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Journal of Biosciences 2024Noradrenaline (NA) and serotonin (5-HT) induce nociception and antinociception. This antagonistic effect can be explained by the dose and type of activated receptors. We...
Noradrenaline (NA) and serotonin (5-HT) induce nociception and antinociception. This antagonistic effect can be explained by the dose and type of activated receptors. We investigated the existence of synergism between the noradrenergic and serotonergic systems during peripheral antinociception. The paw pressure test was performed in mice that had increased sensitivity by intraplantar injection of prostaglandin E (PGE). Noradrenaline (80 ng) administered intraplantarly induced an antinociceptive effect, that was reversed by the administration of selective antagonists of serotoninergic receptors 5-HT isamoltan, 5-HT BRL15572, 5-HT ketanserin, 5-HT ondansetron, but not by selective receptor antagonist 5-HT SB-269970. The administration of escitalopram, a serotonin reuptake inhibitor, potentiated the antinociceptive effect at a submaximal dose of NA. These results, indicate the existence of synergism between the noradrenergic and serotonergic systems in peripheral antinociception in mice.
Topics: Animals; Mice; Norepinephrine; Serotonin; Serotonin Antagonists; Male; Receptors, Serotonin; Dinoprostone; Citalopram; Nociception; Analgesics; Ondansetron; Ketanserin; Pain; Selective Serotonin Reuptake Inhibitors
PubMed: 38920106
DOI: No ID Found -
International Journal of Women's Health 2024To evaluate factors predictive of the success of a slow-release dinoprostone vaginal insert for cervical ripening.
OBJECTIVE
To evaluate factors predictive of the success of a slow-release dinoprostone vaginal insert for cervical ripening.
METHODS
This retrospective study included 187 women who received dinoprostone vaginal inserts for cervical ripening. The participants were divided into two groups: the transvaginal delivery group (n = 87) and cesarean section termination group (n = 100). The correlation between the parameters present before cervical ripening with dinoprostone slow release and its success, as well as complications and adverse outcomes, was analyzed. Cesarean section predictors and area under the curve (AUC) were compared between the two Groups.
RESULTS
There were statistical differences between the two groups in body mass index (BMI), height, cervical Bishop score, cephalic position, time of medication use, and fetal head position at the time of medication use (<0.05). The optimal thresholds for identifying cesarean section in dinoprostone vaginal insert for cervical ripening were 162.5 for height (AUC = 0.61), 10.65 cm for amniotic fluid index (AUC = 0.6), S-2.5 for cephalic position (AUC = 0.61), 5.5 for bishop score of cervix (AUC = 0.65). The height, amniotic fluid index, cephalic position, and Bishop score of the cervix were included in the same model. The AUC value of the combined model was higher than the AUC value of the single factor.
CONCLUSION
The combined model was a better predictor of cesarean section in dinoprostone vaginal inserts for cervical ripening and labor induction. The success of cervical ripening with a dinoprostone slow-release vaginal insert can be predicted by the factors that can be recognized at admission.
PubMed: 38887592
DOI: 10.2147/IJWH.S461094 -
BMC Urology Jun 2024This study investigated the relaxation effect of PGE2 on the ureter and its role in promoting calculi expulsion following calculi development.
BACKGROUND
This study investigated the relaxation effect of PGE2 on the ureter and its role in promoting calculi expulsion following calculi development.
METHODS
By using immunofluorescence and Western blot, we were able to locate EP receptors in the ureter. In vitro experiments assessed the impact of PGE2, receptor antagonists, and agonists on ureteral relaxation rate. We constructed a model of ureteral calculi with flowable resin and collected ureteral tissue from postoperative side of the ureter after obstruction surgery. Western blot analysis was used to determine the protein expression levels of EP receptors and the PGE2 terminal synthase mPGES-1. Additionally, PGE2 was added to smooth muscle cells to observe downstream cAMP and PKA changes.
RESULTS
The expression of EP2 and EP4 proteins in ureteral smooth muscle was verified by Western blot analysis. According to immunofluorescence, EP2 was primarily found on the cell membrane, while EP4 was found in the nucleus. In vitro, PGE2 induced concentration-dependent ureteral relaxation. Maximum diastolic rate was 70.94 ± 4.57% at a concentration of 30µM. EP2 antagonists hindered this effect, while EP4 antagonists did not. Obstructed ureters exhibited elevated mPGES-1 and EP2 protein expression (P < 0.01). Smooth muscle cells treated with PGE2 displayed increased cAMP and phosphorylated PKA.
CONCLUSIONS
PGE2 binding to EP2 induces ureteral relaxation through the cAMP-PKA pathway. This will provide a new theoretical basis for the development of new therapeutic approaches for the use of PGE2 in the treatment of ureteral stones.
Topics: Receptors, Prostaglandin E, EP2 Subtype; Cyclic AMP; Dinoprostone; Cyclic AMP-Dependent Protein Kinases; Ureteral Calculi; Animals; Ureter; Signal Transduction; Male; Muscle Relaxation
PubMed: 38851678
DOI: 10.1186/s12894-024-01504-w -
Molecular Pain 2024Hyperalgesic priming is a preclinical model of the transition from acute to chronic pain characterized by a leftward shift in the dose-response curve for and marked...
Hyperalgesic priming is a preclinical model of the transition from acute to chronic pain characterized by a leftward shift in the dose-response curve for and marked prolongation of prostaglandin E (PGE)-induced mechanical hyperalgesia, in vivo. In vitro, priming in nociceptors is characterized by a leftward shift in the concentration dependence for PGE-induced nociceptor sensitization. In the present in vitro study we tested the hypothesis that a mu-opioid receptor (MOR) agonist opioid analgesic, morphine, can produce priming by its direct action on nociceptors. We report that treatment of nociceptors with morphine, in vitro, produces a leftward shift in the concentration dependence for PGE-induced nociceptor sensitization. Our findings support the suggestion that opioids act directly on nociceptors to induce priming.
Topics: Morphine; Animals; Nociceptors; Dinoprostone; Receptors, Opioid, mu; Analgesics, Opioid; Male; Rats; Ganglia, Spinal; Hyperalgesia; Rats, Sprague-Dawley; Dose-Response Relationship, Drug
PubMed: 38828868
DOI: 10.1177/17448069241260348 -
Journal of Musculoskeletal & Neuronal... Jun 2024To investigate the effects of the combined application of percutaneous vertebroplasty and zoledronic acid on bone mineral density (BMD), bone metabolism, neuropeptide Y...
Effects of Combined Application of Percutaneous Vertebroplasty and Zoledronic Acid on Bone Mineral Density, Bone Metabolism, NPY and PGE2 in Elderly Patients with Osteoporotic Lumbar Vertebral Compression Fracture.
OBJECTIVE
To investigate the effects of the combined application of percutaneous vertebroplasty and zoledronic acid on bone mineral density (BMD), bone metabolism, neuropeptide Y (NPY) and prostaglandin E2 (PGE2) in elderly patients with osteoporotic lumbar vertebral compression fracture (OVCF).
METHODS
The medical records of 118 elderly patients with OVCF who received treatment at our hospital from March 2018 to March 2020 were collected and analyzed retrospectively. Vertebral body height, spinal function, pain degree, and lumbar BMD were compared between the two groups upon admission and three years after the operation. Additionally, the levels of bone-specific alkaline phosphatase (BALP), 25-hydroxyvitamin D (25-(OH)D), beta collagen degradation fragments (β-CTx), neuropeptide Y (NPY), and prostaglandin E2 (PGE2) in the two groups were measured at admission and three years after the operation. Furthermore, complications in the two groups within three years after the operation were documented.
RESULTS
After three years post-operation, the combination group showed a significantly greater improvement in vertebral body height compared to the control group (P<0.05). Moreover, the combination group exhibited a significantly lower Oswestry Disability Index (ODI) score compared to the control group (P<0.05).
CONCLUSION
In elderly patients with OVCF, the combined use of zoledronic acid and percutaneous vertebroplasty is effective in improving lumbar function, BMD, and bone metabolism indices, while reducing pain and the levels of NPY and PGE2.
Topics: Humans; Aged; Female; Fractures, Compression; Zoledronic Acid; Male; Vertebroplasty; Lumbar Vertebrae; Dinoprostone; Bone Density; Spinal Fractures; Neuropeptide Y; Osteoporotic Fractures; Aged, 80 and over; Bone Density Conservation Agents; Retrospective Studies; Combined Modality Therapy
PubMed: 38826002
DOI: No ID Found -
PloS One 2024The Maternal and Perinatal Death Surveillance and Response (MPDSR) was introduced in Kenya in 2016 and implemented at Kiambu Level 5 Hospital (KL5H) three years later in... (Comparative Study)
Comparative Study
BACKGROUND
The Maternal and Perinatal Death Surveillance and Response (MPDSR) was introduced in Kenya in 2016 and implemented at Kiambu Level 5 Hospital (KL5H) three years later in 2019. During a routine MPDSR meeting at KL5H, committee members identified a possible link between the off-label use of 200mcg misoprostol tablets divided eight times to achieve the necessary dose for labour induction (25mcg) and maternal deaths. Following this, an administrative decision was made to switch from misoprostol to dinoprostone for the induction of labour in June of 2019. This study aimed to assess the overall impact of MPDSR as well as the effect of replacing misoprostol with dinoprostone on uterine rupture, maternal and neonatal deaths at KL5H.
METHODS
We conducted a retrospective cohort study of women who gave birth at KL5H between January 2018 and December 2020. We defined the pre-intervention period as January 2018-June 2019, and the intervention period as July 2019-December 2020. We randomly selected the records of 411 mothers, 167 from the pre-intervention period and 208 from the intervention period, all of whom were induced. We used Bayes-Poisson Generalised Linear Models to fit the risk of uterine rupture, maternal and perinatal death. 12 semi-structured key person questionnaires was used to describe staff perspectives regarding the switch from misoprostol to dinoprostone. Inductive and deductive data analysis was done to capture the salient emerging themes.
RESULTS
We reviewed 411 patient records and carried out 12 key informant interviews. Mothers induced with misoprostol (IRR = 3.89; CI = 0.21-71.6) had an increased risk of death while mothers were less likely to die if they were induced with dinoprostone (IRR = 0.23; CI = 0.01-7.12) or had uterine rupture (IRR = 0.56; CI = 0.02-18.2). The risk of dying during childbearing increased during Jul 2019-Dec 2020 (IRR = 5.43, CI = 0.68-43.2) when the MPDSR activities were strengthened. Induction of labour (IRR = 1.01; CI = 0.06-17.1) had no effect on the risk of dying from childbirth in our setting. The qualitative results exposed that maternity unit staff preferred dinoprostone to misoprostol as it was thought to be more effective (fewer failed inductions) and safer, regardless of being more expensive compared to misoprostol.
CONCLUSION
While the period immediately following the implementation of MPDSR at KL5H was associated with an increased risk of death, the switch to dinoprostone for labour induction was associated with a lower risk of maternal and perinatal death. The use of dinoprostone, however, was linked to an increased risk of uterine rupture, possibly attributed to reduced labour monitoring given that staff held the belief that it is inherently safer than misoprostol. Consequently, even though the changeover was warranted, further investigation is needed to determine the reasons behind the rise in maternal mortalities, even though the MPDSR framework appeared to have been put in place to quell such an increase.
Topics: Humans; Misoprostol; Female; Labor, Induced; Pregnancy; Retrospective Studies; Adult; Dinoprostone; Oxytocics; Uterine Rupture; Infant, Newborn; Young Adult; Perinatal Death; Maternal Mortality
PubMed: 38820427
DOI: 10.1371/journal.pone.0304631 -
World Journal of Gastroenterology May 2024Chronic enteropathy associated with the gene (CEAS) is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic... (Review)
Review
Chronic enteropathy associated with the gene (CEAS) is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss. This review explores the potential mechanisms underlying the pathogenesis of CEAS, focusing on the role of -encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2 (PGE2) levels. Studies have suggested that elevated PGE2 levels contribute to mucosal damage, inflammation, and disruption of the intestinal barrier. The effects of PGE2 on macrophage activation and Maxi-Cl channel functionality, as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of CEAS. Understanding the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel, targeted therapies.
Topics: Humans; Organic Anion Transporters; Intestinal Mucosa; Chronic Disease; Dinoprostone; Intestine, Small; Anti-Inflammatory Agents, Non-Steroidal; Intestinal Diseases; Animals; Gastrointestinal Hemorrhage; Ulcer
PubMed: 38817656
DOI: 10.3748/wjg.v30.i19.2505 -
Scientific Reports May 2024Dietary trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) is a potential candidate in anti-obesity trials. A transgenic mouse was previously successfully...
Dietary trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) is a potential candidate in anti-obesity trials. A transgenic mouse was previously successfully established to determine the anti-obesity properties of t10c12-CLA in male mice that could produce endogenous t10c12-CLA. To test whether there is a different impact of t10c12-CLA on lipid metabolism in both sexes, this study investigated the adiposity and metabolic profiles of female Pai mice that exhibited a dose-dependent expression of foreign Pai gene and a shift of t10c12-CLA content in tested tissues. Compared to their gender-match wild-type littermates, Pai mice had no fat reduction but exhibited enhanced lipolysis and thermogenesis by phosphorylated hormone-sensitive lipase and up-regulating uncoupling proteins in brown adipose tissue. Simultaneously, Pai mice showed hepatic steatosis and hypertriglyceridemia by decreasing gene expression involved in lipid and glucose metabolism. Further investigations revealed that t10c10-CLA induced excessive prostaglandin E2, adrenaline, corticosterone, glucagon and inflammatory factors in a dose-dependent manner, resulting in less heat release and oxygen consumption in Pai mice. Moreover, fibroblast growth factor 21 overproduction only in monoallelic Pai/wt mice indicates that it was sensitive to low doses of t10c12-CLA. These results suggest that chronic t10c12-CLA has system-wide effects on female health via synergistic actions of various hormones.
Topics: Animals; Female; Fibroblast Growth Factors; Mice, Transgenic; Mice; Linoleic Acids, Conjugated; Corticosterone; Dinoprostone; Glucagon; Epinephrine; Thermogenesis; Male; Lipid Metabolism; Adipose Tissue, Brown; Fatty Liver; Lipolysis; Hypertriglyceridemia; Adiposity
PubMed: 38816541
DOI: 10.1038/s41598-024-63282-7 -
The International Journal of... Jul 2024Elevated levels of prostaglandin E have been implicated in the pathophysiology of various diseases. Anti-inflammatory drugs that act through the inhibition of...
Elevated levels of prostaglandin E have been implicated in the pathophysiology of various diseases. Anti-inflammatory drugs that act through the inhibition of cyclooxygenase enzymatic activity, thereby leading to the suppression of prostaglandin E, are often associated with several side effects due to their non-specific inhibition of cyclooxygenase enzymes. Consequently, the targeted suppression of prostaglandin E production with innovative molecules and/or mechanisms emerges as a compelling therapeutic strategy for the treatment of inflammatory-related diseases. Therefore, in this study, a systematic analysis of 28 pyrazole derivatives was conducted to explore their potential mechanisms for reducing prostaglandin E levels. In this context, the evaluation of these derivatives extended to examining their capacity to reduce prostaglandin Ein vitro in human whole blood, inhibit cyclooxygenase-1 and cyclooxygenase-2 enzymes, modulate cyclooxygenase-2 expression, and suppress oxidative burst in human leukocytes. The results enabled the establishment of significant structure-activity relationships, elucidating key determinants for their activities. In particular, the 4-styryl group on the pyrazole moiety and the presence of chloro substitutions were identified as key determinants. Pyrazole 8 demonstrated the capacity to reduce prostaglandin E levels by downregulating cyclooxygenase-2 expression, and pyrazole-1,2,3-triazole 18 emerged as a dual-acting agent, inhibiting human leukocytes' oxidative burst and cyclooxygenase-2 activity. Furthermore, pyrazole 26 demonstrated effective reduction of prostaglandin E levels through selective cyclooxygenase-1 inhibition. These results underscore the multifaceted anti-inflammatory potential of pyrazoles, providing new insights into the substitutions and structural frameworks that are beneficial for the studied activity.
Topics: Humans; Pyrazoles; Dinoprostone; Respiratory Burst; Leukocytes; Cyclooxygenase 2; Cyclooxygenase 1; Anti-Inflammatory Agents; Structure-Activity Relationship; Cyclooxygenase Inhibitors
PubMed: 38797495
DOI: 10.1016/j.biocel.2024.106599 -
Clinical Oral Investigations May 2024Mechano-sensitive odontoblast cells, which sense mechanical loading and various stresses in the tooth structure, synthesize early signaling molecules such as... (Comparative Study)
Comparative Study
The importance of mechanosensitive cell mediated prostaglandin and nitric oxide synthesis in the pathogenesis of apical periodontitis: comparative with chronic periodontitis.
OBJECTIVES
Mechano-sensitive odontoblast cells, which sense mechanical loading and various stresses in the tooth structure, synthesize early signaling molecules such as prostaglandin E2 (PGE2) and nitric oxide (NO) as an adaptive response. It is thought that these synthesized molecules can be used for the diagnosis and treatment of periodontal and periapical diseases. The aim of this study was to investigate the relationship between the severity of apical periodontitis (AP) and chronic periodontitis (CP) and serum (s) TNF-α, IL-10, PGE2 and NO levels, as well as PGE2 and NO levels in gingival crevicular fluid (GCF) samples.
MATERIALS & METHODS
A total of 185 subjects were divided into three categories: AP group (n = 85), CP group (n = 50) and healthy control group (n = 50). The AP group was divided into 3 subgroups according to abscess scoring (AS-PAI 1, 2 and 3) based on the periapical index. The CP group was divided into 4 subgroups according to the periodontitis staging system (PSS1, 2,3 and 4). After recording the demographic and clinical characteristics of all participants, serum (s) and gingival crevicular fluid (GCF) samples were taken. TNF-α, IL-10, PGE2 and NO levels were measured in these samples.
RESULTS
Unlike serum measurements (sTNF-α, sIL-10, sNO and sPGE2), GCF-NO and GCF-PGE levels of the AP group were significantly higher than the control group in relation to abscess formation (54.4 ± 56.3 vs. 22.5 ± 12.6 µmol/mL, p < 0.001 and 100 ± 98 vs. 41 ± 28 ng/L, p < 0.001, respectively). Confirming this, the GCF-NO and GCF-PGE levels of the AS-PAI 1 group, in which abscesses have not yet formed, were found to be lower than those in AS-PAI 2 and 3, which are characterized by abscess formation [(16.7(3.7-117.8), 32.9(11.8-212.8) and 36.9(4.3-251.6) µmol/mL, p = 0,0131; 46.0(31.4-120.0), 69.6(40.3-424.2) and 74.4(32.1-471.0) ng/L, p = 0,0020, respectively]. Consistent with the increase in PSS, the levels of sTNF [29.8 (8.2-105.5) vs. 16.7(6.3-37.9) pg/mL, p < 0.001], sIL-10 [542(106-1326) vs. 190(69-411) pg/mL, p < 0.001], sNO [182.1(36.3-437) vs. 57.0(15.9-196) µmol/mL, p < 0.001], sPGE2 [344(82-1298) vs. 100(35-1178) ng/L, p < 0.001], GCF-NO [58.9 ± 33.6 vs. 22.5 ± 12.6 ng/L, p < 0.001] and GCF-PGE2 [ 99(37-365) vs. 30(13-119), p < 0.001] in the CP group were higher than the control group. Comparison ROC analysis revealed that the GCF-PGE2 test had the best diagnostic value for both AP and CP (sensitivity: 94.1 and 88.0; specificity: 64.0 and 78.0, respectively; p < 0.001).
CONCLUSIONS
GCF-PE2 and GCF-NO have high diagnostic value in the determination of AP and CP, and can be selected as targets to guide treatment. In addition, the measurements of PGE2 and NO in GCF can be used as an important predictor of pulpal necrosis leading to abscess in patients with AP.
CLINICAL RELEVANCE
In this article, it is reported that syntheses of early signaling molecules such as PGE2 and NO can be used for the diagnosis and treatment target of periapical and periodontal infections.
Topics: Humans; Periapical Periodontitis; Male; Female; Chronic Periodontitis; Nitric Oxide; Gingival Crevicular Fluid; Adult; Dinoprostone; Interleukin-10; Tumor Necrosis Factor-alpha; Middle Aged; Enzyme-Linked Immunosorbent Assay; Case-Control Studies
PubMed: 38795217
DOI: 10.1007/s00784-024-05721-3