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Biomedical subjects

L Frank

Publications and source records attributed to L Frank.

At least 19 recordsLinked to original sources
PubMed1995

Failure of premature rabbits to increase lung antioxidant enzyme activities after hyperoxic exposure: antioxidant enzyme gene expression and pharmacologic intervention with endotoxin and dexamethasone.

Premature rabbits, unlike full-term rabbits, are unable to mount a protective increase in pulmonary antioxidant enzyme (AOE) activities in response to 48 h of hyperoxic exposure and demonstrate increased pulmonary O2 toxicity compared with full-term rabbits. To examine AOE gene expression of CuZn superoxide dismutase (SOD), Mn SOD, catalase, and glutathione peroxidase in preterm versus term rabbits in response to hyperoxia, 29.5 d preterm rabbits (delivered by hysterotomy) and term rabbits (spontaneously vaginally delivered) were exposed to 48 h of > 90% O2 or room air. Preterm rabbits had a significant increase in CuZn SOD mRNA without corresponding AOE activity increases, suggesting translational/posttranslational inhibition. In full-term rabbits, the magnitude of lung AOE mRNA changes was associated with concordant magnitude changes in activities of CuZn SOD, Mn SOD, and catalase, suggesting pretranslational regulation of AOE gene expression; glutathione peroxidase, however, appears to be regulated translationally/posttranslationally. To investigate potential pharmacologic means of overcoming the susceptibility of the preterm rabbit to O2 toxicity, 29.5 d preterm rabbits received 20-40 micrograms/kg of Salmonella typhimurium endotoxin or diluent S.C. (after birth and at 24 h); in separate experiments, pregnant rabbits received intramuscular injections of dexamethasone (0.01-0.05 mg/kg) or saline on gestational d 27.5 and 28.5 and underwent hysterotomy at 29.5 d.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Positive regulation of pulmonary antioxidant enzyme gene expression by prenatal thyrotropin releasing hormone plus dexamethasone treatment in premature rats exposed to hyperoxia.

Prenatal administration of thyrotropin releasing hormone (TRH) plus dexamethasone (DEX) to pregnant rats produces significantly depressed fetal lung antioxidant enzyme (AOE) activities and AOE mRNA levels in late gestation. Because of this negative regulation of AOE gene expression in the late fetal lung, we hypothesized that hormonally pretreated prematurely delivered rats might demonstrate inferior tolerance to prolonged hyperoxia. Litters of prenatal TRH+DEX-treated and sham-treated prematurely delivered rat pups (gestational d 21 of 22) were randomized to either > 95% O2 or room air for up to 14 d. The right lungs of 2- and 7-d exposure pups were assayed for AOE activities; the left lungs of the same pups were used to quantitate the concentrations of AOE mRNA by solution hybridization. The prenatal TRH+DEX-treated pups were able to induce adaptive lung AOE mRNA and activity responses to hyperoxia by 2 d of exposure; and by 7 d in O2 they showed greater increases in AOE mRNA concentrations and AOE activities in response to hyperoxic challenge compared with the sham-treated controls. Lung lipid surfactant measurements after hyperoxia were not affected by prenatal TRH+DEX treatment. In addition, TRH+DEX-pretreated premature rats did not show the hypothesized increased susceptibility to O2-induced lung damage and lethality, but, in fact, had slightly improved hyperoxic survival (d 3-7 of O2 exposure) compared with sham-treated controls. Exposure to hyperoxia significantly reduced serum triiodothyronine and thyroxine levels in the sham-control pups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Premature rats treated with propylthiouracil show enhanced pulmonary antioxidant enzyme gene expression and improved survival during prolonged exposure to hyperoxia.

In full-term newborn rats, propylthiouracil (PTU) treatment has been previously shown to decrease susceptibility to O2-induced lung damage and improve survival during hyperoxic exposure. However, no differences were found in lung antioxidant enzyme (AOE) activity responses to hyperoxia compared with O2-exposed untreated (control) term rats. To further explore possible pulmonary protective effects of PTU treatment in prematurely delivered animals, we administered PTU (0.015%) in drinking water to timed-pregnant rats for the final 10 d of gestation prior to delivery 1 d before term, and during lactation; control pregnant/nursing rats received untreated water. Both groups of 21-d premature rat pups were randomized to either > 95% O2 or room air exposure after birth for up to 14 d. The left lungs of 7-d exposure pups were used to quantitate the concentrations of AOE mRNA by solution hybridization; the right lungs of the same pups were assayed for AOE activities. PTU treatment resulted in survival rates of O2-exposed preterm rat pups that were consistently higher at all time periods in hyperoxia including 7 d [PTU, 67 of 82 (82%) versus control pups, 58 of 113 (51%); p < 0.001] and 14 d [PTU, 31 of 39 (79%) versus control, 15 of 66 (23%); p < 0.001]. Further evidence of increased tolerance to > 95% O2 in PTU pups included a significant decrease in the incidence of microscopic intraalveolar edema and a significant increase in lung tissue surfactant-related phospholipids compared with O2-exposed control pups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Effects of the 21-aminosteroid, U74389F, on bleomycin-induced pulmonary fibrosis in rats.

OBJECTIVE: To determine if a new class of agents, the 21-aminosteroids, which are reportedly potent inhibitors of iron-dependent lipid peroxidation, could protect rats from bleomycin-induced pulmonary fibrosis. SUBJECTS: Fifty-five adult male Sprague-Dawley rats. DESIGN: Prospective, randomized, blinded, controlled trial. INTERVENTIONS: The rats were subjected to intratracheal bleomycin (or saline vehicle), and were then treated with the 21-aminosteroid, U74389F (20 mg/kg/day), or vehicle, for the next 7 days. MEASUREMENTS AND MAIN RESULTS: At 21 days after bleomycin administration, pulmonary fibrosis was assessed histologically as percent of lung fields with evidence of fibrosis. Pulmonary fibrosis was assessed biochemically by measuring pulmonary elastin and hydroxyproline content. To determine if a protective effect of U74389F was linked to the 21-aminosteroid's ability to suppress lipid peroxidation, two products of lipid peroxidation were assayed in the lungs at 7 and 14 days after bleomycin exposure. By histologic assessment, the 21-aminosteroid-treated, bleomycin-exposed animals were found to have significantly decreased the extent of pulmonary fibrosis when compared with the bleomycin control group (mean 48.6 +/- 20.0 [SD] % [n = 9] vs. 68.4 +/- 19.6% [n = 11]; p < .05). In addition, lung elastin was decreased by approximately 75% (p < .05) and hydroxyproline was decreased by approximately 50% (NS) in the 21-aminosteroid-treated group when compared with the bleomycin control group. At 7 and 14 days after bleomycin exposure, all bleomycin-exposed animals had evidence of increased lipid peroxidation (conjugated dienes and thiobarbituric acid-reactive substances), but the 21-aminosteroid-treated, bleomycin-exposed animals had significantly decreased evidence of lipid peroxidation when compared with bleomycin controls. CONCLUSIONS: The 21-aminosteroid can substantially protect animals from bleomycin-induced pulmonary fibrosis and may prove useful in other lung diseases where iron-dependent, free-radical reactions and/or lipid peroxidation are presumed mechanisms of toxicity.

Animals↗
PubMed1992

Questions about AIDS.

Explore the source record for details and available documents.

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↗
PubMed1991

Hyperoxic inhibition of newborn rat lung development: protection by deferoxamine.

Prolonged exposure to hyperoxia markedly inhibits normal lung development (alveolarization and respiratory surface area expansion) in immature animals. Since (a) hyperoxia results in excess hydroxyl radical (OH.) formation, (b) (OH.) is implicated in O2-induced lipid peroxidation and DNA alterations, and (c) both OH. formation and its interaction with DNA are Fe++ dependent; chelation of Fe++ should act to protect against pulmonary O2 toxicity and hyperoxic inhibition of lung development. We therefore treated litters of newborn rats with the iron chelator Deferoxamine mesylate (DES) (150 mg/kg/day) during a 10-day exposure to greater than 95% O2. Morphometric analysis demonstrated that compared to the mean airspace size in air control rat pups (Lm = 44.5 microns), hyperoxic exposure resulted in a 34% larger mean air space diameter in O2-saline rat lungs (59.5 microns) versus only an 11% enlargement in O2-DES lungs (51.1 microns*). Lung internal surface area (cm2) per 100-g body weight were air control = 4480, O2-saline = 3570 (decreases 20.3%), and O2-DES = 4125* (decreases 7.9%) (*p less than 0.05 versus O2-saline group). DES-treated animals also had significantly decreased lung conjugated diene levels during hyperoxic exposure and increased lung elastin content (reflective of preserved lung alveolar formation) compared to O2-saline rats. These results indicate that DES treatment substantially ameliorated the inhibitory effects of neonatal hyperoxic exposure on normal lung development.

Aging↗
PubMed1991

Failure of premature rabbits to increase antioxidant enzymes during hyperoxic exposure: increased susceptibility to pulmonary oxygen toxicity compared with term rabbits.

Although the prematurely born are known to have decreased baseline levels of protective antioxidant enzymes (Frank L, Sosenko IRS: J Pediatr 110:9 and 106, 1987), the ability to augment the baseline values during high O2 exposure is the key factor determining O2 tolerance versus O2 susceptibility. We have compared the pulmonary antioxidant enzyme responses of prematurely delivered rabbits (gestational d 29 of 32) and full-term rabbits to 48-72 h of hyperoxic exposure. We found that although full-term newborns exposed to greater than 90% O2 consistently showed elevated superoxide dismutase, catalase, glutathione peroxidase, and glucose-6-phosphate dehydrogenase activities, the premature animals repeatedly failed to respond to hyperoxia with increased antioxidant enzyme activity levels. Consistent with the comparative antioxidant enzyme responses were the evidences of O2 toxicity in the two age groups. The prematurely born rabbits had significantly increased lung lavage protein content, lung conjugated diene levels, and more severe light microscopic lung pathology compared with the full-term animals during equal O2 exposure time. This first reported comparison of prematurely born versus full-term animal responses to hyperoxia might help to explain the clinical observation that the very prematurely born infant is excessively prone to the development of O2-induced lung injury and the progressive development of bronchopulmonary dysplasia.

Animals↗
PubMed1991

Premature weaning of rat pups results in prolongation of neonatal tolerance to hyperoxia.

Neonatal rats usually lose their marked tolerance to hyperoxia at about 1 mo of age. We examined the hypothesis that the marked dietary change that occurs at weaning might be important to this loss of O2 tolerance. We, therefore, prematurely weaned rat pups at 15-17 d of age, expecting to find an earlier loss of O2 tolerance. Surprisingly, the prematurely weaned rats showed consistently prolonged relative O2 tolerance compared with normally weaned rats at all ages tested from 35-85 d of life. For example, when challenged with greater than 95% O2 exposure for 7 d, the composite survival rate of the prematurely weaned rats (at 35-85 d of age) was nearly twice that of the normally weaned group (83 of 107 = 78% versus 44 of 107 = 41%, p less than 0.01). In the two experimental groups, nearly all comparative parameters examined were similar, including: 1) growth rate; 2) lung DNA, RNA, and protein; 3) lung antioxidant enzymes and enzyme responses to hyperoxia; 4) lung morphometry; and 5) lung elastin and collagen content. Only serum corticosterone and triiodothyronine levels differed considerably in the two groups. We conclude that premature weaning has a very marked and sustained positive effect on the relative retention of O2 tolerance in the growing rat.

Age Factors↗
PubMed1991

Intralipid increases lung polyunsaturated fatty acids and protects newborn rats from oxygen toxicity.

Intralipid, derived from soybean oil and containing a high percentage of n-6 family polyunsaturated fatty acids (PUFA) and also linolenic acid, an n-3 family PUFA, is commonly the first fat source provided to very low birth weight premature infants. Following up on our previous reports that newborn rats born to dams fed high-PUFA diets demonstrate superior tolerance to hyperoxia, we examined whether the high-PUFA fat source Intralipid might also protect against oxygen toxicity. Adult female rats were fed either regular Rat Chow or fat-free diet containing 20%-Intralipid as the fat source for 3 wk before and then throughout pregnancy and lactation. One- and 5-d-old offspring of Intralipid diet-fed dams demonstrated significant increases in lung lipid n-6 family PUFA plus elevated linolenic acid compared with regular diet-fed offspring. These characteristic fatty acid patterns, apparent in total lung lipids, were even more pronounced in the triglyceride fraction compared with the phospholipid fraction. Associated with these fatty acid changes were significantly improved hyperoxic survival rates (89 out of 95 = 94% survival after 7 d of greater than 95% O2 exposure) in Intralipid offspring (versus 89 out of 106 = 84%, p less than 0.05 in regular diet offspring) and evidence of superior clinical/pathologic status. No differences in pulmonary antioxidant enzyme or surfactant system development, response of antioxidant enzymes to hyperoxic exposure, or lung prostaglandin E2, 6-keto PGF1-alpha or leukotrienes C4-F4 were present. These findings continue to support the hypothesis that increasing lung PUFA content may provide increased O2 free radical scavenging capacity, thus protecting against hyperoxic lung damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Prenatal hormone treatment with thyrotropin releasing hormone and with thyrotropin releasing hormone plus dexamethasone delays antioxidant enzyme maturation but does not inhibit a protective antioxidant enzyme response to hyperoxia in newborn rat lung.

Whereas glucocorticoid administration to pregnant rats produces parallel acceleration of lung surfactant and antioxidant enzyme system maturation in late gestation, prenatal thyroid hormone treatment results in acceleration of surfactant maturation, with a paradoxical decrease in antioxidant enzyme (AOE) development. In these studies, we tested whether prenatal thyroid releasing hormone (TRH) treatment would act like prenatal thyroid hormone on pulmonary surfactant and AOE system maturation and whether combined prenatal treatment with TRH plus dexamethasone (DEX) would alter these effects. Secondly, we tested whether prenatal TRH and prenatal TRH plus DEX would inhibit the ability of newborn rats to respond to hyperoxia with protective increases in AOE activities. Results of the developmental studies revealed significantly increased fetal lung disaturated phosphatidylcholine content with significantly decreased pulmonary AOE activities as a result of prenatal TRH treatment that was not reversed with the addition of DEX. Combined TRH plus DEX treatment resulted in statistically significant decreases in body weight, lung weight, and lung weight to body weight ratios at both 21 and 22 d of gestation; growth effects were not seen with TRH alone. In terms of hyperoxic AOE response, despite being born with lower baseline AOE levels, the newborn animals prenatally treated with TRH or TRH plus DEX were able to induce a normal pulmonary AOE response to high O2 exposure. Although requiring further investigation, this reassuring finding suggests that clinical prenatal therapy with TRH or the combination of TRH plus DEX is not contraindicated for those infants delivered prematurely who go on to require intensive hyperoxic therapy.

Animals↗