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Biomedical subjects

J E Schneider

Publications and source records attributed to J E Schneider.

At least 19 recordsLinked to original sources

Metabolic signals, hormones and neuropeptides involved in control of energy balance and reproductive success in hamsters.

In the 'postgenome era', most research on the neuroendocrine control of energy homeostasis has focused on hormonal and neuropeptide control of food intake (i.e. the amount of food eaten) in rats and mice. The amount of food consumed is influenced by both the motivation to procure food and the consummatory act of ingestion. In some species, the rate of food intake remains relatively constant, while survival is maintained via changes in food procurement, external storage and internal expenditure. For example, in hamsters, metabolic signals, peripheral hormones and central neuropeptides influence hunger motivation, food hoarding and changes in energy expenditure without necessarily influencing the amount of food ingested. A similar suite of metabolic signals, hormones and neuropeptides is involved in optimizing reproductive success under fluctuating energetic conditions. Reproductive processes are inhibited or delayed when energy expenditure outstrips energy intake and mobilization from storage. Estrous cyclicity in Syrian hamsters is sensitive to the availability of oxidizable glucose, but the presence of central glucose alone is not sufficient for normal estrous cycles. Food deprivation-induced anestrus does not depend upon food deprivation-induced increases in concentrations of adrenal hormones such as glucocorticoids. If hormones such as insulin and leptin play a role, they might do so by modulating the availability of glucose detected at extra-hypothalamic sites, instead of or in addition to direct effects on the mechanisms that control gonadotropin releasing hormone secretion. Despite our ability to measure and manipulate gene transcription, understanding of fuel homeostasis requires examination of indirect effects of hormones and neuropeptides on peripheral metabolism, attention to the motivational as well as consummatory aspects of ingestion, and the study of behaviour in a natural or seminatural context.

Animals↗

Transradial coronary stenting: comparison with femoral access closed with an arterial suture device.

The purpose of this study was to determine if closure of the femoral artery access site using a percutaneous arterial suture device (Perclose, Menlo Park, CA) in patients undergoing coronary stenting can result in the same benefits as seen with radial artery access. A total of 218 consecutive patients underwent coronary stenting (109 femoral, 109 radial) by investigators experienced with each technique. The two groups were matched in terms of sex, age, clinical presentation (50% acute), number of vessels and lesions stented, and lesion morphology. The relative costs of the femoral and radial procedures were examined using a decision analytic model and sensitivity analysis. The suture device was not used in 20/109 patients (18%) for anatomic reasons and failed to obtain hemostasis in 9/89 patients (10%). One radial patient had an occluded radial artery postprocedure, but this was recanalized at follow-up a month later. Primary success, procedural complications, postprocedure length of stay, and the percentage of patients discharged the same day were the same in both groups. Because of the added time to deploy Perclose, total procedure time was significantly longer in the femoral group (57 +/- 22 min femoral vs. 44 +/- 22 min radial, P < 0.01). Access site complications occurred only in the femoral group. More patients were ambulatory the same day of the procedure in the radial group (95% radial vs. 56% femoral, P < 0.01). The cost of the radial approach was substantially less than the femoral approach because of lower supply costs and fewer access complications. The transradial approach is a dominant strategy for coronary stenting, offering better outcomes at lower cost. Cathet. Cardiovasc. Intervent. 49:150-156, 2000.

Aged↗

Leptin and metabolic control of reproduction.

Leptin treatment prevents the effects of fasting on reproductive processes in a variety of species. The mechanisms that underlie these effects have not been elucidated. Progress in this area of research might be facilitated by viewing reproductive processes in relation to mechanisms that maintain fuel homeostasis. Reproduction, food intake, and fuel partitioning can be viewed as homeostatic responses controlled by a sensory system that monitors metabolic signals. These signals are generated by changes in intracellular metabolic fuel availability and oxidation rather than by changes in the amount of body fat or by changes in any aspect of body composition. Leptin might be viewed as either a mediator or as a modulator of the intracellular metabolic signal. Consistent with its purported action as a mediator of the metabolic signal, leptin synthesis and secretion are influenced acutely by changes in metabolic fuel availability, and these changes might lead to changes in reproductive function. The effects of leptin treatment on reproduction are blocked by treatments that inhibit intracellular fuel oxidation. Metabolic signals that inhibit reproduction in leptin-treated animals might act via neural pathways that are independent of leptin's action. Alternatively, both leptin and metabolic inhibitors might interact at the level of intracellular fuel oxidation. In keeping with the possibility that leptin modulates the metabolic signal, leptin treatment increases fuel availability, uptake, and oxidation in particular tissues. Leptin might affect reproduction indirectly by altering fuel oxidation or other peripheral processes such as gastric emptying. Reproductive processes are among the most energetically expensive in the female repertoire. Because leptin increases energy expenditure while simultaneously inhibiting energy intake, it may have limited use as a long-term treatment for infertility.

Adipose Tissue↗

Metabolic control of food intake and estrous cycles in syrian hamsters. I. Plasma insulin and leptin.

The "adipostat hypothesis" refers to the idea that circulating hormone concentrations reflect levels of body adiposity and act as signals to control food intake and reproduction. Implicit in the adipostatic hypothesis are the following two assumptions: 1) plasma levels of adipostatic hormones accurately reflect body fat content and 2) decreased plasma concentrations of adipostatic hormones necessarily result in increased food intake and inhibited reproductive processes. The present experiments are designed to test these assumptions. Fat and lean Syrian hamsters were either fasted for 12, 24, 36, or 48 h or allowed ad libitum access to food. Contrary to the first assumption, plasma leptin and insulin levels in fat hamsters dropped dramatically by 12 h after the start of a fast, with no significant change in body fat content and no postfast hyperphagia. Lean hamsters showed anestrus after a 48-h fast but not after a 24-h fast. Contrary to the second assumption of the lipostatic hypothesis, lean hamsters fasted for 24 h and then refed for the next 24 h had leptin levels that were not significantly elevated compared with those of 48-h-fasted hamsters. Thus, in adult female Syrian hamsters, plasma leptin concentrations do not accurately reflect body fat content under all conditions; normal estrous cyclicity does not necessarily require plasma leptin concentrations higher than those of fasted hamsters; and decreased plasma leptin levels do not result in increased food intake.

Anestrus↗

Leptin, but not immune function, is linked to reproductive responsiveness to photoperiod.

Energetic demands are high while energy availability is minimum during winter. To cope with this energetic bottleneck, animals exhibit numerous energy-conserving adaptations during winter, including changes in immune and reproductive functions. A majority of individual rodents within a population inhibits reproductive function (responders) as winter approaches. A substantial proportion of small rodents within a species, however, fails to inhibit reproduction (nonresponders) during winter in the field or in the laboratory when maintained in winter-simulated day lengths. In contrast, immune function is bolstered by short day lengths in some species. The specific mechanisms that link reproductive and immune functions remain unspecified. Leptin is a hormone produced by adipose tissue, and several studies suggest that leptin modulates reproductive and immune functions. The present study sought to determine if photoperiodic alterations in reproductive function and leptin concentrations are linked to photoperiod-modulated changes in immune function. Siberian hamsters (Phodopus sungorus) were housed in either long (LD 16:8) or short (LD 8:16) day lengths for 9 wk. After 9 wk, blood samples were collected during the middle of the light and dark phase to assess leptin concentrations. One week later, animals were injected with keyhole limpet hemocyanin to evaluate humoral immunity. Body mass, body fat content, and serum leptin concentrations were correlated with reproductive responsiveness to photoperiod; short-day animals with regressed gonads exhibited a reduction in these measures, whereas short-day nonresponders resembled long-day animals. In contrast, immune function was influenced by photoperiod but not reproductive status. Taken together, these data suggest that humoral immune function in Siberian hamsters is independent of photoperiod-mediated changes in leptin concentrations.

Adipose Tissue↗

Interactive effects of central leptin and peripheral fuel oxidation on estrous cyclicity.

A 48-h period of fasting inhibits estrous cycles in Syrian hamsters, and fasting-induced anestrus can be prevented by intracerebroventricular treatment with leptin during the fasting period. In the present experiment, the effects of intracerebroventricular leptin were blocked by systemic treatment with inhibitors of metabolic fuel oxidation. Leptin was infused continuously into the lateral ventricles (1 microgram/day) during fasting on days 1 and 2 of the estrous cycle. Intraperitoneal injection of 2-deoxy-D-glucose (2DG) was used to block both central and peripheral glucose oxidation, and intragastric treatment with methyl palmoxirate (MP) was used to inhibit peripheral long-chain fatty acid oxidation during the fasting and leptin-treatment period. 2DG or MP were administered at doses that did not induce anestrus in ad libitum-fed hamsters. Despite elevated central levels of leptin, fasting-induced anestrus occurred in hamsters treated with either 2DG or MP. Thus an elevated intracerebroventricular leptin concentration is not a sufficient condition for normal estrous cycles when fuel oxidation is inhibited. These results raise the possibility that central leptin influences reproduction by indirect effects on peripheral fuel metabolism.

Anestrus↗

Q beta bacteriophage photoinactivated by methylene blue plus light involves inactivation of its genomic RNA.

Methylene blue (MB) is being used as a sensitizer for the photodynamic inactivation of viral contaminants, including the human immunodeficiency virus, in blood and blood components used in medical treatment. We recently showed that oxygen-dependent photodynamic inactivation of the RNA bacteriophage Q beta with MB plus light (MB + L) is associated with the formation of 8-oxo-7,8-dihydroguanine, protein carbonyls, RNA-protein crosslinkages and minor amounts of RNA strand breaks. We report herein, with the use of infectious RNA assays, that the lethal lesions in Q beta phage following MB + L exposure can be accounted for, and thereby most likely reside in, the RNA component of the phage but that the protein component of the virion contributes to the inactivation. The formation of RNA-protein crosslinkages as the primary inactivating type of lesion is put forth as the most probable model of the inactivation mechanism due to the sensitivity with which RNA-protein crosslinks are formed in response to MB + L exposure and the expectation of the powerful inactivating power of this type of lesion.

Bacteriophages↗

Leptin indirectly affects estrous cycles by increasing metabolic fuel oxidation.

In previous experiments, lean Syrian hamsters fasted on days 1 and 2 of the estrous cycle failed to show sex behavior and ovulation normally expected to occur on the evening of day 4. The first goal of the present experiment was to determine whether systemic treatment with the ob (obese) protein leptin could reverse the effects of fasting on estrous cyclicity, social behaviors, and ovulation rate. Fasting-induced anestrus was reversed and normal sex and social behavior and ovulation rate were restored in hamsters injected intraperitoneally with 5 mg/kg leptin every 12 h during fasting on days 1 and 2 of the estrous cycle. A second goal was to test whether the effects of leptin could be prevented by treatment with pharmacological agents that block the oxidation of metabolic fuels. Glucose oxidation was blocked by treatment with 2-deoxy-d-glucose (2DG) and fatty acid oxidation was blocked by treatment with methyl palmoxirate (MP). 2DG (1000 mg/kg) or MP (20 mg/kg) was administered at doses that did not induce anestrus in hamsters fed ad libitum. As in the first experiment, fasting-induced anestrus was reversed by leptin treatment. However, when each injection of leptin was preceded by an injection of 2DG or MP, leptin treatment did not reverse fasting-induced anestrus. In summary, estrous cyclicity was not restored when oxidation of metabolic fuels was blocked, despite high endogenous levels of leptin. These results are consistent with the hypothesis that leptin acts indirectly on the reproductive system by increasing fuel oxidation.

Aggression↗

Stenting in acute coronary syndromes: a comparison of radial versus femoral access sites.

OBJECTIVES: The purpose of the present study was to compare the radial approach with the femoral approach for coronary stenting in patients with acute coronary syndromes. BACKGROUND: Aggressive anticoagulation in patients with acute coronary syndromes increases the risk of femoral vascular complications. The transradial approach has the potential to significantly reduce the incidence of access site bleeding complications in this group of patients. METHODS: One hundred forty-two patients with acute coronary syndromes undergoing coronary stenting were prospectively randomized to have their procedure performed from either the radial or femoral access site and the results compared. RESULTS: Nine of 74 patients randomized to the radial group crossed over to the femoral group (6 negative Allen tests, 3 access failures). Patient demographics were the same in both groups. Primary success was identical: 96% radial, 96% femoral, ns. There were no procedural myocardial infarctions or deaths, and no patient was referred for emergency bypass surgery. There were no access site bleeding complications in the radial group as opposed to 3 (4%) in the femoral group, p < 0.01. Postprocedure length of stay, days (1.4+/-0.2 radial vs. 2.3+/-0.4 femoral, p < 0.01) as well as total hospital length of stay (3.0+/-0.3 radial vs. 4.5+/-0.5 femoral, p < 0.01) were significantly reduced in the radial group. Total hospital charge was also significantly lower in the radial group ($20,476+/-811 radial versus $23,389+/-1,180 femoral, p < 0.01). CONCLUSION: Coronary stenting from the radial approach is efficacious in patients with acute coronary syndromes. Access site bleeding complications are less, and early ambulation results in a shorter hospital length of stay. There was a 15% reduction in total hospital charge in the radial group.

Aged↗

AP lesions block suppression of estrous behavior, but not estrous cyclicity, in food-deprived Syrian hamsters.

Food deprivation inhibits ovulatory cycles and estrous behavior in Syrian hamsters. Lesions of the area postrema (AP) prevented the suppression of estrous behavior in food-deprived hamsters, but they did not prevent the suppression of estrous cyclicity or the increase in running-wheel activity caused by food deprivation. Food deprivation or treatment with pharmacological inhibitors of glycolysis and fatty acid oxidation decreased estrogen-receptor immunoreactivity (ERIR) in the ventromedial hypothalamus (VMH), increased ERIR in the arcuate nucleus (Arc) and the posterior parvicellular paraventricular nucleus (PaPo), but had no effect on ERIR in the posterodorsal medial amygdala or the anterior parvicellular paraventricular nucleus. Lesions of the AP prevented the food deprivation-induced decrease in VMH ERIR and the increase in Arc ERIR, but they did not prevent the increase in ERIR in the PaPo. Thus, whatever physiological cues are produced by food deprivation, an intact AP is required for their transmission to the neural circuits controlling estrous behavior, VMH ERIR, and Arc ERIR. The AP is not essential for transmission of this information to the neural circuits controlling estrous cyclicity, running-wheel activity, or PaPo ERIR.

Amygdala↗

Potential mechanisms of photodynamic inactivation of virus by methylene blue. I. RNA-protein crosslinks and other oxidative lesions in Q beta bacteriophage.

A spectrum of oxidative lesions was observed in a bacteriophage-based model system that is very sensitive to the photodynamic activity of selected dyes. When suspensions of the intact bacteriophage Q beta were exposed to methylene blue plus light (MB + L), inactivating events, or "hits" occurred that were oxygen-dependent and that were associated with the formation of several specific lesions: (1) carbonyl moieties on proteins, (2) 8-oxo-7,8-dihydroguanine (8-oxoGua), and (3) single-strand breaks (ssb) in the RNA genome and (4) RNA-protein crosslinks. Formation of carbonyl groups associated with protein in the Q beta phage preparation correlated positively with photoinactivation of the phage with increasing doses of either of the sensitizers MB or rose bengal. Strand breaks in the Q beta genomic RNA were observable at high MB concentrations but appeared not to be significant at the lower concentrations of MB, as full-length Q beta RNA was observable well beyond the 99% inactivation point in MB dosage. It was shown that the number of 8-oxoGua lesions were unlikely to be sufficient to account for the number of lethal events. Following exposure to MB + L, crosslink formation between Q beta RNA and protein was observed by virtue of the location of RNA at the interface of phenol-aqueous extractions of phage suspensions. A significant increase over background of RNA-protein complexes (including full-length Q beta RNA) was observed at the lowest concentration of MB tested (0.5 microM), which corresponded roughly to an average of 2 lethal hits per phage or approximately 13% survival compared to the zero MB control (100% survival). Due to its close correlation with Q beta inactivation and its expected lethality, RNA-protein crosslink formation may be important as an inactivating lesion in bacteriophage Q beta following MB + L exposure.

Allolevivirus↗

Central vs. peripheral metabolic control of estrous cycles in Syrian hamsters. I. Lipoprivation.

Metabolic energy availability has profound effects on reproduction in a wide variety of species. We have been studying the effects of fasting on estrous cycles in Syrian hamsters as a model system for metabolic control of reproduction. In previous experiments, a 48-h period of fasting inhibited estrous cycles in lean, but not fat, hamsters. In fat hamsters the effects of fasting may have been offset by the presence of high circulating levels of free fatty acids mobilized from lipids in adipose tissue. Consistent with this idea fat hamsters treated with the inhibitor of fatty acid oxidation methyl palmoxirate (MP) showed fasting-induced anestrus. Experiment 1 was designed to examine whether vagally transmitted signals are critical for the inhibitory effects of fasting and MP treatment. Lean or fat hamsters that had received bilateral subdiaphragmatic vagotomy or sham surgery were fasted and treated with MP or vehicle. In vagotomized and sham-operated hamsters, estrous cycles were inhibited in lean fasted hamsters and in fat fasted hamsters treated with MP, but not in fat fasted hamsters treated with vehicle. Thus the results of experiment 1 indicated that vagally transmitted signals about peripheral fatty acid availability are not critical for the effects of these particular metabolic challenges on estrous cycles in Syrian hamsters. In experiment 2, hamsters without food were allowed to ingest pure glucose or fructose solutions or vegetable shortening. One-half of each group was treated with an inhibitor of glucose utilization, 2-deoxy-D-glucose (2-DG), or vehicle. If ingestion of fructose or shortening, but not glucose, had protected hamsters from 2-DG-induced anestrus, this might have indicated that peripheral fuel availability is critical for anestrus. On the contrary, 2-DG treatment induced anestrus regardless of the type of fuel ingested. Neither experiment yielded results that implicated changes in peripheral fuel availability as a critical signal in metabolic control of estrous cycles.

Anestrus↗

Central vs. peripheral metabolic control of estrous cycles in Syrian hamsters. II. Glucoprivation.

Estrous cycles in Syrian hamsters are inhibited by food deprivation or treatment with pharmacological inhibitors of intracellular glucose utilization (glucoprivic treatments). These same metabolic challenges increase neural stimulation in areas of the caudal brain stem thought to be involved in detection of metabolic signals. Experiment 1 was designed to examine whether vagally transmitted signals are important for glucoprivic effects on estrous cycles and on neural stimulation in the caudal brain stem. Vagotomized or sham-operated hamsters were treated with 2-deoxy-D-glucose (2-DG) at a dose known to decrease cellular glucose utilization and inhibit estrous cycles (1,750 mg/kg). Vagotomized and sham-operated hamsters did not differ significantly in incidence of 2-DG-induced anestrus or in neural stimulation in the caudal brain stem, but the effects of 2-DG on estrous cycles and neural stimulation appeared to have been attenuated in vagotomized hamsters. In experiment 2, hamsters were injected intracerebroventricularly with 2-DG or glucose at doses that did not induce anestrus when injected systemically (125 and 250 mg/kg). Groups treated with intracerebroventricular injections of 2-DG showed a significantly higher incidence of anestrus than those treated with glucose. In experiment 3, effects of systemic injections of 2-DG were prevented by prior injection of glucose or fructose at the same concentration, indicating that 2-DG acts via effects on glucose metabolism, rather than via a nonspecific pharmacological effect or generalized stress response. Results of these experiments and those reported elsewhere (J. E. Schneider, A. J. Hall, and G. N. Wade. Am. J. Physiol. 272 (Regulatory Integrative Comp. Physiol, 41) R400-R405, 1997] are consistent with the notion that central glucoprivation is sufficient, whereas peripheral lipoprivation is not critical, for metabolic effects on estrous cycles.

Anestrus↗

Effects of the fructose analog, 2,5-anhydro-D-mannitol, on food intake and estrous cyclicity in Syrian hamsters.

Hyperphagia and anovulation are both triggered by prior food deprivation or other treatments that decrease intracellular availability of metabolic fuels in most species studied. Syrian hamsters fail to show compensatory hyperphagia, but do show anestrus in response to these energetic challenges. In the present experiments, we examined food intake, plasma glucose levels, and estrous cyclicity in Syrian hamsters in response to 2,5-anhydro-D-mannitol (2,5-AM), a fructose analog that is thought to trigger eating in rats by depleting intracellular levels of ATP. In experiment 1, female estrous cycling hamsters were treated with 100, 200, 400, or 800 mg/kg 2,5-AM or the vehicle by intraperitoneal injection. Food intake was measured 1, 2, 4, 8, and 24 h after treatment. There were no statistically significant increases in food intake in response to any dose of 2,5-AM. In experiment 2, blood samples were drawn at 0, 1, 3, 5, 7, and 25 h after hamsters were treated with 0 or 400 mg/kg 2,5-AM. 2,5-AM treatment resulted in a mild but significant decrease in plasma glucose levels similar to those seen in 2,5-AM-treated rats, suggesting that 2,5-AM has similar effects on fuel metabolism in rats and hamsters. In experiment 3, hamsters received 2,5-AM, 2,5-AM plus the fatty acid oxidation inhibitor methyl palmoxirate, or vehicle every 6 h over the first 48 h of the estrous cycle and were tested for indexes of estrous cyclicity at the end of the cycle. All hamsters showed normal estrous cycles, regardless of treatment. If 2,5-AM has similar metabolic consequences in rats and hamsters, the present results suggest that decreased intracellular levels of ATP and mild hypoglycemia do not increase food intake or inhibit estrous cyclicity in Syrian hamsters.

Animals↗

Control of fertility by metabolic cues.

In female mammals, reproduction is extremely sensitive to the availability of oxidizable metabolic fuels. When food intake is limited or when an inordinate fraction of the available energy is diverted to other uses such as exercise or fattening, reproductive attempts are suspended in favor of processes necessary for individual survival. Both reproductive physiology and sexual behaviors are influenced by food availability. Nutritional effects on reproductive physiology are mediated by changes in the activity of gonadotropin-releasing hormone (GnRH) neurons in the forebrain, whereas the suppression of sexual behaviors appears to be due, at least in part, to decreases in estrogen receptor in the ventromedial hypothalamus. Work using pharmacological inhibitors of glucose and fatty acid oxidation indicates that reproductive physiology and behavior respond to short-term (minute-to-minute or hour-to-hour) changes in metabolic fuel oxidation, rather than to any aspect of body size or composition (e.g., body fat content or fat-to-lean ratio). These metabolic cues seem to be detected in the viscera (most likely in the liver) and in the caudal hindbrain (probably in the area postrema). This metabolic information is then transmitted to the GnRH-secreting or estradiol-binding effector neurons in the forebrain. There is no evidence to date for direct detection of metabolic cues by these forebrain effector neurons. This metabolic fuels hypothesis is consistent with a large body of evidence and seems to account for the infertility that is seen in a number of situations, including famine, eating disorders, excessive exercise, cold exposure, lactation, some types of obesity, and poorly controlled diabetes mellitus.

Animals↗

Glucoprivic treatments that induce anestrus, but do not affect food intake, increase FOS-like immunoreactivity in the area postrema and nucleus of the solitary tract in Syrian hamsters.

Animals make a wide variety of physiological and behavioral adjustments in order to maintain caloric homeostasis. For example, most animals increase food intake when the availability of cellular metabolic fuels is low. The area postrema (AP) and adjacent, reciprocally-innervated nucleus of the solitary tract (NTS) are important brain areas for metabolic control of food intake in rats. However, in Syrian hamsters, food intake is not affected by decreases in metabolic fuel availability such as those that occur with food deprivation or with pharmacological inhibitors of metabolic fuels. Hamsters make other adjustments that conserve energy when the availability of metabolic fuels is low. Estrous cycles are inhibited by treatment with a high dose of 2-deoxy-D-glucose (2DG), a drug that inhibits cellular glucose utilization, but not by treatment with methyl palmoxirate (MP) a drug that inhibits fatty acid utilization. Recent data suggest that the AP/NTS is critical for the effects of glucoprivation on estrous cycles. Lesions of the AP/NTS prevent 2DG-induced anestrus. If the AP/NTS is involved in anestrus induced by glucoprivation, it might be predicted that glucoprivic treatments that induce anestrus would change patterns of neural activation, as measured by FOS-like immunoreactivity (FOS-li), in the AP/NTS. We examined FOS-li in females that were either food deprived or fed ad libitum, and in females treated with 2DG, MP or the appropriate vehicle. FOS-li was increased in the AP/NTS only in hamsters food deprived or treated with 2DG, the two treatments that induce anestrus but have no effect on food intake. These results are consistent with the notion that metabolic control of estrous cycles involves detection of decreases in the availability of metabolic fuels in the AP/NTS.

Anestrus↗

Thermoregulatory and maternal nestbuilding in Syrian hamsters: interaction of ovarian steroids and energy demand.

To investigate the relationship between energy demand, ovarian hormones and behavioral thermoregulation, we measured nestbuilding of female Syrian hamsters (Mesocricetus auratus) under conditions where energy demand and circulating ovarian hormone levels varied. Hamsters increased nestbuilding under conditions of chronically elevated estradiol and progesterone levels (late gestation; ovariectomized animals treated with estradiol +/- progesterone) and increased energy demand (late gestation or cold exposure). When hormone treatments were withdrawn, hamsters gained weight and reduced nestbuilding activity. Nestbuilding was not affected by lactation (characterized by low ovarian steroid levels and high energy demand) or by estrous cycle phase (characterized by relatively transient changes in ovarian steroid levels and subtle changes in energy demand). Thus, nestbuilding in Syrian hamsters was responsive to increased energy demand from cold exposure, late gestation, and to ovarian hormones. However, during lactation and estrous cycles, nestbuilding did not always change predictably according to known changes in energy expenditure and steroid hormone levels. Thus, levels of nestbuilding are influenced by factors in addition to ovarian hormones and energy expenditure under some circumstances.

Animals↗

Cytotoxic effects of autoxidative glycation.

Incubation of the RNA phage Q beta at 37 degrees C with a mixture of 100 mM ribose and 10 microM CuSO4 resulted in a complete loss of viable phage after 20 min. This cytotoxic effect required both ribose and cupric ions. There was a direct correlation between the decrease in the percentage of phage survival and: (a) the length of incubation, and (b) the concentrations of both ribose and CuSO4. Addition of the strong chelator diethylenetriaminepentaacetic acid abolished the cytotoxic effect. These results are consistent with an initial production of superoxide free radicals by transition metal catalyzed autoxidation of ribose and Amadori products, followed by dismutation of superoxide to hydrogen peroxide and generation of lethal hydroxyl radicals by the Fenton reaction. RNA isolated from phage incubated with ribose and CuSO4 retained its infectivity, suggesting that the cytotoxic effect may be mediated by a free radical attack on proteinaceous components of the phage through a site specific generation of hydroxyl radicals on protein-bound transition metal ions.

Copper↗