- Acetaminophen-induced Liver Injury is Attenuated in Transgenic fat-1 Mice Endogenously Synthesizing Long-chain n-3 Fatty Acids. [Journal Article]
- BPBiochem Pharmacol 2018 Apr 18
- Acetaminophen (APAP) overdose-caused hepatotoxicity is the most commonly cause of drugs-induced liver failurecharacterized by oxidative stress, mitochondrial dysfunction, and cell damage. Therapeutic...
Acetaminophen (APAP) overdose-caused hepatotoxicity is the most commonly cause of drugs-induced liver failurecharacterized by oxidative stress, mitochondrial dysfunction, and cell damage. Therapeutic efficacy of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in several models of liver disease is well documented. However, the impacts of n-3 PUFA on APAP hepatotoxicity are not adequately addressed. In this study, the fat-1 transgenic mice that synthesize endogenous n-3 PUFA and wild type (WT) littermates were injected intraperitoneally with APAP at the dose of 400 mg/kg to induce liver injury, and euthanized at 0 h, 2 h, 4 h and 6 h post APAP injection for sampling. APAP overdose caused severe liver injury in WT mice as indicated by serum parameters, histopathological changes and hepatocyte apoptosis, which were remarkably ameliorated in fat-1 mice. These protective effects of n-3 PUFA were associated with regulation of the prolonged JNK activation via inhibition of apoptosis signal-regulating kinase 1 (ASK1) / mitogen-activated protein kinase kinase 4 (MKK4) pathway. Additionally, the augment of endogenous n-3 PUFA reduced nuclear factor kappa B (NF-κB) - mediated inflammation response induced by APAP treatment in the liver. These findings indicate that n-3 PUFA has potent protective effects against APAP-induced acute liver injury, suggesting that n-3 dietary supplement with n-3 PUFA may be a potential therapeutic strategy for the treatment of hepatotoxicity induced by APAP overdose.
- Cyclooxygenase-1 and -2 Play Contrasting Roles in Listeria-Stimulated Immunity. [Journal Article]
- JIJ Immunol 2018 Apr 20
- Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) activity and are commonly used for pain relief and fever reduction. NSAIDs are used following childhood vaccinations and can...
Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) activity and are commonly used for pain relief and fever reduction. NSAIDs are used following childhood vaccinations and cancer immunotherapies; however, how NSAIDs influence the development of immunity following these therapies is unknown. We hypothesized that NSAIDs would modulate the development of an immune response to Listeria monocytogenes-based immunotherapy. Treatment of mice with the nonspecific COX inhibitor indomethacin impaired the generation of cell-mediated immunity. This phenotype was due to inhibition of the inducible COX-2 enzyme, as treatment with the COX-2-selective inhibitor celecoxib similarly inhibited the development of immunity. In contrast, loss of COX-1 activity improved immunity to L. monocytogenes Impairments in immunity were independent of bacterial burden, dendritic cell costimulation, or innate immune cell infiltrate. Instead, we observed that PGE2 production following L. monocytogenes is critical for the formation of an Ag-specific CD8+ T cell response. Use of the alternative analgesic acetaminophen did not impair immunity. Taken together, our results suggest that COX-2 is necessary for optimal CD8+ T cell responses to L. monocytogenes, whereas COX-1 is detrimental. Use of pharmacotherapies that spare COX-2 activity and the production of PGE2 like acetaminophen will be critical for the generation of optimal antitumor responses using L. monocytogenes.
- Effective Postoperative Analgesia Using Intravenous Flurbiprofen and Acetaminophen. [Journal Article]
- JOJ Oral Maxillofac Surg 2018 Mar 28
- CONCLUSIONS: Although recovery time in the operating room of the flurbiprofen and acetaminophen group was markedly shorter than that of the flurbiprofen and fentanyl group, the postoperative analgesic effects of the 2 drugs were equipotent. Therefore, acetaminophen can be an alternative to fentanyl in cases in which narcotic drugs are contraindicated.
- Impact of Intravenous Acetaminophen on Perioperative Opioid Utilization and Outcomes in Open Colectomies: A Claims Database Analysis. [Journal Article]
- AAnesthesiology 2018 Apr 20
- CONCLUSIONS: The demonstrated marginal effects do not support routine use of intravenous acetaminophen given alternative nonopioid analgesic options.
- Intravenous acetaminophen for postoperative supratentorial craniotomy pain: a prospective, randomized, double-blinded, placebo-controlled trial. [Journal Article]
- JNJ Neurosurg 2018 Apr 20; :1-7
- CONCLUSIONS: Patients who received postoperative IV acetaminophen after craniotomy did not have significantly decreased narcotic consumption but did experience significantly lower pain scores after surgery. The drug was well tolerated and safe in this patient population. Clinical trial registration no.: NCT01948505 (clinicaltrials.gov).
- Catastrophic circulatory collapse after inadvertent subcutaneous injection of treprostinil. [Journal Article]
- AJAm J Health Syst Pharm 2018 Apr 19
- CONCLUSIONS: A 29-year-old, 76-kg woman with group 1 pulmonary arterial hypertension managed with subcutaneous treprostinil infusion arrived at the emergency department (ED) with headache, nausea, vomiting, and a syncopal episode. Her vital signs were stable on presentation. Admission orders were placed, and the appropriate 3-mL syringe containing 7.5 mg of treprostinil intended for use with the patient's home microinfusion pump was sent from inpatient pharmacy to the ED. The order in the electronic medical record stated to administer treprostinil as a subcutaneous injection rather than an infusion. The patient's nurse transferred the 7.5 mg (3 mL) of undiluted treprostinil to a standard syringe and administered it as a single subcutaneous injection. Within minutes the patient experienced cardiovascular collapse, with a blood pressure nadir of 50/20 mm Hg. Aggressive resuscitation measures were immediately implemented. Initial management included fluids, bolus-dose vasopressors, multiple high-dose vasopressor infusions, ondansetron, acetaminophen, and loperamide. Hemodynamic stability was achieved, and vasopressors were discontinued 16 hours after the overdose event. Subcutaneous treprostinil was restarted at a reduced dose 12 hours after the overdose event and was adjusted to the patient's home dose 24 hours after the initial event. She was discharged in stable condition 30 hours after the overdose event.A patient who received an inadvertent overdose of subcutaneous treprostinil experienced cardiovascular collapse requiring aggressive resuscitation measures. Successful management of the patient was largely supportive, including fluids, bolus-dose vasopressors, multiple high-dose vasopressor infusions, ondansetron, acetaminophen, and loperamide.
- Reduced graphene oxide-supported gold dendrite for electrochemical sensing of acetaminophen. [Journal Article]
- TTalanta 2018 Jul 01; 184:244-250
- A new nanocomposite was developed based on reduced graphene oxide (RGO) supported gold dendrite and applied for amperometric detection of acetaminophen. The RGO-gold dendrite composite was prepared b...
A new nanocomposite was developed based on reduced graphene oxide (RGO) supported gold dendrite and applied for amperometric detection of acetaminophen. The RGO-gold dendrite composite was prepared by self-assembly of poly (diallyldimethylammonium chloride) (PDDA) functionalized gold dendrite and poly (sodium 4-styrenesulfonate) (PSS) functionalized RGO. The composite electrode material was characterized by Scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), Ultraviolet-vis spectroscopy (UV), X-ray diffraction (XRD), Raman spectroscopy and X-ray photoelectron spectroscopy (XPS). The RGO-gold dendrite composite exhibited enhanced conductivity, catalytic activity and stability for acetaminophen oxidation and determination. The RGO-gold dendrite based electrochemical sensor is competent for detecting acetaminophen with a linear range from 0.07 µM to 3000 µM with a detection limit of 0.005 µM (S/N = 3). Moreover, the sensor was applied for the detection of acetaminophen in tablets and urine samples, which holds great promise in pharmaceutical analysis.
- Effects of opioid- and non-opioid analgesics on responses to psychosocial stress in humans. [Journal Article]
- HBHorm Behav 2018 Apr 16
- Both preclinical and clinical evidence suggests that the endogenous opioid system is involved in responses to stress. For example, in animal models opioid agonists reduce isolation distress whereas o...
Both preclinical and clinical evidence suggests that the endogenous opioid system is involved in responses to stress. For example, in animal models opioid agonists reduce isolation distress whereas opioid antagonists increase isolation distress. We recently reported that the mixed mu agonist and kappa antagonist buprenorphine dampened responses to acute psychosocial stress in humans. Now we extend this to study the effects of a pure mu-opioid agonist, hydromorphone, and a non-opioid analgesic, acetaminophen, on response to social stress. We compared the effect of hydromorphone (2 and 4 mg), acetaminophen (1000 mg) to a placebo using a between subject design. Healthy adult volunteers were randomly assigned to receive placebo (N = 13), 2 mg hydromorphone (N = 12), 4 mg hydromorphone (N = 12), or 1000 mg acetaminophen (paracetamol; N = 13) under double-blind conditions before undergoing a stress task or a control task on two separate sessions. The stress task, consisting of a standardized speaking task and the non-stressful control task were presented in counterbalanced order. Dependent measures included mood ratings, subjective appraisal of the stress (or no-stress) task, salivary cortisol, pupil diameter, heart rate, and blood pressure. The stress task produced its expected increase in heart rate, blood pressure, salivary cortisol, pupil diameter, and subjective ratings of anxiety and negative mood. Hydromorphone dose-dependently dampened cortisol responses to stress, and decreased ratings of how "challenging" participants found the task. Acetaminophen did not affect physiological responses, but, like hydromorphone, decreased ratings of how "challenging" the task was. The hydromorphone results support the idea that the mu-opioid system is involved in physiological responses to acute stress in humans, in line with results from preclinical studies. The non-opioid analgesic acetaminophen did not dampen physiological responses, but did reduce some components of psychological stress. It remains to be determined how both opioid and non-opioid systems mediate the complex physiological and psychological responses to social stress.
- Acute Migraine Headache: Treatment Strategies. [Journal Article]
- AFAm Fam Physician 2018 Feb 15; 97(4):243-251
- Migraine is a primary headache disorder characterized by recurrent attacks. Acetaminophen, nonsteroidal anti-inflammatory drugs, triptans, antiemetics, ergot alkaloids, and combination analgesics hav...
Migraine is a primary headache disorder characterized by recurrent attacks. Acetaminophen, nonsteroidal anti-inflammatory drugs, triptans, antiemetics, ergot alkaloids, and combination analgesics have evidence supporting their effectiveness in the treatment of migraine. Acetaminophen and nonsteroidal anti-inflammatory drugs are first-line treatments for mild to moderate migraines, whereas triptans are first-line treatments for moderate to severe migraines. Although triptans are effective, they may be expensive. Other medications such as dihydroergotamine and antiemetics are recommended for use as second- or third-line therapy for select patients or for those with refractory migraine. The pharmacologic properties, potential adverse effects, cost, and routes of administration vary widely, allowing therapy to be individualized based on the pattern and severity of attacks. Several treatment principles, including taking medication early in an attack and using a stratified treatment approach, can help ensure that migraine treatment is cost-effective.
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- Ibuprofen Plus Acetaminophen Equals Opioid Plus Acetaminophen for Acute Severe Extremity Pain. [Journal Article]
- AFAm Fam Physician 2018 Mar 01; 97(5):348