Biomedical subjects

R F Johnson

Publications and source records attributed to R F Johnson.

At least 19 recordsLinked to original sources

PubMed1992

The effects of ibotenate lesions of the median preoptic nucleus on experimentally-induced and circadian drinking behavior in rats.

Male Sprague-Dawley rats were injected with either ibotenic acid or vehicle in the region of the median preoptic nucleus (MnPO) during methoxyflurane anesthesia. Later, the rats were tested for drinking responses elicited by angiotensin II (1 and 2 mg/kg s.c.) and hypertonic saline (3 and 6% w/v s.c.). Tests were conducted at 3 different phases of a 12:12 light-dark (LD) cycle (in the middle of the light phase and in the early and midportion of the dark phase). The rats with ibotenate lesions of the MnPO drank significantly less than vehicle-injected and lesion control groups regardless of when the tests were conducted. Subsequent monitoring of the diurnal rhythm of drinking, employing electrical lickometers, detected no difference between the rhythms of 4 rats with ibotenate lesions of the MnPO who failed to drink to homeostatic challenges and 4 vehicle-injected control rats. The results indicate that ibotenic acid lesions of the MnPO block drinking behavior stimulated by angiotensin II and hypertonic saline without disrupting the entrainment or pattern of ad libitum drinking.

Angiotensin II↗

PubMed1992

Human placental transfer of zinc: normal characteristics and role of ethanol.

The fetal alcohol syndrome is primarily an impairment of growth and development. Zinc deficiency also causes abnormal fetal growth. Moreover, alcohol has been shown in some rodent studies to impair placental transport of zinc. The purpose of this investigation was to define better normal human placental zinc transport and the effects of alcohol on this process. To do this we employed the isolated perfused single cotyledon human term placental model, as well as the cultured human cytotrophoblast. In the perfused placental studies, it was shown that zinc is transferred by the placenta very slowly, about 6% of the rate of transport of antipyrine, a freely diffusible marker. The transfer is comparable in both directions, maternal to fetal and the reverse. Zinc does not cross the placenta against a zinc concentration gradient, in either direction. Rather there is good evidence of significant uptake (storage) of the zinc by the placenta on the recirculating compartment side of gradient studies. Moreover, when the perfusion fluid was low (0.2 g/100 ml) in albumin, about twice as much zinc accumulated in the perfused cotyledon and there was less zinc in the maternal compartment, as compared to perfusion with ten-fold higher (2.0 g/100 ml) albumin concentrations. Thus, ligand binding in the perfusate importantly influences placental zinc uptake. Interestingly, however, the increased placental binding of zinc did not translate into greater transfer of zinc to the fetal compartment. Thus, normal zinc transfer is slow, equal bidirectionally, and dependent on ligand binding in perfusate and placenta.(ABSTRACT TRUNCATED AT 250 WORDS)

Culture Techniques↗

PubMed1992

Human placental vitamin B6 (pyridoxal) transport: normal characteristics and effects of ethanol.

The aims of this study were to define normal human placental transport of pyridoxal, an important form of vitamin B6 in pregnancy, and to determine the effect of short-term alcohol on this process. Our studies used the isolated single cotyledon from the term placenta. Pyridoxal crossed the human placenta readily in both directions, but the transfer was a little less than half that of antipyrine and was significantly greater in the direction of the fetus. Pyridoxine appeared to have a similar clearance from the maternal compartment as pyridoxal, but transport of intact pyridoxal 5'-phosphate was much smaller. There was no saturable transfer of pyridoxal, and it was not transferred from the maternal to fetal compartments against a concentration gradient. Placental concentration of pyridoxal exceeded both maternal and fetal perfusate pyridoxal concentrations, but this concentration was equal for both perfusion directions. These composite data are most suggestive of passive transport of pyridoxal across the placenta, binding of the vitamin in the placenta as an explanation for its concentration there, and greater phosphorylation of pyridoxal in the placenta when the compound is transferred in the fetal direction, possibly displacing pyridoxal from its binding sites and permitting its greater release into the fetal compartment. Alcohol, 400-250 mg/dl over 2.5 h, inhibited the transport of pyridoxal from the maternal to fetal compartments by approximately 42% (P = 0.03) and resulted in a lower transfer of pyridoxal 5'-phosphate into the fetal perfusate (P = 0.02).

Biological Transport↗

PubMed1992

Acyclovir transport by the human placenta.

Genital Herpes simplex infection is noted increasingly in women of childbearing age and in neonates. Concern about transmission of herpes to the newborn has led to cesarean delivery of many pregnant women with a history of genital herpes. Severe herpes hepatitis has also been noted in pregnancy. Acyclovir is the drug of choice for this infectious organism. Because there are no data on the mechanism(s) of transport of this drug by the human placenta, this study addressed this issue. We used normal term human placentas. For study of overall placental transport of acyclovir, we used the single, isolated perfused cotyledon technique. For assessment of initial acyclovir uptake, we used microvesicles prepared from the maternal-facing syncytiotrophoblast. Overall transfer of acyclovir at therapeutic concentrations from maternal to fetal compartment was at a rate of about 30% that of a freely diffusible marker, antipyrine. The overall transport was not saturable, was not inhibited by 50-fold adenine concentration, and did not proceed against a concentration gradient. There was no placental metabolism of the drug. Fetal-to-maternal transfer of acyclovir was at a similar rate. In maternal-facing microvesicles net uptake of acyclovir was not saturable, but was temperature dependent and was inhibited by high concentrations of adenine and ganciclovir, but not by nucleosides (adenosine, cytidine, cytosine). These data are most consistent with a carrier-dependent, nucleobase-type uptake of the drug, but passive overall net transfer of acyclovir, dependent on its solubility characteristics.

Acyclovir↗

PubMed1991

Insignificant transfer of glyburide occurs across the human placenta.

No data exist concerning human placental transfer of oral hypoglycemic agents during pregnancy. This study characterizes the transport of glyburide in 10 term human placentas with the single-cotyledon placental model. Serial samples were taken from both the maternal and fetal reservoirs during each 3-hour perfusion, and the percent transport and metabolism of tritiated glyburide was calculated with liquid scintillation spectrometry and high-performance liquid chromatography. Antipyrine labeled with carbon 14 was added to the perfusate solution during these experiments as a control. Virtually no transfer of glyburide occurred, and no appreciable metabolism of the drug was detected. Neither variation in the albumin concentration nor increase in the maternal glyburide levels to 100 times therapeutic concentration materially altered the rate of transport. These data show that insignificant transport of glyburide occurs across the human placenta in vitro and suggest that fetal exposure to maternally administered glyburide likewise may be insignificant.

Diazepam↗

PubMed1991

Meal-related and rhythmic drinking: effects of abolition of rat's eating rhythm.

Eating and drinking in the rat, which are both highly rhythmic and nocturnal activities, are temporally and quantitatively associated. The present study abolished the rhythmicity of eating by temporally and quantitatively restricting food access to 12 equally sized bihourly meals daily (total food available was equal to 80% of daily ad libitum intake). Water access remained ad libitum and was monitored and quantified in terms of 1) nocturnality, 2) association with meals, and 3) changes in the association of food and water intake across the phases of the light-dark cycle. Similar parameters were obtained from the same rats with ad libitum access to both food and water. The results indicate that both rhythmic and meal-induced effects are detectable in the drinking of rats with restricted food access, although both the rhythmic and meal-associated factors are reduced compared with drinking under ad libitum food access. Most important, the data clearly demonstrate large changes in the association of food and water intake across the phases of the light-dark cycle. These findings indicate a complex interaction of meal-associated and rhythmic factors in the control of drinking.

Animals↗

PubMed1991

Drinking after osmotic challenge depends on circadian phase in rats with free-running rhythms.

Rhythmic phase-dependent modulation of the amount of water intake of rats occurs after several types of dipsogenic treatments. Previous studies conducted on rats in light-dark cycles confound direct effects of the light-dark cycle with the effects of circadian rhythmicity entrained to the light-dark cycle. The present study isolates the effect of circadian phase on the amount of drinking induced by injection of hypertonic saline. Free-running rhythms were induced in rats, and then water intake was measured after injections of both hypertonic and isotonic saline at different phases of the rats' circadian cycle. After injections of hypertonic saline, rats drank more water in their active phase than in their inactive phase. No difference in the amount of intake was found in rats that received isotonic saline at different phases of their circadian rhythms. The results indicate a circadian modulation of the drinking induced by cellular dehydration.

Activity Cycles↗

PubMed1990

The effect of liver dysfunction on colchicine pharmacokinetics in the rat.

Recent work has shown that colchicine may benefit patients with primary biliary or alcoholic cirrhosis. However, very little is known about its pharmacokinetics in the presence of impaired liver function. To study this we examined the effects of three models of experimental liver dysfunction and one of cytochrome P-450 inhibition on colchicine elimination in the rat. The models of experimental liver dysfunction included bile duct ligation (with sham-operated controls), alpha-naphthylisothiocyanate-induced intrahepatic cholestasis and galactosamine-induced diffuse hepatocellular necrosis. The control group had a colchicine clearance of 77.33 ml/min.kg +/- 8.27 ml/min.kg, a half-life of 16.68 min +/- 0.97 min and a volume of distribution of 1.84 L/kg +/- 0.15 L/kg. Cimetidine administration, 120 mg/kg intraperitoneally 15 min before colchicine administration, caused clearance to decrease by 32% (p less than 0.05) and half-life to increase by 38% (p less than 0.05). Volume of distribution did not change. At 48 hr after bile duct ligation, colchicine clearance decreased by 84% (p less than 0.05), terminal half-life increased to 513.7 min +/- 106.6 min (p less than 0.05) and volume of distribution increased by 175% (p less than 0.05). Colchicine pharmacokinetics in sham-operated rats were not statistically different from the above mentioned controls.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Naphthylisothiocyanate↗

PubMed1990

Light/dark cycle modulates food to water intake ratios in rats.

Ad lib water intake of rats displays two prominent features: Water intake is temporally and quantitatively associated with food intake, and water intake is nocturnal. Physiological mechanisms linking water and food intake suggest that the rhythmicity in water intake may be at least partially driven by a rhythmicity in food intake. The present study examined whether the daily rhythm of rats modulates the association of food and water intake. Rats were housed under light/dark cycles and continuously monitored for temporal and quantitative patterns of ad lib food and water intake. The results indicate that the water/food ratio is much lower for meals consumed in the light phase than in the dark phase. The above results suggest a rhythmic modulation of the mechanisms linking food and water intake. We suggest that much of the complex rhythm of drinking stems from several interacting factors. 1) Food intake is nocturnal. 2) Food intake induces water intake by physiological mechanisms. 3) The amount of water intake induced by food intake is influenced by rhythmic factors.

Animals↗

PubMed1990

Azidothymidine (zidovudine) transport by the human placenta.

The diagnosis of Acquired Immunodeficiency Syndrome (AIDS) is increasingly made in pregnant women, and the disease may be transmitted to the fetus. Azidothymidine (AZT, Zidovudine) is the one therapeutic agent of some promise in this condition. As there is no information on the transport of this drug by the human placenta, such studies were carried out using the single cotyledon placental perfusion system and human placental vesicles. AZT crossed the placenta readily and bidirectionally. The transfer rate was about 70% that of a freely diffusible reference marker, antipyrine, and was comparable in both directions. There was no evidence of active or carrier-mediated transport and no glucuronidated metabolites of the drug were identified in either maternal or fetal compartments. The authors believe that the drug crosses the placenta by diffusion, consistent with its lipophilicity and transport into various blood cells.

Antipyrine↗

PubMed1990

Light-dark cycle modulates drinking to homeostatic challenges.

Both homeostatic and rhythmic variables are empirically and theoretically important controls of behavior. Yet, drinking behavior has been studied largely from one point of view or the other. The present study examined both homeostatic and rhythmic variables and found evidence for an important interaction of these two types of control of drinking behavior. The drinking rhythm of rats on a light-dark cycle was established. Water intake after cellular- or extracellular-related challenges was then measured both at a time of a peak and at a time of a trough of the drinking rhythm. The results indicate that rats drink more water after challenges in their early active phase than in their early inactive phase. The results demonstrate that rhythmic variables modulate the homeostatic controls of drinking behavior. The importance of the interaction of homeostatic and rhythmic variables in models of integrative control of behavior is discussed.

Adolescent↗

PubMed1990

Effects of nerve agent antidote and heat exposure on soldier performance in the BDU and MOPP-IV ensembles.

This study assessed the effects of nerve agent antidote (atropine/2-PAM chloride versus saline placebo) and heat-humidity (95 degrees F/60% RH versus 70 degrees F/30% RH) on repeated performance of militarily relevant psychological tasks while wearing the battle dress uniform (BDU) and while wearing chemical protective clothing (MOPP-IV). All BDU heat sessions (6 hours) were completed, but with some task impairments and a few subjective reactions. MOPP-IV heat sessions could not be continued beyond 2 hours; all tasks were impaired and subjective reactions were numerous and severe. Atropine/2-PAM significantly shortened endurance time for heat sessions in MOPP-IV.

Adolescent↗

PubMed1990

Thiamine-transfer by human placenta: normal transport and effects of ethanol.

Transport of "physiologic" concentrations of thiamine by the normal, term human placenta was studied by using the perfused cotyledon technique. Thiamine, 50 nmol/L, crossed from the maternal to fetal compartment at a rate somewhat below that of antipyrine, a freely diffusible marker drug. The transport was saturable and inhibited by structural analogues of thiamine, implying participation of carriers. Thiamine accumulated in the fetal compartment against a concentration gradient, suggesting active transport. Consistent with this, transfer of thiamine from the fetal to maternal compartment was significantly lower than in the opposite direction. The vitamin was concentrated in the placenta when compared with maternal and fetal levels. There was no evidence of phosphorylation of thiamine during its transfer. Exposure of the placenta to ethanol, 400 mg/dl, for up to 4 hours did not alter maternal-to-fetal transfer of the vitamin.

Antipyrine↗

PubMed1990

Effects of atropine/2-PAM chloride, heat, and chemical protective clothing on visual performance.

Visual acuity, phoria, stereopsis, and contrast sensitivity were assessed over 6 h of continued exposure to combinations of atropine (2 mg) and 2-PAM chloride (600 mg), severe heat/humidity (95 degrees F (35 degrees C); 60% RH), and wearing either the U.S. Army battle dress uniform (BDU) or the BDU and the impermeable chemical protective clothing (MOPP-IV). Subjects were able to complete all 6 h of testing under severe heat when wearing BDU's, but only lasted 2 h under the same severe heat when wearing MOPP-IV. Acuity and phoria were significantly impaired by the drug in the BDU conditions. Acuity, phoria and stereopsis were all significantly impaired by heat, drug and continued exposure under MOPP-IV. Acuity was significantly impaired by drug even during the first 2 h of heat exposure in MOPP-IV. Contrast sensitivity was impaired mainly by continued heat exposure in MOPP-IV.

Adolescent↗

PubMed1989

Regulation of cytochrome P-450 dependent steroid hydroxylase activity in Manduca sexta: evidence for the involvement of a neuroendocrine-endocrine axis during larval-pupal development.

Ecdysone 20-monooxygenase activity and the factors which may regulate this steroid hydroxylase were examined in the midgut of the tobacco hornworm, Manduca sexta, during the last larval stadium. Radioassay experiments revealed that midgut ecdysone 20-monooxygenase undergoes a single 50-fold increase in activity temporally coincident with the onset of the wandering stage. The increase in midgut monooxygenase activity was prevented by actinomycin D and cycloheximide, and could be elicited in head (but not thoracic) ligated animals by a brain-retrocerebral complex factor(s) released at the same time as prothoracicotropic hormone. In contrast, ecdysone or 20-hydroxyecdysone could elicit the increase in enzyme activity in both head and thoracic ligated animals. These data suggest the operation of a neuroendocrine-endocrine axis in the regulation of midgut ecdysone 20-monooxygenase activity.

Animals↗

PubMed1989

Two brain nuclei controlling circadian rhythms are identified by GFAP immunoreactivity in hamsters and rats.

The intergeniculate leaflet (IGL) of the lateral geniculate complex is marked by the presence of neuro-peptide Y-containing neurons that project to the suprachiasmatic nuclei (SCN) of the hypothalamus. In the present study, we demonstrate that both the IGL and SCN in the hamster and rat are specifically delineated by the presence of glial fibrillary acidic protein-like immunoreactivity. This is significantly greater than in most other diencephalic regions and is particularly dense in the hamster brain. These observations suggest that glial-neuronal interactions may participate in circadian rhythm generation and regulation.

Animals↗

PubMed1989

Paraventricular nucleus efferents mediating photoperiodism in male golden hamsters.

Knife cuts were placed around the paraventricular nucleus of the hypothalamus (PVN) in an effort to identify the pathways mediating gonadal regression in male golden hamsters housed in a short photoperiod. Horizontal cuts dorsal to the PVN only affected photoperiodic responsiveness if they actually damaged the PVN. Coronal cuts caudal to the PVN had no effect on testes regression. Parasagittal cuts adjacent to the medial PVN had little or no effect on gonadal regression induced by short photoperiod. We conclude that efferents of the PVN arising dorsally or medially are not necessary for photoperiodic control of testes function, whereas projections from or through the lateral PVN region descending towards the spinal cord are important.

Animals↗

PubMed1989

Localization of spinal cord preganglionic neurons innervating the superior cervical ganglion in the golden hamster.

The retrograde neuronal tracer Fluoro-Gold (FG) was used to determine the location and distribution of preganglionic sympathetic neurons in the spinal cord of the golden hamster. FG was injected unilaterally into the superior cervical ganglia. Labeled neurons were found only ipsilateral to the injection site in segments C8 to T5 of which the segments T1 to T3 contained about 98% of the labeled cells. Neurons were found in four regions of the spinal cord: the intermediolateral nucleus (43%), the lateral funiculus (55%), the central autonomic area (1%) and the intercalated region (less than 1%). In the intermediolateral nucleus, cells often were arranged in clusters of which several were seen in each spinal segment.

Animals↗