From ED to ICU: a focus on prevention of skin breakdown.
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Biomedical subjects
Publications and source records attributed to C Goodrich.
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Experiments were designed to distinguish between central and peripheral effects on temperature preference and body temperature of drugs injected intraperitoneally (IP) in infant mice ranging in age from 3 to 10 days postpartum. These compared a drug restricted to the periphery ("peripheral" drug) with a drug of similar action that reaches the central nervous system (CNS) as well as the periphery. Two different classes of drugs were utilized to test central versus peripheral actions independently with drugs that have different modes of action: 1-aromatic amino acid inhibitors and serotonin receptor antagonists. Although the decarboxylase inhibitor NSD 1015, which reaches the central nervous system from IP injection, can significantly decrease temperature preference (Tpref), the peripheral inhibitor carbidopa had no significant effects on Tpref or on body temperature (Tb). Furthermore, pretreatment with NSD 1015 prevented the elevation of Tpref produced by the serotonin precursor 5-hydroxytryptophan (5-HTP); however carbidopa pretreatment had no effect on the increased Tpref produced by 5-HTP. In other experiments, the peripheral serotonin antagonist BW 501C was not able to prevent elevated Tpref produced by 5-HTP, although the specific 5-HT2 antagonist pirenperone, which reaches the CNS as well as the periphery, blocks the 5-HTP elevation of Tpref. Taking all of these results together, we conclude that the changes in Tb and Tpref following these treatments require a decarboxylase inhibitor or 5-HT antagonist that reaches the CNS. However, the well known and potent peripheral vasoconstrictor action of serotonin requires that peripheral effects of drugs be considered when manipulations are not restricted to the CNS.
The NMR relaxation times T'2, T2, and T1 were measured in isolated rat lungs as functions of external magnetic field B0, temperature, and lung inflation. The observed linear dependence on B0 of the tissue-induced free induction decay rate (T'2)-1 provides independent confirmation of the air/water interface model of the lung. Furthermore, measurements of the Larmor frequency dependence of T1 are consistent with a spin-lattice relaxation rate of the form 1/T1 = A omega -1/2 + B as expected for the case in which the relaxation arises from water-biopolymer cross-relaxation, which should be proportional to the surface area of the lung. This prediction was verified by observations of an approximately linear dependence of 1/T1 on transpulmonary pressure and thus on the lung surface area.
The effect of elevated brain serotonin (5-hydroxytryptamine, 5-HT) on the head twitch was examined to determine an age of onset in mice for this 5-HT mediated motor activity. Two different treatments were used to elevate 5-HT: 100 mg/kg L-tryptophan with 100 mg/kg pargyline; and 100 mg/kg 5-HTP with 25 mg/kg carbidopa. Mice from ages 14 to 42 days postpartum were examined. Both treatments showed an onset of the head twitch at 15 days. Juvenile mice of 15-18 days appeared to differ in their response to the two treatments. Although 5-HTP and carbidopa stimulated head twitches, 5-HTP alone had a greater stimulatory effect at these ages, while in the other experiment only those animals receiving the combined tryptophan and pargyline treatment showed significant responses.
Thermoregulatory effects of the selective 5-HT2 antagonist pirenperone were studied 1 hr after IP injection in mice aged 1, 3, 5, 7 and 10 days postpartum. Compared with vehicle injected littermates, a dose of 0.16 mg/kg decreased temperature preference (T pref) on a thermal gradient at all ages. No significant effects were observed on body temperature (Tb) at any of the ages. An increased dose (0.48 mg/kg) caused no greater effect on T pref and no significant effect on Tb. These results indicate that Tb and T pref are separable on the basis of receptor pharmacology, and are discussed in relation to drug effects on 5-HT2 receptors.
The effects of the 5-HT2 antagonist pirenperone on temperature preference were observed 1 hr after injection in mice aged 3, 5 and 7 days and at doses of 0.16, 0.48 and 1.6 mg/kg body weight. Although all 3 doses produced significant decreases in preferred temperature at 3 days, only the highest dose had significant effects at ages 5 and 7 days. Analysis of the data suggests that the dose-response relationship depends on age in a way that would be consistent with a shift in the dose-response curve with increasing age.
The effects of amphetamine (5-20 mg/kg) were studied 60 min after injection in mice aged 2, 3, 4 and 6 weeks postpartum. Exploratory behavior as indicated by the "head poke" test was depressed at all ages, but appeared to be relatively uncomplicated by other effects at the 5 mg/kg dose. At 4 and 6 weeks control females showed significantly greater activity than males, and amphetamine produced a greater reduction for control levels than in males.
The effects of a single 20 mg/kg dose of citalopram (Lu 10-171) were studied in mice aged 1-10 days. Body temperature measured 2 and 24 hr after treatment was decreased in treated animals as compared with saline injected littermate controls. Two hours after treatment, temperature preference in a thermal gradient was unchanged in animals younger than 6 days; however, in animals 6 days or older, temperature preference was increased as compared with littermate controls. Twenty-four hours after treatment, temperature preference was increased in citalopram-treated animals at all ages tested. The results are discussed in relation to nervous system maturation.
1. The effects of a single dose of reserpine (1 mg/kg body wt) have been studied 1 hr and 24 hr after injection. Young mice were tested on days 3, 7, 10 and 14 after birth and compared with 6-week-old adults. 2. Body temperature (Tb) fell in reserpine-treated young animals 1 hr after injection, as compared with vehicle-treated littermate controls; however, the effect was small in 3- and 7-day animals when compared with 10- and 14-days. 3. Tb was significantly depressed in young reserpine-treated animals 24 hr after injection, with greater effects again found in the 10- and 14-day animals. In contrast, the adult animals failed to show an effect on Tb at either 1 hr or 24 hr after injection. 4. A second dose of reserpine 24 hr after the first dose was ineffective in producing further changes in Tb in 3-, 7-, and 10-day animals; but in 14-day and adult animals the second dose produced a significant decrease in Tb.
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A relationship between the maturational increases in body temperature and brain indoleamines has been explored through altering brain 5-hydroxytryptamine (5-HT) content. Effects on body temperature at approximately constant ambient temperature (about 24 degrees C) have been studied following pharmacological manipulations in mice up to 16 days postpartum. Administration of 5-hydroxytryptophan (5-HTP) to increase 5-HT levels was associated with decreased body temperature throughout the maturational period. Depletion of 5-HT with p-chlorophenylalanine (p-CPA) was associated with increased body temperature at all ages studied, although 5-HT depletion was less effective in young animals than in older animals. The drug NSD-1034 acts at a different enzymatic step, and is effective in both central and peripheral tissues to reduce 5-HT and norepinephrine (NE) levels. NSD-1034 decreased body temperature up to 10 days of age; however, the effect was reversed at about 14 days, and the drug increased body temperature significantly in 16-day-old animals. These results suggest a role for 5-HT in the mechanisms of heat production in early postnatal life.