Acquisition of American sign language by a noncommunicating autistic child

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents. Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1-2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1-2 ppm, the clearance values for hemoperfusion were some 5-7 times higher than those for hemodialysis. In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquats less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.     

Comparative toxicity of azinphos-methyl to house mice, laboratory mice, deer mice, and gray-tailed voles

A laboratory toxicity study on house mice and laboratory mice (Mus musculus), gray-tailed voles (Microtus canicaudus), and deer mice (Peromyscus maniculatus) was conducted as part of a comprehensive laboratory and field study to field validate laboratory-based risk assessment of pesticides. The single dose oral LD50 for the organophosphorus insecticide azinphos-methyl (Guthion) was 10, 11, 32, and 48 mg/kg body weight in wild house mice, laboratory mice, gray-tailed voles, and deer mice, respectively. Ten-day dietary LC50s were 277 ppm for laboratory mice, 297 ppm for gray-tailed voles, and 1,180 ppm for deer mice. All treated animals lost more weight, consumed less food, and had depressed brain cholinesterase (ChE) activity compared to controls. Five-day LC50s were significantly higher than 10-day LC50s for laboratory mice and deer mice. For all three species, animals that died during dietary LC50 tests had mean ChE activity of 50-55% while survivors had 56-70% of controls. The conclusions were that: (1) Laboratory mice were not representative of deer mice or gray-tailed voles with respect to sensitivity to azinphos-methyl, but provided a conservative estimate for risk assessment; (2) 10-day dietary LC50 tests indicate substantially greater estimates of toxicity of azinphos-methyl to rodents than do 5-day tests; and (3) brain ChE depression of 45-50% was lethal in these species.     

Training effects of short and long bouts of brisk walking in sedentary women

This study compared the effects of short and long bouts of brisk walking in sedentary women. Forty seven women aged 44.4 +/- 6.2 yr (mean +/- SD) were randomly assigned to either three 10-min walks per day (short bouts), one 30-min walk per day (long bouts) or no training (control). Brisk walking was done on 5 d x wk(-1), at 70 to 80% of maximal heart rate, typically at speeds between 1.6 and 1.8 m x s(-1) (3.5 and 4.0 mph), for 10 wk. Subjects agreed not to make changes to their diet. Twelve short-bout walkers, 12 long-bout walkers, and 10 controls completed the study. Relative to controls, VO2max (short-bout, +2.3 +/- 0.1 mL x kg(-1) x min(-1); long-bout, +2.4 +/- 0.1 mL x kg(-1) x min(-1); controls, -0.5 +/- 0.1 mL x kg(-1) x min[-1]) and the VO2 at a blood lactate concentration of 2 mmol x L(-1) increased in walkers (both P < 0.05), with no difference in response between walking groups. Neither heart rate during standard, submaximal exercise nor resting systolic blood pressure changed in a different way in walkers and controls. The sum of four skinfold thicknesses decreased in both walking groups (P < 0.05) but body mass (short-bout, -1.7 +/- 1.7 kg; long-bout, -0.9 +/- 2.0 kg; controls, +0.6 +/- 0.7 kg) and waist circumference decreased significantly only in short-bout walkers. Changes in anthropometric variables did not differ between short- and long-bout walkers. Thus short bouts of brisk walking resulted in similar improvements in fitness and were at least as effective in decreasing body fatness as long bouts of the same total duration.     

Determination of organochlorine and organophosphorus pesticide levels in imported beef

A simple and efficient cleanup method was established for capillary gas chromatographic determination of 12 organochlorine and 11 organophosphorus pesticides in beef. Extracted fat was subjected to silica gel dry column chromatography and further cleaned up by Florisil minicolumn chromatography for organochlorine pesticide analysis, while partitioning between n-hexane and acetonitrile of the extract and silica gel minicolumn chromatography were employed for the analysis of organophosphorus pesticides. Several samples (imported Australian beef) were analyzed by the proposed method. DDT was detected in 14 (0.01-0.10 ppm). BHC was found in 11 (0.003-0.031 ppm) and dieldrin was demonstrated in 2 (0.004 and 0.008 ppm). Heptachlors and the 11 organophosphorus pesticides investigated were not detected in any of the meat samples.     

Isotachophoretic separations on a microchip. Normal Raman spectroscopy detection

Isotachophoretic separations of the herbicides paraquat and diquat are performed in a glass microchip etched channel and monitored on-chip by normal Raman spectroscopy. The 40-micron-wide and 75-micron-deep separation channels are chemically etched in a serpentine design to 21-cm total length. A 120-micron-thick glass cover slip is used to seal the channels. Separation field strengths up to 380 V/cm are used. The microchip is directly coupled to a Raman microprobe. No interfacing is required. Raman spectra are generated with a 2-W, 532-nm NdY-VO4 laser and collected at 8-cm-1 resolution with a holographic transmissive spectrograph and a cryogenically cooled CCD. Data acquisition is at 2-5 spectra/s. Raman isotachopherograms of the pesticides at starting concentrations as low as 2.3 x 10(-7) M (60 ppb paraquat/80 ppb diquat) are presented.     

RNA polymerase II transcription complex assembly in nuclear extracts

Variation in superovulatory responses in cattle may be related to the stage of follicular growth at the time of gonadotropin treatment. Waves of follicle growth are regulated by both follicle-stimulating hormone (FSH) and oestradiol. The objective of experiment 1 was to determine the dynamics of follicle wave emergence and the relationship with FSH and oestradiol concentrations, after treatment of heifers with oestradiol benzoate (ODB) in the presence of an intravaginal progesterone-releasing device (CIDR-B). Experiment 2 examined the superovulatory response, embryo yield and quality following treatment with porcine follicle-stimulating hormone (pFSH) at different times relative to ODB injection. In experiment 1, 28 beef heifers were treated with a CIDR for 9 days and allocated at random to one of four groups to receive either: (I) CIDR only, or 5 mg ODB given as a single intramuscular injection at (II) day 0 (d0); (III) day 1.5 (d1.5); or (IV) day 3 (d3) post CIDR insertion. Ovaries were examined using daily ultrasound and blood samples were collected twice daily for 11 days. In experiment 2, 96 heifers were treated with a CIDR and 5 mg ODB as in experiment 1, and were allocated using a 4 x 3 factorial design plan to a superovulation programme using three doses (400 IU; 600 IU; 800 IU) of pFSH. FSH was given for 4 days at 12-h intervals beginning 6.5 days after CIDR insertion. Heifers received prostaglandin analogue 12 h before CIDR removal and were inseminated (AI) at 48 and 60 h post CIDR withdrawal and embryos were recovered 7 days after AI. In experiment 1, the interval from CIDR insertion to follicle wave emergence (FWE) was longer (P < 0.05) in heifers treated with ODB at d1.5 (5.4 +/- 0.4 days) and d3 (5.1 +/- 0.6 days) compared to heifers treated with CIDR only (2.4 +/- 0.4 days). On the basis of time to proposed injection of pFSH heifers would have had follicle emergence 4.4, 2.3, 1.5 and 1.4 days prior to pFSH for groups I, II, III and IV, respectively. In experiment 2, heifers treated with ODB at d1.5 had a higher (P < 0.05) superovulatory response (18.2 +/- 1.7) than heifers treated at d3 (12.8 +/- 1.7), but superovulatory response in both groups did not differ (P > 0.05) from heifers treated at d0 (14.4 +/- 2.0) or with CIDR only (15.0 +/- 1.8). There were fewer (P < 0.05) freezable-grade embryos recovered from heifers treated with ODB at d0 (1.5 +/- 0.7) and d3 (2.1 +/- 0.5) compared to heifers treated at d1.5 (3.0 +/- 0.6) or in heifers treated with CIDR only (3.4 +/- 0.7). Increasing the dose of pFSH caused a linear increase in the superovulatory response (11.7 +/- 1.0, 15.8 +/- 1.4 and 18.0 +/- 1.9) and in the number of embryos recovered (5.8 +/- 0.9, 7.0 +/- 0.8 and 9.1 +/- 1.0) for 400 IU, 600 IU and 800 IU, respectively. In conclusion, heifers treated with ODB had wide variation in time to follicle wave emergence and there was not a consistent beneficial effect of pretreatment with ODB on embryo yield and quality following superovulation.     

Hatching of common carp (Cyprinus carpio L.) embryos stored at 4 and -2 degrees C in different concentrations of methanol and sucrose

The hatching performance of common carp (Cyprinus carpio L.) embryos was examined after 12-72-h storage at 4 and -2 degrees C using different concentrations of sucrose (0.1, 0.25, 0.5 and 1.0 M or 3.42, 8.55, 17.10 and 34.2%), methanol (MeOH) (0.5, 1.0, 1.5, 2.0, 2.5, 3.0 and 3.5 M or 1.6, 3.2, 4.8, 6.4, 8.0, 9.6 and 11.2%), or varying concentrations of methanol in 0.5 M (17.10%) sucrose. For sucrose, 0.5 M (17.10%) showed the maximum survival (41+/-1% (12 h) to 11+/-1.5% (72 h)) at 4 degrees C. No survival was observed at -2 degrees C with any concentration of sucrose. At both temperatures employed, hatching was higher with mixed combination of methanol (1.5 M or 4.8%) and 0.5 M (17.10%) sucrose (4 degrees C: 41+/-1.5% (12 h), 38+/-1.2% (72 h); -2 degrees C: 33+/-1.7% (12 h), 28+/-1.2% (72 h)) compared to methanol alone (4 degrees C: 38+/-1.5% (12 h), 35+/-2.5% (72 h); -2 degrees C: 31+/-2.5% (12 h), 25+/-2% (72 h)). The combination of 1.5 M (4.8%) methanol and 0.5 M (17.10%) sucrose produced the best results among all the concentrations tested at both temperatures.     

Rump white inversion in the mouse disrupts dipeptidyl aminopeptidase-like protein 6 and causes dysregulation of Kit expression

The mouse rump white (Rw) mutation causes a pigmentation defect in heterozygotes and embryonic lethality in homozygotes. At embryonic day (E) 7.5, Rw/Rw embryos are retarded in growth, fail to complete neurulation and die around E 9.5. The Rw mutation is associated with a chromosomal inversion spanning 30 cM of the proximal portion of mouse chromosome 5. The Rw embryonic lethality is complemented by the W19H deletion, which spans the distal boundary of the Rw inversion, suggesting that the Rw lethality is not caused by the disruption of a gene at the distal end of the inversion. Here, we report the molecular characterization of sequences disrupted by both inversion breakpoints. These studies indicate that the distal breakpoint of the inversion is associated with ectopic Kit expression and therefore may be responsible for the dominant pigmentation defect in Rw/+ mice; whereas the recessive lethality of Rw is probably due to the disruption of the gene encoding dipeptidyl aminopeptidase-like protein 6, Dpp6 [Wada, K., Yokotani, N., Hunter, C., Doi, K., Wenthold, R. J. & Shimasaki, S. (1992) Proc. Natl. Acad. Sci. USA 89, 197-201] located at the proximal inversion breakpoint.     

Effect of hexachlorobenzene on some growth parameters of Chlorella pyrenoidosa

Chlorella pyrenoidosa was incubated with HCB (0.001-10.0 ppm) in a "light-thermostat" at 30 degrees C for 46 h with continuous light (4000 Lux) and aeration. HCB decreased growth as deduced from measurements of chlorophyll content, dry matter, carbohydrate content, and total nitrogen. Incubation with HCB for three months in Erlenmeyer-flasks resulted in an increase of chlorophyll over control value in cultures receiving 0.1 and 1.0 ppm HCB. After transfer of the cultures from Erlenmeyer-flasks to growth conditions of a "light-thermostat", growth of the algae was greatly enhanced by all HCB concentrations studied; a concentration of 0.1 ppm being most effective.     

Effects of ammonium dinitramide on preimplantation embryos in Sprague-Dawley rats

Ammonium dinitramide (ADN) is a class 1.1 oxidizer that may be used in rocket propellants and explosives. Previous studies have shown that ADN is a female reproductive toxicant, causing implantation failure in Sprague-Dawley rats when it is administered during the preimplantation period of gestation. The purpose of this follow-up study was to identify the mechanism(s) associated with implantation failure following exposure to ADN. Mated female rats were treated with 2.0 grams per liter (g l-1) ADN in their drinking water for 24, 48, 72, or 96 h before preimplantation embryos were harvested from the oviducts or uterine horns. On gestation day 1 (GD-1), comparable numbers of morphologically normal two-cell embryos were harvested from the oviducts of the treatment and control groups. On GD-2, the development of the embryos harvested from the treated animals was either slowed or halted when compared to the control embryos. By GD-4, 98% of the embryos harvested from the control group had developed to the morula or blastocyst stage; these were collected from the uterine horns. On GD-4 in the treated group, 41% of the harvested embryos remained at the two- to six-cell stage and 59% were degenerate; 82% of these embryos were collected from the oviducts. These data suggest that the implantation failure seen in animals treated with ADN is due to embryolethality.     

Electron capture gas chromatographic analysis of the amine metabolites of pesticides: derivatization of anilines

A number of amines have been shown to result from metabolism of various pesticides. From an epidemiological standpoint, it may be possible to monitor human exposure to these pesticides through the excretion of their corresponding amines in urine. An investigation has been initiated to develop and apply methods of analysis of amines in human urine. The results of a survey of derivatization techniques involving several substituted anilines are presented. These include conditions for derivatization, utilizing a number of halo- and nitro- substituted reagents; electron capture and gas chromatographic properties of the derivatives; and stability of the derivatives to extraction and column chromatography for purposes of separation and cleanup. The recoveries of anilines from spiked water and urine samples at the 1.0 ppm and 0.1 ppm levels were between 85 and 90%. The advantages and disadvantages of the various derivatives and techniques are discussed and a rationale is presented for the preliminary selection of a particular derivative for application of the analysis of aniline metabolites in urine.     

Selenium content in cattle hair in areas with incidence of nutrition-induced muscular dystrophy

In the South Bohemian Region which is an area of enzootic incidence of nutritional muscle dystrophy selenium content in the fur of dairy cows and young cattle was determined. In the breeds in which the "white muscle disease" appeared in the past years in young cattle, lambs and calves the lowest mean selenium values in the fur dry matter found were: 0.18 +/- 0.07, 0.19 +/- 0.06, and 0.21 +/- 0.08 ppm, with repeated findings of mere 0.09 ppm Se. 60 to 100 per cent samples from these farms showed selenium values below the 0.25 ppm level. The fur of heifers which recovered from nutritional muscle dystrophy and were treated 10 days prior to sampling with a selenium preparation in injection form (Selevit inf. SPOFA) contained 0.29 ppm selenium (+/- 0.11). In other breeds 0.30 +/- 0.07 to 3.33 +/- 0.16 ppm selenium was found in the fur of cows and young cattle. The initial field essay of selenium content in cattle fur indicated a relation of low selenium values to the frequency of clinical forms of nutritional muscle dystrophy in domestic ruminants.     

Selenium and lead: mutual detoxifying effects

Antagonistic toxic effects of selenium and lead were studied in growing rats. Chronic lead intoxication was produced by cutaneous application of lead naphthenate solution (80-200 mg Pb/kg body weight) for a period of 8 weeks and chronic selenium intoxication was induced by giving 5 ppm, 10 ppm and 15 ppm selenium in drinking water. The growth rate and food consumption of rats receiving selenium in addition to lead approached normal rate while animals treated with only one of them showed hampered growth rate and lower food consumption. The enzymatic activity of delta-aminolevulinic acid dehydrase (ALA-D) in whole blood, liver and kidney and liver P-450 enzyme activity were normal in rats receiving both selenium and lead. The enzymic activities assayed were, however, depressed in the animals receiving either lead or selenium. Assay of lead and selenium in liver, brain, kidney and blood was carried out. Rats receiving both metals and higher concentrations of these metals in the organs studied, as compared to those only receiving one component. The data seem to indicate that the effect of selenium on the toxic effects of lead is similar to its protective role against methylmercury intoxication.     

90-day feeding and one-generation reproduction study in Crl:CD BR rats with 17 beta-estradiol

Over the past several years, there has been increasing concern that chemicals and pesticides found in the environment may mimic endogenous estrogens, potentially producing adverse effects in wildlife and human populations. Because estrogenicity is one of the primary concerns, a 90-day/one-generation reproduction study with 17 beta-estradiol was designed to set dose levels for future multigenerational reproduction and combined chronic toxicity/oncogenicity studies. The purpose of these studies is to evaluate the significance of a range of responses as well as to provide benchmark data for a risk assessment for chemicals with estrogen-like activities. This 90-day/one-generation reproduction study was conducted in male and female Crl:CD BR rats using dietary concentrations of 0, 0.05, 2.5, 10, and 50 ppm 17 beta-estradiol. Endpoints were chosen in order to evaluate both subchronic and reproductive toxicity. In addition, several mechanistic/biochemical endpoints were evaluated for their usefulness in follow-up studies. In the P1 generation, dietary administration of 2.5, 10, and 50 ppm 17 beta-estradiol produced dose-dependent decreases in body weight, body weight gain, food consumption, and food efficiency. At 10 and 50 ppm 17 beta-estradiol, minimal to mild nonregenerative anemia, lymphopenia, decreased serum cholesterol (50 ppm only), and altered splenic lymphocyte subtypes were also observed in the P1 generation. Additionally, at these concentrations, there were changes in the weights of several organs. Evidence of ovarian malfunction, characterized by reduced numbers of corpora lutea and large antral follicles, was observed at 2.5 ppm 17 beta-estradiol and above. Other pathologic changes in males and females fed 10 and 50 ppm 17 beta-estradiol included centrilobular hepatocellular hypertrophy; diffuse hyperplasia of the pituitary gland; feminization of the male mammary glands; mammary gland hyperplasia in females; increased number of cystic follicles in the ovary; hypertrophy of the endometrium and endometrial glands in the uterus; degeneration of seminiferous epithelium; and atrophy of the testes and the accessory sex glands. In the reproduction portion of this study, rats fed 10 or 50 ppm 17 beta-estradiol did not produce litters. While there was no evidence that the 50 ppm treated rats mated, 33.3% of the rats fed 10 ppm mated but did not produce litters. No effects on mating and fertility indices were observed in rats fed 0.05 and 2.5 ppm 17 beta-estradiol. Pup weights at birth were statistically decreased relative to control in the groups fed 0.05 and 2.5 ppm 17 beta-estradiol. Weights of the rats in the 0.05 ppm group recovered by postnatal day 4 and remained similar to control throughout the remainder of the study. The mean gestation length of the 0.05 ppm group was slightly, albeit not statistically significantly, shorter (0.5 days) than that of the control group, which may have contributed to the decrease in birth weight of the 0.05 ppm group. In contrast, the weights of the F1 generation rats fed 2.5 ppm 17 beta-estradiol remained decreased relative to the control group throughout the study. Parental administration of 17 beta-estradiol did not alter anogenital distance in male or female pups. The onset of sexual maturation, as measured by day of preputial separation in males and day of vaginal opening in females, was delayed in male rats fed 2.5 ppm (by 8.2 days) and was hastened in female rats fed 0.05 and 2.5 ppm (by 1.6 and 8.8 days, respectively). The age at vaginal opening ranged from 26 to 37, 26 to 35, and 21 to 25 days for rats fed 0, 0.05, and 2.5 ppm 17 beta-estradiol, respectively. Hence, the range of age at vaginal opening was similar between the control and 0.05 ppm group. The organ weight and pathologic alterations observed in the adult F1 generation rats were similar to those observed in the P1 generation rats. (ABSTRACT TRUNCATED)     

Familial cerebellar degeneration with slow eye-movements, mental deterioration and incidental nevus of ota (oculo-dermal melanocytosis)

In a bipartite rearing experiment (day 1-24 and 24-45) 72 early-weaned piglets were used to study the effect of varying dietary vitamin B6 contents on renal excretion of xanthurenic and kynurenic acid after a tryptophan load, on urea concentration and activities of two transaminases in serum at the end of each period. The animals, divided into 6 groups, were fed ad libitum a prestarter and a starter in period I and II, respectively, each containing 0.5, 1.2, 2.0, 2.8, 3.5 or 6.6 mg vitamin B6 per kg dry matter. The urinary xanthurenic acid excretion was elevated especially at the vitamin B6 supply of 0.5 ppm and rose severalfold with increasing depletion time (period II). In both periods, the smallest amount was excreted by piglets supplemented with 2.8 ppm. In comparison to groups B (1.2 ppm) and C (2.0 ppm), their average excretion rate was reduced by 29% and 15%, respectively, in period I and by 50% and 22%, respectively, in period II. Analogously to xanthurenic acid, the smallest amount of kynurenic acid was excreted by group D (2.8 ppm). Starting from the lowest vitamin B6 supply, the activity of SGPT showed an almost linear increase in both experimental periods. In contrast, SGOT already reached an upper activity level with the dietary vitamin B6 content of 3.5 and 2.8 ppm at the end of period I and II, respectively. The concentration of serum urea was influenced only by the lowest vitamin B6 supply of 0.5 ppm.     

Heat-induced alterations in embryonic cytoskeletal and stress proteins precede somite malformations in rat embryos

Previous work from this laboratory has demonstrated that heat exposure on gestation day 10 (GD10) resulted in disrupted somite development 24 hr after exposure and subsequent thoracic skeletal malformations in neonates. The purpose of the present study was to examine the effects of in vitro heat shock on de novo protein synthesis and on cytoskeletal protein levels in developing rat embryos. Explanted GD10 embryos were exposed to temperatures of 42-42.5 degrees C for 15 min. At various times postexposure (0-27 hr). embryos were labeled with 35S-methionine and processed for sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) separation. Transient enhanced de novo synthesis of 70- and 90-kD proteins was observed 1-8 hr after exposure. The 70-kD protein was identified as a eukaryotic stress protein and the presence of this protein was detected between 2 and 27 hr posttreatment. Western blot analysis was used to detect quantitative changes in total actin (microfilaments), tubulin (microtubules), and vimentin (intermediate filaments). Immediately following exposure, a reduction of total vimentin to minimal detectable levels was observed in heat-treated embryos. Levels of total vimentin remained depressed for more than 2 hr and gradually returned to control levels 4-8 hr postexposure. No change in total actin or tubulin was detected in treated embryos. The data demonstrate that heat-induced alterations in proteins comprising intermediate filaments occur concomitantly with the induction of stress proteins and precede aberrant somite morphology. These alterations in embryonic proteins may help elucidate the mechanism(s) by which skeletal malformations are produced.     

Postcoital antifertility activity of aminoalcohols

Previously, postcoital antifertility effects of a number of aminoalcohols, including 2-(isopropylamino)-ethanol, have been demonstrated in rodents. In this experiment, we compared the antifertility activity of 2-(isopropylamino)-ethanol to the following analogs: hydroxyethylpiperidine, hydroxyethylpiridine, hydroxyethylpirrolidine, and hydroxyethylpirrolidone. Female rats were gavaged on Days 0 through 5 of gestation with 0.7 mmol/kg/d of these substances. Only 2-(isopropylamino)-ethanol and hydroxyethylpirrolidine showed a strong antifertility activity: females treated with 2-(isopropylamino)-ethanol had no signs of implantation, whereas those treated with hydroxyethylpirrolidine had 100% early resorptions. Treatments with these two substances during the periimplantation period (Days 4 and 5) produced 100% early resorptions. Histologic examination of the implantation sites showed signs of embryonic degeneration starting from Day 6.5 of gestation. The flushing of the uteri of females treated with 2-(isopropylamino)-ethanol on Days 0 through 3 post coitum showed 78% of the embryos at the stage of 1 to 3 blastomeres, whereas the embryos of females treated during the same period with hydroxyethylpirrolidine were normal blastocysts. Therefore, 2-(isopropylamino)-ethanol and hydroxyethylpirrolidine are able to kill embryos during the early implantation stages, whereas 2-(isopropylamino)-ethanol is also able to stop the development of preimplantation embryos.     

Cross-linked DNA duplexes--exonuclease stability and interaction with the nucleic transcription factor of the kappa light-chain enhancer (NF-kappaB)

This study documents the differences in kinetics of 2 h (n = 7) and 4 h (n = 9) of 1.25 minimum alveolar anesthetic concentration (MAC) of desflurane (9.0%) versus (on a separate occasion) sevoflurane (3.0%), both administered in a fresh gas inflow of 2 L/min. These data are extensions of our previous 8-h (n = 7) studies of these anesthetics. By 10 min of anesthetic administration, average inspired (F(I)) and end-tidal concentration (F(A)) (F(I)/F(A); the inverse of the more commonly used F(A)/F(I)) decreased to less than 1.15 for both anesthetics, with the difference from 1.0 nearly twice as great for sevoflurane as for desflurane. During all sevoflurane administrations, F(A)/F(I) for Compound A [CH2F-O-C(=CF2) (CF3); a vinyl ether resulting from the degradation of sevoflurane by Baralyme] equaled approximately 0.8, and the average inspired concentration equaled approximately 40 ppm. Compound A is of interest because at approximately 150 ppm-h, it can induce biochemical and histological evidence of glomerular and tubular injury in rats and humans. During elimination, F(A)/F(A0) for Compound A (F(A0) is the last end-tidal concentration during anesthetic administration) decreased abruptly to 0 after 2 h and 4 h of anesthesia and to approximately 0.1 (F(A) approximately 3 ppm) after 8 h of anesthesia. In contrast, F(A)/F(A0) for desflurane and sevoflurane decreased in a conventional, multiexponential manner, the decrease being increasingly delayed with increasing duration of anesthetic administration. F(A)/F(A0) for sevoflurane exceeded that for desflurane for any given duration of anesthesia, and objective and subjective measures indicated a faster recovery with desflurane. Times (mean +/- SD) to initial response to command (2 h 10.9 +/- 1.2 vs 17.8 +/- 5.1 min, 4 h 11.3 +/- 2.1 vs 20.8 +/- 4.8 min, 8 h 14 +/- 4 vs 28 +/- 8 min) and orientation (2 h 12.7 +/- 1.6 vs 21.2 +/- 4.6 min, 4 h 14.8 +/- 3.1 vs 25.3 +/- 6.5 min, 8 h 19 +/- 4 vs 33 +/- 9 min) were shorter with desflurane. Recovery as defined by the digit symbol substitution test, P-deletion test, and Trieger test results was more rapid with desflurane. The incidence of vomiting was greater with sevoflurane after 8 h of anesthesia but not after shorter durations. We conclude that for each anesthetic duration, F(I) more closely approximates F(A) with desflurane during anesthetic administration, F(A)/F(A0) decreases more rapidly after anesthesia with desflurane, and objective measures indicate more rapid recovery with desflurane. Finally, it seems that after 2-h and 4-h administrations, all Compound A taken up is bound within the body. Implications: Regardless of the duration of anesthesia, elimination is faster and recovery is quicker for the inhaled anesthetic desflurane than for the inhaled anesthetic sevoflurane. The toxic degradation product of sevoflurane, Compound A, seems to bind irreversibly to proteins in the body.