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The Indian Journal of Medical Research Nov 2023Cannabis use has long been associated with celebration and hospitality, although abuse must be confirmed through testing. It has always been difficult to develop an...
BACKGROUND OBJECTIVES
Cannabis use has long been associated with celebration and hospitality, although abuse must be confirmed through testing. It has always been difficult to develop an accurate and reliable confirmatory method for the quantification of tetrahydrocannabinol carboxylic acid (THC-COOH) that meets local requirements. The goal was to develop a rapid, cost-effective analytical technique that can handle large batches.
METHODS
Because of the wide metabolite detection window and ease of collection, urine was preferable sample. The extraction of a pre-screened urine sample (adulteration and multidrug screening) was done on Bond Elut cartridges using a positive pressure vacuum manifold, followed by quantification using a gas chromatograph and mass spectrometer.
RESULTS
The assay was linear between 15 and 300 ng/ml ( r2 of 0.99). The intra-day precision was 8.69 per cent and the inter-day precision was 10.78 per cent, respectively with a 97.5 per cent recovery rate for the lowest concentration. A total of 939 urine samples were examined, with 213 detecting cannabis. Sixty per cent of the total individuals tested positive for simply cannabinoids, 33 per cent for cannabinoids and sedatives, five per cent for cannabinoids and morphine and one for cannabis, morphine and cocaine.
INTERPRETATION CONCLUSIONS
Assay characteristics included modest sample preparation, rapid chromatography, high specificity and small sample volume with a processing time of 12 h. The assay described here can be applied for diagnostic laboratories and in forensic settings as well.
Topics: Humans; Dronabinol; Substance Abuse Detection; Cannabinoids; Hallucinogens; Cannabis; Marijuana Abuse; Morphine Derivatives
PubMed: 37929356
DOI: 10.4103/ijmr.IJMR_3899_20 -
British Journal of Cancer Nov 2023Short-term infusions of dinutuximab beta plus isotretinoin and cytokines administered in previous immunotherapy studies in neuroblastoma were associated with severe...
BACKGROUND
Short-term infusions of dinutuximab beta plus isotretinoin and cytokines administered in previous immunotherapy studies in neuroblastoma were associated with severe pain. Here, long-term, continuous infusion of single-agent dinutuximab beta was evaluated in patients with relapsed/refractory neuroblastoma.
METHODS
In this open-label, single-arm, Phase 2 study, patients with either refractory or relapsed high-risk neuroblastoma received dinutuximab beta by continuous infusion over 10 days of each cycle, for up to five cycles. The primary endpoint was objective response rate 24 weeks after the end of cycle 5. Secondary endpoints included adverse events, intravenous morphine use, best response, duration of response, and three-year progression-free and overall survival.
RESULTS
Of the 40 patients included, 38 had evaluable response. Objective response rate was 26% and best response rate 37%. Median duration of response was 238 days (IQR 108-290). Three-year progression-free and overall survival rates were 31% (95% CI 17-47) and 66% (95% CI 47-79), respectively. Prophylactic intravenous morphine use and duration of use decreased with increasing cycles. The most common grade 3 treatment-related adverse events were pain, diarrhea, and hypokalemia.
CONCLUSION
Long-term continuous infusion of single-agent dinutuximab beta is tolerable and associated with clinically meaningful responses in patients with relapsed/refractory high-risk neuroblastoma.
CLINICAL TRIAL REGISTRATION
The study is registered with ClinicalTrials.gov (NCT02743429) and EudraCT (2014-000588-42).
Topics: Humans; Morphine Derivatives; Neoplasm Recurrence, Local; Neuroblastoma; Pain
PubMed: 37813959
DOI: 10.1038/s41416-023-02457-x -
Gut Microbes Dec 2023Morphine addiction is closely associated with dysbiosis of the gut microbiota. miRNAs play a crucial role in regulating intestinal bacterial growth and are involved in...
Morphine addiction is closely associated with dysbiosis of the gut microbiota. miRNAs play a crucial role in regulating intestinal bacterial growth and are involved in the development of disease. Ginsenoside Rg1 exhibits an anti-addiction effect and significantly improves intestinal microbiota disorders. In pseudo-germfree mice, supplementation with () synergistically enhanced Rg1 to alleviate morphine addiction. However, it is currently unknown the relationship between fecal miRNAs in morphine-exposed mice and their potential modulation of gut microbiome, as well as their role in mediating the resistance of ginsenoside Rg1 to drug addiction. Here, we studied the fecal miRNA abundance in mice treated with morphine to explore the different miRNAs expressed, their association with and their role in the amelioration of morphine reward by ginsenoside Rg1. Our results indicated ginsenoside Rg1 attenuated the significant increase in miR-129-5p expression observed in the feces of morphine-treated mice. The miR-129-5p, specifically, inhibited the growth of by modulating the transcript of the site-tag BVU_RS11835 and increased the levels of 5-hydroxytryptophan and indole-3-carboxaldehyde in vitro. Subsequently, we noticed that oral administration of synthetic miR-129-5p increased 5-HT levels in the hippocampus and inhibited the reversal effect of ginsenoside Rg1 both on the relative abundance of in the feces and CPP effect induced by morphine exposure. In short, Ginsenoside Rg1 might play an indirect role in remodeling the against morphine reward by suppressing miR-129-5p expression. These results highlight the role of miR-129-5p and in morphine reward and the anti-morphine addiction of ginsenoside Rg1.
Topics: Animals; Mice; Gastrointestinal Microbiome; Hippocampus; MicroRNAs; Morphine; Reward; Serotonin
PubMed: 37698853
DOI: 10.1080/19490976.2023.2254946 -
Pain Physician Oct 2023Ultrasound-guided serratus anterior plane block (SAPB) is an efficient perioperative analgesic modality for breast surgeries. SAPB does not block the anterior cutaneous... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Ultrasound-guided serratus anterior plane block (SAPB) is an efficient perioperative analgesic modality for breast surgeries. SAPB does not block the anterior cutaneous branches of the intercostal nerves; thus, it does not provide adequate analgesia for the parasternal region and the medial side of the breast. A new parasternal block, the pectointercostal fascial plane block (PIFB) has been developed to overcome this issue.
OBJECTIVES
The study aimed to evaluate the perioperative analgesic effect of using PIFB in addition to SAPB. The primary outcome was to evaluate the postoperative pain score. The secondary outcomes were to assess perioperative opioid requirements, hemodynamic stability, and the satisfaction of the patient and surgeon.
STUDY DESIGN
The current study was a prospective, double-blinded, randomized controlled study. The current study was registered at the Pan-African Clinical Trials Registry (PACTR202001789968542) and was designed after obtaining ethical institutional approval (Institutional Review Board No 00012098, Federalwide Assurance No 00018699).
SETTING
The study involved 60 women between 21 and 69 years old with breast cancer who were scheduled for modified radical mastectomy or conservative breast surgeries in a university hospital.
METHODS
After verbal and informed written consent, the patients were allocated to Group 1, which received SAPB, and Group 2, which received SAPB with PIFB. We assessed the Visual Analog Scale (VAS), perioperative opioid requirements, intraoperative hemodynamic stability, rescue analgesia, and complications. Patient and surgeon satisfaction were surveyed using a questionnaire where one is very dissatisfied and 5 is very satisfied.
RESULTS
Intraoperative mean arterial blood pressure (MABP) and heart rate were significantly lower in Group 2 (SAPB+PIFB). The number of patients who needed intraoperative fentanyl was also significantly lower in Group 2 (SAPB+PIFB) (P value = 0.010). Postoperative VAS showed no significant difference in both groups. The number of patients who needed postoperative rescue morphine, time for the first rescue analgesia, first morphine dose (mg), and total opioid consumption were also comparable for both groups. Patient satisfaction and surgeon satisfaction were comparable for both groups (P values = 1.000 and 0.496, respectively).
LIMITATIONS
VAS was not recorded during movements and no follow-up was done to detect the potential effect on chronic postmastectomy pain. Moreover, after reviewing the literature, there was no efficient data about adding PIFB with different regional blocks for breast surgery.
CONCLUSIONS
The number of patients who needed intraoperative fentanyl, as well as the MABP and heart rate were significantly lower in Group 2 (SAPB+PIFB). Postoperative vital signs, VAS, postoperative analgesic requirements, and opioid consumption were comparable for both groups. Patient satisfaction was comparable for both groups, while surgeon satisfaction was higher in Group 2 (SAPB+PIFB) but statistically not significant.
Topics: Humans; Female; Young Adult; Adult; Middle Aged; Aged; Breast Neoplasms; Analgesics, Opioid; Mastectomy; Prospective Studies; Pain, Postoperative; Analgesics; Morphine; Fentanyl
PubMed: 37847921
DOI: No ID Found -
Journal of Pain & Palliative Care... Sep 2023
Topics: Humans; Morphine; Naloxone; Injections, Spinal
PubMed: 37314428
DOI: 10.1080/15360288.2023.2219666 -
Neuropharmacology Dec 2023Prenatal opioid exposure is a major health concern in the United States, with the incidence of neonatal opioid withdrawal syndrome (NOWS) escalating in recent years....
Decreased myelin-related gene expression in the nucleus accumbens during spontaneous neonatal opioid withdrawal in the absence of long-term behavioral effects in adult outbred CFW mice.
Prenatal opioid exposure is a major health concern in the United States, with the incidence of neonatal opioid withdrawal syndrome (NOWS) escalating in recent years. NOWS occurs upon cessation of in utero opioid exposure and is characterized by increased irritability, disrupted sleep patterns, high-pitched crying, and dysregulated feeding. The main pharmacological strategy for alleviating symptoms is treatment with replacement opioids. The neural mechanisms mediating NOWS and the long-term neurobehavioral effects are poorly understood. We used a third trimester-approximate model in which neonatal outbred pups (Carworth Farms White; CFW) were administered once-daily morphine (15 mg/kg, s.c.) from postnatal day (P) day 1 through P14 and were then assessed for behavioral and transcriptomic adaptations within the nucleus accumbens (NAc) on P15. We also investigated the long-term effects of perinatal morphine exposure on adult learning and reward sensitivity. We observed significant weight deficits, spontaneous thermal hyperalgesia, and altered ultrasonic vocalization (USV) profiles following repeated morphine and during spontaneous withdrawal. Transcriptome analysis of NAc from opioid-withdrawn P15 neonates via bulk mRNA sequencing identified an enrichment profile consistent with downregulation of myelin-associated transcripts. Despite the neonatal behavioral and molecular effects, there were no significant long-term effects of perinatal morphine exposure on adult spatial memory function in the Barnes Maze, emotional learning in fear conditioning, or in baseline or methamphetamine-potentiated reward sensitivity as measured via intracranial self-stimulation. Thus, the once daily third trimester-approximate exposure regimen, while inducing NOWS model traits and significant transcriptomic effects in neonates, had no significant long-term effects on adult behaviors.
Topics: Pregnancy; Female; Animals; Mice; Analgesics, Opioid; Nucleus Accumbens; Myelin Sheath; Substance Withdrawal Syndrome; Narcotics; Morphine; Neonatal Abstinence Syndrome; Gene Expression; Opioid-Related Disorders
PubMed: 37774943
DOI: 10.1016/j.neuropharm.2023.109732 -
Emergency Medicine Australasia : EMA Aug 2023To evaluate the burden of disease, investigate the treatment and response to treatment caused by exposure to stinging tree plants presenting to Cairns Hospital over a...
OBJECTIVES
To evaluate the burden of disease, investigate the treatment and response to treatment caused by exposure to stinging tree plants presenting to Cairns Hospital over a 3-year period. Our secondary aim was to examine the benefit from treating such exposures with topical dilute hydrochloric acid (HCl).
METHODS
A retrospective chart review of all patients presenting to Cairns ED over a 3-year period because of stinging tree exposure. Symptoms, signs, treatment and outcomes were recorded.
RESULTS
There were 48 presentations, all having immediate pain after contact with the stinging tree, with 87% describing the pain as moderate or severe. Nearly all were stung on limbs (96%). There were 13 different treatments prior to presentation. In hospital, 60% needed opioid analgesia and a median oral morphine dose equivalent of 15 mg. Of the 29 receiving HCl nine patients reported good relief or complete relief.
CONCLUSIONS
Stinging tree exposure results in significant presentations to the Cairns ED each year. Pain is immediate and severe and there are no clear first aid or definitive treatment recommendations. Further work is needed to ascertain the best first aid and definitive treatment including a formal trial of dilute HCl.
Topics: Humans; Trees; Retrospective Studies; Pain; Morphine; Analgesics, Opioid; Hospitals
PubMed: 36700481
DOI: 10.1111/1742-6723.14177 -
Neuropharmacology Aug 2023Opioid addiction is characterized by adaptations in the mesolimbic dopamine system that occur during chronic opioid use. Alterations in dopaminergic transmission...
Opioid addiction is characterized by adaptations in the mesolimbic dopamine system that occur during chronic opioid use. Alterations in dopaminergic transmission contribute to pathological drug-seeking behavior and other symptoms associated with opioid withdrawal following drug discontinuation, making drug abstinence challenging and contributing to high rates of relapse among those suffering from substance use disorder. Recently, the use of dopamine partial agonists has been proposed as a potential strategy to restore dopaminergic signalling during drug withdrawal, while avoiding the adverse side effects associated with stronger modulators of dopaminergic transmission. We investigated the effects of the atypical antipsychotic brexpiprazole, which is a partial agonist at dopamine D2 and D3 receptors, in a mouse model of opioid dependence. The development of opioid dependence in mice is characterized by locomotor sensitization, analgesic tolerance, opioid-induced hyperalgesia, and drug-seeking behavior. We set up four paradigms to model the effects of brexpiprazole on each of these adaptations that occur during chronic opioid use in male and female C57BL/6J mice. Concomitant treatment of brexpiprazole during chronic morphine administration attenuated the development of locomotor sensitization. Brexpiprazole treatment abolished morphine place preference and blocked reinstatement of this behavior following extinction. Brexpiprazole treatment did not alter morphine analgesia, nor did it impact the development of morphine tolerance. However, brexpiprazole treatment did prevent the expression of opioid-induced hyperalgesia in a tail-withdrawal assay, while failing to improve somatic withdrawal symptoms. Altogether, these results provide preclinical evidence for the efficacy of brexpiprazole as a modulator of dopamine-dependent behaviors during opioid use and withdrawal.
Topics: Mice; Male; Female; Animals; Antipsychotic Agents; Dopamine; Analgesics, Opioid; Hyperalgesia; Mice, Inbred C57BL; Morphine; Dopamine Agonists; Opioid-Related Disorders; Substance Withdrawal Syndrome
PubMed: 37068603
DOI: 10.1016/j.neuropharm.2023.109546 -
The Journal of Surgical Research Nov 2023Some surgeons have raised concerns regarding the sympathectomy-like effect of epidural anesthesia during lower limb microvascular reconstruction. The combined... (Review)
Review
INTRODUCTION
Some surgeons have raised concerns regarding the sympathectomy-like effect of epidural anesthesia during lower limb microvascular reconstruction. The combined spinal-epidural (CSE) anesthetic technique incorporates several benefits of spinal and epidural techniques in a single approach. The aim of this study was to analyze the postoperative outcomes of patients undergoing soft-tissue reconstruction of the lower limb by implementing the CSE anesthesia approach.
METHODS
We reviewed medical records from patients who underwent lower limb reconstructive procedures under CSE anesthesia with free tissue transfer from January 2017 to December 2020. We evaluated the postoperative outcomes.
RESULTS
Thirty-eight patients underwent microvascular reconstructive procedures of the lower extremity over the study period. The average age and BMI were 38.4-year and 28 kg/m. All patients only had one postoperative rescue dose with epidural anesthesia. The most common type of flap used was the anterolateral thigh flap (53%). The average splinting time and length of stay (LoS) were 8.4 days and 18.4 days, respectively. Donor-site complications included wound dehiscence (3%) and surgical site infection (3%). Recipient-site complications included partial flap loss (8%) and total flap loss (10%). No pro re nata morphine analgesia was used. Tramadol and/or ketoprofen were administered for postoperative analgesia. The average time to start physiotherapy and to resume daily activities were 10 days and 29 days, respectively.
CONCLUSIONS
The CSE anesthesia for microvascular reconstruction of the lower limb demonstrated a similar success rate compared to historical records. CSE provided adequate pain management and none of the patients required postoperative monitoring in the ICU.
Topics: Humans; Anesthesia, Epidural; Anesthesia, Spinal; Surgical Flaps; Thigh; Morphine; Lower Extremity
PubMed: 37562232
DOI: 10.1016/j.jss.2023.07.026 -
Analytical Methods : Advancing Methods... Nov 2023Colloidal gold immunoassay is the most widely used method in the field of drug detection. However, this method often has poor quantitative identification ability and low...
Colloidal gold immunoassay is the most widely used method in the field of drug detection. However, this method often has poor quantitative identification ability and low analytical sensitivity, which is not suitable for the analysis of hair poisoning ingredients. In order to solve these limitations, we developed an immunochromatographic test strip for simultaneously screening multiple drugs in this study. This hand-held test strip used fluorescent nanoparticles loaded with lanthanide chelates as the signal carrier of fluorescence reading, and conducted quantitative testing of various drugs based on the competitive immune reaction between the analyte and antigen. Under the optimal conditions, the competition curves of morphine (MOP), methamphetamine (MET) and ketamine (KET) were obtained on a single band. The detection limit (LOD) of this analytical method was 100-1000 times lower than that of colloidal gold test strips. The detection limits of MOP, MET and KET were 0.06 ng mL, 0.1 ng mL and 1.0 ng mL, respectively. No cross-reaction was observed when morphine, methamphetamine and ketamine were tested simultaneously with this method. And 184 hair samples were tested simultaneously, and the detected amount was very close to the results of LC-MS. The immunochromatographic strip showed good stability in repeated tests, and the coefficient of variation was less than 15%. Fluorescence immunochromatography strips and handheld strip readers have the characteristics of portability, speed, ease of operation and high sensitivity, and may become powerful tools for screening drug abuse in hair in forensic medicine.
Topics: Morphine; Ketamine; Limit of Detection; Methamphetamine; Lanthanoid Series Elements; Chromatography, Affinity; Gold Colloid; Hair
PubMed: 37861716
DOI: 10.1039/d3ay01280h