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PubMed2005

Comparison of two flow generators with a noninvasive ventilator to deliver continuous positive airway pressure: a test lung study.

OBJECTIVE: To compare the performance of two continuous flow generators with a ventilator designed for noninvasive positive pressure ventilation (NPPV) to deliver continuous positive airway pressure (CPAP). The performance of flow generators using different oxygen pressure supplies was also compared. DESIGN AND SETTING: Experimental study using a mechanical lung model in a university research laboratory. MEASUREMENTS: Two flow generators supplied at 100, 200, and 300 kPa and an NPPV ventilator were compared at CPAP of 5, 10, and 15 cmH2O in: (a) area under the adjusted CPAP level during inspiration, (b) capacity to attain the preset CPAP, and (c) tidal volume. RESULTS: The NPPV ventilator attained the preset CPAP better than flow generators, but its area under adjusted CPAP was similar to or higher than that of flow generators when these were adjusted to their better pressure supply. Both flow generators had better performance with an output flow around 100 l/min, which was achieved at 100 kPa with one flow generator and 300 with the other. Flow generators and the NPPV ventilator generated similar tidal volumes. CONCLUSIONS: Flow generators performance showed large variations among different devices and oxygen pressure supplies. Adjusted to their better pressure supply, flow generators had a similar or better capacity to maintain the CPAP level, but the NPPV ventilator was more reliable to attain the preset CPAP. Flow generators could be an alternative to provide CPAP in low-income areas, usually with scarce medical equipment availability.

Artificial Organs↗

PubMed2000

Involvement of superoxide generated by polymorphonuclear leukocytes in endotoxin-induced uveitis.

BACKGROUND: Although superoxide is thought to be involved in the development of endotoxin-induced uveitis (EIU), the role of superoxide generation by polymorphonuclear leukocytes (PMNs) has not been fully elucidated. The purpose of this study was to investigate the role of peripheral blood PMNs in the development of EIU. METHODS: EIU was induced in Lewis rats by injection of lipopolysaccharide (LPS) in one hind footpad. Superoxide generation was assayed by measuring the reduction of ferricytochrome c (cyt c). EIU severity was assessed by histological examination, and the relationship between the injected dose of LPS in vivo and the intensity of superoxide generation by peripheral PMNs or intraocular PMNs was studied. Twenty-four hours after the injection of LPS (2, 20, or 200 microg/rat), peripheral blood PMNs were collected and stimulated with phorbol 12-myristate 13-acetate (PMA). The time course of superoxide generation by PMNs after LPS injection (3, 6, 12, 24, 48, and 72 h) was also investigated. To test the possible inhibition of superoxide generation by protein kinase C (PKC) inhibitors, H-7 and staurosporine were added for the incubation. In addition to the measurement of cyt c reduction, western blotting was used to detect PKC activity. The direct effect of LPS on PMNs was tested by priming naive PMNs with LPS in vitro. RESULTS: The intensity of superoxide generation by PMNs and the severity of EIU were dependent on the dose of injected LPS. No apparent superoxide generation was detected from intraocular PMNs. The time course of superoxide generation was similar to that of EIU severity. H-7 or staurosporine inhibited superoxide generation dose dependently and suppressed phosphorylation of PKC. Priming with LPS in vitro prompted minimal superoxide generation by naive PMNs. CONCLUSION: Superoxide generation by peripheral blood PMNs but not by intraocular PMNs from rats with EIU was demonstrated, and it is suggested that superoxide generation by PKC cascade might be involved in the pathogenesis of EIU.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1993

Swelling-induced O2- generation in guinea-pig neutrophils.

Without the addition of any exogenous stimuli, neutrophils generated O2- and then ceased in a reversible manner that correlated with cellular swelling and contraction. The nature of the possible mechanism responsible for this O2- generation was studied and compared with that observed in the triggering of stimulant-dependent O2- generation (respiratory burst). The swelling-induced O2- generation was inhibited by diphenyliodonium, and was independent of the functional distortion of mitochondrial and/or microsomal electron transport and xanthine oxidase. This suggested that such generation was involved in respiratory-burst oxidase activation; however, this generation was not accompanied by any new phosphorylation of the 47-kDa protein or of tyrosine proteins. Dihydrocytochalasin B potentiated the O2- generation. The cellular swelling produced a priming effect on the triggering of respiratory burst with different stimuli. Cellular contraction, conversely, suppressed the respiratory burst. The structural specificity of the swelling-induced plasma membrane modulation for the O2- generation was suggested by the finding that modulation of plasma membrane structures by various non-ionic detergents per se inhibited O2- generation. Lipophilic and positively-charged agents inhibited the generation and this inhibition was abrogated by negatively-charged, but not by non-ionic agents. Negatively-charged agents potentiated the O2- generation. These results suggest that both the interaction of the plasma membrane with the cytoskeleton and an increase in net negative charges at the plasma membrane play important role in evoking O2- generation; this is discussed and compared with the signal transduction reported previously for respiratory burst.

Animals↗

PubMed1997

Characterization of the prostanoid receptor(s) on human blood monocytes at which prostaglandin E2 inhibits lipopolysaccharide-induced tumour necrosis factor-alpha generation.

1. The prostanoid receptor(s) that mediates inhibition of bacterial lipopolysaccharide (LPS)-induced tumour necrosis factor-alpha (TNF-alpha) generation from human peripheral blood monocytes was classified by use of naturally occurring and synthetic prostanoid agonists and antagonists. 2. In human monocytes that were adherent to plastic, neither prostaglandin D2 (PGD2), prostaglandin E2 (PGE2), prostaglandin F(2 alpha) (PGF(2 alpha)) nor the stable prostacyclin and thromboxane mimetics, cicaprost and U-46619, respectively, promoted the elaboration of TNF alpha-like immunoreactivity, as assessed with a specific ELISA, indicating the absence of excitatory prostanoid receptors on these cells. 3. Exposure of human monocytes to LPS (3 ng ml-1, approximately EC84) resulted in a time-dependent elaboration to TNF alpha which was suppressed in cells pretreated with prostaglandin E1 (PGe1), PGE2 and cicaprost. This effect was concentration-dependent with mean pIC50 values of 7.14, 7.34 and 8.00 for PGE1, PGE2 and cicaprost, respectively. PGD2, PGF(2 alpha) and U-46619 failed to inhibit the generation of TNF alpha at concentrations up to 10 microM. 4. With respect to PGE2, the EP-receptor agonists, 16,16-dimethyl PGE2 (non-selective), misoprostol (EP2/EP3-selective), 11-deoxy PGE1 (EP2-selective) and butaprost (EP2-selective) were essentially full agonists as inhibitors of LPS-induced TNF alpha generation with mean pIC50 values of 6.21, 6.02, 5.67 and 5.59, respectively. In contrast to the results obtained with butaprost and 11-deoxy PGE1, another EP2-selective agonist, AH 13205, inhibited TNF alpha generation by only 21% at the highest concentration (10 microM) examined. EP-receptor agonists which have selectively for the EP1- (17-phenyl-omega-trinor PGE2) and EP3-receptor (MB 28,767, sulprostone) were inactive or only weakly active as inhibitors of TNF alpha generation. 5. Pretreatment of human monocytes with the TP/EP4-receptor antagonist, AH 23848B, at 10, 30 and 100 microM suppressed LPS-induced TNF alpha generation by 10%, 28% and 77%, respectively, but failed to shift significantly the location of the PGE2 concentration-response curves. 6. Given that AH 13205 was a poor inhibitor of TNF alpha generation, studies were performed to determine if it was a partial agonist and whether it could antagonize the inhibitory effect of PGE2. Pretreatment of human monocytes with 10 and 30 microM AH 13205 inhibited the generation of TNF alpha by 31% and 53%, respectively, but failed to shift significantly the location of the PGE2 concentration-response curves at either concentration examined. 7. Since PGD2 and 17-phenyl-omega-trinor PGE2 (EP1-agonist) did not suppress TNF alpha generation, the EP1/EP2/DP-receptor antagonist, AH 6809, was employed to assess if EP2-receptors mediated the inhibitory effect of PGE2. Pretreatment of human monocytes with 10 microM AH 6809 did not affect LPS-induced TNF alpha generation but produced a parallel 3.5 fold rightwards shift of the PGE2 concentration-response curve. 8. Collectively, these data suggest that human peripheral blood monocytes express at least two distinct populations of inhibitory prostanoid receptors that mediate inhibition of LPS-induced TNF alpha generation. One of these probably represents i.p. receptors based upon the selectivity of cicaprost for this subtype. The other population has the pharmacology of EP-receptors, but the rank of potency for a range of synthetic EP-receptor agonists was inconsistent with an interaction with any of the currently defined subtypes. Given the pharmacological behaviour of butaprost, AH 6809 and AH 23848B in these cells, we propose that multiple (EP2- and/or EP-4- and/or i.p.) or novel EP-receptors mediate the inhibitory effect of PGE2 on TNF alpha generation.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1992

Mobilization of cognitive resources and the generation effect.

The generation effect refers to the memory advantage of words that have been generated rather than read. Such a read-generate comparison confounds qualitative task differences and raises methodological problems. A revised methodology is proposed circumventing these problems in that the encoding task is held constant and all stimuli have to be generated, but the degree of generativeness (i.e. the amount of cueing) is varied. In Experiment 1, 1, the (refined version of the) generation effect is demonstrated in a within-subjects design; with increasing generation activity left to the subject, free recall performance increases. No effect is obtained for degree of target masking. The same finding is replicated and shown to be independent of self-paced study time when generative activity is manipulated between subjects (Experiment 2) or within subjects (Experiment 3). As all learning trials involve generation, encoding time is controlled statistically, and free recall is used as a measure of memory, this refined generation effect cannot be explained as an artifact of selective attention or elaboration. Rather, generative activity seems to increase the mobilization of cognitive resources. This motivational account is supported by Experiment 4 showing an enhanced generation effect for positive mood.

Adult↗

PubMed2006

Comparing millennial and generation X medical students at one medical school.

PURPOSE: Two main generational cohorts comprising students enrolled in medical schools today are Generation Xers (born 1965-1980) and Millennial students (born 1981-1999). A subset is Cuspars (born 1975-1980), who share traits with both generations. Population theorists ascribe different personal characteristics, attitudes, and preferences to each group. The authors examined whether selected characteristics describing Generation X and Millennial students were quantifiable using a personality measure. Differences among Generation X, Millennial, and Cuspar medical students were investigated. METHOD: Eight hundred and nine medical students (399 females and 410 males) who matriculated between 1989-94 and 2001-04 at the Northeastern Ohio Universities College of Medicine completed the 16 Personality Factor Questionnaire (16PF). Differences in responses to the 16PF among the three generations were analyzed using multivariate analysis of variance (MANOVA). RESULTS: Analyses showed significant differences for Generation X versus Millennial students on 10 of the 16 personality factors. Millennial students scored significantly higher than Generation X students on factors including Rule-Consciousness, Emotional Stability, and Perfectionism; Generation X students scored higher than Millennials on Self-Reliance. Millennials also were significantly different from Generation Xers on several other factors. Significant differences were noted among Cuspars, Generation Xers, and Millennials. CONCLUSIONS: The 16PF is a useful tool to examine differences among these groups and to help understand the factors that constitute their personalities. Given differences among the generational groups, the authors forecast possible educational implications for medical school academic affairs and student services, and suggest areas for future research.

Adolescent↗

PubMed1969

Adaptation of the generator potential in the crayfish stretch receptors under constant length and constant tension.

1. Generator potentials were investigated in stretch receptors of crayfish after abolishing spike potentials with tetrodotoxin.2. The time courses of the decline of generator potential (generator adaptation) were almost the same in the slowly and rapidly adapting receptors.3. The time courses of the tension changes after suddenly stretching the receptor muscles did not differ much between the two receptor types.4. The amplitudes of generator potential per unit stress or per unit strain in the receptor muscle were roughly the same in the two receptor types.5. By comparing generator adaptation under length-clamp and tension-clamp in the slowly adapting receptors, it was suggested that roughly 70% of the generator adaptation could be explained by a simple visco-elastic property of the receptor muscle, when observed for 1 sec after the beginning of the stretch.6. It was concluded that the marked differences in the receptor adaptation between the two receptor types were attributable to the differences in the properties of spike generating membrane rather than to the properties of the generator potentials.7. In each type of receptor, both the generator adaptation and the adaptation of spike generating mechanisms contributed to determining the whole rates of receptor adaptation. In the slowly adapting receptor, however, the generator adaptation seemed more important, while in the rapidly adapting receptor the spike generating mechanisms seemed more important.

Adaptation, Physiological↗

PubMed1992

Enhanced generation of free radicals from phagocytes induced by mineral dusts.

Several studies have suggested that pulmonary toxicity to asbestos and silica may be mediated through oxidant-induced cell injury. We have reported recently that surface radicals associated with freshly fractured silica may be an important factor in cell injury and induction of pulmonary disease. Although the generation of oxygenated radicals in dust-cell interactions has been demonstrated, there are no data correlating the toxicity of a dust with the level of oxygen radical generation by the dust during its interaction with phagocytic cells. In the present study, we have investigated the in vitro generation of oxygen free radicals from human neutrophils and rat alveolar macrophages stimulated with freshly fractured silica, aged silica, amosite, crocidolite, chrysotile, and nontoxic dust, barite. Electron spin resonance (ESR) with the aid of a spin trap phenyl-N-tert-butyl nitrone (PBN) was used to measure the oxygen radicals generated during phagocytosis of the dusts. The relative toxicity index and ESR peak heights, on an equal surface area basis and normalized to barite as one, showed a direct relationship. The normalized toxicity indices and peak heights were: silica, 3.5 versus 2; chrysotile, 4 versus 2; crocidolite, 11 versus 8; and amosite, 26 versus 13. Addition of hydroxyl radical scavengers such as catalase, dimethyl sulfoxide, 1,3 dimethyl-2-thiourea (DMTU), sodium benzoate, and mannitol prevented the radical generation. Carmustine, a glutathione reductase-glutathione peroxidase inhibitor, caused a 5-fold increase in the radical generation. These results indicate that a nontoxic dust such as barite generates toxic oxygen radicals at a minimal level that can be quenched by the normal cellular defense system. For toxic dusts such as silica, amosite, chrysotile, and crocidolite, the potential for oxygen radical generation is enhanced by their surface properties, physical dimensions, and the surface-based radical-generating redox sites. The enhanced radical generation may impair the cellular defense system, resulting in cell injury. Use of scavengers, chelators, and potentiating agents suggests the membrane-based oxidase system as the probable primary source of the radical-generating system. The data presented herein suggest the generation of oxygen free radicals as an important primary event in silica- as well as asbestos-induced cell injury.

Animals↗

PubMed1976

The generation of fibrinopeptide A in clinical blood samples: evidence for thrombin activity.

Plasma fibrinopeptide A (FPA) concentrations were measured in clinical blood samples incubated in the collecting syringe for different time periods before addition to heparin and Trasylol, and the rate of in vitro generation of FPA was calculated as the mean increment in FPA concentration per minute over the linear portion of the generation curve. 36 normal individuals had a mean plasma FPA level of 0.64 +/- 0.56 pmol/ml and an FPA generation rate of less than 0.5 pmol/ml per min. Clinical samples with elevated plasma FPA levels manifested slow (less than 1 pmol/ml per min) (28 patients) or rapid FPA generation (greater than 1 pmol/ml per min) (33 patients). Slow FPA generation was found in 10/10 patients with venous thrombosis, in 4/4 with aortic aneurysm, and in several patients with acquired hypofibrinogenemia. In one such patient, addition of fibrinogen resulted in rapid FPA generation whereas thrombin addition was without effect. Rapid FPA generation was generally linear, was usually associated with slower fibrinopeptide B generation and was inhibited by parenteral or in vitro heparin. It is thought to reflect increased thrombin activity and was seen in patients with pulmonary embolism, active systemic lupus erythematosus, renal transplant rejection, and after infusion of prothrombin concentrates. The initial rate of FPA cleavage by thrombin at fibrinogen concentrations from 0.05 to 4 mg/ml showed little change between 2 and 4 mg/ml with a Km of 2.99 muM. At a fibrinogen concentration of 2.5 mg/ml the FPA cleavage rate was 49.2 +/- 1.6 nmol/ml per min per U of thrombin. Exogenous thrombin added to normal blood generated 21.7 nmol/ml per U of thrombin FPA in the first minute with a nonlinear pattern reflecting inactivation of thrombin and the presence of alternative substrates. Hence, the thrombin concentration in the blood cannot be calculated from the FPA generation rate. The FPA generation rates in clinical samples with rapid generation (1-28 pmol/ml per min) could be produced by 2 X 10(-5) to 5.6 X 10(-4) thrombin U/ml acting on purified fibrinogen at physiological conditions of pH, ionic strength, and temperature.

Fibrinogen↗

PubMed1979

The role of sulfhydryl groups on the impaired hepatic 3',3,5-triiodothyronine generation from thyroxine in the hypothyroid, starved, fetal, and neonatal rodent.

The role of nonprotein sulfhydryl groups (NPSH) in the decreased in vitro hepatic 3',3,5-triiodothyronine (T(3)) generation from thyroxine (T(4)) in the starved, hypothyroid, fetal and 1- to 4-d-old neonatal rat and dwarf mouse was assessed. NPSH were measured in fresh 25% liver homogenates prepared in 0.1 M PO(4)/10 mM EDTA buffer. As compared with values in adult male rats, NPSH concentration was decreased in the 2-d-starved (1.1+/-0.04 (mean+/-SE) vs. 2.2+/-0.15 mmol/250 g wet liver weight, P < 0.001), fetal (1.0+/-0.04 vs. 3.2+/-0.08, P < 0.001), 1-d-old neonatal (1.1+/-0.03 vs. 2.1+/-0.04, P < 0.001), and hypothyroid (thyroidectomized 60 d) (1.4+/-0.06 vs. 2.2+/-0.15 P < 0.001) rat. NPSH were also decreased in the hypothyroid, hypopituitary dwarf mouse as compared with values in their normal litter mates (1.3+/-0.03 vs. 2.0+/-0.2, P < 0.01). Chronic administration of T(3) (0.5 mug/100 g body wt per d) markedly increased hepatic T(3) generation from T(4) in the thyroidectomized rat and in the dwarf mouse to values similar to those observed in the normal rodent without affecting NPSH concentration. In contrast, T(3) administration to the starved rat did not alter either hepatic T(3) generation from T(4) or NPSH. Reduced glutathione concentration was also markedly decreased in the starved rat (fed; 1.05+/-0.075 mmol/250 g wet tissue vs. starved 0.38+/-0.02, P < 0.001). Dithiothreitol (DTT), a thiol reducing agent, increased hepatic T(3) generation from T(4) in the normal adult male rat by 45+/-5% in six experiments. When compared to DTT-stimulated control homogenates, the addition of DTT completely restored hepatic T(3) generation in starved rats, partially restored T(3) generation in 1- and 4-d-old neonates, but had little or no effect in the fetal and hypothyroid rat and dwarf mouse. Liver homogenates stored for 6 mo at -20 degrees C lost their capacity to generate T(3) from T(4). NPSH concentrations in the frozen homogenates decreased progressively with increasing storage and were absent by 6 mo. 5'-Deiodinase activity correlated with NPSH concentration in the stored homogenates (r = 0.95, P < 0.005). Addition of DTT partially restored hepatic T(3) generation in the frozen homogenate. It is concluded that NPSH are important for the action of the liver 5'-deiodinase. The decreased hepatic T(3) generation in the starved rat is associated with decreased NPSH but not with a decrease in the absolute quantity of 5'-deiodinase because provision of sulfhydryl groups restored hepatic T(3) generation to normal. In contrast, the decreased hepatic T(3) generation in the adult hypothyroid rodent and in the fetal rat is probably due to a decrease in the enzyme concentration per se. In the 1- and 4-d neonatal rat, the decrease in hepatic T(3) generation is secondary to a decrease in NPSH and the deiodinating enzyme.

Aging↗

PubMed1998

Effects of 17 beta-estradiol on serum hormone concentrations and estrous cycle in female Crl:CD BR rats: effects on parental and first generation rats.

The recently passed Food Quality Protection Act of 1996 requires the U.S. EPA to implement screening strategies for endocrine active compounds (EACs) within the next 2 years. Interpreting results from screening tests is complicated by the absence of traditional dietary rodent bioassay data with model estrogenic compounds such as 17 beta-estradiol. Thus, a 90-day/one-generation reproduction study with 17 beta-estradiol was designed to: (1) provide such baseline data; (2) set dose levels for multigeneration reproduction and combined chronic toxicity/oncogenicity studies; and (3) evaluate various mechanistic/biochemical endpoints for inclusion in these follow-up studies. The current article describes the effects of dietary administration of 0, 0.05, 2.5, 10, and 50 ppm 17 beta-estradiol on the serum hormone concentrations and estrous cyclicity of female Crl:CD BR rats and evaluates a sampling strategy for measuring serum hormone levels in cycling female rats. Serum hormones were measured at three time points during a 90-day dietary exposure (1 week, 28 days, and 90 days) and in the F1 generation rats on postnatal day 98. Over the course of the 90-day feeding study for the P1 generation and from postnatal days 21 to 98 for the F1 generation, the estrous cycle was monitored daily in 10 rats/group. In P1 generation rats, dietary administration of 2.5, 10, and 50 ppm 17 beta-estradiol produced a dose-dependent increase in serum estradiol (E2) concentrations at all time points. In contrast, administration of 0.05, 2.5, 10, and 50 ppm 17 beta-estradiol produced a dose-dependent decrease in serum progesterone (P4) concentrations on test day 90, which correlated with an absence of corpora lutea and ovarian atrophy. At 10 and 50 ppm 17 beta-estradiol, serum luteinizing hormone (LH) concentrations were consistently decreased at all time points and were decreased at 2.5 ppm on test day 90. Serum prolactin (PRL) concentrations were increased at 50 ppm 17 beta-estradiol on test day 90. Serum follicle stimulating hormone (FSH) concentrations were either similar to the control levels or minimally changed at all time points. No F1 generation rats were produced at 10 or 50 ppm 17 beta-estradiol. In F1 generation rats, serum E2 concentrations were increased and P4 concentrations were decreased at a dietary concentration of 2.5 ppm 17 beta-estradiol, while serum concentrations of LH, FSH, and PRL were similar to the control. Dietary administration of 17 beta-estradiol at concentrations of 2.5 (both generations) and 10 and 50 ppm (P1 generation only) produced marked effects on the estrous cycle: decreased number of cycles, increased mean cycle length, and decreased number of normally cycling rats. The estrous cyclicity of rats fed 2.5 ppm 17 beta-estradiol appeared more severely affected in rats of the F1 generation than in rats of the P1 generation. Whether this increase in severity is related to an in utero exposure and/or greater mean daily intake of 17 beta-estradiol in the F1 generation rats in the postnatal period is unclear. Another goal of this study was to evaluate whether a single time point sampling strategy using cycling female rats could be used to detect compound-related changes in serum hormone concentrations. In evaluating a sampling strategy for measuring serum hormone levels, it appears that detection of compound-related alterations in serum hormone concentrations can be best detected by sampling during diestrus. Since the stage of the cycle dramatically influences hormone concentrations, large sample sizes (n = 50) are needed if serum hormone measurements are not matched with the stage of the cycle. The data indicate that this strategy of measuring serum hormone concentrations has utility in detecting compound-related effects within the confines of a traditional guideline study (subchronic, chronic, or multigenerational reproduction study).

Animals↗

PubMed2006

A two-generation chronic mixture toxicity study of Clophen A60 and diethyl phthalate on histology of adrenal cortex and thyroid of rats.

This study was undertaken to observe the type of interaction that exists between polychlorinated biphenyls (Clophen A60) and diethyl phthalate (DEP) on the adrenal and thyroid glands of male and female Wistar rats. Animals were divided into four groups of six animals each, group I male and female rats were fed on a normal diet and water ad libitum. Groups II, III and IV male and female rats were given Clophen A60, DEP, or mixture of Clophen A60 and DEP, respectively, each dissolved in corn oil mixed with the diet at 50mg/kg of the diet/day. One hundred days after treatment, females were mated with males for 10 days. Exposure to the pollutants was continued throughout mating, gestation (21 days) until termination at weaning (21 days), which was 150 days of total treatment period of the parental generation. When the F1-generation pups (six males and six females of each group) were 75-100g in weight, they were treated in a similar manner to the parental generation, again for a period of 150 days, with the dose reduced to 25mg/kg of the diet/day in all treated groups. After 150 days of treatment, animals were sacrificed and histology of the adrenal and thyroid glands was asessed. An antagonistic interactive effect of treatment was seen in male parental and F1-generation rats, while an inhibitory type of interactive effect was observed in female rats. In the zona fasciculata region of the adrenal cortex of treated rats of both generations, vacuolations and degeneration were seen in samples from male animals and intracellular vacuolations in samples from females. A synergistic interactive toxic effect to the thyroid gland was observed in treated parental generation male rats, and mild changes in F1-generation-treated male rats, showing follicular shrinkage, loss of thyroglobulin and fibrosis of the interfollicular epithelium. In females, an antagonistic effect to the thyroid gland was observed in both parental and F1-generation-treated rats, showing similar effects as observed in males. From this study, we can conclude that combined administration of Clophen A60 and DEP shows an enhanced toxic effect on adrenal glands of F1-generation male and female rats, but the effect is much more marked in the thyroid gland of F1-generation male rats, and seen to a lesser extent in F1-generation female rats.

Adrenal Cortex↗

PubMed1996

Antecedents and contexts of generativity motivation at midlife.

A semiprojective measure of generativity motivation--the desire to contribute to the welfare of society--was developed and applied to a longitudinal sample of educated women. In support of previous theory that generativity represents a fusion of agency and communion, generativity at midlife was related to a combination of adolescent scores on achievement, affiliation, and power motivation. The measure was also related to independent indexes of generative wishes and Q-sort generativity. The importance of contextualizing generativity motivation is demonstrated: Generative women with careers found gratification through work, whereas generative women not working in careers experienced gratification through parenting. Generativity was also related to political consciousness. Finally, as young adults, generative women expressed gratitude toward mentors. The authors discuss theoretical implications for E. H. Erikson's (1950) concept of psychosocial generativity.

Achievement↗

PubMed2003

Reduction of the diagnostic window in three cases of human immunodeficiency-1 subtype E primary infection with fourth-generation HIV screening assays.

BACKGROUND AND OBJECTIVES: The influence of genetic variability on the sensitivity of serological diagnosis of human immunodeficiency virus (HIV) infection has, to date, been poorly investigated. The aim of the present study was to assess whether fourth-generation assays for the combined detection of HIV antigen and antibodies to HIV (anti-HIV) permit a reduction of the diagnostic window in comparison to third-generation antibody enzyme immunoassays (EIAs), which so far have shown a poor sensitivity for detection of HIV-1 non-subtype B primary infections. MATERIALS AND METHODS: Three patients with primary HIV-1 subtype E (CRF01-AE) infection were tested with different third- and fourth-generation assays, stand-alone HIV antigen (Ag) EIAs and reverse transcription-polymerase chain reaction (RT-PCR). Additionally, virus lysates from HIV-1 Group M and O and HIV-2, at concentrations of p24 Ag close to the detection limit of licensed HIV Ag EIAs, were investigated with fourth-generation EIAs and HIV Ag EIAs. RESULTS: In the first blood donor, the most sensitive fourth-generation assay detected HIV-1 infection 11 days earlier than five of the eight third-generation antibody assays. Fourth-generation EIAs, with a high sensitivity for HIV antigen, detected HIV-1 subtype E infection simultaneously or 4 days later than HIV-1 RT-PCR on pooled samples. Low concentrations of virus lysates of different HIV-1 subtypes A-H and group O, tested positive with fourth-generation EIAs, with a high sensitivity of the antigen-detection module. CONCLUSIONS: Fourth-generation EIAs, especially those with a high sensitivity for HIV-1 p24 antigen, reduce the diagnostic window for primary HIV-1 subtype E infection in comparison with third-generation antibody-screening assays. These preliminary data from seroconversions and virus lysates indicate that the genetic diversity of HIV-1 does not represent a major challenge for the most sensitive EIAs of this new assay generation.

Antigenic Variation↗

PubMed1988

Measurement of endothelial cell free radical generation: evidence for a central mechanism of free radical injury in postischemic tissues.

Oxygen free radicals have been demonstrated to be important mediators of postischemic reperfusion injury in a broad variety of tissues; however, the cellular source of free radical generation is still unknown. In this study, electron paramagnetic resonance measurements with the spin trap 5,5'-dimethyl-1-pyrroline-N-oxide (DMPO) demonstrate that bovine endothelial cells subjected to anoxia and reoxygenation become potent generators of superoxide and hydroxyl free radicals. A prominent DMPO-OH signal aN = aH = 14.9 G is observed on reoxygenation after 45 min of anoxic incubation. Quantitative measurements of this free radical generation and the time course of radical generation are performed. Both superoxide dismutase and catalase totally abolish this radical signal, suggesting that O2 is sequentially reduced from O2-. to H2O2 to OH.. Addition of ethanol resulted in trapping of the ethoxy radical, further confirming the generation of OH.. Endothelial radical generation was shown to cause cell death, as evidenced by trypan blue uptake. Radical generation was partially inhibited and partially scavenged by the xanthine oxidase inhibitor allopurinol. Marked inhibition of radical generation was observed with the potent xanthine oxidase inhibitor oxypurinol. These studies demonstrate that endothelial cells subjected to anoxia and reoxygenation, conditions observed in ischemic and reperfused tissues, generate a burst of superoxide-derived hydroxyl free radicals that in turn cause cell injury and cell death. Most of this free radical generation appears to be from the enzyme xanthine oxidase. Thus, endothelial cell free radical generation may be a central mechanism of cellular injury in postischemic tissues.

Animals↗

PubMed1996

Generation of reactive oxygen species by Co(II) from H2O2 in the presence of chelators in relation to DNA damage and 2'-deoxyguanosine hydroxylation.

The generation of reactive oxygen species by Co(II) from H2O2 in the presence of chelators and related DNA damage was investigated by electron spin resonance (ESR), electrophoretic assays, and high-performance liquid chromatography (HPLC). Incubation of Co(II) with beta-alanyl-3-methyl-L-histidine (anserine) and H2O2 generated .OH radicals. Omission of any one component sharply reduced the amount of .OH radicals generated, indicating that anserine modulated the oxidation potential of Co(II) to enhance its capability to generate .OH radicals from H2O2. Formate only moderately decreased the .OH radical generation, while ethanol had no observable effect, indicating that the generation of .OH radical is site specific. The metal ion chelator 1,10-phenanthroline reduced the .OH radical generation, and deferoxamine suppressed it with the formation of deferoxamine nitroxide radical. Electrophoretic assays using both lambda Hind III linear DNA and PM2 supercoiled DNA showed that .OH radicals generated from a mixture of Co(II), H2O2, and anserine caused DNA strand breaks. A mixture of Co(II), H2O2, and 1,10-phenanthroline also caused DNA strand breaks, which were inhibited by sodium azide, indicating that 1O2 was involved in DNA damage. HPLC measurements showed that .OH radicals and 1O2 generated by Co(II) reactions caused 2'-deoxyguanosine hydroxylation to form 8-hydroxy-2'-deoxyguanosine. ESR spin trapping measurements provided evidence for 1O2 generation by Co(II) from H2O2 in the presence of 1,10-phenanthroline. The results indicate that the oxidation potential of Co(II) can be modulated by chelators to facilitate its generation of reactive oxygen species from H2O2. These species may be involved in Co(II)-induced cellular damage.

Anserine↗

PubMed2005

FFT analysis of the X-ray tube voltage waveforms of high-frequency generators for radiographic systems.

PURPOSE: To present a novel method for analyzing the voltage waveform from high-frequency X-ray generators for radiographic systems. MATERIAL AND METHODS: The output signal of the actual voltage across the tube of a high-frequency generator was measured using the built-in voltage sense taps that are used for voltage regulation feedback in X-ray generators. The output signal was stored in an analyzing recorder, and the waveforms were analyzed using FFT analysis. The FFT analysis of high-frequency generators consisted of obtaining the power spectrum, comparing the major frequency components in the tube voltage waveforms, and examining the intensity of each frequency component. RESULTS: FFT analysis enables an objective comparison of the complex tube voltage waveforms in high-frequency X-ray generators. FFT analysis detected the change in the X-ray tube voltage waveform that occurred when there were problems with the high-frequency generator. CONCLUSION: High-frequency X-ray generators are becoming the universal choice for radiographic systems. The X-ray tube voltage and its waveform are important features of an X-ray generator, and quality assurance (QA) is important, too. As a tool for engineers involved in the design and development of X-ray generators, we can see that our methods (FFT analysis) might have some value as a means of describing generator performance under varying conditions. Furthermore, since the X-ray tube voltage waveform of a high-frequency generator is complex, FFT analysis may be useful for QA of the waveform.

Algorithms↗

PubMed1982

Subcellular localization of O2- generating enzyme in guinea pig polymorphonuclear leukocytes; fractionation of subcellular particles by using a Percoll density gradient.

An iso-osmotic Percoll density gradient was applied to determine the subcellular localization of the O2- generating enzyme, NADPH oxidase, in guinea pig polymorphonuclear leukocytes (PMN). [14C]Myristate (MA) was employed as a metabolic stimulant in order to clarify whether the myristate binding site on PMN membrane was identical with the O2- generating site. The distribution pattern of the O2- generating activity of MA-activated PMN was compared with that of unactivated PMN in parallel experiments to find fractions showing an enhanced O2- generating activity (i.e., above the background values due to O2-generation by other electron-transport systems). We observed very high O2- generating activity concentrated in a single peak with MA-activated PMN but little activity was seen with unactivated PMN in the Percoll density gradient. The O2- generating activity of MA-activated PMN was consistently associated with 5'-nucleotidase activity as a membrane marker enzyme, but was not associated with lysosomal marker enzymes such as myeloper-oxidase and lysozyme. O2- generating and 5'-nucleotidase activities in the peak fraction of MA-activated PMN were increased to about six and four times those of whole cells in terms of specific activity, respectively. These results indicate that the O2- generating enzyme is located on PMN plasma membrane. Furthermore, [14C]myristate-binding activity was mainly found in the peak fraction containing O2 - generating enzyme. This suggests that [14C]myristate binds to plasma membrane, and the O2 - generating enzyme may thus be activated.

5'-Nucleotidase↗