Identification and Quantitation of Drugs in Human Amniotic Fluid

Kr, Sommer; Rm, Hill; Mg, Horning

doi:10.1016/b978-0-08-021308-8.51245-x

Cited by 7 publications

(6 citation statements)

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“…At present it appears that very few foreign compounds would be expected to serve as substrates for human, placental, monooxygenase systems (Juchau 1975). Caffeine and its metabolites: theobromine, theophylline, and paraxanthine have all been identified in human amniotic fluid, but it Is debatable whether they are from a maternal or fetal source (Sommer et al 1975).…”

Section: Teratogenicitymentioning

confidence: 99%

The Pharmacology and Toxicology of Caffeine

Lachance

1982

Journal of Food Safety

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The widespread use of caffeine is most commonly linked to the stimulatory action it has on the central nervous system. Generally, adverse effects include gastrorrhea, insomnia, and diuresis. Tolerance and withdrawal symptoms have been observed and excessive consumption can lead to an anxiety neurosis condition (caffeinism). The actions of caffeine may involve its effects on neurotransmitter turnover and metabolism; its promotion of the cellular messenger, cAMP; its sensitization of the calcium releasing mechanisms of cellular reticulum; or its antagonism of the autacoid, adenosine. Caffeine lethality is rare in man but caffeine poisoning with its gastrointestinal, CNS, and cardiovascular stimulation could especially be hazardous to children. Most of the mutagenicity work has been performed in organisms whose cellular DNA synthesis and repair mechanism vary significantly from those found in man. The work in human cell lines suggests that caffeine‐induced chromosomal breakage, with its lack of chromatid exchange would promote cell lethality, not muta‐genticity. Nothing but circumstantial evidence implicates caffeine as a human carcinogen or teratogen. Involvement of caffeine as a cocarcinogen or a coteratogen (which includes effects on gamete production or fetal development) appears far more likely, but neither has even begun to be truly evaluated. Basic metabolism of caffeine involves the processes of N‐demethylation, hydration, and oxidation; and most likely requires the cytochrome P1‐450 system. Though various metabolites of caffeine are pharmacologically active, the extent of involvement of individual metabolites in the pharmacological or toxicological responses of caffeine in man is still unknown.

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Section: Teratogenicitymentioning

confidence: 99%

The Pharmacology and Toxicology of Caffeine

Lachance

1982

Journal of Food Safety

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“…In a study of aborted hu man fetuses, an intravenous injection of 574 mg of caffeine to the mother resulted in a fetal tissue level equivalent to that of the maternal plasma level [2]. The presence of caffeine in uterine secretions and blastocyst [3], amniotic fluid [4] and cord blood [5] has also been reported. Since caffeine has a mul titude of pharmacological actions, its effects on the growing fetuses require extensive study.…”

Section: Introductionmentioning

confidence: 99%

Various Levels of Maternal Caffeine Ingestion during Gestation Affects Biochemical Parameters of Fetal Rat Brain Differently

Yazdani¹,

Joseph²,

Grant³

et al. 1990

Dev Pharmacol Ther

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Pregnant dams were divided into four groups on day 10 of gestation. Dams of group 1 were fed an 20% protein diet as controls. Dams of groups 2, 3 and 4 were fed a 20% protein diet supplemented with 0.5 mg, 1 mg and 2 mg caffeine/100 g body weight of dams, respectively. Pups were delivered surgically on day 22, and their brains were rapidly removed and analyzed for DNA, protein, cholesterol, zinc and alkaline phosphatase activity. The dams’ brains were analyzed for the same parameters as those of the pups. Plasma and brain caffeine levels were also determined in caffeine-supplemented groups. The pups’ brains in group 2 were heavier than those in group 4. The DNA concentration of group 2 was higher than that of the other groups. The protein concentration of group 4 was higher than that of the other groups. The cholesterol concentration of group 3 and 4 was less than that of the controls. The zinc concentration of group 4 was less than that of group 2. Alkaline phosphatase activity was decreased in groups 3 and 4 compared with either controls or group 2. Dams showed no significant difference among the groups in the same biochemical parameters except for cholesterol concentration that was higher in groups 2, 3 and 4 than in the controls. Plasma and brain caffeine levels of the fetuses and plasma caffeine of the dams in group 4 were higher than those of either group 2 or 3. It is concluded that various amounts of maternal caffeine intake exert different effects on fetal brain growth. In contrast, the effect of caffeine on the dams’ brain is relatively minor.

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“…This indicates that most human fetuses are exposed to caffeine during gestation. The presence of caffeine in uterine secretions [2], amniotic fluid [3] and cord blood [4] has been well documented. Intravenous caffeine given to the pregnant human female results in fetal tissue levels equivalent to maternal plasma levels [5], In animal studies, caffeine affects brain protein synthesis in the young growing rats [6], min eral content [7] and myelin formation in post natal pups [8].…”

Section: Introductionmentioning

confidence: 99%

Relationship of Prenatal Caffeine Exposure and Zinc Supplementation on Fetal Rat Brain Growth

Yazdani

Fontenot²,

Gottschalk³

et al. 1992

Dev Pharmacol Ther

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Pregnant rat dams were divided into four groups on the 3rd day of gestation. Group 1 dams were fed a 20% protein diet as controls. Dams of group 2 were fed a 20% protein diet supplemented with zinc (0.6 g ZnCl(2)/kg diet). Group 3 dams were fed a 20 % protein diet supplemented with caffeine (2 mg/100 g body weight) and dams of group 4 were fed a 20% protein diet supplemented with both caffeine and zinc. Fetuses were surgically delivered on day 22, and brains were removed and analyzed for alkaline phosphatase activity, protein, zinc, cholesterol and DNA concentrations. Fetal brain caffeine levels, as well as maternal and fetal plasma caffeine levels, were determined in caffeine-supplemented groups. The body weight of group 4 and brain weights of groups 3 and 4 were higher than those of groups 1 and 2. Alkaline phosphatase activity of group 3 was less than that of group 1. The brain zinc concentration of group 2 was higher than in the other groups, but that of group 4 was less than that of group 1. The present study indicated that the supplementation of caffeine to the maternal diet decreased zinc levels in the fetal brain, and the addition of extra zinc to this diet did not return the zinc level to that of the control level as we had expected. In addition, the supplementation of caffeine and zinc together increased the body weights of the fetuses compared to the controls, but the addition of only one of these substances had no effect, suggesting that the combination of caffeine and zinc may have unique effects on fetal growth.

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Identification and Quantitation of Drugs in Human Amniotic Fluid

Cited by 7 publications

References 0 publications

The Pharmacology and Toxicology of Caffeine

The Pharmacology and Toxicology of Caffeine

Various Levels of Maternal Caffeine Ingestion during Gestation Affects Biochemical Parameters of Fetal Rat Brain Differently

Relationship of Prenatal Caffeine Exposure and Zinc Supplementation on Fetal Rat Brain Growth

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