BACKGROUND AND OBJECTIVES: Contrast-induced nephropathy (CIN) is associated with increased morbidity and mortality in coronary angiography. Although the mechanism is unclear, N-acetylcysteine (NAC) is known to protect against CIN. Preliminary studies with NAC have found conflicting results for the prevention of CIN in patients undergoing coronary angiography. This study was designed to evaluate the efficacy and safety of NAC for the prevention of CIN in patients undergoing coronary angiography. SUBJECTS AND METHODS: 48 patients with chronic renal insufficiency (mean [+/-SD] serum creatinine concentration, 2.06+/-0.56 mg/dL), who were undergoing coronary angiography with a nonionic, low-osmolar contrast agent, were prospectively studied. Patients were randomly assigned to receive either the antioxidant, NAC (600 mg orally twice daily), and 0.45% saline intravenously (n=25), before and after administration of contrast agents, or saline only (n=23). The renal function parameters were assessed 48 hour before and after radiocontrast media administration. RESULTS: 14 of the 48 patients (29%) showed an increase in the 0.5 mg/dL serum creatinine concentration after 48 hours of contrast media administration: 4 of the 25 patients in the NAC group (16%) and 10 of the 23 in the control group (43%; p=0.036; relative risk, 0.37; 95% confidence interval, 1.04 to 7.79). In the NAC group, the mean serum creatinine concentration insignificantly increased (p=0.54), from 2.2+/-0.8 to 2.3+/-0.9 mg/dL, after 48 hours of contrast media administration; whereas, in the control group, the mean serum creatinine concentration significantly increased (p=0.011), from 1.9+/-0.4 to 2.2+/-0.8 mg/dL. The absolute change in serum creatinine concentration was significantly greater in the control than the NAC group (p=0.044). CONCLUSION: Prophylactic oral administration of the antioxidant NAC, along with hydration, prevents the decrease in the renal function induced by a nonionic, low-osmolality contrast agent in patients with chronic renal insufficiency.
Acetylcysteine* ; Administration, Oral ; Contrast Media ; Coronary Angiography* ; Creatinine ; Humans ; Mortality ; Prospective Studies ; Renal Insufficiency, Chronic

PURPOSE: Serious acetaminophen (AAP) poisoning causes hepatotoxicity. N-acetylcysteine (NAC) is the most effective therapy for AAP poisoning and can be administered orally and intravenously (IV). Several studies have compared the efficacy of these two routes of administration and the results have been controversial. The purpose of this study was to compare the efficacy of oral and IV NAC for the prevention of hepatic toxicity in Korean patients whose serum AAP levels were higher than normal. METHODS: A retrospective before/after study was performed, in which the patients presented to the emergency department with an AAP overdose from February 1995 to March 2012. A 3-day oral NAC regimen was used in the beginning, and a 20-hr intravenous regimen was then used from 2007. This study assessed the complications of an AAP overdose, such as hepatotoxicity, hepatic failure and renal failure as well as the side effects of the treatment regimen. RESULTS: A total of 41patients was enrolled in this study. The median ALT and AST were 63 (IU/L) and 57 (IU/L) for the oral NAC treated patients, and 14 (IU/L) and 20 (IU/L) for the IV NAC treated patients (p=0.004 and p=0.001, respectively). The incidence of complications was similar in the treatment groups (p=0.399). Among the patients, 7 patients developed hepatotoxicity and were treated successfully with oral or IV NAC. CONCLUSION: This study suggests that IV NAC and oral NAC can prevent and successfully treat hepatic toxicity in patients whose serum AAP levels are higher than normal.
Acetaminophen ; Acetylcysteine ; Administration, Intravenous ; Emergencies ; Humans ; Incidence ; Liver Failure ; Oligopeptides ; Renal Insufficiency ; Retrospective Studies

PURPOSE: The purpose of this study was to develop therapeutic decision guidelines on N-acetylcysteine (NAC) treatment for acetaminophen (AAP) overdose in a situation where a serum level determination is not available within 8 hours. METHODS: We reviewed retrospectively the medical records of patients admitted for AAP overdose from January 2001 to February 2004. Forty-nine patients met inclusion criteria; patients with acute AAP overdose who were exposed to 7.5 g or 140 mg/kg or greater, determination of the serum level was not available within 8 hours, and NAC treatment was started empirically before identification of the serum level. The patients had been treated with a 72hour oral or a 20hour intravenous (IV) NAC treatment protocol. RESULTS: Patients were classified into an Oral NAC (n=24) group and an IV NAC (n=25) group based on the treatment protocol. There were no significant intergroup differences in patient characteristics, time variables, distribution of risk categories, and hepatotoxicity. All the patients in both toxic groups were fully recovered, and the difference in the number of adverse reactions during NAC treatment were not significant between the two groups (Oral NAC vs IV NAC, 4 (16%) vs. 2 (8%), respectively; p=0.417). The numbers of patients who discontinued the NAC treatment were 14 (58%) in the Oral NAC group and 8 (32%) in the IV NAC group (p=0.088). The six patients in the nontoxic category of IV NAC group were already completed before determination of the serum level. CONCLUSION: Therapeutic decisions for AAP overdose which are based entirely on ingestion history have some limitations. IV NAC is as effective as oral treatment for patients with acute AAP overdose. If the serum level is not available within 8 hours, the clinician should preventively administer the first dose of oral NAC to patients without severe vomiting. Subsequently, when the serum level is determined, the need for additional therapy should be determined to reduce unnecessary use of NAC. However, if the patients present with severe vomiting or contraindications to oral treatment, intravenous administration is required.
Acetaminophen* ; Acetylcysteine* ; Administration, Intravenous ; Clinical Protocols ; Eating ; Humans ; Medical Records ; Retrospective Studies ; Vomiting

Acetaminophen ; administration & dosage ; poisoning ; Acetylcysteine ; administration & dosage ; pharmacology ; therapeutic use ; Brunei ; Drug Overdose ; drug therapy ; physiopathology ; Humans

BACKGROUND: The purpose of this study was to determine the adequate loading and maintenance doses of N-acetylcyseteine (NAC) for patients suffering from acute ROS-induced injury. METHODS: Concentrations of extra cellular NAC, cysteine (Cys), cystine (Cyst2), and methionine (Met) were measured in vitro, at which more than 50% of the intracellular ROS raised by paraquat were suppressed using Swiss 3T3 fibroblasts. An in vivo pharmacokinetic study followed on a healthy subject to determine the proper loading and maintenance doses of reduced NAC following intravenous administration of 25 mg/kg NAC. RESULTS: In vivo, NAC suppressed ROS in a dose dependant manner. 10 mM of NAC suppressed about 50% of ROS, and was comparable to 10 micro M of Cys and Met and 400 micro M of Cys2. In vitro, the elimination of half-life was achieved at 2.88+/-1.14 h for NAC and at 3.68+/-1.84 h for total NAC. The body clearances were 1.23+/-0.77 L h (-1) kg (-1) and 0.56+/-0.27 L h (-1) kg (-1) and the volumes of distribution were 3.07+/-0.10 L kg (-1) and 3.00+/-0.11 L kg (-1), respectively. The loading and maintenance NAC doses used to reach the target concentration of 10 mM, were 5010 mg. kg (-1) and 2250 mg min (-1) kg (-1), respectively. CONCLUSION: NAC provides an antioxidant effect on ROS produced by paraquat in vivo. However, in vitro, our results showed that the intravenous NAC dose could not be estimated from NAC plasma concentration or its metabolites.
Sulfur/*blood ; Reactive Oxygen Species ; Humans ; Glutathione/blood ; Amino Acids/*blood/chemistry ; Acetylcysteine/*administration & dosage/pharmacokinetics/pharmacology

Curcumin( Cur) is a natural active substance extracted from the roots or tubers of traditional Chinese medicinal materials. It has anti-inflammatory and anti-tumor activities on brain diseases. Due to the poor stability,low solubility,poor absorption and low bioavailability of curcumin,N-acetyl-L-cysteine( NAC) was used as an absorption enhancer and mixed with curcumin to improve the absorption of curcumin in the body. In this paper,curcumin was smashed by airflow pulverization,and Cur-NAC mixtures were prepared by being grinded with liquid. Then,the raw material and the product were analyzed by differential scanning calorimetry( DSC),X-ray diffraction( XRD) for structural characterization. The dissolution was determined by high performance liquid chromatography( HPLC) analysis. The characteristic peaks of the samples prepared by grinding method were similar to those of the raw materials,while the melting temperature and the accumulated dissolution degree were not significantly changed. The crystal forms of the products were not changed,and no new crystal form was formed after grinding. After the administration of intranasal powder,blood samples were collected from the orbit,while the whole brain tissues were removed from the skull and dissected into 10 anatomical regions. The concentrations of curcumin in these samples were determined by UPLC-MS/MS. The concentrations of curcumin in plasma and brain were compared at different time points. After intranasal administration of two drugs,it was found that the concentration of curcumin after sniffing up the mixtures in plasma was high,and the concentration of the drug in the olfactory bulb,hippocampus,and pons was increased significantly. Within 0. 083-0. 5 h,the olfactory bulb,piriform lobe and hippocampus remained high concentrations,the endodermis,striatum,hypothalamus and midbrain reached high concentrations within 1-3 h; and the cerebellum,pons and brain extension maintained relatively high concentrations within 3-7 h. The experiment showed that nasal administration of Cur-NAC mixtures can significantly improve the bioavailability of curcumin,and lead to significant differences in brain tissue distribution.
Acetylcysteine ; pharmacology ; Administration, Intranasal ; Animals ; Biological Availability ; Brain ; Brain Chemistry ; Chromatography, Liquid ; Curcumin ; pharmacokinetics ; Rats ; Tandem Mass Spectrometry ; Tissue Distribution

OBJECTIVE: To evaluate the protective effects of oral administration of N-acetyl-cysteine (NAC) on noise-induced hearing loss. METHOD: Three hundred sixty three volunteers were recruited and randomly divided into two groups: experimental group (n=223) and control group (n=140). The subjects had received oral administration of NAC in the experimental group and placebo in the control group before noise exposure. The routine audiometric evaluation and ABR testing were performed and recorded pre- and post-noise exposure. The statistical analysis was carried out on the data obtained from two groups with SPSS 11.0. RESULT: The hearings of all the participatory were changed after noise exposure, but there were statistically significant differences between two groups. CONCLUSION The protective effects of NAC were prominent on the noise-induced hearing loss.
Acetylcysteine ; administration & dosage ; therapeutic use ; Adult ; Hearing Loss, Noise-Induced ; drug therapy ; prevention & control ; Humans ; Male ; Military Personnel ; Young Adult

INTRODUCTIONParacetamol overdose is the most common drug overdose worldwide. To our knowledge, the maximum number of paracetamol tablets ingested reported in the literature is 45 g.

CLINICAL PICTUREWe describe a 21-year-old patient who acutely ingested 120 tablets, each 500 mg paracetamol (i.e., 60 g equivalent to 1200 mg/kg body weight) in a suicidal attempt. Our patient also drank 2 bottles of codeine-based cough syrup equivalent to 360 mg of codeine. At 6 hours post ingestion, her serum paracetamol level was 207 mg/L. The poor prognostic factors for paracetamol overdose in our patient included massive paracetamol ingestion (confirmed by blood levels), codeine co-ingestion and elevated serum amylase (189 U/L).

TREATMENTShe was treated with a 3-day modified regimen of intravenous N-acetylcysteine.

OUTCOMEThe liver function tests and the prothrombin time remained normal over the second and third day of admission and the patient was discharged without complications on the fifth day.

CONCLUSIONFrom this experience we feel that in very severe paracetamol poisoning, a modified regime of intravenous N- acetylcysteine for 3 days is safe and efficacious.

Acetaminophen ; blood ; poisoning ; Acetylcysteine ; administration & dosage ; Adult ; Amylases ; blood ; Antidotes ; administration & dosage ; Codeine ; poisoning ; Drug Overdose ; Female ; Humans ; Liver Function Tests ; Narcotics ; poisoning ; Suicide, Attempted ; Tablets ; Time Factors

OBJECTIVETo investigate whether the protective effect of therapy with different combined neuroprotectant agents was better than that of single agent on focal cerebral ischemia.

METHODSThe right middle cerebral artery in the rats was occluded with suture occlusion technique. The rats were divided into five groups treated with FDP (50 mg/kg, n = 10), MK-801 (1 mg/kg, n = 10) and NAC (150 mg/kg, n = 10) singly, or in combination, respectively, by intraperitoneal infusion 30 minutes after vessel occlusion. The rats were weighed and assessed neurologically, based on a 5-point scale, six and 24 hours after focal cerebral ischemia. The expression of anti-apoptotic protein bcl-2 was observed with SDS-PAGE protein electrophoresis and Western blot technique.

RESULTThe optical density of bcl-2 increased more distinctly in the rats treated with combined neuroprotective agents than that with any single agent six and 24 hours after cerebral ischemia, with a statistically significant difference (P < 0.05).

CONCLUSIONSTreatment with combined neuroprotectant agents could un-regulate the anti-apoptotic protein bcl-2 more distinctly than that with any single agents. Combined use of neuroprotectants might be more effective than that of single agent in protecting rats' brain from ischemia.

Acetylcysteine ; administration & dosage ; Actins ; analysis ; Animals ; Brain Ischemia ; drug therapy ; metabolism ; Dizocilpine Maleate ; administration & dosage ; Drug Therapy, Combination ; Fructosediphosphates ; administration & dosage ; Male ; Molecular Weight ; Neuroprotective Agents ; administration & dosage ; Proto-Oncogene Proteins c-bcl-2 ; analysis ; Rats ; Rats, Wistar

OBJECTIVETo observe the urinary S-phenylmercapturic acid (S-PMA) variation in the benzene dynamic exposed rat models and benzene exposed workers, and study the feasibility of use of urinary S-PMA as the biomarker in benzene exposed.

METHODSIn an animal model study, forty-eight adult Wistar rats were randomly divided into 4 groups: the control group, low-dose group, middle-dose group and high-dose group. The exposed groups were dynamically exposed for 28 days (4 periods) by benzene and the concentration was monitored. The urine was immediately collected after every exposure period and detected by the liquid chromatographic/mass spectrometry methods. In a cohort study, eighty benzene exposed workers in a ship-yard in Guangzhou were selected as the exposed subjects while forty healthy officers in the same shipyard who were not occupationally exposed to benzene were treated as the control. The urine was collected after work shift. The urinary S-PMA and the benzene in the workplace was treated as the rat model.

RESULTSIn the animal model study, the urinary S-PMA increased along with the environment benzene in every period and had significantly difference in the different exposed groups (P < 0.01 or P < 0.05), but did not change along with the exposed time course (P > 0.05). In the cohort study, the urinary S-PMA in the high-dose group [(27.2 +/- 7.9)microg/L] was significantly higher than the low-dose group [(13.6 +/- 3.4)microg/L] (P < 0.01). Otherwise, the background of urinary S-PMA was lower than 5microg/L in both workers and rat models.

CONCLUSIONThe urinary S-PMA can be proposed as a sensitive biomarker of occupational benzene exposure.

Acetylcysteine ; analogs & derivatives ; urine ; Adult ; Animals ; Benzene ; administration & dosage ; toxicity ; Environmental Exposure ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Rats ; Rats, Wistar ; Young Adult