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Immunity, Inflammation and Disease Sep 2023Endometrial injury is a common disease in women caused by intrauterine inflammation, infections, and endocrine disorders. Human endometrial stromal cells (hEndoSCs) can...
BACKGROUND
Endometrial injury is a common disease in women caused by intrauterine inflammation, infections, and endocrine disorders. Human endometrial stromal cells (hEndoSCs) can maintain endometrial homeostasis and play an important role in repairing endometrial injury. Mifepristone, a steroidal anti-progesterone drug, is widely used in the field of reproductive medicine worldwide. Mifepristone-induced hEndoSC injury has been used to study endometrial injury in vitro. At present, the pathogenesis and potential regulatory mechanisms of oxycodone in endometrial injury remain unknown.
AIMS
We aimed to evaluate the functions of oxycodone in mifepristone-stimulated hEndoSC injury and analyze its potential molecular mechanism.
MATERIALS & METHODS
hEndoSC viability, cytotoxicity, and apoptosis were analyzed using the methyl thiazolyl tetrazolium assay, the lactate dehydrogenase assay, and flow cytometry, respectively. Furthermore, the levels of cleaved-Caspase3, Keap1, Nrf2, HO-1, and NQO1 were assessed using reverse transcription quantitative polymerase chain reaction and western blot analysis, and the release of inflammatory cytokines was determined using the enzyme-linked immunosorbent assay.
RESULTS
We observed that oxycodone had no adverse effects on hEndoSCs; rather, it protected hEndoSCs against mifepristone-induced endometrial damage, as confirmed by the enhanced cell viability, reduced number of apoptotic cells, decreased Caspase3 activity and inflammatory cytokine secretion, and increased Keap1/Nrf2/HO-1 pathway-related protein expression. In addition, we found that the protective effects of oxycodone on mifepristone-induced hEndoSC injury were inhibited by ML385 (a Keap1/Nrf2/HO-1 inhibitor).
CONCLUSION
In summary, we confirmed that oxycodone alleviates mifepristone-induced hEndoSC injury by activating the Keap1/Nrf2/HO-1 signaling pathway.
PubMed: 37773689
DOI: 10.1002/iid3.1008 -
BioRxiv : the Preprint Server For... May 2024Oxycodone abuse begins with prescription oral oxycodone, yet vulnerability factors determining abuse are largely undefined. We evaluated genetic vulnerability in a rat...
Oxycodone abuse begins with prescription oral oxycodone, yet vulnerability factors determining abuse are largely undefined. We evaluated genetic vulnerability in a rat model of oral oxycodone self-administration (SA): increasing oxycodone concentration/session (0.025-0.1mg/ml; 1,4,16-h) followed by extinction and reinstatement. Active licks and oxycodone intake were greater in females than males during 4-h and 16-h sessions (p< 0.001). Each sex increased intake during 16-h vs 4-h sessions (p<2e-16), but a subset of strains dramatically augmented intake at 16-h (p=0.0005). Heritability ( ) of active licks/4-h at increasing oxycodone dose ranged from 0.30-0.53. Under a progressive ratio schedule, breakpoints were strain-dependent (p<2e-16). Cued reinstatement was greater in females (p<0.001). Naive rats were assessed by elevated plus maze (EPM), open field (OF) and novel object interaction (NOI). We correlated these behaviors with 28 parameters of oxycodone SA. Anxiety-defining EPM traits were most associated with SA in both sexes, whereas more OF and NOI traits were SA-associated in males. Sex and heredity are major determinants of motivation to take and seek oxycodone; intake augments dramatically during extended access in specific strains; and pleiotropic genes affect anxiety and multiple SA parameters.
PubMed: 38076806
DOI: 10.1101/2023.11.26.568753 -
BMJ Paediatrics Open Mar 2024Selective dorsal rhizotomy (SDR) is a neurosurgical procedure that reduces lower limb spasticity, performed in some children with spastic diplegic cerebral palsy....
BACKGROUND
Selective dorsal rhizotomy (SDR) is a neurosurgical procedure that reduces lower limb spasticity, performed in some children with spastic diplegic cerebral palsy. Effective pain management after SDR is essential for early rehabilitation. This study aimed to describe the anaesthetic and early pain management, pain and adverse events in children following SDR.
METHODS
This was a retrospective cohort study. Participants were all children who underwent SDR at a single Australian tertiary hospital between 2010 and 2020. Electronic medical records of all children identified were reviewed. Data collected included demographic and clinical data (pain scores, key clinical outcomes, adverse events and side effects) and medications used during anaesthesia and postoperative recovery.
RESULTS
22 children (n=8, 36% female) had SDR. The mean (SD) age at surgery was 6 years and 6 months (1 year and 4 months). Common intraoperative medications used were remifentanil (100%), ketamine (95%), paracetamol (91%) and sevoflurane (86%). Postoperatively, all children were prescribed opioid nurse-controlled analgesia (morphine, 36%; fentanyl, 36%; and oxycodone, 18%) and concomitant ketamine infusion. Opioid doses were maximal on the day after surgery. The mean (SD) daily average pain score (Wong-Baker FACES scale) on the day after surgery was 1.4 (0.9), decreasing to 1.0 (0.5) on postoperative day 6 (POD6). Children first attended the physiotherapy gym on median day 7 (POD8, range 7-8). Most children experienced mild side effects or adverse events that were managed conservatively. Common side effects included constipation (n=19), nausea and vomiting (n=18), and pruritus (n=14). No patient required return to theatre, ICU admission or prolonged inpatient stay.
CONCLUSIONS
Most children achieve good pain management following SDR with opioid and ketamine infusions. Adverse events, while common, are typically mild and managed with medication or therapy. This information can be used as a baseline to improve postoperative care and to support families' understanding of SDR before surgery.
Topics: Child; Humans; Female; Male; Rhizotomy; Pain Management; Analgesics, Opioid; Retrospective Studies; Ketamine; Australia; Pain, Postoperative
PubMed: 38490692
DOI: 10.1136/bmjpo-2023-002381 -
BMC Anesthesiology Jan 2024Although video-assisted thoracoscopic surgery (VATS) has advantages of reduced injury and faster healing, patients still endure moderate and severe postoperative pain.... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy of postoperative analgesia with intravenous paracetamol and mannitol injection, combined with thoracic paravertebral nerve block in post video-assisted thoracoscopic surgery pain: a prospective, randomized, double-blind controlled trial.
BACKGROUND
Although video-assisted thoracoscopic surgery (VATS) has advantages of reduced injury and faster healing, patients still endure moderate and severe postoperative pain. Paracetamol and mannitol injection, the first acetaminophen injection in China, has the advantages of convenient administration, rapid onset of action, and no first-pass effect. This aim of this study was to investigate the efficacy of postoperative analgesia with paracetamol and mannitol injection, combined with thoracic paravertebral nerve block (TPVB) in post VATS pain.
METHODS
This study was a single-center, prospective, randomized, double-blind controlled clinical trial. Patients scheduled for VATS were randomly divided into three groups, general anesthesia group (Group C), TPVB group (Group T) and TPVB + paracetamol and mannitol injection group (Group TP). In this study, the primary outcome was determined as visual analog scale (VAS) scores at rest and coughing, the secondary observation outcomes were the first time to use analgesic pump, the total consumption of oxycodone in the analgesic pump, number of effective and total analgesic pump compressions at first 48 h postoperatively, the perioperative consumption of sufentanil, time to extubation, hospital length of stay, urine volume, and the incidence of adverse events.
RESULTS
In a state of rest and cough, patients in the Group TP showed significantly lower VAS pain scores at 1, 12, 24, and 48 postoperative-hour compared with Group C and Group T. Intraoperative sufentanil and postoperative oxycodone consumption, the first time to press analgesic pump, the times of effective and total compressions of patient- controlled analgesia (PCA) were lower than those of the Group C and Group T. Interestingly, urine output was higher in Group TP. There were no differences between the three groups in terms of extubation time, length of hospital stay and adverse effects, indicating that intravenous paracetamol and mannitol injection is an effective and safe perioperative analgesia method.
CONCLUSIONS
Paracetamol and mannitol injection, combined with TPVB may provide important beneficial effects on acute pain control and reduce the consumption of opioid in patients undergoing VATS.
TRIAL REGISTRATION
The trial was registered on Jun 19, 2023 in the Chinese Clinical Trial Registry ( https://www.chictr.org.cn/showproj.html?proj=199315 ), registration number ChiCTR2300072623 (19/06/2023).
Topics: Humans; Acetaminophen; Thoracic Surgery, Video-Assisted; Sufentanil; Oxycodone; Prospective Studies; Nerve Block; Pain, Postoperative; Analgesics; Analgesia, Patient-Controlled; Cough; Mannitol
PubMed: 38172686
DOI: 10.1186/s12871-023-02386-5 -
Viruses Sep 2023In the 21st century, the effects of HIV-associated neurocognitive disorders (HAND) have been significantly reduced in individuals due to the development of...
In the 21st century, the effects of HIV-associated neurocognitive disorders (HAND) have been significantly reduced in individuals due to the development of antiretroviral therapies (ARTs). However, the growing epidemic of polysubstance use (PSU) has led to concern for the effects of PSU on HIV-seropositive individuals. To effectively treat individuals affected by HAND, it is critical to understand the biological mechanisms affected by PSU, including the identification of novel markers. To fill this important knowledge gap, we used an in vivo HIV-1 Transgenic (HIV-1 Tg) animal model to investigate the effects of the combined use of chronic methamphetamine (METH) and oxycodone (oxy). A RNA-Seq analysis on the striatum-a brain region that is primarily targeted by both HIV and drugs of abuse-identified key differentially expressed markers post-METH and oxy exposure. Furthermore, ClueGO analysis and Ingenuity Pathway Analysis (IPA) revealed crucial molecular and biological functions associated with ATP-activated adenosine receptors, neuropeptide hormone activity, and the oxytocin signaling pathway to be altered between the different treatment groups. The current study further reveals the harmful effects of chronic PSU and HIV infection that can subsequently impact neurological outcomes in polysubstance users with HAND.
Topics: Animals; Humans; HIV Infections; Oxycodone; RNA-Seq; Neurocognitive Disorders; HIV-1; Methamphetamine
PubMed: 37766354
DOI: 10.3390/v15091948 -
Neuropharmacology Jan 2024Individuals with opioid use disorder (OUD) frequently use other substances, including cocaine. Opioid withdrawal is associated with increased likelihood of cocaine use,...
Individuals with opioid use disorder (OUD) frequently use other substances, including cocaine. Opioid withdrawal is associated with increased likelihood of cocaine use, which may represent an attempt to ameliorate opioid withdrawal effects. Clinically, 30% of co-using individuals take opioids and cocaine exclusively in a sequential manner. Preclinical studies evaluating mechanisms of drug use typically study drugs in isolation. However, polysubstance use is a highly prevalent clinical issue and thus, we established a novel preclinical model of sequential oxycodone and cocaine self-administration (SA) whereby rats acquired oxycodone and cocaine SA in an A-B-A-B design. Somatic signs of withdrawal were evaluated at 0, 22, and 24h following oxycodone SA, with the 24h timepoint representing somatic signs immediately following cocaine SA. Preclinically, aberrant glutamate signaling within the nucleus accumbens core (NAcore) occurs following use of cocaine or opioids, whereby medium spiny neurons (MSNs) rest in a potentiated or depotentiated state, respectively. Further, NAcore glial glutamate transport via GLT-1 is downregulated following SA of either drug alone. However, it is not clear if cocaine can exacerbate opioid-induced changes in glutamate signaling. In this study, NAcore GLT-1 protein and glutamate plasticity were measured (via AMPA/NMDA ratio) following SA. Rats acquired SA of both oxycodone and cocaine regardless of sex, and the acute oxycodone-induced increase in somatic signs at 22h was positively correlated with cocaine consumption during the cocaine testing phase. Cocaine use following oxycodone SA downregulated GLT-1 and reduced AMPA/NMDA ratios compared to cocaine use following food SA. Further, oxycodone SA alone was associated with reduced AMPA/NMDA ratio. Together, behavioral signs of oxycodone withdrawal may drive cocaine use and further dysregulate NAcore glutamate signaling.
Topics: Rats; Animals; Cocaine; Oxycodone; Glutamic Acid; Rats, Sprague-Dawley; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Analgesics, Opioid; N-Methylaspartate; Cocaine-Related Disorders; Nucleus Accumbens; Self Administration
PubMed: 37865136
DOI: 10.1016/j.neuropharm.2023.109773 -
Palliative Medicine Reports 2023Spinal metastasis pain includes both inflammatory and neuropathic pain, and opioids, which have only a μ-opioid receptor-stimulating effect, are generally less...
BACKGROUND
Spinal metastasis pain includes both inflammatory and neuropathic pain, and opioids, which have only a μ-opioid receptor-stimulating effect, are generally less effective in neuropathic pain. However, no previous study has been conducted for the comparisons of the efficacy of opioids in treating spinal metastasis pain.
OBJECTIVE
To compare the efficacy of tapentadol and methadone with other opioids for back pain caused by a metastatic spinal tumor.
DESIGN
Retrospective cohort study.
SETTING/SUBJECTS
A total of 274 patients were enrolled, who started a tapentadol extended-release tablet, methadone tablet, hydromorphone extended-release tablet, oxycodone extended-release tablet, or transdermal fentanyl patch for cancer pain due to spinal metastasis in Japan from January 1, 2013 to October 31, 2021.
MEASUREMENTS
The primary endpoint, the difference in the numerical rating scale (NRS) scores before and seven days after each opioid administration, was compared among the five groups.
RESULTS
In patients with numbness, a decrease of the NRS score on day seven compared with before starting each opioid was significantly higher in the tapentadol group than those in the hydromorphone, oxycodone, and fentanyl groups and comparable to that in the methadone group. In patients without numbness, no significant differences were observed in decreases of the NRS scores on day seven among the five groups.
CONCLUSIONS
Tapentadol and methadone may be more effective than hydromorphone, oxycodone, and fentanyl for cancer pain due to spinal metastasis with numbness.
PubMed: 37637760
DOI: 10.1089/pmr.2023.0018 -
Plastic and Reconstructive Surgery.... Aug 2023This trial aimed to compare the efficacy of a multimodal analgesic regimen with gabapentin to a multimodal nonsteroidal anti-inflammatory drug (NSAID) regimen following...
UNLABELLED
This trial aimed to compare the efficacy of a multimodal analgesic regimen with gabapentin to a multimodal nonsteroidal anti-inflammatory drug (NSAID) regimen following cosmetic surgery. This was a prospective randomized study of 106 patients undergoing elective outpatient cosmetic surgery.
METHODS
Patients were randomly assigned to a multimodal regimen of postoperative acetaminophen, gabapentin, and oxycodone with an acetaminophen and gabapentin preload or postoperative ibuprofen and oxycodone-acetaminophen protocol without a preload. Data on compliance, number of narcotic pills consumed, duration of analgesic use, pain levels, patient satisfaction, time from incision close to postanesthesia care unit (PACU) admission, and incidence of bleeding-related complications were collected and analyzed.
RESULTS
Patients from both regimens reported equivalent postoperative pain control with the exception of pain in PACU. NSAID patients exhibited a 9.3% higher rate of compliance ( = 0.01), a 6.0% higher rate of satisfaction with pain control ( = 0.04), a 25.2% shorter interval between closure and PACU (=0.01), and an 8.2% lower rate of bleeding-related complications, all of which were statistically significant ( < 0.05).
CONCLUSIONS
Both regimens are viable tools in combating opioid overprescription as they both effectively reduce postoperative pain. However, the NSAID protocol resulted in greater satisfaction related to pain management and was more cost-effective by reducing emergence time from anesthesia. As there were no hematomas associated with the use of NSAIDs and a significantly higher rate of compliance, the use of NSAIDs in enhanced recovery after surgery protocols is supported.
PubMed: 37577251
DOI: 10.1097/GOX.0000000000005181 -
Annals of Medicine Dec 2024Adverse effects of opioids are common among older individuals, and undertreatment as well as overuse can be an issue. Epidemiological data on opioid use in older...
Adverse effects of opioids are common among older individuals, and undertreatment as well as overuse can be an issue. Epidemiological data on opioid use in older individuals are available, but scarce in hospitalized patients. The aim of this study is to examine the one-day prevalence of opioid use among older inpatients and identify the factors associated with both opioid use and dosage. One-day cross-sectional study with data collected from geriatric units across 14 Belgian hospitals. The primary focus of the study is to assess the prevalence of opioid use and dosage, along with identifying associated factors. To achieve this, a multiple binary logistic regression model was fitted for opioid use, and a multiple linear regression model for opioid dose. Opioids were used in 24.4% of 784 patients, of which 57.9% was treated with tramadol, 13.2% with oxycodone or morphine and 28.9% with transdermal buprenorphine or fentanyl. The odds for opioid use were 4.2 times higher in patients in orthogeriatric units compared to other patients (OR=4.2, 95% CI=2.50-7.05). The prevalence of opioid use was 34% higher in patients without dementia compared to patients with dementia (OR=0.66, 95% CI=0.46-0.95). The overall mean daily dosage was 14.07mg subcutaneous morphine equivalent. After adjustment for age, gender and dementia, dosage was only associated with type of opioid: the estimated mean opioid dose was 70% lower with tramadol (mean ratio=0,30,95% CI=0,23-0,39) and 67% lower with oxycodone and morphine (mean ratio=0,33, 95% CI=0,22-0,48) compared to transdermal buprenorphine and transdermal fentanyl. One in four patients received opioid treatment. It is not clear whether this reflects under- or overtreatment, but these results can serve as a benchmark for geriatric units to guide future pain management practices. The utilization of transdermal fentanyl and buprenorphine, resulting in higher doses of morphine equivalent, poses significant risks for side effects.
Topics: Humans; Aged; Analgesics, Opioid; Oxycodone; Tramadol; Cross-Sectional Studies; Belgium; Prevalence; Fentanyl; Morphine; Buprenorphine; Dementia
PubMed: 38294956
DOI: 10.1080/07853890.2024.2310132 -
European Journal of Pharmaceutical... Mar 2024The concomitant administration of ritonavir and oxycodone may significantly increase the plasma concentrations of oxycodone. This study was aimed to simulate DDI between...
The concomitant administration of ritonavir and oxycodone may significantly increase the plasma concentrations of oxycodone. This study was aimed to simulate DDI between ritonavir and oxycodone, a widely used opioid, and to formulate dosing protocols for oxycodone by using physiologically based pharmacokinetic (PBPK) modeling. We developed a ritonavir PBPK model incorporating induction and competitive and time-dependent inhibition of CYP3A4 and competitive inhibition of CYP2D6. The ritonavir model was evaluated with observed clinical pharmacokinetic data and validated for its CYP3A4 inhibition potency. We then used the model to simulate drug interactions between oxycodone and ritonavir under various dosing scenarios. The developed model captured the pharmacokinetic characteristics of ritonavir from clinical studies. The model also accurately predicts exposure changes of midazolam, triazolam, and oxycodone in the presence of ritonavir. According to model simulations, the steady-state maximum, minimum and average concentrations of oxycodone increased by up to 166% after co-administration with ritonavir, and the total exposure increased by approximately 120%. To achieve similar steady-state concentrations, halving the dose with an unchanged dosing interval or doubling the dosing interval with an unaltered single dose should be practical for oxycodone, whether formulated in uncoated or controlled-release tablets during long-term co-medication with ritonavir. The results revealed exposure-related risks of oxycodone-ritonavir interactions that have not been studied clinically and emphasized PBPK as a workable method to direct judicious dosage.
Topics: Ritonavir; Oxycodone; Cytochrome P-450 CYP3A; Midazolam; Drug Interactions; Models, Biological
PubMed: 38199444
DOI: 10.1016/j.ejps.2024.106697