesis: We hypothesized that inhibition of prostaglandin synthesis by local COX blockade would attenuate the MSNA and BP responses to peripheral venous distension. Methods: Nineteen healthy volunteers (age, 27 ± 5 years) participated in the study with a randomized, double-blind, placebo-controlled, and crossover study design with two separate visits. To induce venous distension, a volume of solution (saline alone or 9 mg ketorolac tromethamine in saline) was infused into the vein in the antecubital fossa of an arterially occluded forearm. During the procedure, beat-by-beat heart rate (HR), BP, and MSNA were recorded simultaneously. The vein size at the site with the catheter for the infusion was measured with ultrasound. This study is associated with a registered clinical trial (NCT03513770). Data and a summary of the results: In both visits, the venous distension procedure significantly increased the vein size, and the increase in vein size was not different between the visits (P &gt; 0.05). A significant decrease (P &lt; 0.001) in TXB2 level (an index for prostaglandin synthesis) by the procedure was observed only in the ketorolac visit. In both visits, the venous distension procedure significantly increased BP, HR, and MSNA (all, P &lt; 0.05). The increase in mean arterial pressure (MAP) and MSNA in the ketorolac visit was significantly lower than in the control visit (ΔMAP, 7.0 ± 6.2 vs. 13.8 ± 7.7 mmHg; ΔMSNA, 6.0 ± 7.1 vs. 14.8 ± 7.7 bursts/minute; both, P &lt; 0.05). Discussion and conclusion: The presented data show that COX blockade attenuates the responses in MSNA and BP to peripheral venous distension. The results suggest that COX products play a key role in evoking afferent activation responsible for the VDR. Vein size was measured with ultrasonography only at the catheter site. Some members of COX products have vasoactive effects. Future studies evaluating the effect of COX blockade on vein size in more detail using other approaches (e.g., magnetic resonance imaging) are warranted to verify the detailed mechanism of the attenuated VDR by the COX blockade. This study was supported by National Institutes of Health Grants R01 HL144781 (to J.C. and L.I.S). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Phytochemical Estimation and Therapeutic Amelioration of Aesculus hippocastanum L. Seeds Ethanolic Extract in Gastric Ulcer in Rats Possibly by Inhibiting Prostaglandin Synthesis.

To quantify phytochemicals using liquid chromatography and mass spectroscopy (LCMS) analysis and explore the therapeutic effect of Aesculus hippocastanum L. (AH) seeds ethanolic extract against gastric ulcers in rats. Preliminary phytochemical testing and LCMS analysis were performed according to standard methods. For treatment, the animals were divided into 7 groups including normal control, ulcer control, self-healing, AH seeds low and high doses, ranitidine and per se groups. Rats were orally administered with 10 mg/kg of indomethacin, excluding the normal control group (which received 1% carboxy methyl cellulose) and the per se group (received 200 mg/kg AH seeds extract). The test group rats were then given 2 doses of AH seeds extract (100 and 200 mg/kg, respectively), while the standard group was given ranitidine (50 mg/kg). On the 11th day, rats in all groups were sacrificed, and their stomach was isolated to calculate the ulcer index, and other parameters such as blood prostaglandin (PGE2), tissue superoxide dismutase (SOD), catalase (CAT), malonyldialdehyde (MDA), and glutathione (GSH). All isolated stomach tissues were analyzed for histopathological findings. The phytochemical examination shows that the AH seeds contain alkaloids, flavonoids, saponins, phenolic components, and glycosides. LCMS analysis confirms the presence of quercetin and rutin. The AH seeds extract showed significant improvement in gastric mucosa conditions after indomethacin-induced gastric lesions (P<0.01). Further marked improvement in blood PGE2 and antioxidant enzymes, SOD, CAT, MDA and GSH, were observed compared with self-healing and untreated ulcer-induced groups (P<0.01). Histopathology results confirmed that AH seeds extract improved the mucosal layer and gastric epithelial membrane in treated groups compared to untreated ulcer-induced groups. LCMS report confirms the presence of quercetin and rutin in AH seeds ethanolic extract. The therapeutic effect of AH seeds extract against indomethacin-induced ulcer in rat model indicated the regenerated membrane integrity, with improved cellular functions and mucus thickness. Further, improved antioxidant enzyme level would help to reduce PGE2 biosynthesis.

Protective Effect of the Phycobiliproteins from Arthrospira maxima on Indomethacin-Induced Gastric Ulcer in a Rat Model.

Gastric ulcers (GU) constitute a disease with a global prevalence ≈ 8.09 million. Of their causes, non-steroidal anti-inflammatory drugs (NSAIDs) such as indomethacin (IND) rank as the second most frequent etiologic agent. The pathogenic process of gastric lesions is given by the overproduction of oxidative stress, promotion of inflammatory processes, and inhibition of prostaglandin synthesis. Spirulina Arthrospira maxima (SP) is a cyanobacterium with a wide variety of substances with high nutritional and health values such as phycobiliproteins (PBPs) that have outstanding antioxidant activity, anti-inflammatories effects, and accelerate the wound healing process. This study aimed to determine the protective effect of PBPs in GU induced by IND 40 mg/kg. Our results show that the PBPs protected against IND-induced damage with a dose-dependent effect. At a dose of 400 mg/kg, a marked decrease in the number of lesions is observed, as well as the recovery of the main markers of oxidative stress damage (MDA) and antioxidant species (SOD, CAT, GPx) at close to baseline levels. The evidence derived from the present investigation suggests that the antioxidant effect of PBPs, together with their reported anti-inflammatory effects to accelerate the wound healing process, is the most reliable cause of their antiulcerogenic activity in this GU model.

Nursing Intervention of Red Ginger Warm Compress To Reduce Pain Levels In The Elderly

Background: Gout arthritis or often known by the public as uric acid is a degenerative problem that attacks the joints and is most often found in society, especially in the elderly. Often found complaints of joint pain in gout sufferers, the way to deal with pain is by warm compresses of red ginger. The goal is to reduce pain and improve blood circulation. Methods: Case study by providing nursing care to Mrs.S who is 60 years old with complaints of joint pain. Results: Based on a case study conducted by the author for 7 days, joint pain due to increased uric acid was reduced from pain scale 5 to scale 1. Conclusion: Giving red ginger warm compresses regularly can inhibit prostaglandin synthesis so as to reduce joint pain or tension muscle because it contains olerasin, namely gingerol, zingeron and shogaol.

Effect of Cyclooxygenase Inhibition on Peripheral Venous Distension Reflex in Healthy Humans.

Peripheral venous distension evokes a pressor reflex (venous distension reflex). Afferent group III and IV nerves innervating veins are suggested as the afferent arm of the venous distension reflex. Prostaglandins stimulate/sensitize group III/IV nerves. We hypothesized that inhibition of prostaglandin synthesis by local cyclooxygenase blockade would attenuate the muscle sympathetic nerve activity (MSNA) and blood pressure responses to venous distension. Nineteen healthy volunteers (age, 27±5 years) participated in the study with 2 visits. To induce venous distension, a volume of solution (saline alone or 9 mg ketorolac tromethamine in saline) was infused into the vein in the antecubital fossa of an arterially occluded forearm. During the procedure, beat-by-beat heart rate, blood pressure and MSNA were recorded simultaneously. The vein size was measured with ultrasound. In both visits, the venous distension procedure significantly increased blood pressure, heart rate, and MSNA (all, P<0.05). The increase in mean arterial pressure and MSNA in the ketorolac visit was significantly lower than in the control visit (∆ mean arterial pressure, 7.0±6.2 versus 13.8±7.7 mm Hg; ∆MSNA, 6.0±7.1 versus 14.8±7.7 bursts/min; both, P<0.05). The increase in vein size induced by the infusion was not different between visits. The presented data show that cyclooxygenase blockade attenuates the responses in MSNA and blood pressure to peripheral venous distension reflex. The results suggest that cyclooxygenase products play a key role in evoking afferent activation responsible for the venous distension reflex.

Role of intraluteal and intrauterine prostaglandin signaling in LH-induced luteolysis in pregnant rats.

Luteal dysfunctions lead to fertility disorders and pregnancy complications. Normal luteal function is regulated by many factors, including luteinizing hormone (LH).The luteotropic roles of LH have been widely investigated but its role in the process of luteolysis has received little attention. LH has been shown to have luteolytic effects during pregnancy in rats and the role of intraluteal prostaglandins (PGs)in LH-mediated luteolysis has been demonstrated by others. However, the status of PG signaling in the uterus during LH-mediated luteolysis remains unexplored. In this study, we utilized the repeated LH administration (4×LH)model for luteolysis induction. We have examined the effect of LH-mediated luteolysis on the expression of genes involved in luteal/uterine PG synthesis, luteal PGF2α signaling, and uterine activation during different stages (mid and late) of pregnancy. Further, we analyzed the effect of overall PG synthesis machinery blockage on LH-mediated luteolysis during late pregnancy. Unlike the midstage of pregnancy, the expression of genes involved in PG synthesis, PGF2α signaling, and uterine activation in late-stage pregnant rats' luteal and uterine tissue increase 4×LH. Since the cAMP/PKApathway mediates LH-mediated luteolysis, we analyzed the effect of inhibition of endogenous PG synthesis on the cAMP/PKA/CREBpathway, followed by the analysis of the expression of markers of luteolysis. Inhibition of endogenous PG synthesis did not affect the cAMP/PKA/CREBpathway. However, in the absence of endogenous PGs, luteolysis could not be activated to the full extent. Our results suggest that endogenous PGs may contribute to LH-mediated luteolysis, but this dependency on endogenous PGs is pregnancy-stage dependent. These findings advance our understanding of the molecular pathways that regulate luteolysis.

N-3 polyunsaturated fatty acids (PUFAs) and physical exercise have the potential to reduce pain intensity in women with primary dysmenorrhea: Systematic Review

This review aims to highlight the potential of n-3 PUFAs and physical exercise in reducing pain intensity in women with primary dysmenorrhea. This type of research is a systematic review using comprehensive strategies such as searching for articles in research journal databases. The databases used are Pubmed/MEDLINE, Scopus, Web of Science, and Embase. The populations analyzed in this paper are: the potential of n-3 PUFAs and physical exercise to reduce primary dysmenorrhea. The inclusion criteria in this study were journals that discussed n-3 PUFAs, exercise, primary dysmenorrhea, and menstrual pain. The exclusion criteria in this study were disreputable international journals. For standard operationalization, This study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). This review explains that N-3 PUFAs given at the right dose, around 1000 mg/day have the potential to reduce pain intensity by suppressing the production of pro-inflammatory cytokines and eicosanoids. In addition, N-3 PUFAs have the potential to prevent and reduce pain intensity by inhibiting prostaglandin synthesis. Progesterone is very important in women with primary dysmenorrhea in order to control prostaglandin secretion. This review explains that regular exercise with low to moderate intensity (30-75% of maximum ability) performed 3 times in 1 week can increase progesterone concentrations. Physical exercises that can be done to reduce pain intensity due to primary dysmenorrhea include stretching exercises, jogging, and yoga exercises. Keywords: N-3 PUFAs, Physical Exercise; Dismenore Primer; Menstrual Pain