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Biomedical subjects

M Webb

Publications and source records attributed to M Webb.

At least 163 records · Page 9Linked to original sources
PubMed1982

Responses of menstrual women, amenorrheal women, and men to exercise in a hot, dry environment.

Rectal (Tre) and mean skin temperatures, heart rate (fc) and sweat rate (Msw) during exercise in a hot, dry environment were compared among four menstrual women (both before and after ovulation), four amenorrheal women and four men, all with similar aerobic capacities. Progesterone and estrogen were compared in a pair of monozygotic twins (one menstrual and one amenorrheal) who participated in the study. Before acclimation, subjects were given a heat-stress test (HST) consisting of treadmill walking at 25%-30% VO2 max in a hot, dry environment (Tdb/Twb = 48/25 degrees C) until Tre reached 39 degrees C or fc reached 160 beat . min-1. Subjects were then acclimated to the dry heat with conventional acclimation procedures. After acclimation, subjects were given a HST which continued for 3 h. Before acclimation Tre and fc increased more rapidly in the women, with the men. Following acclimation all subjects maintained similar Tre, fc, and sweat rates. There were no differences between the exercise/heat-stress responses of the preovulatory menstrual women, postovulatory menstrual women, and amenorrheal women. Although the estrogen concentrations were normal in the menstrual twin, her progesterone concentrations were significantly depressed. Both hormones were depressed in the amenorrheal twin. Following acclimation thermoregulatory function in dry heat did not differ between the sexes when fitness level was similar. Neither were there any differences in thermoregulation between the pre- and postovulatory phases of the menstrual cycle or between the menstrual and amenorrheal women.

Acclimatization↗
PubMed1982

The effects of cadmium and copper on the renal uptake and metallothionein binding of gold in the rat and hamster.

Rats and hamsters, (pre)-treated with copper and cadmium, were used to investigate whether species-differences in renal metallothionein synthesis in response to gold were determined by changes in the kidney concentrations of other metals. The effects of both dietary copper limitation and excess on the renal metabolism of gold also were studied in the rat. In this species, all of the pre-treatments affected the renal concentrations of total and metallothionein-bound copper, but none of them altered either the kidney uptake or thionein-binding of gold. Incorporation of zinc into the metallothionein, which accompanied the binding of gold in this fraction of the kidney, however, was influenced slightly by the pretreatments, In hamsters, pretreatment with cadmium, which increased the concentrations of total and thionein-bound zinc in the kidneys, also did not affect the renal uptake of gold, although it increased significantly the binding of gold to the metallothionein fraction of the renal cytosol. This increased binding of gold also was accompanied by further increases in the zinc and copper contents of the metallothionein; the contents of total and thionein-bound cadmium, however, remained essentially unchanged. Concentrations of copper and zinc in the hamster kidney were not affected significantly by subcutaneous administration of copper alone (five daily doses, each of 3.2 mg Cu/kg body wt.), but were increased when gold was given during the copper-treatment. The concentrations of gold, copper and zinc in the renal metallothionein fraction also were increased under these conditions. From these results it seems that kidney metallothionein synthesis in response to gold may be related to the changes in either the concentration or distribution of zinc, rather than copper.

Animals↗
PubMed1982

Dimethoxyethyl phthalate: embryopathy, teratogenicity, fetal metabolism and the role of zinc in the rat.

A single intraperitoneal injection (0.6 ml/kg) of dimethoxyethyl phthalate (DMEP) was given to groups of Wistar strain rats on day 10, 11, 12, 13 or 14 of gestation. Control rats received 0.6 ml/kg of physiological saline intraperitoneally. In phthalate-treated rats, embryopathy was manifested by a high incidence (12-79%) of fetal deaths and fetal resorptions. Fetotoxic effects were expressed by a significant reduction in fetal weights. Hydrocephalus interna, a congenital malformation of the brain, was caused by DMEP. Congenital skeletal deformities (66-96%), with multiple skeletal (14-64%) and appendicular malformations (25-57%), were also induced by DMEP. Control rats exhibited no congenital malformations of the brain and no appendicular or multiple skeletal deformities. DMEP caused a significant decrease in the zinc content of the fetus. Fetoplacental metabolism 1 and 4 hr after intravenous administration of 14C-DMEP suggested rapid transfer of the parent compound to the fetus across the placenta and that DMEP is a teratogenic moiety. The possible role of zinc in phthalate-induced teratogenesis in rats is also discussed.

Animals↗
PubMed1981

The tissue distribution of gold, copper and zinc in animals treated with Au (III); species differences in the binding of these metals in the kidney.

Whole body retention of Au and the distribution of Au, Cu and Zn have been measured in female rats, rabbits, guinea-pigs, hamsters and mice after either a single injection or multiple doses of Au(III). At 24 h after a single intraperitoneal injection whole body retention of Au was about 65% of the dose in the rabbit and 50% of the dose in other species. After five doses, retention (as a percentage of the total dose) ranged from 36% in mice to 49% in rats. Concentrations of Au in the kidneys were lowest in mice and highest in rats but, in all species, were greater than in other organs. In rats and guinea-pigs, but not in hamsters, rabbits and mice, treatment with Au(III) increased the Cu content of the kidneys and of the soluble fraction isolated therefrom. The latter from the rat and guinea-pig kidney contained both Au and Cu in association with a low molecular weight metalloprotein (metallothionein), which also contained Zn and was separated by ion exchange chromatography into three subspecies. Binding of Au by these metalloproteins appeared to be related to the renal accumulation of Cu. Apart from the mouse, in which renal accumulation of Au was low, slight damage resulted in the kidneys of all species after treatment with Au. It appears, therefore, that nephrotoxicity cannot be explained simply by the renal concentration of Au and the form in which it is accumulated within the tubular cells.

Animals↗
PubMed1981

The acute toxicity and teratogenicity of cadmium in the pregnant rat.

Until the 16th day of gestation the intravenous LD50 of Cd2+ in the pregnant Wistar-Porton rat is higher, but not significantly different from that (1.8 mg Cd2+ per kg body weight) in nulliparous females. At 20 days it is 1.1 mg Cd2+ kg per body weight. This decrease is related to the rapid increase in weight of the conceptuses in late gestation and to the retention of most of the dose in the maternal compartment. If the dose is based on body weight at conception, the LD50 for the 20-day pregnant rat (1.6 mg Cd2+ per kg body weight) and non-gravid female do not differ significantly. Nevertheless, after the same Cd2+ dose, hepatic and renal Cd2+ concentrations are less in the pregnant than in the non-pregnant animal. The Cd2+ concentrations, therefore, do not determine the liver and kidney damage, which is restricted to the pregnant rat. Placentae also accumulate Cd2+ and placental haemorrhage follows the injection of the appropriate Cd2+ LD50 on day 12-20 of gestation. In those animals that die between 16 and 30 h after dosing, haemorrhage and death appear to be correlated. Renal damage, therefore, probably results from haemorrhagic shock. It is not dependent on the transfer of protein-bound Cd2+ from the necrotic placentae to the kidney. Between the 8th and 15th day of gestation, Cd2+ (1.25 mg per kg body weight) is highly teratogenic. Hydrocephalus is the most frequent abnormality when the dose is given between the 8th and 12th day. Other malformations include eye defects, gastroschiasis and umbilical hernia.

Abnormalities, Drug-Induced↗
PubMed1981

Placental transport and embryonic utilization of essential metabolites in the rat at the teratogenic dose of cadmium.

Administration of Cd2+ to the 12-day pregnant rat caused a dose-dependent inhibition of placental 65Zn2+ transport. At 4 h after the injection of the teratogenic dose (1.25 mg Cd2+ per kg body weight), transport of 65Zn2+ to the embryo was inhibited by 75%. This inhibition decreased with time and at 48 h was no longer statistically significant. In contrast with Zn2+, the administration of Cd2+ did not affect the transport of sugar, amino acids and nucleic acid precursors from the maternal circulation to the embryo at any time. The incorporation of [14C]thymidine into embryonic DNA, however, was inhibited by about 50% at 4 h and by 75% at 20 h. By 48 h it returned to control levels. Incorporation of [14C]formate into DNA also was reduced. Inhibition of the incorporation of L-[14C]leucine into protein was apparent at 20 h, but not at 4 h, after the administration of Cd2+. Inhibition of DNA synthesis, which led to a significant reduction in embryonic DNA concentration at 20 h, was associated with a marked decrease in the activity in embryonic thymidine kinase. In extracts of embryos from Cd2+-treated dams, the activity of this enzyme was restored to the control level by the addition of 7.7 microM zinc acetate to the assay system. In vivo, the simultaneous injection of Zn2+ at a 2:1 atomic ratio with Cd2+ prevented the inhibition of thymidine incorporation into DNA. At the teratogenic dose, only about 16 ng Cd2+ per g wet weight is incorporated into the embryo. The inhibition of placental transport, particularly of Zn2+, therefore, may be of prime importance in the teratogenic response.

Animals↗
PubMed1981

Comparative studies on the distribution of gold, copper and zinc in the livers and kidneys of rats and hamsters after treatment with sodium [195Au]-aurothiomalate.

The distribution of gold, copper and zinc in the livers and kidneys of female rats and hamsters was determined after intraperitoneal injection of sodium [195Au]-aurothiomalate. After five doses of sodium [195Au]-aurothiomalate (1 mg Au(I) per kg body weight), the hepatic and renal concentrations of Au were greater in rats than in hamsters. In the former species, treatment with the Au(I)-compound led to an increase in the Cu-concentration of the kidney and to the synthesis of a (Cu, Au)-metallothionein. In either species binding of Au to the hepatic metallothionein was insignificant. The renal (Cu, Au)-metallothionein from the sodium [195Au]-aurothiomalate-treated rat appeared to be extremely heterogeneous and was resolved into at least four components on ion exchange chromatography.

Animals↗
PubMed1981

Metabolism of zinc and copper in the neonate: accumulation and function of (Zn, Cu)-metallothionein in the liver of the newborn rat.

1. Measurements were made of the hepatic concentrations and contents of total and thionein-bound zinc and copper in late foetal and newborn rats and of the distribution of these metals between the particulate and soluble components of the liver. 2. The decrease in the hepatic concentration of thionein-bound Zn, which occurred with age after birth, was proportional to the increase in liver weight until the 16th day post partum; thereafter it was greater. 3. Throughout the period from birth to 25 d of age the Zn concentration remained constant in the cytosolic non-thionein fraction (i.e. total cytoplasmic Zn--thionein-bound Zn), but decreased in other compartments of the liver. 4. The same constant concentration of cytoplasmic non-thionein-bound Zn also was observed in animals with reduced total hepatic Zn contents, but normal body-weights, and in 20-d-old Zn-deficient pups. 5. The concentration of thionein-bound Cu increased significantly only between the 6th and 14th day post partum. The age-related variations in Cu contents of the particulate components closely paralleled those in the whole liver, whereas the Cu contents of the cytosolic thionein and non-thionein fractions did not increase appreciably until after the 10th day. 7. It is concluded that the cytosolic non-thionein fraction of newborn rat liver may contain particularly important metabolic sites that require Zn and a major function of Zn-thionein is to regulate the supply of the metal to these sites. As, from birth to 26 d of age, the sum of the concentrations of thionein-bound Zn and Cu was correlated with whole liver Zn, the accumulation of Cu as a soluble metallothionein seems to be a secondary event, dependent on the hepatic Zn concentration.

Aging↗
PubMed1981

Metabolism of zinc and copper in the neonate: accumulation of Cu in the gastrointestinal tract of the newborn rat.

1. The concentration of copper in the rat intestine was found to increase rapidly after birth to a maximum greater than 140 microgram/g wet weight at 2 d of age and then to decline, at first slowly to 90 microgram/g wet weight on day thirteen and then rapidly to 40 microgram/g and 3 . 4 microgram/g wet weight on the 15th and 19th day respectively. The intestinal concentration of Zn, which doubled between 1 d prepartum and 2 d post partum, also fell slowly until 10 d of age, but thereafter remained constant. 2. From the 2nd to the 15th day post partum approximately 60% of the total Cu and 50% of the total zinc in the intestine was located in the soluble fraction of the tissue. Most of the Zn in this fraction was bound by proteins of molecular weights greater than 13700 daltons, whereas most of the Cu was present as an extremely polydisperse complex of lower molecular weight. This complex in the intestine of the 5-d-old rat, in contrast with the soluble proteins of higher molecular weight, did not incorporate either 3H or 35S within 4 h of the administration of L-[4,5-3H]leucine and L-[35S]cystine. 3. The loss of Cu from the intestine between the 13th and 15th day of post-natal age occurred mainly from this complex and was accompanied by the transient appearance of Cu in a fraction of low molecular weight. 4. At 21 d of age the soluble fraction of the intestine contained only a small amount of Cu. This was distributed between two protein fractions, one of which contained Zn and appeared to be a metallothionein. 5. The results are discussed in relation to the control of Zn and Cu absorption.

Aging↗
PubMed1981

Acute immune intravascular hemolysis due to hydrochlorothiazide.

Acute near-fatal intravascular hemolysis and renal failure developed in a patient after he had ingested 15 to 20 tablets of both methyldopa (Aldomet) nd hydrochlorothiazide (HydroDiuril). Serologic test results were inconsistent with those associated with methyldopa-induced hemolytic anemia and suggested that hemolysis was caused by hydrochlorothiazide antibodies reacting by an immune complex mechanism.

Acute Kidney Injury↗