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European Review For Medical and... May 2024Painful peripheral diabetic neuropathy (PRDN) is a common disabling condition. Pregabalin and amitriptyline are commonly prescribed as the first-line for PPDN despite... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Painful peripheral diabetic neuropathy (PRDN) is a common disabling condition. Pregabalin and amitriptyline are commonly prescribed as the first-line for PPDN despite the contradicting recommendations. There is a need to inform the scientific community regarding first-line pain control among patients with PPDN. This meta-analysis assessed pregabalin and amitriptyline effects on PPDN.
PATIENTS AND METHODS
We searched PubMed, MEDLINE, Cochrane Library, EBSCO, and Google Scholar; the terms used were amitriptyline, pregabalin, painful diabetic neuropathy, antidepressant, gabapentinoids, quality of life, and adverse events. Boolean operators like AND, and OR were used. Six hundred and thirty-one studies were retrieved, and 37 full texts were screened. However, only six randomized controlled trials fulfilled the inclusion and exclusion criteria.
RESULTS
No significant statistical differences between amitriptyline and pregabalin regarding pain score and significant pain reduction (odd ratio, -0.82, 95% CI, -2.21-0.58, and odd ratio, 1.16, 95% CI, 0.76-1.76 respectively). Quality of life, total adverse events, and drug discontinuation were not different between the two drugs (odd ratio, 0.89, 95% CI, -2.11-3.89, odd ratio, 0.98, 95% CI, 0.52-1.85, and odd ratio, 0.51, 95% CI, 0.08-3.15, respectively).
CONCLUSIONS
No significant statistical differences between amitriptyline and pregabalin regarding their effects on pain and quality of life. The drugs showed similar total adverse events and drug withdrawal. Further larger real-world studies are needed.
Topics: Pregabalin; Amitriptyline; Humans; Diabetic Neuropathies; Analgesics; Quality of Life
PubMed: 38856135
DOI: 10.26355/eurrev_202405_36296 -
Biomedicine & Pharmacotherapy =... Jul 2024Fibromyalgia is characterised by widespread chronic pain and is often accompanied by comorbidities such as sleep disorders, anxiety, and depression. Because it is often...
Fibromyalgia is characterised by widespread chronic pain and is often accompanied by comorbidities such as sleep disorders, anxiety, and depression. Because it is often accompanied by many adverse symptoms and lack of effective treatment, it is important to search for the pathogenesis and treatment of fibromyalgia. Astaxanthin, a carotenoid pigment known for its anti-inflammatory and antioxidant properties, has demonstrated effective analgesic effects in neuropathic pain. However, its impact on fibromyalgia remains unclear. Therefore, in this study, we constructed a mouse model of fibromyalgia and investigated the effect of astaxanthin on chronic pain and associated symptoms through multiple intragastrical injections. We conducted behavioural assessments to detect pain and depression-like states in mice, recorded electroencephalograms to monitor sleep stages, examined c-Fos activation in the anterior cingulate cortex, measured activation of spinal glial cells, and assessed levels of inflammatory factors in the brain and spinal cord, including interleukin (IL)-1β, IL-6, and tumour necrosis factor- α(TNF-α).Additionally, we analysed the expression levels of IL-6, IL-10, NOD-like receptor thermal protein domain associated protein 3 (NLRP3), Apoptosis-associated speck-like protein containing CARD, and Caspase-1 proteins. The findings revealed that astaxanthin significantly ameliorated mechanical and thermal pain in mice with fibromyalgia and mitigated sleep disorders and depressive-like symptoms induced by pain. A potential mechanism underlying these effects is the anti-inflammatory action of astaxanthin, likely mediated through the inhibition of the NLRP3 inflammasome, which could be one of the pathways through which astaxanthin alleviates fibromyalgia. In conclusion, our study suggests that astaxanthin holds promise as a potential analgesic medication for managing fibromyalgia and its associated symptoms.
Topics: Animals; Xanthophylls; Fibromyalgia; NLR Family, Pyrin Domain-Containing 3 Protein; Inflammasomes; Depression; Mice; Male; Mice, Inbred C57BL; Disease Models, Animal; Analgesics; Anti-Inflammatory Agents; Chronic Pain; Cytokines; Spinal Cord; Behavior, Animal
PubMed: 38852510
DOI: 10.1016/j.biopha.2024.116856 -
BMC Veterinary Research Jun 2024When inhalant anesthetic equipment is not available or during upper airway surgery, intravenous infusion of one or more drugs are commonly used to induce and/or maintain... (Comparative Study)
Comparative Study
BACKGROUND
When inhalant anesthetic equipment is not available or during upper airway surgery, intravenous infusion of one or more drugs are commonly used to induce and/or maintain general anesthesia. Total intravenous anesthesia (TIVA) does not require endotracheal intubation, which may be more difficult to achieve in rabbits. A range of different injectable drug combinations have been used as continuous infusion rate in animals. Recently, a combination of ketamine and propofol (ketofol) has been used for TIVA in both human patients and animals. The purpose of this prospective, blinded, randomized, crossover study was to evaluate anesthetic and cardiopulmonary effects of ketofol total intravenous anesthesia (TIVA) in combination with constant rate infusion (CRI) of midazolam, fentanyl or dexmedetomidine in eight New Zealand White rabbits. Following IV induction with ketofol and endotracheal intubation, anesthesia was maintained with ketofol infusion in combination with CRIs of midazolam (loading dose [LD]: 0.3 mg/kg; CRI: 0.3 mg/kg/hr; KPM), fentanyl (LD: 6 µg/kg; CRI: 6 µg/kg/hr; KPF) or dexmedetomidine (LD: 3 µg/kg; CRI: 3 µg/kg/hr; KPD). Rabbits in the control treatment (KPS) were administered the same volume of saline for LD and CRI. Ketofol infusion rate (initially 0.6 mg kg minute [0.3 mg kg minute of each drug]) was adjusted to suppress the pedal withdrawal reflex. Ketofol dose and physiologic variables were recorded every 5 min.
RESULTS
Ketofol induction doses were 14.9 ± 1.8 (KPM), 15.0 ± 1.9 (KPF), 15.5 ± 2.4 (KPD) and 14.7 ± 3.4 (KPS) mg kg and did not differ among treatments (p > 0.05). Ketofol infusion rate decreased significantly in rabbits in treatments KPM and KPD as compared with saline. Ketofol maintenance dose in rabbits in treatments KPM (1.0 ± 0.1 mg/kg/min) and KPD (1.0 ± 0.1 mg/kg/min) was significantly lower as compared to KPS (1.3 ± 0.1 mg/kg/min) treatment (p < 0.05). Ketofol maintenance dose did not differ significantly between treatments KPF (1.1 ± 0.3 mg/kg/min) and KPS (1.3 ± 0.1 mg/kg/min). Cardiovascular variables remained at clinically acceptable values but ketofol infusion in combination with fentanyl CRI was associated with severe respiratory depression.
CONCLUSIONS
At the studied doses, CRIs of midazolam and dexmedetomidine, but not fentanyl, produced ketofol-sparing effect in rabbits. Mechanical ventilation should be considered during ketofol anesthesia, particularly when fentanyl CRI is used.
Topics: Animals; Rabbits; Fentanyl; Dexmedetomidine; Midazolam; Ketamine; Anesthesia, Intravenous; Propofol; Anesthetics, Intravenous; Cross-Over Studies; Male; Female; Heart Rate; Prospective Studies; Blood Pressure; Anesthetics, Combined; Infusions, Intravenous; Hypnotics and Sedatives
PubMed: 38851722
DOI: 10.1186/s12917-024-04112-w -
Trials Jun 2024Obese patients undergoing laparoscopic sleeve gastrectomy (LSG) are particularly at risk of opioid-related side effects. To reduce patient exposure to opioids,...
The effect of pre-emptive oral pregabalin on opioid consumption in patients undergoing laparoscopic sleeve gastrectomy with an analysis of intraoperative hemodynamic stability and quality of recovery: study protocol for a randomized, prospective, double-blind study.
BACKGROUND
Obese patients undergoing laparoscopic sleeve gastrectomy (LSG) are particularly at risk of opioid-related side effects. To reduce patient exposure to opioids, multimodal analgesia, which involves the use of drugs of different classes, may be utilized. One of the drugs under consideration is pregabalin. Despite an opioid-sparing potential, few studies assess the role of pregabalin as an element of multimodal analgesia in LSG. Considering the limited number and inconsistent results of available studies, we decided to conduct a randomized, prospective study on the effect of preemptive pregabalin administration in obese patients on opioid consumption, pain scores, the incidence of opioid side effects, and hemodynamical stability.
METHODS
The study is designed as a prospective randomized controlled trial with double-blinding. Randomization will be performed in a block with a parallel 1:1 allocation. The intervention will involve receiving a pregabalin 150 mg capsule 1-2 h before the surgery, whereas the control group will receive an identically looking placebo. The primary outcome measure will be total oxycodone consumption in the first 24 h following surgery. Secondary outcome measures will be pain severity assessed using the Numerical Rating Scale (NRS) 1, 6, 12, and 24 h after surgery, postoperative sedation on the Ramsay scale, PONV impact scale, the incidence of desaturation episodes < 94%, and episodes of blurred vision at 1, 6, 12, and 24 h after surgery, intraoperative hemodynamic parameters such as heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), total fluid volume, and total ephedrine dose. Patient comfort will be additionally assessed using the QoR-40 questionnaire at discharge.
DISCUSSION
The study will explore the efficacy and safety of preemptive pregabalin in a dose of 150 mg as a co-analgesic used in multimodal analgesia for LSG. As studies on opioid-sparing regimes concern the safety of obese patients, we aim to contribute objective data with a relatively large study sample size. The result of the present clinical trial may support the reassessment of recommendations to use pregabalin in the studied population.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05804591. Registered on 07.04.2023.
Topics: Humans; Pregabalin; Double-Blind Method; Prospective Studies; Analgesics, Opioid; Gastrectomy; Pain, Postoperative; Laparoscopy; Hemodynamics; Randomized Controlled Trials as Topic; Adult; Treatment Outcome; Pain Measurement; Administration, Oral; Analgesics; Middle Aged; Male; Time Factors; Female; Young Adult; Recovery of Function; Oxycodone
PubMed: 38849875
DOI: 10.1186/s13063-024-08225-3 -
BMC Neurology Jun 2024Dexmedetomidine (Dex), midazolam, and propofol are three distinct sedatives characterized by varying pharmacological properties. Previous literature has indicated the... (Comparative Study)
Comparative Study
BACKGROUND
Dexmedetomidine (Dex), midazolam, and propofol are three distinct sedatives characterized by varying pharmacological properties. Previous literature has indicated the positive impact of each of these sedatives on ICU patients. However, there is a scarcity of clinical evidence comparing the efficacy of Dex, midazolam, and propofol in reducing mortality among people with epilepsy (PWE). This study aimed to assess the impact of Dex, midazolam, and propofol on the survival of PWE.
METHODS
The data were retrospectively retrieved from the Medical Information Mart for Intensive Care (MIMIC)-IV database (version 2.0). PWE were categorized into Dex, midazolam, and propofol groups based on the intravenously administered sedatives. PWE without standard drug therapy were included in the control group. Comparative analyses were performed on the data among the groups.
RESULTS
The Dex group exhibited a significantly lower proportion of in-hospital deaths and a markedly higher in-hospital survival time compared to the midazolam and propofol groups (p < 0.01) after propensity score matching. Kaplan-Meier curves demonstrated a significant improvement in survival rates for the Dex group compared to the control group (p = 0.025). Analysis of Variance (ANOVA) revealed no significant differences in survival rates among the Dex, midazolam, and propofol groups (F = 1.949, p = 0.143). The nomogram indicated that compared to midazolam and propofol groups, Dex was more effective in improving the survival rate of PWE.
CONCLUSION
Dex might improve the survival rate of PWE in the ICU compared to no standard drug intervention. However, Dex did not exhibit superiority in improving survival rates compared to midazolam and propofol.
Topics: Humans; Dexmedetomidine; Midazolam; Propofol; Male; Female; Middle Aged; Hypnotics and Sedatives; Retrospective Studies; Intensive Care Units; Epilepsy; Adult; Aged; Databases, Factual; Hospital Mortality
PubMed: 38849716
DOI: 10.1186/s12883-024-03693-1 -
Issues in Mental Health Nursing Jun 2024
Topics: Humans; Trazodone; Sleep Initiation and Maintenance Disorders; Selective Serotonin Reuptake Inhibitors; Sleep Wake Disorders
PubMed: 38843027
DOI: 10.1080/01612840.2024.2356501 -
The Science of the Total Environment Sep 2024Triclosan (TCS), a commonly used antibacterial agent, is associated with various harmful effects on mammalian neurodevelopment, particularly when exposed prenatally....
Neurotoxic effects of triclosan in adolescent mice: Pyruvate kinase M2 dimer regulated Signal transducer and activator of transcription 3 phosphorylation mediated microglia activation and neuroinflammation.
Triclosan (TCS), a commonly used antibacterial agent, is associated with various harmful effects on mammalian neurodevelopment, particularly when exposed prenatally. This study investigated the impact of long-term exposure to TCS on the prefrontal cortex development in adolescent mice. We evaluated the motor ability, motor coordination, and anxiety behavior of mice using open field tests (OFT) and elevated cross maze tests (EPM). An increase in movement distance, number of passes through the central area, and open arm retention time was observed in mice treated with TCS. Hematoxylin eosin staining and Nissl staining also showed significant adverse reactions in the brain tissue of TCS-exposed group. TCS induced microglia activation and increased inflammatory factors expression in the prefrontal cortex. TCS also increased the expression of pyruvate kinase M2 (PKM2), thereby elevating the levels of PKM2 dimer, which entered the nucleus. Treatment with TEPP46 (PKM2 dimer nuclear translocation inhibitor) blocked the expression of inflammatory factors induced by TCS. TCS induced the phosphorylation of nuclear signal transducer and activator of transcription 3 (STAT3) in vivo and in vitro, upregulating the levels of inflammatory cytokines. The results also demonstrated the binding of PKM2 to STAT3, which promoted STAT3 phosphorylation at the Tyr705 site, thereby regulating the expression of inflammatory factors. These findings highlight the role of PKM2-regulated STAT3 phosphorylation in TCS-induced behavioral disorders in adolescents and propose a reliable treatment target for TCS.
Topics: Animals; Triclosan; Mice; Microglia; Pyruvate Kinase; STAT3 Transcription Factor; Phosphorylation; Neuroinflammatory Diseases; Anti-Infective Agents, Local; Male
PubMed: 38839007
DOI: 10.1016/j.scitotenv.2024.173739 -
Luminescence : the Journal of... Jun 2024The study's objective is to establish an eco-friendly, sensitive and economical quantitative methodology for the concurrent analysis of donepezil HCl (DPZ) and trazodone...
A green micelle-enhanced first derivative synchronous fluorescence approach for determination of donepezil HCl and trazodone HCl in their pure state, pharmaceutical dosage form and spiked human plasma.
The study's objective is to establish an eco-friendly, sensitive and economical quantitative methodology for the concurrent analysis of donepezil HCl (DPZ) and trazodone HCl (TRZ) in raw materials, tablets and human plasma. The first derivative synchronous fluorescence spectroscopic (FDSFS) technique was applied at constant wavelength difference (∆λ = 120) for assessment of DPZ and TRZ at each other's zero-crossing point at 279 nm and 297 nm, respectively. The submitted technique was validated in accordance with ICH Q2 R1 guidelines and the linearity of the standard calibration curve was observed over the concentration range of 10-500 ng/ml for DPZ and 20-1,000 ng/ml for TRZ. The detection limits (LOD) were found to be 2.65 and 5.4 ng/ml, and the limits of quantitation (LOQ) were 8.05 and 16.3 ng/ml for DPZ and TRZ, respectively. This technique was used further to quantify the studied medications in their laboratory-prepared mixtures, commercial tablets and spiked plasma samples. The results obtained were not significantly different from those acquired from the comparison methods, indicating the high accuracy and precision of the proposed method. Furthermore, the ecological friendliness of the suggested method was evaluated and proven to be excellent using Green Analytical Procedure Index (GAPI) and Analytical GREEnness (AGREE) evaluation tools.
Topics: Humans; Trazodone; Donepezil; Spectrometry, Fluorescence; Tablets; Micelles; Limit of Detection
PubMed: 38837846
DOI: 10.1002/bio.4797 -
Cell Communication and Signaling : CCS Jun 2024Neuroinflammation is widely acknowledged as a characteristic feature of almost all neurological disorders and specifically in depression- and anxiety-like disorders. In...
BACKGROUND
Neuroinflammation is widely acknowledged as a characteristic feature of almost all neurological disorders and specifically in depression- and anxiety-like disorders. In recent years, there has been significant attention on natural compounds with potent anti-inflammatory effects due to their potential in mitigating neuroinflammation and neuroplasticity.
METHODS
In the present study, we aimed to evaluate the neuroprotective effects of oleacein (OC), a rare secoiridoid derivative found in extra virgin olive oil. Our goal was to explore the BDNF/TrkB neurotrophic activity of OC and subsequently assess its potential for modulating neuroinflammatory response using human neuroblastoma cells (SH-SY5Y cells) and an in vivo model of depression induced by lipopolysaccharide (LPS)-mediated inflammation.
RESULTS
In SH-SY5Y cells, OC exhibited a significant dose-dependent increase in BDNF expression. This enhancement was absent when cells were co-treated with inhibitors of BDNF's receptor TrkB, as well as downstream molecules PI3K and MEK. Whole-transcriptomics analysis revealed that OC upregulated cell cycle-related genes under normal conditions, while downregulating inflammation-associated genes in LPS-induced conditions. Furthermore, surface plasmon resonance (SPR) assays demonstrated that OC exhibited a stronger and more stable binding affinity to TrkB compared to the positive control, 7,8-dihydroxyflavone. Importantly, bioluminescence imaging revealed that a single oral dose of OC significantly increased BDNF expression in the brains of Bdnf-IRES-AkaLuc mice. Furthermore, oral administration of OC at a dosage of 10 mg/kg body weight for 10 days significantly reduced immobility time in the tail suspension test compared to the LPS-treated group. RT-qPCR analysis revealed that OC significantly decreased the expression of pro-inflammatory cytokines Tnfα, Il6, and Il1β, while simultaneously enhancing Bdnf expression, as well as both pro and mature BDNF protein levels in mice hippocampus. These changes were comparable to those induced by the positive control antidepressant drug fluoxetine. Additionally, microarray analysis of mouse brains confirmed that OC could counteract LPS-induced inflammatory biological events.
CONCLUSION
Altogether, our study represents the first report on the potential antineuroinflammatory and antidepressant properties of OC via modulation of BDNF/TrkB neurotrophic activity. This finding underscores the potential of OC as a natural therapeutic agent for depression- and anxiety-related disorders.
Topics: Animals; Humans; Receptor, trkB; Brain-Derived Neurotrophic Factor; Lipopolysaccharides; Mice; Neuroinflammatory Diseases; Cell Line, Tumor; Cyclopentane Monoterpenes; Male; Neuroprotective Agents; Mice, Inbred C57BL; Olive Oil; Anti-Inflammatory Agents; Inflammation; Aldehydes; Membrane Glycoproteins; Phenols
PubMed: 38835076
DOI: 10.1186/s12964-024-01691-x -
Neurologia Jun 2024Status epilepticus is an important cause of pediatric neurological emergency. Immediate treatment is essential to prevent definitive neurological damage. Several...
INTRODUCTION
Status epilepticus is an important cause of pediatric neurological emergency. Immediate treatment is essential to prevent definitive neurological damage. Several antiepileptic drugs are available for the management of status epilepticus.
METHODS
Retrospective study of patients admitted at the emergency department of a tertiary hospital for 5 years (2014-2019). We analyzed the compliance to the treatment guidelines for pediatric status epilepticus.
RESULTS
One hundred and seventeen admissions were identified, 23.9% of these were febrile status epilepticus. Among the other cases, the most frequent cause was genetic (22.2%). The majority were convulsive status epilepticus (93.1%), 58.7% of which were generalized tonic-clonic seizures. Benzodiazepines were the most used first and second line drug (98.2% and 94.8%). The most frequent third drug used was diazepam (56.4%) followed by phenytoin (18.2%). An infra-therapeutic antiepileptic drug dose was given in 48.7% of cases. 49.6% presented with a prolonged status epilepticus and 6.8% needed intensive care. Incorrect sequence of drugs and infra-therapeutic doses were associated with prolonged status (p<0.001 and p<0.05) and an increased number of antiepileptic drugs used (p<0.001 and p<0.05).
CONCLUSIONS
Benzodiazepines were the most frequently first and second line drugs used for status epilepticus management. Surprisingly, the most frequently third line drugs used were also benzodiazepines. These findings were partially explained by the misuse of infra-therapeutic doses of these drugs. Noncompliance with the implemented guidelines was associated with unfavorable outcomes.
Topics: Humans; Status Epilepticus; Anticonvulsants; Retrospective Studies; Female; Male; Emergency Service, Hospital; Child; Child, Preschool; Infant; Benzodiazepines; Guideline Adherence; Adolescent; Diazepam
PubMed: 38830721
DOI: 10.1016/j.nrleng.2021.09.014