A 22-year-old woman was referred to our emergency department for the treatment of a chemical injury on her arm. She had accidentally spilled 99% trifluoroacetic anhydride (TFAA) over her left forearm during an organic chemistry experiment. She visited a primary care unit, and then she was referred to our hospital for inactivation of the released fluoride ions. Her skin lesions were different from those caused by hydrofluoric acid (HF) injury. The injured area showed painful whitish maculae and patchy areas with accentuated rim. No vesiculation and bulla formation was detected. We intradermally injected a 5% solution of calcium through a 24-gauge needle into the burned skin. After the injection, she complained of more severe pain. Although TFAA contains fluorine, it does not release free fluoride ions on contact with the skin, unlike HF. In fact, application of calcium gluconate for TFAA burns is not recommended. Rather, it should be avoided since it increases pain and local abscess formation.
Abscess ; Acetic Anhydrides ; Arm ; Blister ; Burns ; Burns, Chemical ; Calcium ; Calcium Gluconate ; Chemistry, Organic ; Emergencies ; Female ; Fluorides ; Fluorine ; Fluoroacetates ; Forearm ; Gluconates ; Humans ; Hydrofluoric Acid ; Ions ; Needles ; Primary Health Care ; Skin ; Trifluoroacetic Acid ; Young Adult

Child ; Child, Preschool ; Female ; Fluoroacetates ; poisoning ; Hemoperfusion ; Humans ; Infant ; Male

Acute Disease ; Aged, 80 and over ; Fluoroacetates ; poisoning ; Humans ; Male

Succinic acid has received a great deal of attention as an important green chemical stock for the manufacture of synthetic resins, biodegradable polymers and chemical intermediates. In this paper, the breeding mechanism of Actinobacillus succinogenes based on metabolic flux analysis was demonstrated to improve the yield of succinic acid by fermentation. After the NTG treatment, mutants from A. succinogenes CGMCC 1593 which were able to grow in medium containing concentrations of about 50-100 mmol/L of sodium monofluoroacetate were obtained. Among them, a mutant SF-9 was selected for producing more succinic acid and less acetic acid. When fermentations were conducted in a 5 L bioreactors, the final succinic acid concentration of SF-9 (34.8 g/L) increased 23.4%, and the mass ratio of succinic acid/acetic acid increased from 3.3 to 9 compared with those of the parent strain. Based on the metabolic flux analysis of A. succinogenes, PEP was found to be a key node which has an important effect on the production of succinic acid, and the flux ratio of by-productions (acetic, formic, lactic acid) was influenced by PYR node. Compared with the parent strain, the flux to succinic acid of mutant (A. succinogenes SF-9) was significantly increased, while the flux to by-productions had an obvious decline. Therefore, PEP and PYR are not rigid nodes in the metabolic regulation of A. succinogenes.
Actinobacillus ; genetics ; growth & development ; metabolism ; Drug Tolerance ; Fermentation ; Fluoroacetates ; metabolism ; Metabolic Networks and Pathways ; Mutation ; Succinic Acid ; metabolism

The highly toxic sodium monofluoroacetate (SMFA) was banned as a rodenticide in this country in the 1980s. The fluoroacetate metabolite, fluorocitric acid blocks cellular metabolism by inhibiting the Klebs cycle, producing wide spread clinical effects including respiratory, neurologic, cardiologic, and fluid-electrolyte abnormalities. We report the survival case by continuous renal replacement therapy from fatal complications after beta-fluoroethyl acetate ingestion. 61-year old male was brought to our emergency center with chief complaint of beta-fluoroethyl acetate ingestion. Soon after 80 minutes of hospital admission, he developed the symptoms of mild metabolic acidosis, respiratory failure, coma, transient tachycardia, and refractory hypotension. On the second hospital day, we guessed that drug induced severe rhabdomyolysis and renal failure were in progress. At 28 hours after hospital admission, we started the continuous renal replacement therapy (CRRT) with the informed consent. Dramatically, at 24 hour after beginning the CRRT, the patient were completely recovered from coma, respiratory failure, and refractory shock, although severe rhabdomyolysis and renal failure still existed. Additionally, four times of hemodialysis were performed. On 25th hospital admission, he discharged with non oliguric renal failure state, arranging to return to out patient department.
Acidosis ; Coma ; Eating ; Emergencies ; Fluoroacetates ; Humans ; Hypotension ; Informed Consent ; Male ; Renal Dialysis ; Renal Insufficiency ; Renal Replacement Therapy ; Respiratory Insufficiency ; Rhabdomyolysis ; Rodenticides ; Shock ; Sodium ; Tachycardia

OBJECTIVEIn the past the mortality and sequelae rate of the patients with severe fluoroacetamide (FAM) poisoning treated only with traditional remedies was high. During the recent ten years the authors treated children with severe FAM poisoning with charcoal hemoperfusion (HP) and achieved better results. However evidence was not sufficient to show that reduced mortality and sequelae rates were obtained from HP without traditional treatment because of lack of prospective randomized, controlled clinical studies. Thus, a dog model for FAM poisoning was designed in order to study the therapeutic effect, high-efficiency time of HP, the time of tissue-poisoning to release after HP, and to investigate the toxicokinetics of the poison in the course of treatment and after HP.

METHODFourteen dogs were given intraperitoneal FAM at a dose of 0.3 mg/kg body weight. HP was performed on 9 poisoned dogs for 30 - 120 minutes post intoxication. Each procedure lasted for 4 hours. Blood samples of the 9 poisoned dogs were collected before HP and 30, 60, 90, 120, 180, 240 minutes during HP and 2, 6, 24 hours after HP. Blood plasma was separated from blood samples and stored at -20 degrees C. The concentration of the poison was measured by gas chromatography (GC). The clinical symptoms of all the dogs were observed for one day.

RESULTSThe FAM concentration (ng/ml) of blood samples in poisoned dogs before HP, and 60, 120, 180, 240 minutes during HP were 230.11 +/- 52.48, 184.56 +/- 62.57, 141.00 +/- 44.83, 126.78 +/- 61.04, 113.11 +/- 54.65 respectively. The differences were significant (chi(2) = 31.978, P < 0.0005). The dispersion count between pre-HP and HP for 1 was 45.55, between 1 h and 2 h was 43.56, between 2 h and 3 h was 14.22 and between 3 h and 4 h was 13.67. The values of FAM had declined by 38.7%, 45.0% and 50.8% respectively at 2 h, 3 h, 4 h of HP compared with pre-HP. The rate of cleaning efficacy of FAM of every hour during HP were 19.79%, 23.6%, 10.09% and 10.78% respectively during HP 1, 2, 3, 4 h. The cleaning efficacy of HP was high within 2 hours during HP. The concentration of FAM slightly rose again 6 h after HP. The level of FAM had declined at 24 hour after HP when compared with pre-HP level. The reduction rate of FAM level for every hour during HP was higher than that after HP (12.71% vs 0.27% - 2.22%). The t(1/2) of FAM with and without HP were (4.50 +/- 1.20) h and (49.60 +/- 10.56) h. All the 5 poisoned dogs not treated with HP died. However 6 poisoned dogs treated with HP kept alive after HP. Three dogs had frequent seizures again 4h after HP. After HP the charcoal container was washed by 0.9% saline and FAM could not be detected in the douche.

CONCLUSIONSCharcoal HP was an effective treatment for severe FAM poisoning. T(1/2) of the poison was shortened, and the poison clearing rate was accelerated by HP. The high-efficiency time of HP was 2 - 2.5 h. Activated charcoal can adsorb the poison vigorously, and return of blood to the body after HP by using 0.9% saline was feasible and safe.

Animals ; Charcoal ; therapeutic use ; Dogs ; Fluoroacetates ; poisoning ; Hemoperfusion ; methods ; Metabolic Clearance Rate ; Poisoning ; metabolism ; therapy ; Poisons ; toxicity ; Seizures ; chemically induced ; Treatment Outcome

OBJECTIVETo observe the heart damage in 10 patients with acute fluoroacetamide poisoning.

METHODSMonitoring serum activities of myocardial enzymes [creatine kinase (CK), asparate aminotransferase (AST), lactate dehydrogenase(LDH) and hydroxybutyrate dehydrogenase(HBDH)] and recording ECG on these 10 patients were performed during the period of their hospitalization. In the mean while, 24 hour dynamic ECG were also recorded and analysed using GP7000L Holter.

RESULTS(1) Urinary fluorine ion concentrations were increased in 9 patients before therapy and in all these 10 patients during therapeutic period. (2) The activities of serum CK in 2 patients and that of serum HBDH in one patient were increased before therapy. However, the serum activities of one or more than one myocardial enzymes were increased in all these 10 patients during therapeutic period. (3) Four patients had abnormal change of ECG before therapy and 5 patients during therapeutic period. (4) 24 hour dynamic ECG records showed that there were heart electrical alternans in 9 patients. One patient had wandering pacemaker and 6 patients had arythmia.

CONCLUSIONFluoroacetamide may cause obvious heart damage, and also heart electrical alternation.

Acute Disease ; Alanine Transaminase ; blood ; Creatine Kinase ; blood ; Electrocardiography ; drug effects ; Fluoroacetates ; poisoning ; Heart ; drug effects ; Humans ; Hydroxybutyrate Dehydrogenase ; blood ; L-Lactate Dehydrogenase ; blood

OBJECTIVETo observe the effect of fluoroacetamide on cardiomyocytes of rat and the antidotal effect of acetamide.

METHODS4 groups of SD rats were treated with various dosages of fluoroacetamid(p.o.) and 2 groups of them were treated with acetamide(i.p.). The changes of cardiomyocytes and serum AST, LDH, CK, CK-MB and HBDH were measured at different intervals after poisoning.

RESULTSIn the group treated with fluoroacetamid 8 mg/kg. bw, serum AST[(589.58 +/- 821.72) U/L], CK[(916.78 +/- 343.55) U/L], HBDH[(504.47 +/- 148.88) U/L] raised obviously compared with control[(187.70 +/- 46.87), (755.65 +/- 498.90), (347.25 +/- 228.40) U/L respectively] (P < 0.01), and the pathological findings such as degeneration, liquefactive necrosis and filtration of inflammatory cells in cardiac muscles were observed 24 hours later, while all the male dead within 3 days. In the group treated with fluoroacetamid 4 mg/kg. bw, serum LDH and HBDH rose significantly compared with control(P < 0.01) 5 day later. On the day of 10, myocardial enzymes restored in all experiment groups with some interstitial fibroblastic proliferation. The pathological changes were reduced in the group treated with acetamide synchronously (100 mg/kg. bw).

CONCLUSIONAcute intoxication of fluoroacetamide could damage cardiomyocytes while acetamide could reduce the injury of them, but the injury was reversible. The levels of serum myocardial enzymes could be a usable index for early diagnosis.

Acetamides ; pharmacology ; Alanine Transaminase ; blood ; Animals ; Antidotes ; pharmacology ; Creatine Kinase, MB Form ; blood ; Fluoroacetates ; toxicity ; L-Lactate Dehydrogenase ; blood ; Myocytes, Cardiac ; drug effects ; pathology ; Rats ; Rats, Sprague-Dawley

The liver is the major site of endogenous and exogenous drug metabolism. The primary result of drug metabolism is the production of more water-soluble and therefore more easily excreted drug metabolites. Drugs are sometimes biotransformed into more reactive metabolites, which may lead to toxicity. Volatile anesthetics, like most drugs, undergo metabolism in the body and are sometimes associated with toxic reactions. Here, author will discuss the metabolism and hepatic toxicity of inhaled anesthetics. Toxicity and liver injury have been reported after repeated exposure on subsequent occasions to different fluorinated anesthetics. This phenomenon of cross-sensitization has also been reported with the chlorofluorocarbon(CFC) replacement agents, the hydrochlorofluorocarbons(HCFCs). Halothane, enflurane, sevoflurane, isoflurane, desflurane are all metabolized to trifluoroacetic acid, which have been reported to induce liver injury in susceptible patients. The propensity to produce liver injury appears to parrel metabolism of the parent drug: halothane(20%) >>>> enflurane(2.5%) >> sevoflurane(1%) > isoflurane(0.2%) > desflurane(0.02%). The use of any anesthetic must be based on its benefits and risks, how it may produce toxicity, and in which patients it may be most safely administered. Nonhalogenated inhaled anesthetics (nitrous oxide, xenon) chemically inert and not metabolized in human tissue. The perfect anesthetic agents dose not exist. But ongoing research attempts to uncover emerging toxicities. Xenon is not currently approved for clinical use. Other than the expense associated with its use, it may be the most ideal anesthetic agent. In general, surgical manipulation or disturbance of the surgical site appears to be more important in decreasing hepatic blood flow than current anesthetic agents such as isoflurane, sevoflurane, and desflurane or technique. However, the clinician is challenged to balance new information with current clinical practices and choice the safest, most effective agents for each patient.
Anesthetics* ; Enflurane ; Halothane ; Humans ; Isoflurane ; Liver* ; Metabolism ; Parents ; Risk Assessment ; Trifluoroacetic Acid ; Xenon

This paper is to establish a reversed-phase ion-pair chromatography (RP-IPC) method for universal estimation of the octanol/water partition coefficients (logP) of a wide range of structurally diverse compounds including acidic, basic, neutral and amphoteric species. The retention factors corresponding to 100% water (logk(w)) were derived from the linear part of the logk'/phi relationship, using at least four isocratic logk' values containing different organic compositions. The logk(w) parameters obtained were close to the corresponding logP values obtained with the standard "shake flask" methods. The mean deviation for test drugs is 0.31. RP-IPC with trifluoroacetic acid as non classic ion-pair agents can be applicable to determine the logP values for a variety of drug-like molecules with increased accuracy.
1-Octanol ; chemistry ; Chromatography, Reverse-Phase ; methods ; Hydrogen-Ion Concentration ; Octanols ; chemistry ; Trifluoroacetic Acid ; Water ; chemistry