PURPOSE: Acetanilide has been in widespread use as an amide herbicide compound. However, available data regarding acute human poisoning is scarce. The aim of this study was to analyze the clinical characteristics of acetanilide poisoning in order to identify the risk factors associated with severity. METHODS: We conducted a retrospective observational study encompassing the period January 2005 to December 2010, including adult ED patients suffering from acetanilide intoxication. Toxicological history, symptoms observed, clinical signs of toxicity, and laboratory test results were collected for each patient. The patients were classified into two groups for analysis, according their poisoning severity score (PSS). Resulting clinical data and prognostic variables were compared between mild-to-moderate poisoning (PSS 1/2 grades), and severe poisonings and fatalities (PSS 3/4 grades). RESULTS: There were a total of 37 patients, including 26 alachlor, 6 s-metolachlor, 4 mefenacet, and 1 butachlor cases. The majority of patients (81.1%) were assigned PSS 1/2 grades. Changes in mental status and observation of adverse neurologic symptoms were more common in the PSS 3/4 group. The median ingested volume of amide herbicide compound was 250 ml (IQR 200-300 ml) in the PSS 3/4 group, and 80 ml (IQR 50-138 ml) in the PSS 1/2 group. Also, the median GCS observed in the PSS 3/4 group was 13 (IQR 10-14), which was markedly low as compared to a median GCS of 15 in the PSS 1/2 group. Overall mortality rate was 5.4%, and profound cardiogenic shock was observed prior to death in all fatalities. CONCLUSION: When compared to previous reports, acute acetanilide poisoning resulted in relatively moderate severity. The presence of neurologic manifestations, hypotension, lower GCS score, and larger ingested volumes was associated with more serious effects and mortalities.
Acetamides ; Acetanilides ; Adult ; Benzothiazoles ; Humans ; Hypotension ; Neurologic Manifestations ; Retrospective Studies ; Risk Factors ; Shock, Cardiogenic ; Stress, Psychological

Glyphosate surfactant herbicide (N-Phosphonomethyl glycine) is a nonselective herbicide used and studied worldwide because it is less toxic than paraquat is. Alachlor, an acetanilide agrichemical, is a herbicide that is selectively absorbed in the young buds of gramineae weeds. The selective functional mechanism of alachlor is not clear, but it is known to disturb the physio-chemical response. Human abuse can lead to intoxication and injury of the intestinal mucosa, abdominal pain, vomiting, diarrhea, hypotension, dyspnea, metabolic acidosis, respiratory distress, and death. The authors diagnosed a rare case of erythema multiforme without systemic symptoms.
Abdominal Pain ; Acetamides ; Acetanilides ; Acidosis ; Diarrhea ; Dyspnea ; Erythema ; Erythema Multiforme ; Glycine ; Humans ; Hypotension ; Intestinal Mucosa ; Paraquat ; Poaceae ; Vomiting

The development of discolored urine may have many possible causes. Here we present the case of a 76-year-old woman who was admitted after ingesting the inorganic herbicides, mefenacet and imazosulfuron. Her urine color changed to green almost immediately. Since the patient had no specific medication or medical history we considered that the most likely cause of the change in urine color was the ingestion of the herbicides. Spectrophotometric analysis of the urine was conducted and a peak was observed in the green area of the wavelength spectrum. These findings show that mefenacet and imazosulfuron should be considered in the differential diagnosis of green discolored urine.
Acetanilides/*poisoning/urine ; Aged ; Benzothiazoles/*poisoning/urine ; Color ; Eating ; Female ; Herbicides/*poisoning/urine ; Humans ; Poisoning/diagnosis/urine ; Pyridines/*poisoning/urine ; Pyrimidines/*poisoning/urine ; Urinalysis

OBJECTIVETo determine the contents of the residual solvents, methanol, ethanol, toluene, dichloromethane and dioxane in ranolazine raw material.

METHODSHeadspace gas chromatography was used to analyze the residual solvents quantitatively. Samples were analyzed on an HP-INNOWAX column with column temperature at 45 degrees Celsius; using water as solvent.

RESULTSFive residual solvents were completely separated. The liner range and recoveries were satisfied. RSD of precision and accuracy was less than 8% with average recoveries between 87.1% and 105.6%.

CONCLUSIONThe method could be used for the quality control of ranolazine raw material.

Acetanilides ; analysis ; Chromatography, Gas ; methods ; Drug Contamination ; prevention & control ; Enzyme Inhibitors ; analysis ; Ethanol ; analysis ; Methanol ; analysis ; Piperazines ; analysis ; Ranolazine ; Reproducibility of Results ; Solvents ; analysis ; Toluene ; analysis

OBJECTIVE: To explore the effects of pesticide exposure on the auditory system, specifically on hearing status based on auditory brainstem responses.

METHODS: A cohort of pregnant women was identified in several communities in a rural area from April 2002 to February 2003 and followed up until delivery. Mother-infant dyads were assessed for exposure to pesticides. Maternal and fetal exposures to environmental toxic products were determined by measuring levels in maternal hair and blood, and infant cord blood, hair, and meconium, respectively. Hearing status was measured using otoacoustic emissions (OAE) and confirmed by diagnostic auditory brainstem responses (ABR) measured at 80, 60, and 40 decibels. Waves I, III, V were identified and absolute latencies measured, including inter-peak latencies from waves 11III, I-V, and III-V. Pesticide exposure was then correlated with latencies of Waves I, III, V, and interpeak latencies of waves I-III, IIV, and III-V. Hearing loss and pesticide exposures were correlated with Griffiths Mental Development Scores (GMDS).

RESULTS: Significant delays in the ABR wave latencies were noted in the group with exposure to pesticides. Propoxur was the most common toxic product detected in infants and meconium the best substrate for its detection. There was a 1.4% risk of hearing loss with exposure to propoxur (RR=0.52 (0.12-2.30), p = 0.06), a 6.25% risk with cypermethrin exposure (RR= 4.53 (0.61133.64), P = 0.10) and 6.25% risk with pretilachlor exposure (3.13 (0.44-22.30), p = 0.07). Griffith's Mental Developmental Scale scores (GMDS- hearing and speech subscale and general quotient scores) were not significantly different between exposed and unexposed groups. However, three infants with positive exposures and hearing loss had below average, or low to average scores using this scale.

CONCLUSION: Maternal exposure to environmental toxic products may affect the auditory pathway in infants at birth. Pregnant women should limit their exposure to such toxic products in order to avoid neurodevelopmental effects particularly on hearing because this is very important in the critical stage of language and speech development.

Human ; Male ; Female ; Infant Newborn ; Auditory Pathways ; Maternal Exposure ; Meconium ; Speech ; Otoacoustic Emissions, Spontaneous ; Hearing Loss ; Deafness ; Hearing Tests ; Acetanilides ; Pesticides ; Hair

Chloracetanilide herbicides (alachlor, butachlor, metachlor) are used widely. Although there are much data about chronic low dose exposure to chloracetanilide in humans and animals, there are few data about acute chloracetanilide poisoning in humans. This study investigated the clinical feature of patients following acute oral exposure to chloracetanilide. We retrospectively reviewed the data on the patients who were admitted to two university hospitals from January 2006 to December 2010. Thirty-five patients were enrolled. Among them, 28, 5, and 2 cases of acute alachlor, metachlor, butachlor poisoning were included. The mean age was 49.8 +/- 15.4 yr. The poison severity score (PSS) was 17 (48.6%), 10 (28.6%), 5 (14.3%), 2 (5.7%), and 1 (2.9%) patients with a PSS of 0, 1, 2, 3, and 4, respectively. The age was higher for the symptomatic patients (1-4 PSS) than that for the asymptomatic patients (0 PSS) (43.6 +/- 15.2 vs 55.7 +/- 13.5). The arterial blood HCO3 was lower in the symptomatic patients (1-4 PSS) than that in the asymptomatic patients (0 PSS). Three patients were a comatous. One patient died 24 hr after the exposure. In conclusion, although chloracetanilide poisoning is usually of low toxicity, elder patients with central nervous system symptoms should be closely monitored and cared after oral exposure.
Acetamides/*poisoning ; Acetanilides/*poisoning ; Acute Disease ; Adult ; Aged ; Bicarbonates/blood ; Central Nervous System Diseases/diagnosis ; Female ; Herbicides/*poisoning ; Humans ; Male ; Middle Aged ; Poisoning/*diagnosis ; Retrospective Studies ; Severity of Illness Index ; Suicide, Attempted

The formalin test is a commonly used animal model of acute and tonic pain. However, the molecular targets of formaldehyde (FA, the main ingredient of the formalin solution) on primary nociceptor cells remain controversial. In this report, the effects of FA on electrophysiologically-identified primary nociceptor cells were evaluated in vitro and the roles of the vanilloid receptor TRPV1 in FA-produced activation of primary nociceptors were also examined at both cellular and behavioral levels. Of 92 acutely dissociated dorsal root ganglion (DRG) cells recorded by current patch-clamp technique, 34% were discharged by FA application with the mean onset latencies of the first action potential (AP) being (367.34+/-32.96) s. All the FA-sensitive cells were identified as nociceptor cells by their distinguishable features of AP including longer duration, existence of a hump (a shoulder or inflection) on the repolarizing phase, and longer after-hyperpolarization of APs. Co-application of capsazepine (CPZ), a competitive antagonist of TRPV1 receptors, could block FA-evoked firing with partial inhibition on the membrane depolarization of all cells tested. Of another 160 cells examined by confocal calcium imaging, 32% were shown to respond to FA with an intracellular Ca(2+) rise. Of 51 FA-sensitive cells, 67% were suppressed by CPZ, suggesting partial involvement of TRPV1 in mediation of the FA-evoked intracellular Ca(2+) rise. Under voltage-clamp mode, 41% of DRG cells were evoked to give rise to inward current with the remaining 59% being unchanged. In separate experiments on the other 56 FA-sensitive cells, concentration-dependent increase in the FA-evoked current amplitude was demonstrated. In comparison with controls, the FA-evoked inward current could be significantly suppressed by CPZ that was further enhanced by HC-030031, a TRPA1 selective antagonist. Finally, local effects of CPZ were confirmed in the formalin test and it was shown that the formalin-induced paw flinches were strongly suppressed by CPZ in phase 1 but with phase 2 being significantly suppressed only during 25-55 min. It is therefore concluded that FA can directly activate a subpopulation of primary nociceptor cells and the FA-induced AP discharges are likely to contribute mainly to phase 1, but not phase 2 of the formalin-induced nociception. The activation of primary nociceptor cells by FA is likely to be mediated, at least in part, through TRPV1 and/or TRPA1 receptors.
Acetanilides ; pharmacology ; Action Potentials ; Animals ; Capsaicin ; analogs & derivatives ; pharmacology ; Formaldehyde ; pharmacology ; Ganglia, Spinal ; physiology ; Nociceptors ; physiology ; Pain ; physiopathology ; Pain Measurement ; Patch-Clamp Techniques ; Purines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; TRPV Cation Channels ; physiology

Ranolazine and metabolites in dog urine were identified by LC-MS(n). Dog urine samples were collected after ig 30 mg x kg(-1) ranolazine, then the samples were enriched and purified through solid-phase extraction cartridge. The purified samples were analyzed by LC-MS(n). The possible metabolites were discovered by comparing the full scan and SIM chromatograms of the test samples with the corresponding blanks. Seventeen phase I metabolites and fourteen phase II metabolites were identified in dog urine. Three metabolites were identified by comparing with the control article. The metabolites were formed via the following metabolic pathways: O-demethylation, O-dearylation, hydroxylation, N-dealkylation, amide hydrolysis, glucuronidation and sulfation. The LC-MS(n) method is suitable for the rapid identification of drug and its metabolites in biologic samples.
Acetanilides ; administration & dosage ; metabolism ; urine ; Administration, Oral ; Animals ; Chromatography, Liquid ; Dogs ; Female ; Male ; Piperazines ; administration & dosage ; metabolism ; urine ; Ranolazine ; Solid Phase Extraction ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry

The objectives of this study were to investigate the effects of veratridine (VER) on persistent sodium current (I(Na.P)), Na(+)/Ca(2+) exchange current (I(NCX)), calcium transients and the action potential (AP) in rabbit ventricular myocytes, and to explore the mechanism in intracellular calcium overload and myocardial contraction enhancement by using whole-cell patch clamp recording technique, visual motion edge detection system, intracellular calcium measurement system and multi-channel physiological signal acquisition and processing system. The results showed that I(Na.P) and reverse I(NCX) in ventricular myocytes were obviously increased after giving 10, 20 μmol/L VER, with the current density of I(Na.P) increasing from (-0.22 ± 0.12) to (-0.61 ± 0.13) and (-2.15 ± 0.14) pA/pF (P < 0.01, n = 10) at -20 mV, and that of reverse I(NCX) increasing from (1.62 ± 0.12) to (2.19 ± 0.09) and (2.58 ± 0.11) pA/pF (P < 0.05, n = 10) at +50 mV. After adding 4 μmol/L tetrodotoxin (TTX), current density of I(Na.P) and reverse I(NCX) returned to (-0.07 ± 0.14) and (1.69 ± 0.15) pA/pF (P < 0.05, n = 10). Another specific blocker of I(Na.P), ranolazine (RAN), could obviously inhibit VER-increased I(Na.P) and reverse I(NCX). After giving 2.5 μmol/L VER, the maximal contraction rate of ventricular myocytes increased from (-0.91 ± 0.29) to (-1.53 ± 0.29) μm/s (P < 0.01, n = 7), the amplitude of contraction increased from (0.10 ± 0.04) to (0.16 ± 0.04) μm (P < 0.05, n = 7), and the baseline of calcium transients (diastolic calcium concentration) increased from (1.21 ± 0.08) to (1.37 ± 0.12) (P < 0.05, n = 7). After adding 2 μmol/L TTX, the maximal contraction rate and amplitude of ventricular myocytes decreased to (-0.86 ± 0.24) μm/s and (0.09 ± 0.03) μm (P < 0.01, n = 7) respectively. And the baseline of calcium transients reduced to (1.17 ± 0.09) (P < 0.05, n = 7). VER (20 μmol/L) could extend action potential duration at 50% repolarization (APD(50)) and at 90% repolarization (APD(90)) in ventricular myocytes from (123.18 ± 23.70) to (271.90 ± 32.81) and from (146.94 ± 24.15) to (429.79 ± 32.04) ms (P < 0.01, n = 6) respectively. Early afterdepolarizations (EADs) appeared in 3 out of the 6 cases. After adding 4 μmol/L TTX, APD(50) and APD(90) were reduced to (99.07 ± 22.81) and (163.84 ± 26.06) ms (P < 0.01, n = 6) respectively, and EADs disappeared accordingly in 3 cases. It could be suggested that: (1) As a specific agonist of the I(Na.P), VER could result in I(Na.P) increase and intracellular Na(+) overload, and subsequently intracellular Ca(2+) overload with the increase of reverse I(NCX). (2) The VER-increased I(Na.P) could further extend the action potential duration (APD) and induce EADs. (3) TTX could restrain the abnormal VER-induced changes of the above-mentioned indexes, indicating that these abnormal changes were caused by the increase of I(Na.P). Based on this study, it is concluded that as the I(Na.P) agonist, VER can enhance reverse I(NCX) by increasing I(Na.P), leading to intracellular Ca(2+) overload and APD abnormal extension.
Acetanilides ; pharmacology ; Action Potentials ; Animals ; Calcium ; metabolism ; Myocardial Contraction ; Myocytes, Cardiac ; cytology ; drug effects ; Patch-Clamp Techniques ; Piperazines ; pharmacology ; Rabbits ; Ranolazine ; Sodium-Calcium Exchanger ; metabolism ; Tetrodotoxin ; pharmacology ; Veratridine ; pharmacology

OBJECTIVETo study the derivatives of 1,2,4-triazino[5,6-b]indole-3-thione for antidepressant activity in olfactory bulbectomized (OBX) rats. Out of various derivatives tested for acute tail suspension test, the two derivatives showing prominent action were selected for bilateral olfactory bulbectomy model of chronic depression in rats.

METHODSThe sub acute effects of 14-day oral pretreatment of two derivatives labeled as 3a (70 mg/kg) and 3r (70 mg/kg), imipramine (20 mg/kg), fluoxetine (30 mg/kg) and moclobemide (15 mg/kg) were evaluated on bilateral bulbectomy induced rise in body weight, hyperphagia, hyperactivity, and on sexual dysfunction. The serum sodium concentration, body temperature, and heart rate were also recorded.

RESULTSThe derivatives 3a and 3r showed reversal of drop in body weight, reversed OBX induced hyperactivity, normalized body temperature, heart rate, and serum sodium concentration. In elevated maze test, moclobemide, 3a, 3r treatment significantly reduced time spent in open arm as compared to OBX rats. 3a and 3r also improved sexual behavior parameters.

CONCLUSIONSThe present study shows promising antidepressant action and provides a proof of concept for the chronic treatment of 3a, 3r to treat depression.

Acetamides ; pharmacology ; Acetanilides ; pharmacology ; Animals ; Antidepressive Agents ; pharmacology ; Behavior, Animal ; drug effects ; Depression ; drug therapy ; etiology ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Female ; Fluoxetine ; pharmacology ; Imipramine ; pharmacology ; Male ; Moclobemide ; pharmacology ; Olfaction Disorders ; complications ; pathology ; Olfactory Bulb ; surgery ; Rats ; Rats, Sprague-Dawley ; Triazines ; pharmacology