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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 -
BMC Pregnancy and Childbirth Jun 2024The practice of intrapartum use of oxytocin for induction and augmentation of labour is increasing worldwide with documented wide variations in clinical use, especially...
BACKGROUND
The practice of intrapartum use of oxytocin for induction and augmentation of labour is increasing worldwide with documented wide variations in clinical use, especially dose administrations. There is also evidence of intrapartum use by unauthorized cadre of staff.
AIM
This study assessed the patterns - frequency of intrapartum use of oxytocin, the doses and routes of administration for induction and augmentation of labour, and identified the predictors of oxytocin use for induction and augmentation of labour by healthcare providers in Nigeria.
METHODS
This was a cross-sectional study conducted among healthcare providers - doctors, nurses/midwives and community health workers (CHWs) in public and private healthcare facilities across the country's six geopolitical zones. A multistage sampling technique was used to select 6,299 eligible healthcare providers who use oxytocin for pregnant women during labour and delivery. A self-administered questionnaire was used to collect relevant data and analysed using STATA 17 statistical software. Summary and inferential statistics were done and further analyses using multivariable regression models were performed to ascertain independent predictor variables of correct patterns of intrapartum oxytocin usage. The p-value was set at < 0.05.
RESULTS
Of the 6299 respondents who participated in the study, 1179 (18.7%), 3362 (53.4%), and 1758 (27.9%) were doctors, nurses/midwives and CHWs, respectively. Among the respondents, 4200 (66.7%) use oxytocin for augmentation of labour while 3314 (52.6%) use it for induction of labour. Of the 1758 CHWs, 37.8% and 49% use oxytocin for induction and augmentation of labour, respectively. About 10% of the respondents who use oxytocin for the induction or augmentation of labour incorrectly use the intramuscular route of administration and about 8% incorrectly use intravenous push. Being a doctor, and a healthcare provider from government health facilities were independent positive predictors of the administration of correct dose oxytocin for induction and augmentation of labour. The CHWs were most likely to use the wrong route and dose administration of oxytocin for the induction and augmentation of labour.
CONCLUSION
Our study unveiled a concerning clinical practice of intrapartum oxytocin use by healthcare providers in Nigeria - prevalence of intrapartum use of oxytocin, inappropriate routes of administration for induction and augmentation of labour, varied and inappropriately high start dose of administration including unauthorized and high intrapartum use of oxytocin among CHWs.
Topics: Humans; Oxytocin; Nigeria; Female; Pregnancy; Cross-Sectional Studies; Labor, Induced; Oxytocics; Adult; Health Personnel; Practice Patterns, Physicians'; Surveys and Questionnaires; Labor, Obstetric; Male; Young Adult
PubMed: 38824569
DOI: 10.1186/s12884-024-06593-x -
Reproductive Health Jun 2024In 2006, a Constitutional Court ruling partially decriminalized abortion in Colombia, allowing the procedure in cases of rape, risk to the health or life of the woman,...
Motivations for using misoprostol for abortion outside the formal healthcare system in Colombia: a qualitative study of women seeking postabortion care in Bogotá and the Coffee Axis.
BACKGROUND
In 2006, a Constitutional Court ruling partially decriminalized abortion in Colombia, allowing the procedure in cases of rape, risk to the health or life of the woman, and fetal malformations incompatible with life. Despite this less prohibitive law, some women and pregnant people preferred self-managing their abortions outside the formal healthcare system, often without accurate information. In 2018, we undertook a study to understand what motivated women to self-manage using medications that they acquired informally. Colombia has since adopted a progressive law in 2022, permitting abortion on request through the 24th week of pregnancy. However, the implementation of this law is still underway. Examining the reasons why women chose to informally self-manage an abortion after 2006 may not only highlight how barriers to legal services persisted at that time, but also could inform strategies to increase knowledge of the current abortion law and improve access to services going forward.
METHODS
In-depth interviews were conducted in 2018 with 47 women aged 18 and older who used misoprostol obtained outside of health facilities to induce an abortion, and who were receiving postabortion care in two private clinics. Interviews explored what women knew about the 2006 abortion law which was then in effect, and the reasons why they preferred informal channels for abortion care over formal healthcare services.
RESULTS
Women's motivations to use misoprostol obtained outside the formal healthcare system were influenced by lack of trust in the healthcare system along with incomplete and inaccurate knowledge of the abortion law. Conversely, women considered misoprostol obtained outside the healthcare system to be effective, affordable, and easier to access.
CONCLUSIONS
Obtaining misoprostol outside the formal healthcare system offered a more accessible and appealing prospect for some women given fears of legal repercussion and stigma toward abortion. Though this preference will likely continue despite the more liberal abortion law, strategies should be implemented to broaden knowledge of the recent change in law and to combat misinformation and stigma. This would support knowledge of and access to legal abortion for those who wish to avail themselves of these services.
Topics: Humans; Female; Misoprostol; Adult; Colombia; Pregnancy; Abortion, Induced; Motivation; Qualitative Research; Abortifacient Agents, Nonsteroidal; Young Adult; Aftercare; Adolescent; Health Services Accessibility
PubMed: 38824533
DOI: 10.1186/s12978-024-01814-0 -
Physiology & Behavior Aug 2024Cocaine addiction is the third largest cause of overdose-related deaths in the United States. Research investigating therapeutic targets for cocaine reward processes is...
Cocaine addiction is the third largest cause of overdose-related deaths in the United States. Research investigating therapeutic targets for cocaine reward processes is key to combating this issue. The neuropeptide oxytocin (OXT) has been shown to reduce cocaine reward processes, though specific mechanisms are not understood. This study examines the effect of intra-dorsal hippocampal (DH) OXT on the expression of cocaine context associations using a conditioned place preference (CPP) paradigm. In this paradigm, one of two visually distinct chambers is paired with a drug. With repeated pairings, control animals display preference for the drug-associated context by spending more time in that context at test. In the present study, four conditioning days took place where male and female rats were injected with either cocaine or saline and placed into the corresponding chamber. On test day, rats received infusions of OXT or saline (VEH) into the DH and were allowed access to both chambers. The results show that while VEH-infused rats displayed cocaine CPP, OXT-infused rats did not prefer the cocaine-paired chamber. These findings implicate the DH as necessary in the mechanism by which OXT acts to block the expression of cocaine-context associations, providing insight into how OXT may exert its therapeutic effect in cocaine reward processes.
Topics: Animals; Oxytocin; Cocaine; Male; Female; Hippocampus; Rats; Dopamine Uptake Inhibitors; Rats, Sprague-Dawley; Reward
PubMed: 38823754
DOI: 10.1016/j.physbeh.2024.114599 -
Immunity Jun 2024Severe asthma and sinus disease are consequences of type 2 inflammation (T2I), mediated by interleukin (IL)-33 signaling through its membrane-bound receptor, ST2....
Severe asthma and sinus disease are consequences of type 2 inflammation (T2I), mediated by interleukin (IL)-33 signaling through its membrane-bound receptor, ST2. Soluble (s)ST2 reduces available IL-33 and limits T2I, but little is known about its regulation. We demonstrate that prostaglandin E (PGE) drives production of sST2 to limit features of lung T2I. PGE-deficient mice display diminished sST2. In humans with severe respiratory T2I, urinary PGE metabolites correlate with serum sST2. In mice, PGE enhanced sST2 secretion by mast cells (MCs). Mice lacking MCs, ST2 expression by MCs, or E prostanoid (EP) receptors by MCs showed reduced sST2 lung concentrations and strong T2I. Recombinant sST2 reduced T2I in mice lacking PGE or ST2 expression by MCs back to control levels. PGE deficiency also reversed the hyperinflammatory phenotype in mice lacking ST2 expression by MCs. PGE thus suppresses T2I through MC-derived sST2, explaining the severe T2I observed in low PGE states.
Topics: Animals; Interleukin-1 Receptor-Like 1 Protein; Mast Cells; Dinoprostone; Mice; Interleukin-33; Humans; Mice, Knockout; Lung; Asthma; Receptors, Prostaglandin E, EP2 Subtype; Mice, Inbred C57BL; Inflammation; Female; Male; Signal Transduction; Pneumonia
PubMed: 38821053
DOI: 10.1016/j.immuni.2024.05.003 -
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 -
PloS One 2024The current study aimed to investigate the impact of oxytocin on emotion recognition, trust, body image, affect, and anxiety and whether eating disorder (ED) symptoms... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
The current study aimed to investigate the impact of oxytocin on emotion recognition, trust, body image, affect, and anxiety and whether eating disorder (ED) symptoms moderated any of these relationships.
METHOD
Participants (n = 149) were female university students, who were randomly allocated to receive in a double-blind nature, a single dose of oxytocin intranasal spray (n = 76) or a placebo (saline) intranasal spray (n = 73). Participants were asked to complete an experimental measure of emotion recognition and an investor task aimed to assess trust.
RESULTS
The oxytocin group exhibited better overall performance on the emotion recognition task (especially with recognising positive emotions), and a decline in state positive affect than the control group at post-intervention. However, these effects were not moderated by ED symptom severity, nor were effects found for state anxiety, negative affect, body image and recognising negative emotions in the emotion recognition task.
CONCLUSION
The current findings contribute to the growing literature on oxytocin, emotion recognition and positive affect and suggest that ED pathology does not moderate these relationships. Future research would benefit from examining the efficacy of an oxytocin intervention using a within-subjects, cross-over design, in those with sub-clinical and clinical EDs, as well as healthy controls.
Topics: Humans; Oxytocin; Female; Emotions; Young Adult; Trust; Adult; Double-Blind Method; Feeding and Eating Disorders; Administration, Intranasal; Adolescent; Anxiety; Body Image; Recognition, Psychology
PubMed: 38820421
DOI: 10.1371/journal.pone.0303824 -
PloS One 2024Misoprostol treatment for early pregnancy loss has varied success demonstrated in previous studies. Incorporating predictors in a single clinical scoring system would be...
BACKGROUND
Misoprostol treatment for early pregnancy loss has varied success demonstrated in previous studies. Incorporating predictors in a single clinical scoring system would be highly beneficial in clinical practice.
OBJECTIVE
To develop and evaluate the accuracy of a scoring system to predict misoprostol treatment outcomes for managing early pregnancy loss.
STUDY DESIGN
Retrospective cohort and validation study.
METHODS
Patients discharged from the gynecologic emergency department from 2013 to 2016, diagnosed with early pregnancy loss, who were treated with 800 mcg misoprostol, administrated vaginally were included. All were sonographically reevaluated within 48-72 hours. Patients in whom the gestational sac was not expelled or with endometrial lining >30 mm were offered a repeat dose and returned for reevaluation after seven days. A successful response was defined as complete expulsion. Clinical data were reviewed to identify predictors for successful responses. The scoring system was then retrospectively evaluated on a second cohort to evaluate its accuracy. Multivariate logistic regression was performed to identify factors most predictive of treatment response.
RESULTS
The development cohort included 126 patients. Six factors were found to be most predictive of misoprostol treatment effectiveness: nulliparity, prior complete spontaneous abortion, gestational age, vaginal bleeding, abdominal pain, and mean sac diameter, yielding a score of 0-8 (the MISOPRED score), where 8 represents the highest-likelihood of success. The score was validated retrospectively with 119 participants. Successful response in the group with the lowest likelihood score (score 0-3) was 9%, compared with 82% in the highest likelihood score group (score 7-8). Using the MISOPRED score, approximately 15% of patients previously planned to receive misoprostol treatment can be referred for surgical management.
CONCLUSIONS
MISOPRED score can be utilized as an adjunct tool for clinical decision-making in cases of Early pregnancy loss. To our knowledge, this is the first scoring system suggested to predict the success rate in these cases.
Topics: Humans; Misoprostol; Female; Pregnancy; Adult; Retrospective Studies; Abortion, Spontaneous; Abortifacient Agents, Nonsteroidal; Treatment Outcome
PubMed: 38820313
DOI: 10.1371/journal.pone.0303607 -
Physiology International Jun 2024This study explored the effects of fructose-induced obesity and metabolic disorders on peripheral inflammatory hyperalgesia, employing quantitative sensory testing with...
This study explored the effects of fructose-induced obesity and metabolic disorders on peripheral inflammatory hyperalgesia, employing quantitative sensory testing with the von Frey test and measuring paw edema to assess inflammatory responses. Wistar rats were administered water or 10% fructose solution ad libitum over a period of 5 weeks. After intraplantar administration of inflammatory agents such as carrageenan (1 mg/paw), lipopolysaccharide (LPS; 100 µg/paw), or prostaglandin E2 (PGE2, 100 ng/paw), we conducted mechanical hyperalgesia tests and paw edema evaluations. The fructose diet resulted in dyslipidemia, elevated insulin and leptin plasma levels, insulin resistance, and increased epididymal and retroperitoneal adiposity compared to control animals. In response to inflammatory agents, the fructose group displayed significantly enhanced peripheral hyperalgesia and more pronounced paw edema. Our results demonstrate that fructose not only contributes to the development of obesity and metabolic disorder but also exacerbates peripheral inflammatory pain responses by enhancing prostaglandin sensitivity.
Topics: Animals; Fructose; Rats, Wistar; Male; Hyperalgesia; Rats; Inflammation; Metabolic Diseases; Obesity; Carrageenan; Dinoprostone; Edema; Insulin Resistance; Lipopolysaccharides; Disease Models, Animal
PubMed: 38819928
DOI: 10.1556/2060.2024.00376