- Combination pharmacotherapy for the treatment of fibromyalgia in adults. [Review]
- CDCochrane Database Syst Rev 2018 Feb 19; 2:CD010585
- CONCLUSIONS: There are few, large, high-quality trials comparing combination pharmacotherapy with monotherapy for fibromyalgia, consequently limiting evidence to support or refute the use of combination pharmacotherapy for fibromyalgia.
- EXTRAHEPATIC TOXICITY OF ACETAMINOPHEN: CRITICAL EVALUATION OF THE EVIDENCE AND PROPOSED MECHANISMS. [Journal Article]
- JCJ Clin Transl Res 2018 Jan 15; 3(3)
- Research on acetaminophen (APAP) toxicity over the last several decades has focused on the pathophysiology of liver injury, but increasing attention is being paid to other known and possible adverse ...
Research on acetaminophen (APAP) toxicity over the last several decades has focused on the pathophysiology of liver injury, but increasing attention is being paid to other known and possible adverse effects. It has been known for decades that APAP causes acute kidney injury, but confusion exists regarding prevalence, and the mechanisms have not been well investigated. More recently, a number of experimental, clinical and epidemiological studies have reported evidence for pulmonary, endocrine, neurological and neurodevelopmental toxicity, but the quality of evidence from those studies varies. It is important to consider these data due to implications for regulation and clinical practice. Here, we review the evidence and proposed mechanisms for extrahepatic adverse effects of APAP and weigh weaknesses and strengths in the data. We consider results from clinical, epidemiological and experimental research. Our goal is to determine the strength of claims regarding extrahepatic toxicity of APAP and to identify areas of need for future research. It is especially important to view claims of developmental effects of antenatal APAP exposure with a critical eye because APAP is currently the only over-the-counter medication recommended for pregnant women to self-treat pain and fever.
- Japanese traditional herbal medicine reduces use of pregabalin and opioids for pain in patients with lumbar spinal canal stenosis: a retrospective cohort study. [Journal Article]
- JCJA Clin Rep 2017; 3(1):60
- CONCLUSIONS: Kampo led to discontinuation of opioid use for pain in patients with LSCS, and patients who were treated with Kampo were more likely to continue treatment.
- Anesthetic management of a patient with narcolepsy by combination of total intravenous and regional anesthesia: a case report. [Journal Article]
- JCJA Clin Rep 2017; 3(1):37
- Narcolepsy is a neurological disease characterized by excessive daytime sleepiness, cataplexy, and/or a sudden loss of muscle tone due to malfunction of the orexinergic system, which may cause delaye...
Narcolepsy is a neurological disease characterized by excessive daytime sleepiness, cataplexy, and/or a sudden loss of muscle tone due to malfunction of the orexinergic system, which may cause delayed emergence from general anesthesia. We report a successful anesthetic management of 24-year-old female narcoleptic patient undergoing left anterior cruciate ligament reconstruction. Anesthesia was induced and maintained with total intravenous anesthesia (TIVA) using propofol and remifentanil. Ultrasound-guided left femoral nerve block was also performed with 0.375% ropivacaine 20 ml. Acetaminophen 1000 mg was intravenously administered as part of a multimodal analgesia. After the surgery, the trachea was extubated 9 min after termination of TIVA, and then, the patient correctly responded to verbal commands. The postoperative course was uneventful without any narcoleptic symptoms.
- A case of a warfarinized renal cancer patient monitored for prothrombin time-international normalized ratio during methadone introduction. [Journal Article]
- JCJA Clin Rep 2017; 3(1):35
- CONCLUSIONS: In an oral warfarinized patient, methadone seemed to undergo different metabolism than oxycodone. When warfarin and methadone are used together, we have to consider their interaction by comparing the competitive inhibition of CYP2C9 to the induction of CYP3A4 by methadone, because CYP3A4 metabolize various drugs including oxycodone.
- Plasminogen Activator Inhibitor-1 Reduces tPA-Dependent Fibrinolysis and Intrahepatic Hemorrhage in Experimental Acetaminophen Overdose. [Journal Article]
- AJAm J Pathol 2018 Feb 15
- Acetaminophen (APAP)-induced liver injury in mice is associated with activation of the coagulation cascade and deposition of fibrin in liver. Plasminogen activator inhibitor-1 (PAI-1) is an important...
Acetaminophen (APAP)-induced liver injury in mice is associated with activation of the coagulation cascade and deposition of fibrin in liver. Plasminogen activator inhibitor-1 (PAI-1) is an important physiological inhibitor of tissue-type plasminogen activator (tPA) and plays a critical role in fibrinolysis. PAI-1 expression is increased in both experimental APAP-induced liver injury and patients with acute liver failure. Prior studies have shown that PAI-1 prevents intrahepatic hemorrhage and mortality after APAP challenge, but the downstream mechanisms are not clear. We tested the hypothesis that PAI-1 limits liver-related morbidity after APAP challenge by reducing tPA-dependent fibrinolysis. Compared to APAP-challenged (300 mg/kg) wild-type mice, hepatic deposition of cross-linked fibrin was reduced, with intrahepatic congestion and hemorrhage increased in PAI-1-deficient mice 24 hours after APAP overdose. Administration of recombinant wild-type human PAI-1 reduced intrahepatic hemorrhage 24 hours after APAP challenge in PAI-1-/-mice, whereas a mutant PAI-1 lacking antiprotease function had no effect. Interestingly, tPA deficiency alone did not affect APAP-induced liver damage. In contrast, fibrinolysis, intrahepatic congestion and hemorrhage, and mortality driven by PAI-1 deficiency were reduced in APAP-treated tPA-/-/PAI-1-/-double knockout mice. The results identify PAI-1 as a critical regulator of intrahepatic fibrinolysis in experimental liver injury. Moreover, the results suggest that the balance between PAI-1 and tPA activity is an important determinant of liver pathology after APAP overdose.
- The effect of tube versus bottle feeding colostrum on immunoglobulin G absorption, abomasal emptying, and plasma hormone concentrations in newborn calves. [Journal Article]
- JDJ Dairy Sci 2018 Feb 14
- The objective of this study was to determine if feeding colostrum to newborn calves through an esophageal tube, compared with a nipple bottle, would delay abomasal emptying, which would in turn decre...
The objective of this study was to determine if feeding colostrum to newborn calves through an esophageal tube, compared with a nipple bottle, would delay abomasal emptying, which would in turn decrease passive transfer of IgG and plasma glucose, insulin, and glucagon-like peptide (GLP) 1 and GLP-2 concentrations. Twenty newborn Holstein bull calves were fed 3 L of colostrum replacer (200 g of IgG) through either an esophageal tube or nipple bottle at 2 h after birth followed by feeding pooled whole milk every 12 h after birth. Acetaminophen was mixed into the colostrum meal as a marker for abomasal emptying. A jugular catheter was inserted 1 h after birth and blood was sampled frequently to analyze serum for IgG and acetaminophen and plasma for glucose, insulin, GLP-1, and GLP-2. Feeding method did not affect abomasal emptying, and as a result no treatment effect was present on serum IgG concentrations. Maximum concentration of serum IgG was 24.4 ± 0.40 mg/mL (± standard error), which was reached at 14.6 ± 1.88 h after the colostrum meal for both groups. Apparent efficiency of absorption at maximum concentration of IgG was 52.9%, indicating high efficiency of passive transfer of IgG for both treatments. Tube feeding increased glucose and insulin area under the curve before the first milk meal, most likely due to the decreased time to consume the colostrum meal. In addition, tube-fed calves consumed 0.5 ± 0.13 L more milk in their first milk meal than bottle-fed calves. No treatment effect on plasma concentrations of GLP-1 or GLP-2 was present, but both hormones increased after colostrum feeding. These findings confirm that there is no effect on absorption of IgG from colostrum when feeding good-quality colostrum at a volume of 3 L through either an esophageal tube or nipple bottle.
- Postoperative pain and analgesia administration in children after urological outpatient procedures. [Journal Article]
- JPJ Pediatr Urol 2018 Jan 31
- CONCLUSIONS: The combination of scheduled non-opioid medications for maintenance and opioids for breakthrough pain provided satisfactory pain control after outpatient urologic surgery in children. There were no specific patient, anesthetic or surgical factors that predicted postoperative opioid requirements.
- Preoperative pain measures ineffective in outpatient abdominal surgeries. [Journal Article]
- AJAm J Surg 2018 Feb 06
- CONCLUSIONS: The results call into question the efficacy of the American Pain Society recommendations as they increase time in recovery room but do not decrease the quantity of narcotics used in the recovery room, nor do they improve pain satisfaction responses.
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- SIRT2 regulates oxidative stress-induced cell death through deacetylation of c-Jun NH2-terminal kinase. [Journal Article]
- CDCell Death Differ 2018 Feb 15
- c-Jun NH2-terminal kinases (JNKs) are responsive to stress stimuli and their activation regulate key cellular functions, including cell survival, growth, differentiation and aging. Previous studies d...
c-Jun NH2-terminal kinases (JNKs) are responsive to stress stimuli and their activation regulate key cellular functions, including cell survival, growth, differentiation and aging. Previous studies demonstrate that activation of JNK requires dual phosphorylation by the mitogen-activated protein kinase kinases. However, other post-translational mechanisms involved in regulating the activity of JNK have been poorly understood. In this work, we studied the functional significance of reversible lysine acetylation in regulating the kinase activity of JNK. We found that the acetyl transferase p300 binds to, acetylates and inhibits kinase activity of JNK. Using tandem mass spectrometry, molecular modelling and molecular dynamics simulations, we found that acetylation of JNK at Lys153 would hinder the stable interactions of the negatively charged phosphates and prevent the adenosine binding to JNK. Our screening for the deacetylases found SIRT2 as a deacetylase for JNK. Mechanistically, SIRT2-dependent deacetylation enhances ATP binding and enzymatic activity of JNK towards c-Jun. Furthermore, SIRT2-mediated deacetylation favours the phosphorylation of JNK by MKK4, an upstream kinase. Our results indicate that deacetylation of JNK by SIRT2 promotes oxidative stress-induced cell death. Conversely, SIRT2 inhibition attenuates H2O2-mediated cell death in HeLa cells. SIRT2-deficient (SIRT2-KO) mice exhibit increased acetylation of JNK, which is associated with markedly reduced catalytic activity of JNK in the liver. Interestingly, SIRT2-KO mice were resistant to acetaminophen-induced liver toxicity. SIRT2-KO mice show lower cell death, minimal degenerative changes, improved liver function and survival following acetaminophen treatment. Overall, our work identifies SIRT2-mediated deacetylation of JNK as a critical regulator of cell survival during oxidative stress.