Search PubMed⌕ Search

Biomedical subjects

B Mackler

Publications and source records attributed to B Mackler.

At least 37 records · Page 2Linked to original sources

Iron deficiency in the rat: effects on neutrophil activation and metabolism.

Studies were performed to determine the effects of iron deficiency in the rat on neutrophil activation and on levels of neutrophil myeloperoxidase and cytochrome b. The period of time required for neutrophil activation was not significantly affected by iron deficiency, but the maximum rates of respiration attained after activation were markedly lower (60% decrease) in iron-deficient neutrophils than in control cells. The myeloperoxidase activity of neutrophils from iron-deficient rats was also markedly decreased (approximately 75%) compared with the activity of control cells; however, the concentration of cytochrome b in the neutrophils was unaffected by iron deficiency.

Anemia, Hypochromic↗

Iron deficiency in the rat: biochemical studies of fetal metabolism.

The effects of dietary-induced iron deficiency on fetal and maternal metabolism were studied in the rat. Concentrations of phenylalanine, but not tyrosine, were significantly elevated in plasma from iron-deficient maternal and fetal rats at day 20 of gestation with individual fetal plasma levels of phenylalanine as high as 10 mg per 100 ml. Concentrations of total 5-hydroxyindole compounds were significantly decreased in brain tissue from iron-deficient fetuses (day 20 of gestation), suggesting that synthesis of the compounds may be inhibited by iron deficiency. Mitochondrial NADH oxidase activity was markedly decreased (60%) in homogenates of fetuses at day 14 of gestation and may account for the high fetal resorption rate and small fetal size observed in the rat in iron deficiency.

Animals↗

Fetal iron balance in the rat.

Maternal and fetal iron balance through pregnancy was examined in the rat. The 20th day was selected for detailed study because of the peak iron requirements at that time. The standard diet provided a borderline iron supply to the fetus due to the limited availability of its iron for absorption. When a more available form of iron was used, normal fetal development occurred over a range of dietary iron content from 16 to 2500 mg/kg. At a level of 5 to 8 mg/kg, there was attrition of placental tissues with frequent fetal death and resorption. When the iron-deficient pregnancy was sustained, both maternal and fetal iron deficiency were present. At progressively higher levels of dietary iron, feto-placental iron content was constant despite a progressive increase in maternal iron stores. Fetal iron supply appeared to be determined primarily by plasma iron concentration, and, at normal levels, about 25% of transferrin iron passing through the uterine vasculature, was removed by the intact placentas. Low levels of plasma iron resulted in damage to fetal tissues and reduced the capacity of placental tissues to take up iron. At high levels of plasma iron, plasma iron turnover initially increased 5-fold over basal levels in nonpregnant animals due to increased placental uptake. However, with continued hyperferremia, uptake was regulated so as to maintain fetal iron at a normal level. A comparison of these data with human iron requirements explained the occurrence of both maternal and fetal iron deficiency in the rat, but only maternal iron deficiency in the human.

Animals↗

Electron transport systems of Candida utilis: purification and properties of the respiratory chain-linked external NADH dehydrogenase.

The respiratory chain-linked external NADH dehydrogenase has been isolated from Candida utilis in highly purified form. The enzyme is soluble and has a molecular weight of approx. 1.5 x 10(6). The enzyme contains two moles of FMN per mole of enzyme and is composed of two large subunits of mol. wt. 270 000 and eight smaller subunits of mol. wt. 135 000. Iron and copper are present in the preparations, but appear to be contaminants. The enzyme catalyzes the oxidation of NADH and NADPH at nearly equal rates and reacts readily with 2,6-dichlorophenolindophenol, CoQ6 and CoQ1 derivatives as acceptors. Rotenone (10(-5) M) and seconal (10(-3) M) do not inhibit enzymatic activity.

Candida↗

Reproductive studies in the iron-deficient rat.

Severe iron-deficient anemia was produced in the rat by diet. Controls consisted of animals raised on the same diet but injected with iron intraperitoneally. The deficient rats were bred and found to have normal numbers of corpora leutea of pregnancy and implantation sites. Resorptions were very common, and only about 25% of the deficient fetuses were viable on day 20. The peak mortality occurred on about day 12 of gestation. The viable fetuses were smaller than the controls, and a predominance of females was found. More eye defects occurred in the deficient groups, but a significantly increased gross defect rate over controls did not occur. The deficient maternal hemoglobins dropped during pregnancy, and the maternal and fetal hemoglobins on day 20 of gestation averaged 4.5 and 4.7 gm/dl, respectively. Partial treatment of the deficient animals by iron injection on days 0 and 7, or on day 7, prevented embryonic and fetal loss and partially corrected both fetal and maternal hemoglobin concentrations.

Anemia, Hypochromic↗

Hypothermia in iron deficiency due to altered triiodothyronine metabolism.

Iron-deficient rats become hypothermic and have an excessive catecholamine response when exposed to an ambient temperature of 4 degrees C. This is not due to changes in body insulation, since thickness is unaltered, since differences persist after removal of hair, and since cutaneous vasoconstriction is intact. On the other hand, oxygen consumption of iron-deficient animals at 4 degrees C is reduced, 39 +/- 3 ml . kg-1 . min-1 compared to 63 +/- 2 in control animals. Thyroxine (T4) values at 4 degrees C were 4.34 +/- 0.20 microgram/dl sera as compared to control values of 3.6 +/- 0.32. Triiodothyronine (T3) values of iron-deficient animals in the cold were 48 +/- 6.8 ng/dl as compared to 72 +/- 5.6 in control animals. Treatment of iron-deficient animals with iron was shown to normalize the plasma T3 response at 4 degrees C within 6 days. Thyroidectomized iron-deficient animals injected with T3 did not show hypothermia at 4 degrees C, whereas thyroidectomized iron-deficient animals injected with T4 showed hypothermia, increased catecholamines, and decreased T3 levels as compared to non-iron-deficient animals similarly treated. It is proposed that iron deficiency impairs conversion of T4 to T3 and that this is primarily responsible for the hypothermia observed.

Animals↗

Catecholamine elevation in iron deficiency.

Iron-deficient rats have increased blood and urinary catecholamines regardless of whether anemia is or is not present. The catecholamine response in both iron-deficient and control animals is largely temperature dependent, showing little difference at the isothermic temperature of 30 degrees C but a two- to threefold increase in iron-deficient animals over controls at lower temperatures. The iron-deficient rat is unable to maintain body temperature at 4 degrees C and this is independent of anemia or of food intake. When animals are run on the treadmill for 4 h, body temperatures increase but the difference observed at 4 degrees C between iron-deficient and control animals persists. The underlying abnormality in temperature regulation and in catecholamine response disappeared after 6 days of iron therapy.

Animals↗

Lactic acidosis as a result of iron deficiency.

Iron-deficient rats have an impaired work performance, even when their anemia is corrected by exchange transfusion. Muscle activity is associated with a higher blood lactate concentration than is observed in iron-replete animals. The accumulation of lactate is a result of excessive production as lactate clearance from the blood was shown to be unaffected. By adjusting the work load to a lower level, it was possible to divide iron-deficient animals into two groups, one capable of continued treadmill running and another in which animals stopped before 20 min. In the former, blood lactate concentration reached a plateau at moderate levels, whereas it continued to increase in the latter until the animal stopped running. Levels of alpha-glycerophosphate oxidase in skeletal muscle mitochondria were found to be much lower in the second group (P < 0.001). Lactate infusion into normal animals was shown to interfere with work performance, and maintenance of a normal pH in iron-deficient and iron-replete animals did not prevent the impairment in work associated with high blood lactate concentrations. Additional evidence was obtained that energy substrate (blood glucose and free fatty acids, muscle glycogen) was adequate in irondeficient animals. Oxygen tension in their vena caval blood was higher than in controls. Furthermore, the in situ behavior of electrically stimulated gastroenemius and soleus muscles appeared similar to that of control animals. Because the stimulation of the single muscle in the iron-deficient animal did not result in appreciable elevation of blood lactate and did not show impaired contractility further supported the hypothesis that the elevation of blood lactate caused the decreased work performance. It is concluded that iron deficiency by a depletion in the iron-containing mitochondrial enzyme, alpha-glycerophosphate oxidase, impairs glycolysis, resulting in excess lactate formation, which at high levels leads to cessation of physical activity.

Acidosis↗

Iron deficiency in the rat: effects on phenylalanine metabolism.

Concentrations of phenylalanine in the plasma were markedly elevated in iron-deficient rats and appeared to vary directly with the degree of iron deficiency. Plasma concentrations of phenylalanine returned to control levels within one week after treatment of the iron-deficient rats with iron dextran. The elevated levels of plasma phenylalanine were probably not produced by a deficiency in liver phenylalanine hydroxylase because levels of activity of the enzyme were found to be normal in the livers of the iron-deficient animals.

Animals↗

Effects of maternal absorption of phenobarbital upon rat offspring development and function.

Sixty Sprague-Dawley derived primaparous rats were administered Luminal (sodium phenobarbital) subcutaneously in doses of either 80 mg/kg, 40 mg/kg, or 0 mg/kg (saline) on Days 9-21 of gestation. The two drug groups delivered litters significantly later with evidence of increased resorption at the higher dose. The higher dose offspring were lighter in weight at birth and at adulthood, but not at weaning. The lower drug dose offspring were developmentally accelerated compared with the other two groups. Acquisition of a conditioned avoidance response (CAR) was negatively correlated with increased drug dose. In appetitive operant paradigms, saline offspring received more reinforcements on fixed ratio sequential schedules, and the lower drug dose offspring received significantly fewer reinforcements than either of the other two groups on an FR-concurrent schedule. Both groups of drug offspring were able to obtain their reinforcements with a lower expenditure of effort than the saline offspring. The higher drug dose offspring made significantly more incorrect (early and late) responses on a schedule which rewarded a delayed response (DRL).

Animals↗

Iron deficiency in the rat: biochemical studies of brain metabolism.

Studies were performed to determine the effects of iron deficiency on brain metabolism in rats. Concentrations of cytochrome pigments, oxidative phosphorylation, and catalase and monoamine oxidase activities in brain tissue were unaffected by iron deficiency. However, activities of aldehyde oxidase, a key enzyme in the pathway of serotonin degradation, were significantly reduced, and concentrations of serotonin and total 5-hydroxyindole compounds were elevated in brain tissue of iron-deficient animals. Aldehyde oxidase activities and concentrations of 5-hydroxyindole compounds in brain tissues returned to approximately normal values one week after treatment of iron deficient animals with iron dextran.

Aldehyde Oxidoreductases↗

Clofibrate effects: mitochondria vs exercise tolerance in aging hamsters.

Mitochondria in skeletal and cardiac muscle have been found to be less stable in aging hamsters, in contrast to preparations from young animals. We have found previously that clofibrate (Atromid-S) will reverse this degeneration in the older hamsters. This study examined the exercise tolerance of aged hamsters, to see if clofibrate had a parallel effect on exercise tolerance as had been shown for muscle mitochondria stability. Maximal duration of exercise for hamsters on a treadmill was measured in a control and treatment group before and after treatment with clofibrate. There was no improvement in exercise tolerance with clofibrate. We conclude that inferences of functional effects in intact animals from changes found in isolated tissue preparations should be drawn with caution.

Aging↗

Iron deficiency in the rat. Physiological and biochemical studies of muscle dysfunction.

Work performance on a treadmill has been evaluated in normal and iron-deficient rats. Anemia was removed as a variable by adjusting the hemoglobin of all animals to the same concentration. At a hemoglobin compatible with normal work performance, iron-deficient animals showed a marked impairment of running ability as compared to control animals. Iron therapy corrected the disability within 4 days. Concentrations of the cytochrome pigments and myoglobin, and rates of oxidative phosphorylation with pyruvate-malate, succinate, and alpha-glycerophosphate as substrates were all reduced in mitochondrial preparations from skeletal muscle of iron-deficient rats, but only the rate of phosphorylation with alpha-glycerophosphate as substrate increased significantly and in parallel with the recovery in work performance of the iron-deficient rats treated with iron dextran.

Anemia, Hypochromic↗

Further characterization of a low-molecular weight allergen fragment isolated from the green pea.

A low molecular weight allergen fragment present in the pea dialysate fraction was purified by ion-exchange chromatography and gel filtration. The highly purified allergen fragment inhibits both antigen-indiced passive cutaneous anaphlaxix reactions in guinea-pigs sensitized with rabbit anti-pea extract sera and Prausnitz-Küstner reactions in non-allergic volunteers sensitized with the sera of patients sensitive to green peas. Preliminary analysis of the purified allergen fragment indicates that it is a glycoprotein with a molecular weight of 1800 +/- 250.

Allergens↗

Studies of the development of congenital anomalies in rats. III. Effects of inhibition of mitochondrial energy systems on embryonic development.

Pregnant rats were treated with various inhibitors of mitochondrial oxidative energy metabolism and with lowered oxygen tension, and the embryo fetuses examined for the occurrence of congenital malformations and for changes in enzymatic activities. Treatment with all agents tested resulted in the production of skeletal anomalies. Sodium phenobarbital was the most teratogenic of the drugs tested and produced a high incidence of malformations which included cleft palate, tail anomalies, spinal retroflexion, domed head, and facial hypoplasia. Diphenylhydantoin produced a low incidence of syndactyly and oligodactyly. In addition to its effects on fetal growth and development chloramphenicol appeared to interfere with implantation. Tissue preparations from embryos exposed to sodium phenobarbital and chloramphenicol showed markedly lowered levels of DPNH oxidase activity. Cytochrome oxidase activity was also markedly lowered in the preparations from chloramphenicol-exposed embryos. Enzyme activities in preparations from embryos exposed to malonate and diphenylhydantoin appeared unaffected, although the drugs are strong inhibitors of electron transport in vitro; the lack of apparent effect may be due to the fact that both drugs do not bind to the enzyme preparations and were diluted 100- to 200-fold during preparation and assay of the tissue homogenates.

Abnormalities, Drug-Induced↗