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L Frank

Publications and source records attributed to L Frank.

At least 73 records · Page 4Linked to original sources
PubMed1994

Propylthiouracil treatment decreases the susceptibility to oxygen radical-induced lung damage in newborn rats exposed to prolonged hyperoxia.

In newborn rats, antenatal thyroid stimulation with thyroid-releasing hormone is associated with developmental decreases in pulmonary antioxidant enzyme activities and decreased survival rates during prolonged hyperoxic exposure, with pathologic evidence of increased O2-induced lung damage. Propylthiouracil (PTU), in addition to its antithyroid effects, reportedly has antioxidant properties. To explore possible pulmonary protective effects from both the antithyroid and antioxidant properties of PTU, we administered PTU (0.015%) in drinking water to timed-pregnant rats for the final 10 d of gestation and during lactation; control rats received untreated water. The survival rate of the PTU-treated pups when placed in more than 95% O2 at birth was consistently higher at all time periods in hyperoxia from 6 d [PTU, 81 of 81 (100%); control pups, 70 of 84 (83%); p < 0.01] to 14 d [PTU, 41 of 53 (77%); control pups = 14 of 56 (25%); p < 0.01]. Further evidence of increased tolerance to more than 95% O2 in PTU pups included a significant decrease in the incidence of microscopic intraalveolar edema, decreased lipid peroxidation (malondialdehyde), and a significant increase in lung tissue surfactant-related phospholipids compared with O2-exposed control pups. No differences were present in lung structural maturation, antioxidant enzyme activity response to hyperoxia, or lung tissue O2 radical formation in more than 95% O2. We conclude that PTU treatment has important postnatal effects that protect newborn rats against oxidant-induced lung injury and lethality during hyperoxia, which may be related to PTU inhibition of thyroid hormone production, effect on O2 metabolism, or its direct antioxidant properties.

Animals↗
PubMed1993

Does lung NAD(P)H:quinone reductase (DT-diaphorase) play an antioxidant enzyme role in protection from hyperoxia?

NAD(P)H:quinone reductase, or DT-diaphorase, has been studied primarily in the liver where it appears to function as an antioxidant-like enzyme in the 2-electron reduction of some quinones to less toxic hydroquinones. This property together with new molecular biology evidence that oxidants such as H2O2 can induce gene transcription of DT-diaphorase provide especially intriguing reasons to examine the possibility that lung DT-diaphorase could have an important antioxidant enzyme role versus pulmonary O2 toxicity during exposure to hyperoxia. We found that similar to the 'classical' lung antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) DT-diaphorase activity increased significantly in the late gestational fetal lung; also its activity was altered in the same way as the antioxidant enzymes by prenatal hormonal treatment. Another similarity is that DT-diaphorase activity was induced in the neonatal animal lung during hyperoxia, but not in the adult animal lung. However, using various drug treatments which markedly increased lung DT-diaphorase activity (e.g., 3-methylcholanthrene, butylated hydroxyanisole, methimazole) we found no improved hyperoxic survival in the treated adult rats. Also, dicumarol treatment, which markedly depressed DT-diaphorase activity, did not diminish the hyperoxic survival rate in an O2-tolerant adult rat model. Thus, we conclude that unlike the classical antioxidant enzymes, increased pulmonary DT-diaphorase activity is probably neither necessary nor sufficient to protect against pulmonary O2 toxicity during hyperoxia.

Aging↗
PubMed1993

The effect of an AMPA antagonist (NBQX) on postischemic neuron loss and protein synthesis in the rat brain.

Two groups of rats were subjected to 12 min of global cerebral ischemia and 6 days recirculation using the four-vessel occlusion model with hypotension and then treated with the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) antagonist NBQX [2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F) quinoxalinedione (Honoré et al. 1988]. One group was used for routine and quantitative histology and immunostaining for glial fibrillary acidic protein (GFAP). The second group was subjected to autoradiographic studies of regional cerebral protein synthesis, with special emphasis on the hippocampus, the frontal cortex, and the thalamus. It was found that neuroprotective treatment with NBQX normalized cerebral protein synthesis rate (CPSR) in all investigated regions 6 days after ischemia. In untreated ischemic animals CPSR was normalized in all regions except for the CA3 and thalamus, where it had increased by 29% and 41%, respectively. Treatment of controls with NBQX had no effect on CPSR after 6 days. The histological investigations revealed that NBQX did not protect vulnerable cells in the dentate hilus and the reticular thalamic nucleus (RTN). In these regions reactive astrocytosis visualized by GFAP immunostaining was equally pronounced in both ischemic and NBQX-treated animals, and most neurons in the RTN were eosinophilic. The 80-100% pyramidal neuron loss in CA1 was accompanied by a high degree of reactive astrocytosis, whereas the NBQX-treated animals showed no signs of astrocytosis in this region. The ischemic CA1 pyramidal layer was also massively invaded by microglia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Negative regulation of antioxidant enzyme gene expression in the developing fetal rat lung by prenatal hormonal treatments.

Prenatal administration of thyrotropin-releasing hormone (TRH) or TRH plus dexamethasone (DEX) to pregnant rats accelerates lung surfactant system development in late gestation, but paradoxically depresses the normal late gestational elevation in fetal lung antioxidant enzyme (AOE) activities (Pediatr Res 30:522, 1991). In these present studies, we tested whether both prenatal hormonal treatments act to depress normal fetal lung AOE development by negative regulation of AOE gene expression. We used solution hybridization to quantitate the concentration of AOE mRNA. Results of the developmental studies revealed significantly decreased lung mRNA concentrations of copper-zinc superoxide dismutase, manganese superoxide dismutase, catalase, and glutathione peroxidase in late gestation as a result of prenatal TRH treatment. The addition of DEX administration did not reverse the lowered expression of lung AOE genes due to TRH treatment, but instead resulted in significant additional decreases in pulmonary AOE mRNA levels at both 21 and 22 d of gestation. The tested AOE mRNA half-lives (stabilities) revealed no significant differences between controls (8.0-10.5 h) and TRH-treated (8.2-9.5 h) and TRH-plus-DEX treatment (7.8-10.7 h) groups. These findings suggest that prenatal treatment with TRH and with TRH plus DEX acts to depress the normal late fetal lung AOE activity elevations by (direct) negative regulation of AOE gene expression, and the decreased AOE expression is likely regulated at the level of gene transcription rather than posttranscriptionally.

Animals↗
PubMed1993

Protection against acute and chronic hyperoxic inhibition of neonatal rat lung development with the 21-aminosteroid drug U74389F.

Normal lung development involves septation of the large air saccules present at birth to form smaller diameter alveoli with a much increased surface area for respiratory exchange. This process in the newborn animal is markedly inhibited by hyperoxia, and the altered lung morphology that results may be permanent. We tested whether treatment of neonatal rats with the new 21-aminosteroid (21-AS) drug, U-74389F (15 mg/kg/d), could protect against O2-induced inhibition of normal lung development. By morphometric analysis after 10 d in > 95% O2, the lungs of the animals treated with this potent iron chelator and inhibitor of lipid peroxidation showed a substantial protective effect--with reduced mean air space diameter and significantly increased internal surface area compared with O2 control pups. [Air control mean air space diameter = 47.4 microns, internal surface area = 1014 cm2; O2 controls = 61.0 microns (increases 29%), 769 cm2 (decreases 24%); O2 21-AS = 53.4 microns (increases 13%), 919 cm2 (decreases 9%); p < 0.05 between O2 groups.] Similarly, inhibition of lung elastin deposition (involved in septation process) during hyperoxia was significantly ameliorated by 21-AS treatment. In addition, follow-up studies of young adult rats demonstrated permanently enlarged lung alveoli and reduced surface area after neonatal high O2 exposure. These chronic morphologic effects were also significantly reduced by neonatal 21-AS treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Differential gene expression of antioxidant enzymes in the perinatal rat lung.

It has been previously demonstrated that the developing rat lung markedly increases its catalase (CAT) and glutathione peroxidase (GP) activities during the final 10 to 15% of gestation. In the present studies, we tested whether four major antioxidant enzymes (AOE) in perinatal rat lungs might share a similar pattern of developmental AOE gene expression via a pretranslational mechanism. The left lungs of 18-d to term fetuses and early postnatal rat pups were used to measure the concentrations of AOE mRNA by solution hybridization and the right lungs of the same group of animals were assayed for AOE activities. Results revealed differential AOE gene expression in developing rat lungs. Whereas the CAT and GP activities progressively increased prenatally, the superoxide dismutase (SOD) activity either declined [copper-zinc SOD (Cu, ZnSOD)] or remained constant [manganese SOD (MnSOD)] in late gestation. Postnatally, Cu,ZnSOD and CAT activities progressively increased, whereas MnSOD remained constant and GP activity declined slightly. For Cu,ZnSOD, MnSOD, and CAT, the activity changes were generally consistent with the patterns of changes in their mRNA concentrations in both the prenatal and postnatal period, but for GP they were not. At the time of birth, however, the mRNA levels of Cu,ZnSOD and CAT decreased approximately 40%, whereas their enzyme activities increased. For MnSOD, only a slight rise in mRNA level was observed versus approximately 100% increase in its activity at the time of birth. These findings suggest that the AOE are not coordinately regulated, and that developmental regulation of AOE gene expression in the perinatal rat lung is complex and likely exerted at different levels of regulation.

Animals↗
PubMed1993

The formation of alveoli in rat lung during the third and fourth postnatal weeks: effect of hyperoxia, dexamethasone, and deferoxamine.

Terminal gas-exchange units in the lung of many species are, at birth, relatively large structures termed saccules. Saccules septate postnatally forming smaller units that constitute the final alveoli. In the rat, septation occurs intensively during the first 2 postnatal wk after which it has been considered to stop. Treatment with dexamethasone or exposure to hyperoxia during the first 2 postnatal wk markedly inhibits septation as evidenced by the formation of fewer and bigger alveoli than in normally developed rats. Deferoxamine, an iron chelator, has been reported to protect the lung from the effects of exposure to hyperoxia in early postnatal life. In this study, we investigated the effects of these treatments during the 3rd and 4th postnatal wk, that is, after the early period of rapid alveolarization. Our results show that treatment with dexamethasone no longer had any inhibitory effect on alveoli formation; that exposure to hyperoxia continued to inhibit the formation of new alveoli, resulting in bigger and less numerous alveoli; that treatment of animals exposed to hyperoxia with deferoxamine still protected their lungs against hyperoxic inhibition; and that elastin fiber length density in the lung was significantly reduced in hyperoxic-exposed animals. These results suggest that septation continues beyond the 2nd postnatal wk and does not stop abruptly at age 14 d in air-breathing rats and that hyperoxic inhibition of alveolarization during the 3rd and 4th postnatal wk is due to the inhibition of septation of existing or newly generated gas-exchange units during that period of lung development.

Age Factors↗
PubMed1993

Epidermal growth factor increases antioxidant enzyme and surfactant system development during hyperoxia and protects fetal rat lungs in vitro from hyperoxic toxicity.

Epidermal growth factor (EGF) has been shown to accelerate fetal lung maturation in rabbits, lambs, and rhesus monkeys in vivo and increase surfactant synthesis in vitro. Its effect on the maturation of the lung antioxidant enzyme system, however, is unknown. We studied the effect of EGF (10 nM) on 19-d fetal rat lung explant cultures in serum-free medium in air/5% CO2 or > 90% O2/5% CO2 compared with similarly grown control cultures in air or hyperoxia at 72 h. Fetal lung activities of superoxide dismutase and catalase were unchanged by EGF in air, whereas glutathione peroxidase activity was significantly decreased (p < 0.05 versus air control). However, in hyperoxia, EGF-treated fetal lung cultures had significantly elevated superoxide dismutase and catalase activities (p < 0.01) versus O2-exposed controls, and glutathione peroxidase activity similar to that of controls. The mRNA levels for all the antioxidant enzymes showed patterns similar to the enzyme activities except in the case of Cu,Zn-superoxide dismutase mRNA, which increased in EGF-air cultures. EGF decreased the rate of 3H-choline incorporation into disaturated phosphatidylcholine in air (p < 0.01 versus air control), but increased disaturated phosphatidylcholine synthesis in response to hyperoxia (p < 0.01 versus O2 control). The histologic appearance of EGF-treated cultures in O2 was superior to that of O2-exposed controls, which showed thickened septal walls, decreased surfactant in the air spaces, and epithelial cell mitochondrial swelling. EGF therefore accelerates antioxidant enzyme and disaturated phosphatidylcholine maturation under hyperoxic conditions and protects fetal rat lung cultures from hyperoxic injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Questions about AIDS.

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Acquired Immunodeficiency Syndrome↗
PubMed1992

Cholinergic pruritus in a horse.

An 8-year-old gelding, with a 1-year history of intense pruritus only after exercise, was diagnosed as having cholinergic pruritus. Provocative testing, using exercise and hot-water baths to increase core body temperature, assisted in the diagnosis. Cholinergic pruritus in human beings is a variant of the more common syndrome, cholinergic urticaria, which is characterized by intense pruritus and pinpoint urticaria. With cholinergic pruritus, intense itching results without urticaria. Specific diagnostic laboratory tests have not been developed.

Animal Feed↗
PubMed1992

Regional cerebral protein synthesis after transient ischemia in the rat: effect of the AMPA antagonist NBQX.

Normothermic rats with 12 min, complete cerebral ischemia were treated with the AMPA antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F) quinoxalinedione (NBQX) [10], which prevents CA1 pyramidal neuron loss. Twenty hours after ischemia, cerebral protein synthesis rate (CPSR) was measured autoradiographically using [35S]methionine. Ischemia caused a 38% decrease of CPSR in CA1, and postischemic treatment with NBQX caused a 66% decrease in this region. Also treatment with NBQX alone resulted in a decrease (22% in CA1) of the CPSR. Since some evidence exists that the neuroprotective effect of NBQX is related to blockade of the fast AMPA-mediated transmission, the further decrease of the postischemic CPSR in CA1 could be a mere side effect.

Animals↗
PubMed1992

Prenatal dexamethasone treatment improves survival of newborn rats during prolonged high O2 exposure.

Prenatal dexamethasone (DEX) treatment is known to accelerate the maturation of both the surfactant system and the fetal lung antioxidant enzyme (AOE) system (Frank L, Lewis P, Sosenko IRS: Pediatrics 75:569-574, 1985). Because of this stimulatory effect of prenatal DEX on the normal late gestational development of the AOE system, we questioned whether this treatment might have a salutary effect on the ability of the newborn rat to tolerate early and prolonged exposure to hyperoxia, inasmuch as the AOE are the primary lung defensive system against high O2 challenge. In nine experiments with term newborn rats in greater than 95% O2, the composite percentage of survival was significantly greater in the prenatal DEX pups at all time periods in hyperoxia from 7 d [control pups, 67 of 94 (71%); prenatal DEX, 96 of 99 (97%)] to 14 d [controls, 10 of 32 (31%); prenatal DEX, 18 of 33 (55%)] (p less than 0.01). In addition to survival per se, the prenatal DEX pups showed significantly decreased lung wet weight/dry weight ratios, pathologic evidence of pulmonary edema, and lung conjugated dienes versus the O2 control newborn group. Of the many comparative parameters examined, the major difference found between the two groups was in the pulmonary AOE responses to hyperoxia. By 2 d in hyperoxia, the prenatal DEX rat pups showed significantly elevated superoxide dismutase, catalase, and glutathione peroxidase activities compared to air control pups, and at 4 and 7 d in O2 the AOE levels were consistently greater in the DEX group than the AOE responses in the control O2 pups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Prenatal thyroid releasing hormone and thyroid releasing hormone plus dexamethasone lessen the survival of newborn rats during prolonged high O2 exposure.

Newborn rats prenatally treated with TRH or the combination of TRH + DEX have lower lung antioxidant enzyme activities at birth than control newborns but are able to induce an adaptive antioxidant enzyme response to hyperoxic exposure of similar or even greater magnitude compared to O2 control offspring. Because of this greater antioxidant enzyme response, we hypothesized that the hormonally pretreated newborns might demonstrate superior tolerance to prolonged high O2 exposure. However, when placed in greater than 95% O2 at birth, the survival rates were consistently lower in the TRH- and TRH + DEX-treated pups at all time periods in hyperoxia from 9 d [control = 74 of 92 (80%); TRH + DEX = 32 of 47 (68%); TRH = 29 of 48 (60%); p less than 0.05] to 14 d [control = 43 of 92 (47%); TRH + DEX = 11 of 47 (23%); TRH = nine of 48 (19%); (p less than 0.05)]. Other evidence of poorer O2 tolerance in the prenatal hormone-treated pups included a greater incidence of intraalveolar edema and elevated lung conjugated dienes, an index of lipid peroxidation, at 3, 5, and 7 d of O2 exposure. There was also a persistent elevation in 3,5,3'-triiodo-L-thyronine and thyroxine serum levels in the 10-d-old TRH-treated offspring. We conclude that prenatal TRH treatment, possibly working through the secretion of 3,5,3'-triiodo-L-thyronine and thyroxine, has some important lasting postnatal effect (not completely reversed by dexamethasone) that predisposes newborn rats to greater O2 radical-induced lung sequelae of prolonged hyperoxic exposure.

Animals↗
PubMed1992

[Analytic and biological standardization of Prunus avium extracts].

Novicardine, the acetonic extract of P. avium peduncle which has advantageous cardiotonic effect, was standardized chemically and biologically. Flavonones, flavones, isoflavones and their glycosides were (methanolbuffer solution eluent, gradient elution) detected by reverse phase HPLC technique. It has been found that substances produced from different varieties of cherry peduncle originated from various lands, have the same components and their ratios are similar, but a contradictory statement could be made in the case of sour cherry. The allowed area ratios belonging to some ingredients were stated with reference to dihydrowogonine-7-O-glucoside. The biological experiments were performed on isolated heart preparations. In the organ bath with Locke's solution content the suspended left atrium and the papillary muscle were driven by rectangular electric impulses of 1 msec duration and of 1.7 Hz frequency, whereas the right atria were beating spontaneously. The result of experiments demonstrated that the standard Novicardine improves the contraction force of heart muscle by some 20-25%, and at the same time doesn't exert influence on the basic electrophysiological parameters and doesn't cause significant changes in heart rate. On the basis of investigation of substances having modified componentratio it was stated that extracts could be isolated which have cardiotonic effect four times stronger than that of Novicardine, on the other hand there were some extracts having negative inotropic effect. These effects were brought into connection with families of compounds (mainly glycosides and aglycones). It seems that the big variety of Novicardine can be assigned to the individual sensitivity of heart preparations, and the ratios of the above mentioned compounds.

Animals↗
PubMed1992

Antioxidants, nutrition, and bronchopulmonary dysplasia.

The immaturity of the lung of the very prematurely delivered newborn appears to make it hypersusceptible to injury by those very therapeutic measures that the infant requires shortly after birth--mechanical ventilation and hyperoxia. There is good experimental evidence to relate the immature lung's susceptibility to early hyperoxia-induced lung damage to deficient antioxidant defensive systems. Less than fully adequate nutritional support of these tiny newborns can have extremely detrimental effects on their lungs' ability to resist and repair on-going injury and to continue developing normally. Promising experimental means of possible protection from hyperoxic lung damage and progression to chronic lung disease (bronchopulmonary dysplasia) are reviewed.

Animals↗
PubMed1991

Developmental aspects of experimental pulmonary oxygen toxicity.

One of the more fascinating aspects of in vivo research on pulmonary O2 toxicity is the striking difference in the response of the neonatal versus the adult animal to hyperoxia. In general, neonatal animals are much more resistant to the characteristic O2-induced lung pathology seen in adult animals in hyperoxia. Neonatal animals are also able to rapidly mount a protective lung biochemical response to high O2 exposure [increased pulmonary antioxidant enzyme (AOE) activities], an adaptive response which adult animals have lost the ability to manifest in greater than 95% O2. This review focuses on the disparate AOE responses of the neonatal versus adult animal in hyperoxia. It also explores other possible explanations for the striking O2 tolerance of young versus adult animals, including comparative O2 free radical production rates, inflammatory cell responses, lung lipid composition, repair capabilities, etc. Discussion also centers on a less well studied toxic complication associated with hyperoxic exposure in the neonatal animal, i.e., the marked inhibitory effect of O2 exposure on normal lung growth and development of an alveolarized lung with an expanded respiratory exchange surface area. Finally, effective experimental means of protecting adult (and neonatal) animals from pulmonary O2 toxicity are reviewed. A closing section considers the enlightening new information that molecular biology has revealed about the regulation of AOE gene expression during normal development and under conditions of hyperoxidant challenge.

Aging↗