Anestesia intracervical para la realización del legrado uterino instrumental / Intracervical anesthetic infiltration for use with instrumental uterine curettage

OBJETIVO: En esta investigación se evaluó la infiltración anestésica intracervical en pacientes en situación de aborto para realizar el legrado uterino instrumental. Pacientes y métodos Se estudió una muestra de 20 pacientes en situación de aborto. El estudio fue abierto, prospectivo y exploratorio. La edad de las pacientes tuvo un rango de 17 a 49 años de edad, con una media y desviación estándar de 26,95 ± 9,2058. La edad de la gestación tuvo un rango de 5 a 14 semanas con una media y desviación estándar de 8,75 ± 2,4622. Para el análisis estadístico se usó el programa SPSS. Para la anestesia intracervical se utilizó lidocaína al 1%, 10 ml; 5 ml en cada una de las infiltraciones, la primera a las III y la segunda a las IX de las manecillas del reloj. RESULTADOS: La duración de la anestesia tuvo un rango de 30 a 70 min, con una media y desviación estándar de 48,25 ± 13,8992. CONCLUSIÓN: La duración del tiempo quirúrgico desde la infiltración anestésica y el legrado uterino tuvieron un rango de 7 a 14min, con una media y desviación estándar de 10,9 ± 2,1886. El sangrado tuvo un rango de 50 a 150ml, con una media y desviación estándar de 100 ± 44,7213. Todos los estudios fueron longitudinales

Objetive: We performed an open, prospective, exploratory and longitudinal study to evaluate the use of intracervical anesthetic infiltration with instrumental uterine curettage in 20 women undergoing pregnancy termination. PATIENTS AND METHODS: The patients' age ranged from 17 to 49 years (mean and SD:26.95±9.2058). The length of gestation ranged from 5 to 14 weeks (mean and SD:8.75±2.4622). The SPSS program was used for the statistical analysis. RESULTS: For intracervical anesthesia, 10 ml lidocaine at 1% was used; 5ml was applied at infiltration points III and IX clockwise. Anesthesia lasted 30 to 70 minutes (mean and SD: 48.25 ± 13.8992). CONCLUSIONS: Operating time (infiltration and curettage) ranged from 7 to 14 minutes (mean and SD: 10.9 ± 2.1886). Blood loss ranged from 50 to 150ml (mean and SD: 100 ± 44.7213). All studies were longitudinal

Correlacion clínico-gráfica entre la frecuencia cardiaca y la hipomotilidad fetal / Clinical-cardiotocographic correlation between fetal heart rate and hypomotility

Objetivo: El objetivo de la investigación fue determinar la morfología y las alteraciones de la frecuencia cardiaca en fetos con hipomotilidad. Material y método La muestra la integraron 40 pacientes, que se dividió en 2 grupos: grupo 1 (problema), 20 pacientes embarazadas con diagnóstico de hipomotilidad fetal; grupo 2 (testigo), 20 pacientes con embarazo normal. Se practicaron registros de frecuencia cardíaca fetal (FCF) y contractilidad uterina; la duración fue de 2h. Se utilizó un cardiotocógrafo Corometrics Modelo 0115JAA, Serie 0488301.ResultadosEl análisis de la FCF Basal entre los grupos problema y testigo reveló que en el primero la media y la desviación estándar fueron de 136,91±8,75 lat./min, al compararla con el segundo grupo la media (..) (AU)

Objective: To determine the morphological consequences and heart rate alterations in fetuses with hypomotility. Material and method: A sample of 40 patients was divided into 2 groups. Group 1 (the problem group) consisted of 20 pregnant patients who had been diagnosed with fetal hypomotility. Group2 (the control group) consisted of 20 patients with a normal pregnancy. Fetal heart rate (FHR) and uterine contractility were measured for 2 hours. A Corometrics cardiotocograph model 0115JAA, series 0488301 was used. Results: The baseline FHR of the two groups was compared. The mean and standard deviation (SD) were 136.91 ± 8.75 beats/min in group 1 and 135.5 ± 10.57 beats /min in group 2. The difference between the means was one beat and the t-value was 0.46. This difference was not significant. The mean and SD of the amplitude of the accelerations were calculated in both groups, obtaining values of 22.47 ± 7.76 in group 1 and 24.81 ± 7.41 in group 2. The difference between (..) (AU)

La frecuencia cardiaca fetal en pacientes con diagnóstico de embarazo prolongado / Fetal heart rate in patients with prolonged pregnancy

Se determinaron los valores de la frecuencia cardiaca fetal (FCF) basal y la amplitud de las aceleraciones en pacientes con embarazo prolongado para equipararlos con un grupo testigo. El diseño del estudio fue: abierto, prospectivo, comparativo y exploratorio. La muestra la integraron 40 pacientes, se dividió en 2 grupos: Grupo 1 o problema: 20 pacientes con embarazo prolongado. Grupo 2 o testigo: 20 pacientes con embarazo normal. Con ultrasonido se determinó el diámetro biparietal. Se les practicaron registros de FCF y contractilidad uterina durante 2h.En los grupos problema y testigo, se equipararon la FCF basal y la amplitud de las aceleraciones, en el primer grupo la FCF se incrementó 3 latidos, la diferencia entre medias fue altamente significativa; en la amplitud no lo fue.En 2 trazos de FCF se registraron Dips Tipo II de mediana amplitud en medio de un patrón reactivo. Se elaboraron diagramas de dispersión y se calculó la regresión a una recta, utilizando los valores del diámetro biparietal de productos de embarazo prolongado, la ecuación de la recta fue y=2,2183x+7,6909 y el coeficiente de correlación de R2=0,8877. En el grupo con distribución normal, la ecuación de la recta fue y=2,0344x +12,944; y el coeficiente de correlación de R2=0,9981.En los grupos problema y el testigo, se (..) (AU)

Basal values of fetal heart rate (FHR) and amplitude of the accelerations were determined in patients with prolonged pregnancy and were compared with those in a control group. The study design was open, prospective, comparative and exploratory. The sample consisted of 40 patients divided into two groups. Group 1 (problem group) was composed of 20 patients with prolonged pregnancies. Group 2 (control group) consisted of 20 patients with a normal pregnancy. Ultrasound was used to determine parietal diameter. FHR and uterine contractility were measured for 2 h. Basal FHR and the amplitude of the accelerations in the two groups were compared. In group1, FHR was 3 beats higher and the difference between the means was highly significant. The difference in amplitude was not significant. In two FHR recordings, Type II Dips of moderate amplitude were registered during a reactive pattern. Dispersion diagrams were drawn and the linear regression of the biparietal diameter values of group 1 fetuses was calculated. The equation was y=2.2183x + 7.6909 and the correlation coefficient was R2=0.8877. In group 2 (normal distribution) the linear regression equation was y=2.0344x + 12.944. The correlation coefficient was R2=0.9981.The means of the biparietal diameters of the two groups were also compared but no significant differences were found. The mean values for uterine height and abdominal perimeter were 37.15cm. and 109.10cm, respectively. The physical status of the newborns was evaluated using the Apgar test at 1 and 5 minutes. Three children were born depressed with a score of 2. Three other children were not tested. Fourteen showed a score in the range of 7-8. At 5min their score was 9. Two neonates remained depressed. The weights of the neonates in the two groups were compared and those in group 1 were 418g heavier. The difference between mean weights was significant. Height was not significantly different(AU)

La frecuencia cardiaca fetal en embarazadas adolescentes / Fetal heart rate in pregnant adolescents

Se determinaron los valores de la frecuencia cardiaca fetal (FCF) basal y la amplitud de las aceleraciones en embarazadas adolescentes para compararlos con un grupo testigo. El diseño del estudio fue: abierto, prospectivo, comparativo y exploratorio. La muestra la integraron 40 pacientes: grupo 1 o problema,20 embarazadas adolescentes, grupo 2 o testigo, 20 pacientes con embarazo normal. Con ultrasonido se determinó el diámetro biparietal. Se les practicaron registros de FCF y contractilidad uterina durante 2:00h. Se utilizó un cardiotocógrafo HP, modelo 1350, serie 50XM. Todos los estudios fueron longitudinales. En los grupos problema y testigo, se compararon la FCF basal y la amplitud de las aceleraciones, en el primero la FCF se incremento 4 latidos, la diferencia fue altamente significativa y la amplitud descendió 1 latido. En 2 trazos de FCF se registraron Dips Tipo ir de pequeña y gran amplitud en medio de un patrón reactivo. Se elaboraron diagramas de dispersión, en el grupo problema se calculó la regresión a una recta, se utilizaron los valores del diámetro biparietal de fetos de embarazadas adolescentes, el coeficiente de correlación fue muy bueno R2=0,9579. En el grupo con distribución normal, el coeficiente de (..) (AU)

Basal values of fetal heart rate (FHR) and amplitude of the accelerations were determined in pregnant adolescents and compared with those of a control group. The study design was open, prospective, comparative and exploratory. The sample consisted of 40 patients divided into two groups. Group 1 (the problem group)was composed of 20 pregnant adolescents. Group 2 (the control group) consisted of 20 patients with a normal pregnancy. Ultrasound was used to determine the biparietal diameters of the fetuses. FHR and uterine contractility were measured for 2 h. An HP cardiotocograph, model 1350, series 50 XM was used. All these studies were longitudinal. Basal FHR and the amplitude of the accelerations of the two groups were compared. In group1, FHR was 4 beats higher and this difference was highly significant. Amplitude was 1 beatlower. In two FHR recordings, Type II Dips of moderate and large amplitude were registered (AU)

La frecuencia cardiaca en fetos con restricción en el crecimiento y desarrollo / Heart rate in fetuses with restricted growth and development

Se determinaron los valores de la FCF y las aceleraciones en fetos con restricción en el crecimiento y desarrollo y se equipararon con un grupo testigo. El estudio fue abierto, prospectivo, comparativo y exploratorio. La muestra la integraron 40 pacientes, se dividió en 2 grupos: grupo 1 o problema: 20 pacientes embarazadas con diagnóstico de RCF; grupo 2 o testigo: 20 pacientes con embarazo normal. Con ultrasonido se determinó el diámetro biparietal del feto. Se realizaron registros de FCF y contractilidad uterina. El estado físico de los RN se valoró con la prueba de Apgar, se les pesó y determinó la talla. En los grupos problema y testigo se equipararon la FCF basal y la amplitud de las aceleraciones. En el primero, la FCF se incrementó 5 latidos y la amplitud decreció 3 latidos, las diferencias fueron altamente significativas. Se elaboraron diagramas de dispersión, se calculó la regresión a una recta utilizando los valores del diámetro biparietal de fetos con restricción en el crecimiento, la ecuación fue y=0,547 x+64,38 y el coeficiente de correlación de R2=0,3561. En el grupo con distribución normal, la ecuación de la recta fue y=2,0344 x+12,944 y el coeficiente de correlación de R2=0,9981.Se equipararon las medias del diámetro biparietal entre los grupos problema y testigo. La diferencia no fue significativa. Se calcularon las medias de la altura uterina y el perímetro abdominal, los valores fueron de 33,45 y 101,15.El estado físico de los RN se valoró de acuerdo con la prueba de Apgar. En el 1.ermin, 2 neonatos nacieron deprimidos con calificación de 6;12, vigorosos con rango de 7–9 y en los 6 restantes no se aplicó la prueba; en el 5.°min la calificación fue de 7–9.Al confrontar los grupos problema y testigo, en primero el peso y la talla de los recién nacidos sufrieron un decremento de 243g y de 2c.p< indicó que las diferencias fueron significativas(AU)

Fetal heart rate (FHR) values and accelerations were determined in fetuses with restricted growth and development and were compared with those in a control group. The study design was open, prospective, comparative and exploratory. The sample consisted of 40 patients divided into two groups. Group 1 (problem group) was composed of 20 pregnant women diagnosed with restricted fetal growth and development. Group 2 (control group) consisted of 20 patients with normal pregnancies. Ultrasound was used to determine the biparietal diameter of the fetuses. FHR and uterine contractility were measured. The Apgar test was used to evaluate neonatal status. Neonates were weighed and measured. Basal FHR in group 1 was 5 beats higher with an amplitude of 3 beats less than in the control group. These differences were highly significant. Dispersion diagrams were drawn and linear regression was calculated for the parietal diameters of fetuses with restricted growth. The equation was y=0.547x+64.38 and the correlation coefficient was R2=0.3561. In the control group the equation for the linear regression was y=2.0344x+12.944 and the correlation coefficient was R2=0.9981.The means of the biparietal diameters of groups 1 and 2 were compared but no significant differences were found. The mean values for uterine height and abdominal perimeter for the two groups were 33.45cm and 101.15cm, respectively. The physical status of the newborns was evaluated using the Apgar test. At 1min, two neonates were depressed with an Apgar score of 6. Twelve neonates were vigorous with scores ranging from 7 to 9 and the six remaining neonates were not tested. At 5min, scores ranged from 7 to 9.When the two groups of neonates were compared, the weights and heights of those in group 1 were 243g and 2cm lower and these differences were significant (p<0.05)(AU)

Carrier detection and prenatal molecular diagnosis in a Duchenne muscular dystrophy family without any affected relative available.

In this paper we report a family where the affected DMD patients were not available for study and a molecular strategy was used for female carriers detection and for prenatal diagnosis. Linkage analysis was performed with two markers within the DMD gene, in all family members screened. DMD markers used (pERT87.8/Taq1 and pERT87.15/Xmn1) seemed not to be informative because the propositas mother (II-2) was homozygous for the minor allele at each marker (T2 and X2), however, the proposita and one sister carried only the major allele, which was inherited from the father. These results suggested that a deletion involving both markers could be present, and was inherited from the mother to both daughters. Quantitative multiplex PCR confirmed the deletion in female carriers, involving at least exons 12 to 17. DNA studies of cultured amniotic fluid cells at 14 weeks gestation, by amplification of specific Y-chromosome sequences, followed by multiplex PCR, lead to the diagnosis of a male fetus affected by DMD.

Chromosomal translocation 3;22 in an infertile man.

OBJECTIVE: To present the first case of an infertile male with a normal phenotype and chromosomal translocation 3;22. DESIGN: Case report. SETTING: POVISA Medical Center. PATIENT(S): A 45-year-old man with primary infertility for 13 years and with different partners; the patient has a family history of recurrent miscarriages and low fertility. INTERVENTION(S): Lymphocytic karyotype and electron microscopy. MAIN OUTCOME MEASURE(S): Physical examination and semen analysis. RESULT(S): The semen analysis revealed oligoasthenoteratospermia. The lymphocytic karyotype detected a translocation 3;22, and electron microscopy showed a lack of the central microtubule pair and peripheral doublet. CONCLUSION(S): An association between translocation 3;22 and other abnormalities in infertile males has been reported, but no such association has ever been described in men whose only clinical manifestation is infertility.

[Folic acid levels, homocysteine and polymorphism of methylenetetrahydrofolate reductase enzyme (MTHFR) in patients with pre-eclampsia and eclampsia]. / Niveles de ácido fólico, homocisteína y polimorfismo de la enzima metilentetrahidrofolatorreductasa (MTHFR) en pacientes con preeclampsia severa y eclampsia.

UNLABELLED: Preeclampsia and eclampsia are the primary causes of maternal mortality. In the state of Nuevo León, from 1990 to 1998, these conditions represented 44.1% of maternal deaths. The presence of thrombogenic substances (homocysteine, C protein, and anticardiolipin antibodies) in the mother's blood has been related to this problem. The C677T polymorphism of the enzyme methylene tetrahydrofolate reductase (MTHFR) favors the increase of homocysteine levels, while folic acid (FA) supplementation decreases its levels. OBJECTIVE: To establish the role of FA in the physiopathology of preeclampsia in our environment. KIND OF STUDY: Longitudinal, prospective and comparative. CASES: Women with severe preeclampsia and/or eclampsia (n-13). CONTROLS: Women in the third trimester of a normal pregnancy (n + 15). 20 mL Blood samples were taken during the first 24 hours of puerperium, and their AF, homocysteine and MTHFR polymorphism were measured. The t Student test and the Exact Fisher test were used to compare between both groups. RESULTS: The values obtained for homocysteine were (x + SD): CASES: 9.85 micromoles/L + 2.88, and controls: 7.61 micromoles/L + 1.32 (p < 0.04). The frequency (%) of the genetic polymorphism for MTHFR was: positive homozygotes (T/T): 38.46 vs. 20, heterozygotes (C/T): 38.46 vs. 26.6, negative homozygotes (C/C): 23 vs 53, for cases and controls, respectively. CONCLUSIONS: According to our study, the frequency of the homozygote state (T/T) of MTHFR and increased blood levels of homocysteine is greater in women suffering from preeclampsia.

[Abnormalities of sex chromosomes and relationship with reproduction disorders]. / Alteraciones de los sexocromosomas y su relación con los trastornos de la reproducción.

One third of the reproductive failure with genetic aetiology are explained by chromosomal rearrangements; the purpose of the study was to find the frequency of sex chromosome anomalies in Mexican population with amenorrhea, sterility or infertility at the National Institute of Perinatology. We realized cytogenetic studies at the Genetics' laboratory in blood samples from 1st january 1984 to 31st December 1995, with the next indications: amenorrhea, sterility, infertility and history of congenital defects that suggest chromosomal anomalies and correlated with the clinical findings. From 3,201 cytogenetic studies we performed in peripheral blood samples, we detected: 61 patients with anomalies of the sex chromosomes predominantly mosaics. We found sex chromosome rearrangements in 1.5% of the patients studied, so it's important to consider this aetiology in the study of infertility and sterility.

Oral-facial-digital (OFD) syndrome with associated features: a new syndrome or genetic heterogeneity and variability?

We report a male patient with clinical characteristics compatible with an OFD syndrome and previously unassociated findings such as myelomeningocele, stenosis of aqueduct of Sylvius and heart anomalies, that we feel that may represent a new type of OFD syndrome (XII).

[Usefulness of ultrasonographic markers in chromosomal abnormalities]. / Utilidad de los marcadores ultrasonográficos de cromosomopatía.

During a 3 and 1/2 years, 132 pregnancies were diagnosed as having a wide variety of congenital abnormalities. A high resolution ultrasound and multidisciplinary approach was used. In 95 cases fetal karyotyping was made. In this group the incidence of chromosomal abnormalities diagnosed during the period and phenotypic expression of the different types of chromosomal abnormalities was investigated. 29 abnormal karyotypes were found; 11 trisomy 18, 7 in monosomy X, 4 in trisomy 21, 3 in trisomy 13, 1 with tetraploidy (92XXYY), 1 Turner mosaic (45XO 68% 46XY 32%), 2 inversions of choromosome 9. Of the total abnormal chromosomal diagnosed during the period (N = 57), this group represented 49.2%, compared to 5 to 15% found in other risk groups. 224 congenital abnormalities were found. 43 (19%) isolated, and 181 (81%) associated. Of the 224 congenital abnormalities diagnosed, 80 (36%) were associated with chromosomal abnormalities. The most associated markers were duodenal atresia, heart defect, microcephaly, enlarged posterior fossa, and cystic hygromata. A specific markers pattern was found for each aneuploidy; heart defects for trisomy 18, holoprosencephaly and faciel cleft for trisomy 13, and cystic hygromata for monosomy X. It was concluded that the ultasound can be the most useful method to select the group of pregnant women with a higher risk of abnormal karyotype.

A case of mosaic Down's syndrome with two Robertsonian translocations.

A baby with stigmata of Down's syndrome was found to be a mosaic with two different cell lines: 45,XX,der(14q;21q)/46,XX,der(21q;21q)+21. The chromosome rearrangements appeared to have risen de novo. Four mechanisms are discussed for the origin of the mosaicism: dissociation of a translocation (14q;21q) chromosome already present in the 45,XX, der(14q;21q) zygote; two translocation events occurring sequentially at the first and second zygote (46,XX) divisions; a chromatid translocation in a 47,XX,+21 zygote; and an independent origin of the two cell lines.

[Multidisciplinary assessment of the fetus with hydrocephalus: study protocol and results]. / Evaluación multidisciplinaria del feto con hidrocefalia: protocolo de estudio y resultados.

The objective was to make the confirmation-exclusion diagnosis of fetal hydrocephaly, to study its etiology and identify associated anomalies. 67 cases with suspected fetal hydrocephaly were studied at 30 weeks of mean gestational age. Serial studies of ultrasonography, TORCH serology and fetal karyotype were made. Postnatal correlation was made. 14 cases were not confirm and 53 were. 6 cases (11.3%) were classified as isolated hydrocephaly and 47 (88.7%) with associated anomalies. In this group, 15 with only intracranial anomalies and 32 intracranial and extracranial anomalies. All chromosomic anomalies were found in this latter group. Proved in all the cases of hydrocephaly and most of its associated anomalies were documented. Fetal hydrocephaly can be accurately diagnosed with the technology presently available. The diagnosis of associated anomalies is more difficult to obtain, but can be reached using serial studies and multidisciplinary approach.

[Reye's syndrome in an adult. Review of pathogenic mechanisms]. / Síndrome de Reye en un adulto. Revisión de los mecanismos patogénicos.

Reye's syndrome is considered a disease of the pediatric age. It is characterized by a prodrome of viral illness followed by vomiting and encephalopathy with associated hepatic dysfunction. This syndrome is potentially life-threatening with high morbidity and mortality rates. There are 27 other cases of adult onset Reye's syndrome reported in the literature. We describe a 18-year-old woman who developed varicella and four days later started with vomiting, delirium and in the following day she became comatose. Laboratory tests of liver function and pathology of a liver biopsy proved the diagnosis. The patient survived. A review of the proposed pathogenic mechanisms are presented. Our patient represents case the number 28 in world literature and the first in the mexican literature.

Contextual interference effects with skilled baseball players.

The learning benefits of contextual interference have been frequently demonstrated in different settings using novice learners. The purpose of the present study was to test such effects with skilled athletic performers. Scheduling differences for biweekly additional ("extra") batting-practice sessions of a collegiate baseball team were examined. 30 players (ns = 10) were blocked on skill and then randomly assigned to one of three groups. The random and blocked groups received 2 additional batting-practice sessions each week for 6 wk. (12 sessions), while the control group received no additional practice. The extra sessions consisted of 45 pitches, 15 fastballs, 15 curveballs, and 15 change-up pitches. The random group received these pitches in a random order, while the blocked group received all 15 of one type, then 15 of the next type, and finally 15 of the last type of pitch in a blocked fashion. All subjects received a pretest of 45 randomly presented pitches of the three varieties. After 6 wk. of extra batting practice, all subjects received two transfer tests, each of 45 trials; one was presented randomly and one blocked. The transfer tests were counterbalanced across subjects. Pretest analysis showed no significant differences among groups. On both the random and blocked transfer tests, however, the random group performed with reliably higher scores than the blocked group, who performed better than the control group. When comparing the pretest to the random transfer test, the random group improved 56.7%, the blocked group 24.8%, and the control group only 6.2%.(ABSTRACT TRUNCATED AT 250 WORDS)

Toxicity and tissue distribution of methacrylonitrile in rats.

The toxicity, uptake, tissue distribution, elimination, and covalent binding of 2-[14C]methyl-[2.3-14C]acrylonitrile (MeAN) in male Sprague-Dawley rats were investigated. Following an oral administration of 100 mg/Kg body weight (0.5 LD50, 8 microCi/Kg bw) the rats exhibited several signs of toxicity including ataxia, convulsions, mild diarrhea, salivation, lacrimation, and bladder urine retention. The treated animals excreted 43% of the 14C in the urine, 14% in the feces, and 2.5% in the expired air as 14CO2 in 10 days. Hydrogen cyanide was not detectable. Red blood cells retained significant amounts of radioactivity for more than 10 days after treatment. MeAN was extensively absorbed through the gastrointestinal tract and distributed in all the tissues of the rats. The major concentrations of the radioactivity were found with up to 25% of the administered dose in bone, liver, spleen, kidney, blood, and the gastrointestinal tract. This study indicates that MeAN is rapidly absorbed and distributed and the major route of excretion is urinary.

Metabolism of methacrylonitrile to cyanide: in vitro studies.

In liver fractions from male Sprague-Dawley rats, the metabolism of methacrylonitrile (MeAN) to cyanide (CN-) was localized in microsomal fraction and required reduced nicotinamide adenine dinucleotide phosphate (NADPH) and oxygen for maximal activity. The biotransformation of MeAN to CN- was characterized with respect to time, microsomal protein concentration, pH, and temperature. Metabolism of MeAN was increased in microsomes obtained from phenobarbital-treated rats (310% of control) and decreased with CoCl2 and SKF 525 A treatments (55% and 61%, respectively). Addition of the epoxide hydratase inhibitor, 1,1,1-trichloropropane 2,3-oxide, decreased the formation of CN- from MeAN. Addition of glutathione, cysteine, D-penicillamine, and 2-mercaptoethanol enhanced the released of CN- from MeAN. These findings indicate that MeAN is metabolized to CN- via a cytochrome P-450-dependent mixed-function oxidase system.

Disposition of methacrylonitrile in rats and distribution in blood components.

The interaction of 2[14C]methyl-2,3[14C]acrylonitrile (MeAN) with the components of blood and its disposition in male Sprague-Dawley rats has been investigated. Following an oral administration of 100 mg/kg (0.5 LD50, 8 microCi/kg), the rats excreted 43% of the [14C] in the urine, 15% in the feces and 2.5% in the expired air as 14CO2 in 5 days. Hydrogen cyanide (H14CN) was not detectable. The red blood cells retained significant amounts of radioactivity for more than five days after administration, whereas the [14C]-activity in plasma declined sharply. More than 50% of the radioactivity in erythrocytes was detected as covalently bound to cytoplasmic (hemoglobin) and membrane proteins. A small amount of radioactivity was also found in the heme fraction. About 13% of the total dose administered was recovered as thiocyanate in the plasma and the urine. These results suggest that the toxicity of MeAN may be attributable to the whole molecule and not entirely to the in vivo liberation of cyanide.

Interaction of methacrylonitrile with glutathione.

The interaction of methacrylonitrile (MeAN) with glutathione (GSH) was evaluated in aqueous solution and its in vivo potential to deplete GSH in male Sprague Dawley rats at the 0.5 LD50 dose of 100 mg MeAN/Kg body weight was investigated. Addition of MeAN (0-40 mM) to a solution of 0.3 mM GSH in 2 mM EDTA, pH 7.4, resulted in a time and concentration dependent depletion of GSH determined as nonprotein sulfhydryl. Thin layer chromatography analysis of incubation mixtures of MeAN with GSH and cysteine showed the appearance of distinct spots representing the adducts S-cyanopropyl GSH and S-cyanopropyl cysteine. Oral administration of MeAN to the rats resulted in significant depletion of GSH in the liver, kidney, heart, lung, brain and spleen. The maximum GSH depletion was noticed in the liver (approximately 39% of control) and in other organs it ranged between 26-34% of control. It is likely that the toxicity of MeAN may be related to in vivo GSH depletion.