Depletion study of three formulations of flumequine in edible tissues and drug transfer into chicken feathers.

To ensure the delivery of safe animal products to consumers, withdrawal times (WDT) of drugs must be respected. Drugs administered in therapies can also reach nonedible tissues (for humans) such as feathers; this transfer is of concern as feather meal is used in diets of food producing animals, being this a possible source of residue contamination of final products for human consumption. WDTs of three flumequine formulations (10%, 80% premix powder and 20% solution) as well as the transfer of this drug into feathers were determined. One hundred and twenty broiler chickens were allocated into four experimental groups (36 birds each). Three of them were treated with 24 mg/kg bw orally for five consecutive days of each flumequine formulation, whereas one group remained untreated (12 birds as control group). After the treatment ended, six chickens of each experimental group and two controls were slaughtered daily for 6 days. Samples of muscle, liver and feathers were collected and analyzed by liquid chromatography tandem mass spectrometry (LC MS/MS). The WDTs showed differences between formulations. Flumequine concentrations found in feathers remained high during WDT and after this period, thus suggesting that the WDTs estimated for the pharmaceutical formulation of flumequine do not guarantee the absence of this drug in chicken nonedible tissues such as feathers.

MDMA-induced indifference to negative sounds is mediated by the 5-HT2A receptor.

BACKGROUND: MDMA has been shown to induce feelings of sociability, a positive emotional bias and enhanced empathy. While previous research has used only visual emotional stimuli, communication entails more than that single dimension and it is known that auditory information is also crucial in this process. In addition, it is, however, unclear what the neurobiological mechanism underlying these MDMA effects on social behaviour is. Previously, studies have shown that MDMA-induced emotional excitability and positive mood are linked to the action on the serotonin (5-HT) 2A receptor. AIM: The present study aimed at investigating the effect of MDMA on processing of sounds (Processing of Affective Sounds Task (PAST)) and cognitive biases (Approach-Avoidance Task (AAT)) towards emotional and social stimuli and the role of 5-HT2A receptor in these effects. METHODS: Twenty healthy recreational users entered a 2 × 2, placebo-controlled, within-subject study with ketanserin (40 mg) as pre-treatment and MDMA (75 mg) as treatment. Behavioural (PAST, AAT) measures were conducted 90 min after treatment with MDMA, respectively, 120 min after ketanserin. Self-report mood measures and oxytocin concentrations were taken at baseline and before and after behavioural tests. RESULTS: Findings showed that MDMA reduced arousal elicited by negative sounds. This effect was counteracted by ketanserin pre-treatment, indicating involvement of the 5-HT2 receptor in this process. MDMA did not seem to induce a bias towards emotional and social stimuli. It increased positive and negative mood ratings and elevated oxytocin plasma concentrations. The reduction in arousal levels when listening to negative sounds was not related to the elevated subjective arousal. CONCLUSION: It is suggested that this decrease in arousal to negative stimuli reflects potentially a lowering of defences, a process that might play a role in the therapeutic process.

Peripheral endocannabinoid concentrations are not associated with verbal memory impairment during MDMA intoxication.

BACKGROUND: Preclinical data have suggested involvement of the endocannabinoid (eCB) system in MDMA-induced memory impairment. Clinical research has shown that blockade of the 5-HT2 receptor nulls memory impairment during MDMA intoxication. Interestingly, studies have demonstrated that the eCB and the 5-HT system interact. It was hypothesized that MDMA would cause an increase in eCB concentrations together with a decrease in memory performance, and that combining MDMA with a 5-HT2 receptor blocker ketanserin would lead to a counteraction of the MDMA effects on eCB concentrations and memory. METHODS: Twenty healthy recreational polydrug users entered a double-blind placebo-controlled within-subject study. Participants received a pre-treatment (ketanserin 40 mg, placebo) followed 30 min later by a treatment (MDMA 75 mg, placebo). Verbal memory was tested by means of a 30-word learning test. Endocannabinoid concentrations (anandamide (2-AG); N-arachidonylethanolamine (AEA)) were assessed in blood at baseline, before (90 min post-treatment) and after cognitive tests (150 min post-treatment). RESULTS: Findings showed that MDMA impaired memory 90 min post-treatment in the word learning task. This effect was a replication of previous studies using the same dose of MDMA (75 mg) and the same learning paradigm. Contrary to our hypothesis, MDMA did not affect eCB concentrations, nor did ketanserin block MDMA-induced memory impairment. Ketanserin caused an increase in AEA concentrations, 180 min after administration. CONCLUSION: Current findings suggest that peripherally measured endocannabinoids are not associated with the verbal memory deficit during MDMA intoxication. TRIAL REGISTRATION NUMBER: NTR3691.

[Management of difficult airway with inhalation induction in a patient with Lennox-Gastaut syndrome and neck injury]. / Manejo de vía aérea difícil con inducción inhalatoria en paciente con síndrome de Lennox-Gastaut y traumatismo cervical.

Lennox-Gastaut syndrome is a childhood epileptic encephalopathy, and is characterized by frequent and difficult to treat seizures associated with mental retardation. The case is presented of a 21 year-old male with Lennox-Gastaut syndrome, with bilateral cervical facet joint dislocation fracture at C6-C7 and spinal canal compression as a result of a fall during a seizure. In this case the management of the difficult airway expected in an awake and uncooperative patient, with cervical spinal cord injury is described. An airway management strategy was proposed, that allowed a rapid and safe airway control with the best possible tolerance and maintaining the neck immobilised, so as not to increase neurological injury. Within this strategy, plan A was defined as inhalation induction with sevoflurane to maintain spontaneous breathing and tracheal intubation with Airtraq®. We believe that the Airtraq® video laryngoscope with inhalational induction with sevoflurane is a valid and effective alternative in the management of expected difficult airway.

Pharmacology of MDMA in humans.

MDMA given at recreational doses (range tested 50 to 150 mg) to healthy volunteers, produced mydriasis and marked increases in systolic and diastolic blood pressure, heart rate, and pupillary diameter. MDMA induced changes on oral temperature. The time course of this observation was biphasic, as a slight decrease at 1 h and a slight increase at 2 and 4 h were observed. MDMA induced a slight dose-dependent impairment on psychomotor performance. MDMA produced a marked rise in plasma cortisol and prolactin concentrations. The elimination half-life of MDMA was about 8-9 h. Drug concentrations increased, and a parallel increase in physiologic and hormonal measures was observed. Both peak concentrations and peak effects were obtained between 1 and 2 h and decreased to baseline values 4-6 h after drug administration.

Micellar electrokinetic capillary chromatography of macrolide antibiotics. Separation of tylosin, erythromycin and their related substances.

The separation of tylosin by micellar electrokinetic capillary chromatography with a mixed micelle system is described. Good selectivity was obtained with sodium phosphate buffer (80 mM, pH 7.5) containing 20 mM sodium cholate and 7 mM cetyltrimethylammonium bromide (CTAB). This method permits tylosin to be separated from its closely related substances within 15 min. The influences of type of buffer, buffer pH, the concentrations of sodium cholate and CTAB were investigated. The robustness of the method was examined for tylosin by means of a full-fraction factorial design. Quantitative results are presented. Using a similar buffer system (80 mM sodium phosphate, pH 6.0, 20 mM sodium cholate and 5 mM CTAB), separation of erythromycin and its main related substances was also obtained. However, detection sensitivity and resolution are not sufficient for analysis of related substances in erythromycin commercial samples.

High-performance liquid chromatography with electrochemical detection applied to the analysis of 3,4-dihydroxymethamphetamine in human plasma and urine.

Metabolic activation in the disposition of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") has been implicated in some of its pharmacological and toxicological effects, with the major metabolite 3,4-dihydroxymethamphetamine (HHMA) as a putative toxicant through the formation of thioether adducts. We describe the first validated method for HHMA determination based on acid hydrolysis of plasma and urine samples, further extraction by a solid-phase strong cation-exchange resin (SCX, benzenesulfonic acid), and analysis of extracts by high-performance liquid chromatography with electrochemical detection. The chromatographic separation was performed in an n-butyl-silane (C4) column and the mobile phase was a mixture of 0.1 M sodium acetate containing 0.1 M 1-octanesulphonic acid and 4 mM EDTA (pH 3.1) and acetonitrile (82:18, v/v). Compounds were monitored with an electrochemical cell (working potentials 1 and 2, +0.05 and +0.35 V, respectively, gain 60 microA). A mobile phase conditioning cell with a potential set at +0.40 V was connected between the pumping system and the injector. Calibration curves were linear within the working concentration ranges of 50-1000 microg/L for urine and plasma. Limits of detection and quantification were 10.5 and 31.8 microg/L for urine and 9.2 and 28.2 microg/L for plasma. Recoveries for HHMA and DHBA (3,4-dihydroxybenzylamine, internal standard) were close to 50% for both biological matrices. Intermediate precision and inter-day accuracy were within 3.9-6.5% and 7.4-15.3% for urine and 5.0-10.8% and 9.2-13.4% for plasma.

Quantification of amphetamine plasma concentrations by gas chromatography coupled to mass spectrometry.

We developed a fast and sensitive method for identification and quantification of plasma concentrations of amphetamine using gas chromatography with mass spectrometry detection (GC-MS). Amphetamine-d8 served as internal standard. The method involves a single extraction procedure and an easy treatment of the samples that allowed no losses during the evaporation process. Derivatisation of amphetamine with N-methyl-bis(trifluoroacetamide), a potent acylating agent, provides many advantages to the method compared with common derivatisation reactions usually used for amphetamines. The limits of detection and quantification following this method were 0.43 and 1.42 ng/ml, respectively. The assay has been successfully employed in the quantification of amphetamine in plasma samples from healthy volunteers at four different doses.

Quantification of 3,4-methylenedioxymetamphetamine and its metabolites in plasma and urine by gas chromatography with nitrogen-phosphorus detection.

A gas chromatographic method with nitrogen-phosphorus detection involving a solid-liquid extraction phase was developed and validated for the simultaneous quantification of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) in plasma. A modification of this method was validated for the analysis of MDMA, MDA, 4-hydroxy-3-methoxymethamphetamine (HMMA) and, 4-hydroxy-3-methoxyamphetamine (HMA) in urine. Under the analytical conditions described, the limits of detection in plasma and urine were less than 1.6 microg/l and 47 microg/l, respectively, for all the compounds studied. Good linearity was observed in the concentration range evaluated in plasma (5-400 microg/l) and urine (100-2000 microg/l) for all compounds tested. The recoveries obtained from plasma were 85.1% and 91.6% for MDMA and MDA, respectively. Urine recoveries were higher than 90% for MDMA and MDA, 74% for HMMA, and 64% for HMA. Methods have been successfully used in the assessment of plasma and urine concentrations of MDMA and its main metabolites in samples from clinical studies in healthy volunteers.

3,4-Dihydroxymethamphetamine (HHMA). A major in vivo 3,4-methylenedioxymethamphetamine (MDMA) metabolite in humans.

There is evidence that some heavy users of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) show signs of neurotoxicity (a cognitive dysfunction, a larger incidence of psychopathology). It has been postulated that the catechol intermediates of methylenedioxyamphetamines such as 3,4-dihydroxymethamphetamine (HHMA), a metabolite of MDMA, may play a role in their neurotoxicity by formation of thioether adducts. This study describes the first validated method for HHMA determination in plasma and urine by strong cation-exchange solid-phase extraction high-performance liquid chromatography/electrochemical detection (HPLC/ED) analysis. The method has been applied for the determination of HHMA in plasma and urine samples from a clinical study in healthy volunteers of MDMA and provides preliminary kinetic data on this metabolite. HHMA appeared to be a major MDMA metabolite with plasma concentrations as high as the parent compound. Thus, HHMA C(max) (154.5 microg/L) and AUC(0-24h)(1990.9 microg/L h) were similar to those obtained in previously published reports for MDMA (181.6 microg/L and 1465.9 microg/L h, respectively). The 24-h urinary recovery of HHMA accounted for 17.7% of the MDMA dose administered and increases the total 24 h recovery of MDMA and metabolites to 58% of the 100 mg dose administered. The determination of HHMA in plasma and urine samples is of interest in order to establish its relevance in MDMA metabolism and its possible contribution to MDMA neurotoxicity in humans. Its validation showed appropriate accuracy and precision for its use in pharmacokinetic studies.

Ictiosis ligada al sexo. / Ichthyosis linked to sex

Se estudio un paciente con ILS efectuandose una revision bibliografica de la fisiopatologia, conjuntamente con la deficiencia de la enzima sulfatasa esteroidea y se estudiaron los mecanismos por los cuales se producen alteraciones en el trabajo de parto

Manejo de los pólipos colorrectales / Management of colorectal polyps

Se revisa en forma retrospectiva la experiencia del Servicio de Cirugía del Hospital Regional de Talca en el manejo de los pólipos colorrectales, desde el 1 de enero de 1995 hasta el 30 de junio de 1997. La serie está constituida por 42 pacientes a los que se le extirparon 53 pólipos. Veinticuatro pacientes (57 por ciento) fueron mujeres y 18 (43 por ciento) hombres, la edad promedio fue de 53 años. Dos (4,7 por ciento) pacientes tenían antecedentes de cáncer colorrectal operado. La localización de los pólipos fue el recto en 20 (37,7 por ciento), sigmoides en 23 (43,4 por ciento), descendente en 7 (13,2 por ciento), transverso en 2 (3,8 por ciento) y no se consegnó en 1 (1,9 por ciento); 51 pólipos fueron extirpados endoscópicamente (96,4 por ciento), 2 debieron ser extirpados por laparotomía (3,8 por ciento). No hubo morbilidad ni mortalidad en la serie. La histopatología demostró adenomas tubulares o tubulovellosos en 32 pólipos (60,3 por ciento), de ellos el 46 por ciento tenían displasia leve y el 54 por ciento displasia moderada o intensa, 1 con Ca invasor. Los otros 20 pólipos (37,7 por ciento) fueron juveniles, hiperplásicos o inflamatorios. En los casos de adenomas con algún grado de displasia se recomienda control colonoscópico a los 6 y 18 meses y luego cada 3 años. En aquellos con cáncer invasor se sugiere aplicar los criterios de Morson para decidir complementar con tratamiento quirúrgico

Manejo del Síndrome de Ogilvie / Management of Ogilvie's syndrome

El Síndrome de Ogilvie es una condición caracterizada por marcada dilatación segmentaria o total de colon. Se observa en pacientes con patología médica o quirúrgica grave y en el postoperatorio de intervenciones obstétricas. El manejo es inicialmente conservador aunque puede requerir cirugía. Se revisan, retrospectivamente, las fichas clínicas de todos los enfermos tratados por un Síndrome de Ogilvie entre el 1 de julio de 1996 y el 31 de junio de 2002. La serie está constituida por 12 pacientes, el promedio de edad fue de 55 años. La patología de base que explicó el Síndrome de Ogilvie fue cardiovascular en 5 (41,7 por ciento), gíneco-obstétrica en 2 (16,6 por ciento) y otras en 5 (41,7 por ciento), además se consideró como causa desencadenante al uso de nifedipino en 2 casos. El diagnóstico fue realizado por Rx de Abdomen simple en todos los casos, el manejo se realizó con colonoscopia, sonda rectal y suspensión de nifedipino cuando correspondió. No hubo complicaciones ni mortalidad atribuibles al Síndrome de Ogilvie o a su manejo. Diez enfermos necesitaron sólo 1 colonoscopia y 2 requirieron de 2 procedimeintos. Fallecieron 5 pacientes (41,7 por ciento) debido a su patología de base.

Hepaticoyeyunostomía: resultados inmediatos / Hepatic jejunostomy: immediate results

La obstrucción del flujo biliar al tubo digestivo es siempre un problema muy grave; de no solucionarse termina con la vida del paciente y a veces en forma lenta y tormentosa. Cuando esto sucede una forma de reconstrucción de este flujo, de acuerdo a la anatomía resultante es la hepaticoyeyunostomía. En este trabajo se presenta la experiencia y resultados inmediatos en esta técnica en el Servicio de Cirugía entre octubre de 1993 y junio de 1997. La serie está formada por 13 pacientes, 5 hombres y 8 mujeres. La edad promedio fue 40 años. La razón de la obstrucción biliar fue iatrogenia en 11 y patología benigna en 2. La hepaticoyeyunostomía sólo en 2 casos se realizó en la misma operación, motivo del accidente, y el los otros 4 en cirugía abierta. En 2 casos de colecistectomía laparoscópica no se notificaron incidentes en el momento de ella apareciendo la complicación en meses posteriores. En la serie no hubo fallecidos pero sí complicaciones en 8 de los 13 pacientes (61 por ciento); 3 fueron reoperados. Se concluye que los resultados son satisfactorios pues no hubo mortalidad aunque la morbilidad fue elevada. La evaluación definitiva de éstos sólo se puede efectuar a largo plazo