Acetaminophen (APAP) known as paracetamol is the main ingredient in Tylenol, which has analgesic and anti-pyretic properties. Inappropriate use of APAP causes major morbidity and mortality secondary to hepatic failure. Overdose of APAP depletes the hepatic glutathione (GSH) rapidly, and the metabolic intermediate leads to hepatocellular death. This article reviews the mechanisms of hepatotoxicity and provides an overview of current research studies. Pharmacokinetics including metabolism (activation and detoxification), subsequent transport (efflux)-facilitating excretion, and some other aspects related to toxicity are discussed. Nuclear factor erythroid 2-related factor 2 (Nrf2)-regulated gene battery plays a critical role in the multiple steps associated with the mitigation of APAP toxicity. The role of Nrf2 as a protective target is described, and potential natural products inhibiting APAP toxicity are outlined. This review provides an update on the mechanism of APAP toxicity and highlights the beneficial role of Nrf2 and specific natural products in hepatoprotection.
Acetaminophen* ; Biological Agents ; Glutathione ; Liver Failure ; Metabolism ; Mortality ; Pharmacokinetics

PURPOSE: E2F-1 is a transcriptor that converts G1 to S in the cell cycle, and Topoisomerase II-alpha is a key enzyme in the metabolism of DNA, and an indicator of cell replication. The purpose of this study was to evaluate the clinical validity of E2F-1 and Topoisomerase II-alpha as prognostic factors in colorectal cancer. METHODS: The expressions of E2F-1 and Topoisomerase II-alpha were studied immunohistochemically using tumor specimen sections fixed with formalin and paraffin-embedded for 84 cases of colorectal cancer. The correlation between E2F-1 and Topoisomerase II-alpha expressions, and their relationship with the clinicopathological factors, such as tumor differentiation, tumor invasion, lymph node metastasis and tumor stage were investigated. RESULTS: Of the 84 specimens, 43 (51.2%) were immunohistochemically negative for E2F-1, and 41 (48.8%) were positive. The expression of E2F-1 correlated with poor tumor differentiation, increased lymph node metastasis and high tumor stage. The expression of Topoisomerase II-alpha also correlated with poor tumor differentiation, increased lymph node metastasis and high tumor stage. The E2F-1 and Topoisomerase II-alpha expressions indices were significantly correlated. CONCLUSION: These results suggest that the expressions of E2F-1 and DNA Topoisomerase II-alpha may play a role as a prognostic factor for colorectal cancer, but further studies will be required for its comfirmation.
Cell Cycle ; Colorectal Neoplasms* ; DNA ; DNA Topoisomerases, Type I* ; Formaldehyde ; Lymph Nodes ; Metabolism ; Neoplasm Metastasis

Cervicogenic headache is a syndrome characterized by chronic hemicranial pain referred to the head from either bony structures or soft tissues of the neck. Although the pathophysiology and source of pain in this condition have been debated, the pain is believed to be referred from one or more muscles, occipital nerves, facet joints, intervertebral discs, or vascular structures. Among the various possible pain sources, cervicogenic headache from discogenic origin (disc herniation or damaged annulus fibrosus) has been called "discogenic cervical headache". We report a case of cervicogenic headache caused by C3-C4 intervertebral disc herniation. A 33-year-old man presented with headache and posterior neck and right shoulder pain. These symptoms did not improve after therapy with medication, trigger point injection, intramuscular stimulation, greater occipital nerve block, third occipital nerve block, or cervical medial branch block. However, after diagnostic cervical epidural block, the patient's symptoms improved dramatically. Diagnostic magnetic resonance imaging findings confirmed C3-C4 intervertebral disc herniation.
Adult ; Head ; Headache ; Humans ; Injections, Intramuscular ; Intervertebral Disc ; Magnetic Resonance Imaging ; Muscles ; Neck ; Nerve Block ; Post-Traumatic Headache ; Shoulder Pain ; Trigger Points ; Zygapophyseal Joint

Blotting, Western ; Conjunctival Diseases ; Dry Eye Syndromes ; Epithelial Cells ; Fluorescent Antibody Technique ; Humans ; Immunohistochemistry ; Inflammation ; Interleukin-6 ; Necrosis ; Phosphorylation ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Tears ; Tumor Necrosis Factor-alpha ; Wounds and Injuries

Background: Data on liver cirrhosis (LC) patients undergoing continuous renal replacement therapy (CRRT) are lacking despite the dismal prognosis. We therefore evaluated clinical characteristics and predictive factors related to mortality in LC patients undergoing CRRT. Methods: We performed a retrospective observational study at two tertiary hospitals in Korea. A total of 229 LC patients who underwent CRRT were analyzed. Patients were classified into survivor and non-survivor groups. We used multivariable Cox regression analyses to identify factors predictive of in-hospital mortality. Results: During a median follow-up of 5 days (interquartile range, 1–19 days), in-hospital mortality rate was 66.4%. In multivariable analysis, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.01–1.06; p = 0.02), Model for End-Stage Liver Disease (MELD) score (HR, 1.08; 95% CI, 1.04–1.11; p <0.001), and delivered CRRT dose (HR, 0.95; 95% CI, 0.92¬–0.98; p = 0.002) were significant risk factors for in-hospital mortality. Patients with a CRRT delivered dose < 25 mL/kg/hr had a higher mortality rate than those with a delivered dose > 35 mL/kg/hr (HR, 3.13; 95% CI, 1.62–6.05; p = 0.001). Subgroup analysis revealed that a CRRT delivered dose < 25 mL/kg/hr was a significant risk factor for in-hospital mortality among LC patients with a MELD score ≥ 30. Conclusion High APACHE II score, high MELD score, and low delivered CRRT dose were significant risk factors for in-hospital mortality. CRRT delivered dose impacted mortality significantly, especially in patients with a MELD score ≥ 30.