The objectives of this study were to evaluate the transplacental kinetics and effects on placental function of the angiotensin converting enzyme (ACE) inhibitor, enalaprilat, in the dually perfused human placental lobule system. When placed in the maternal perfusate at a high therapeutic serum concentration (150 ng/ml), enalaprilat was rapidly transferred from the maternal perfusate into placental tissue followed by a gradual release from the placenta into the fetal perfusate. Cmax and AUC values for enalaprilat in the maternal perfusate were approximately 3 times higher than in the fetal perfusate, and drug levels did not equilibrate between maternal and fetal perfusates during the 4-6 hours of perfusion. The more highly perfused regions of the placental lobule had higher drug levels than non-perfused areas. At the end of the perfusion period, the mean percent of total drug added in the maternal perfusate was 59%, with 23% in the fetal perfusate and the remainder (18%) in placental tissue. Despite the relatively high levels of drug found in placental tissue, there were no alterations in placental function as measured by fetal volume loss, fetal pressure, glucose utilization, lactate production, hCG release, net fetal oxygen transfer, and oxygen consumption. Results from this study clearly document placental transfer of enalaprilat in the perfused human placental lobule system. The lack of effect on placental function suggests that enalaprilat has no direct effect on fetoplacental vascular beds, and that fetal hypotension occurring from ACE inhibitor exposure may be due to direct effects on the fetal kidney and not to decreased perfusion of fetoplacental vascular beds; these findings require further validation in an in vivo model.

Area Under Curve↗

PubMedDate not supplied

A legacy of violence in nonorganic failure to thrive.

It is often postulated that a mother's past experiences influence her ability to function as a parent. If those past experiences involve her as a victim of abuse, what lies ahead for her offspring? We studied 59 mothers of children referred for nonorganic failure to thrive (NOFTT) to the University of Colorado Health Sciences Center and compared their abuse history with a group of 131 mothers of children with normal growth. The mothers of NOFTT children were younger but of the same socioeconomic groups as the comparison mothers. Mothers of NOFTT children had a significantly higher history of abuse when compared to the comparison group p < 0.001. A surprising 80% of mothers of NOFTT children reported they were victims of abuse. We alert clinicians to the likelihood that mothers of children with NOFTT may be victims of abuse and that successful treatment of the child depends upon treatment of the mother-child dyad.

Adult↗

PubMedDate not supplied

Cis-acting human ApoE tissue expression element is associated with human pattern of intraneuronal ApoE in transgenic mice.

Apolipoprotein E polymorphic variants (ApoE-epsilon2, epsilon3, and epsilon4) are associated with the age of onset distribution and risk of Alzheimer disease. The question of whether ApoE is expressed at a comparatively low level in human neurons compared to astrocytes, or whether ApoE enters neuronal cytoplasm via altered endosomal metabolism is important to understanding potential pathogenic roles for ApoE as a susceptibility gene in Alzheimer disease. ApoE deficient ("knock-out") mice received large human genomic DNA fragment transgenes for each of the three common apoE alleles. All transgenic mice demonstrated glial/astrocytic (normal rodent pattern), as well as cortical intraneuronal ApoE immunoreactivity with all three human isoforms and at multiple ApoE human allele doses (Xu et al. (32)). To test whether ApoE intraneuronal immunoreactivity was due to ApoE gene sequences between mouse and human, we examined another set of mice constructed using targeted replacement so that the human ApoE gene was placed under mouse gene promoters. Current analyses show that targeted replacement recombinant mice show normal rodent glial expression pattern, but no ApoE neuronal immunoreactivity through six months of age compared to large human genomic DNA fragment transgenic mice, which show neuronal content of ApoE throughout adult life. We conclude that cis-acting DNA sequences, rather than the specific sequence of the ApoE gene, may be responsible for low levels of transcription activity in cortical neurons.

Alleles↗

PubMedDate not supplied

Treatment for the mallet finger injuries of surgeons.

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Finger Injuries↗

PubMedDate not supplied

Topical imiquimod treatment of human papillomavirus in a patient with human immunodeficiency virus.

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AIDS-Related Opportunistic Infections↗

PubMedDate not supplied

A survey of the occurrence of aflatoxin M1 in UK-produced milk for the period 1981-1983.

A UK survey for the occurrence of aflatoxin M1 in bulked dried milks (totalling 277 samples) obtained at monthly intervals from a number of commercial creameries in the UK over a two-year period (1981-1983), showed 98% of the samples to have levels below 0.03 micrograms/kg. For liquid milks sampled from individual farms over the same period (totalling 409 samples), 94% of the samples had aflatoxin M1 levels below 0.01 micrograms/kg. All samples were initially screened by a two-dimensional thin layer chromatographic method and quantification of positive results was by reverse phase h.p.l.c. with fluorescence detection. The results of this survey show that UK milk is largely free of aflatoxin M1 contamination, the incidence and levels, where observed, being significantly lower than for other European countries, which demonstrates the effectiveness of UK legislative action controlling feedstuff contamination.

Aflatoxin M1↗

PubMedDate not supplied

An investigation of HPLC post-column iodination conditions for the enhancement of aflatoxin B1 fluorescence.

A systematic investigation was carried out of the conditions employed for the post-column iodination reaction used to enhance fluorescence sensitivity of aflatoxins B1 and G1 in reverse-phase HPLC. The effect of post-column reaction coil tubing dimensions, coil temperature, eluent and reagent flow rates and reagent concentration were examined and the optimum choice of each established. The maximum achievable sensitivity was shown to be 20 pg of B1 injected on column.

Aflatoxin B1↗

PubMedDate not supplied

Automated headspace GC-MS analysis of ethylene dibromide fumigant residues in fresh fruits.

An automated headspace capillary column GC-MS method using selected ion monitoring was developed for the analysis of ethylene dibromide (EDB) residues in fresh fruits. The method was shown to be rapid, to give good agreement with more conventional methods involving distillative extraction, to be free from interferences and to have a limit of detection of 1 microgram/kg. A small survey of a range of fresh fruits including oranges, grapefruit, lemons and mangoes showed no detectable EDB residues in a total of 45 samples obtained from various retail outlets.

Citrus↗

PubMedDate not supplied

A limited survey of retail apple and grape juices for the mycotoxin patulin.

A retail survey (38 samples) of apple, grape and other juice-based products for the mycotoxin patulin has been carried out using HPLC analysis. Positive results were confirmed by GC-MS of the TMS derivative using chemical ionization selected ion monitoring. No grape juice or mixed juice product contained detectable patulin (limit 5 micrograms/l), nor did the majority (58%) of the apple juices. Low levels of patulin (in the range 5-10 micrograms/l) were present in six apple juices and the remaining four positive samples contained 16, 18, 30 and 56 micrograms/l.

Beverages↗

PubMedDate not supplied

A survey of aflatoxins in peanut butters, nuts and nut confectionery products by HPLC with fluorescence detection.

A preliminary survey in 1982 of aflatoxin levels in peanut butters indicated that 31 out of 32 samples of major national brand-named products examined contained less than 10 micrograms/kg aflatoxin B1 and that 59% of these were below the limit of detection (2 micrograms/kg). In contrast, of 25 peanut butters from specialist 'Health Food' outlets, 64% contained less than 10 micrograms/kg aflatoxin B1, the remainder ranging from 16 to 318 micrograms/kg, with one sample having a total aflatoxin concentration of 345 micrograms/kg. Subsequent surveys in 1983 and 1984 of 'Health Food' products confirmed that these manufacturers were still experiencing some difficulty in complying with the 30 micrograms/kg total aflatoxin voluntary guideline limit. A further survey in 1984 was carried out of 228 retail samples of nuts and nut confectionery products comprising peanuts (shelled, unshelled, roasted and salted), mixed nuts, almonds (both unblanched and ground), brazils (in shell), hazelnuts (in shell), chocolate-coated peanuts, peanut brittle and coconut ice. The results showed that 74% of the samples contained less than 0.5 microgram/kg of aflatoxin B1 with 3.1% exceeding the guideline tolerance of 30 micrograms/kg total aflatoxins, these being predominantly peanuts and brazils. The highest total levels of aflatoxins observed were in unshelled peanuts containing 4920 micrograms/kg and in a composite sample of visibly moulded brazils containing 17 926 micrograms/kg.

Aflatoxin B1↗

PubMedDate not supplied

A survey of trialkyl and triaryl phosphates in United Kingdom total diet samples.

Composite total diet samples, representative of 15 different commodity types overall encompassing an average complete adult diet, from each of eight regions in the UK, were analysed for the presence of trialkyl- and triarylphosphates. The analytical method consisted of solvent extraction, size exclusion clean-up and determination of individual phosphates by gas chromatography using phosphorus specific detection (alkali flame or flame photometric detection). Of the food groups offal, other animal products and nuts consistently contained the highest levels of trialkyl/triaryl phosphates, but there was variation in the incidence of individual compounds between different groups. Total phosphate intake was estimated to be between 0.07 and 0.1 mg per person per day.

Chromatography, Gas↗