Effect of sleep restriction on orthostatic cardiovascular control in humans.

We hypothesized that sleep restriction (4 consecutive nights, 4 h sleep/night) attenuates orthostatic tolerance. The effect of sleep restriction on cardiovascular responses to simulated orthostasis, arterial baroreflex gain, and heart rate variability was evaluated in 10 healthy volunteers. Arterial baroreflex gain was determined from heart rate responses to nitroprusside-phenylephrine injections, and orthostatic tolerance was tested via lower body negative pressure (LBNP). A Finapres device measured finger arterial pressure. No difference in baroreflex function, heart rate variability, or LBNP tolerance was observed with sleep restriction (P > 0.3). Systolic pressure was greater at -60 mmHg LBNP after sleep restriction than before sleep restriction (110 +/- 6 and 124 +/- 3 mmHg before and after sleep restriction, respectively, P = 0.038), whereas heart rate decreased (108 +/- 8 and 99 +/- 8 beats/min before and after sleep restriction, respectively, P = 0.028). These data demonstrate that sleep restriction produces subtle changes in cardiovascular responses to simulated orthostasis, but these changes do not compromise orthostatic tolerance.     

Effect of cold hardening, wilting and exogenously applied proline on leaf proline content and frost tolerance of several genotypes of Solanum

Frost tolerance and leaf proline content were examined in a number of potato hybrids selected for frost tolerance and in the cv. Astarte before and after hardening. Cold hardening (2°C for 20 days) in a dry environment (50/90% relative humidity, day/night) resulted in decreased water content, increased proline content and increased frost tolerance of the leaves of all genotypes. Frost tolerance before and after hardening was positively related to leaf proline content, but not to leaf water content. Drought stress alone, imposed by wilting excised leaves for 4 days, resulted in an accumulation of proline comparable to that after hardening in a dry environment, but the increase in frost tolerance was smaller. Cold hardening in a humid environment (90% relative humidity continuously) only caused a minor accumulation of proline and a small increase in frost tolerance, but the increase in frost tolerance was high in relation to the amount of proline accumulated. Proline, exogenously applied to one of the genotypes, was accumulated in the leaves of shoot cultures, resulting in an increase in frost tolerance. A possible role of proline in frost tolerance is discussed.     

Interruption of tolerance toward a haptenic initiator of delayed-type hypersensitivity

We have found that an immunomodulator, dextran, prevents initiation of tolerance for an unrelated haptenic stimulus of contact hypersensitivity, picryl chloride. To prevent tolerance optimally, 1 to 10 mg of dextran per 25g mouse was required to be injected i.v. 2 hr before administering tolerogen. The immunomodulator was seen to be effective in mice with diverse major histocompatibility backgrounds. Furthermore, prevention of tolerance was seen to be independent of the condition of the hapten used to initiate unresponsiveness, since tolerance was abrogated when attempted with uncoupled hapten or with hapten attached to allogeneic or syngeneic spleen cells. In addition, administering dextran before tolerogen did not convert the tolerogenic signal into an immunogenic one so that hapten-specific DTH could be detected. While the precise mechanism of dextran's interruption of immunologic unresponsiveness for DTH has yet to be elucidated, the principle that tolerance can be readily and easily interrupted with this immunomodulating agent has been firmly established.     

Normalization effect of preceding protein meals on “diabetic” oral glucose tolerance in Eskimos

Routine testing of 76 clinically non-diabetic Eskimos showed marked impairment of oral glucose tolerance in 54% but normal intravenous glucose tolerance in most of these.Total insulin output following the glucose drink was not found different in Eskimos with normal and abnormal glucose tolerance nor did lean meat meals given 60 minutes before the glucose significantly increase it.Intolerance to oral glucose loads appeared significantly related to a delay of insulin release and both timing of insulin response and shape of blood glucose curve normalized in the meat-preceded tests.     

Effects of Folic Acid on the Phenylalanine Tolerance Test in Phenylketonuria

Phenylalanine tolerance tests were performed on four untreated children with phenylketonuria, aged 8 to 12 years, before and after 14 days of folic acid administration (70 mg./day). No significant changes were noted in the phenylalanine tolerance tests or in the general condition of the patients. This study was carried out because of recent findings that a folic acid derivative is a co-factor in the conversion of phenylalanine to tyrosine.     

Effect of Propranolol on Exercise Tolerance of Patients with Atrial Fibrillation

Six patients with atrial fibrillation who were taking digitalis were exercised before and after 30 mg. of propranolol twice daily. Though there was a lower pulse rate at rest and on exercise in all patients, three suffered deterioration of exercise tolerance. It is concluded that propranolol does not improve the exercise tolerance of patients with atrial fibrillation whose resting ventricular rate is controlled with digitalis.     

Loss of carrier-determined tolerance in vitro with loss of receptor blockade.

Experiments were done to determine whether carrier-determined tolerance is reversible and whether the loss of tolerance is accompanied by the loss of receptor blockade. Spleen cells from mice made tolerant with DNP-isologous IgG remained tolerant when transferred to irradiated syngeneic mice. If these same tolerant spleen cells were incubated for 24 hr or more before transfer the tolerance was lost. Autoradiology was done on the tolerant cells with either 125I anti-DNP or 125DNP-KLH, before and after incubation in vitro. When the cells were tolerant the number of DNP ABC was decreased whereas cells having DNP on their surface were increased. When the cells lost tolerance after in vitro incubation, the hapten-bearing cells were no longer present although the number of cells free DNP receptors increased to normal. These data suggest that in carrier determined tolerance the reactivation of tolerant lymphocytes may involve reversible receptor blockade.     

Effect of resistance exercise on dehydroepiandrosterone sulfate concentrations during a 72-h recovery: relation to glucose tolerance and insulin response

Serum dehydroepiandrosterone sulfate (DHEA-S) concentration is known to be associated with the whole-body insulin sensitivity. The main purpose of the study was to investigate the effect of resistance exercise on DHEA-S concentration during a 72 h post-exercise recovery, and its relation to glucose tolerance and insulin sensitivity. Morning fasted serum samples was obtained from 19 male volunteers (aged 21.1+/-0.4 years) 24 h before the onset of exercise and 24 h, 48 h, and 72 h following exercise for measurements of DHEA-S, cortisol, and TNF-alpha. Oral glucose tolerance test (OGTT) and insulin response were determined 24 h before and 48 h after exercise. We found that resistance exercise causes a delayed suppression in serum DHEA-S levels during recovery (48 h and 72 h). This exercise challenge did not affect glucose tolerance, but insulin response during OGTT was significantly elevated. The increased insulin level was not associated with serum levels of cortisol and TNF-alpha. In conclusion, the present study found that resistance exercise has a DHEA-S lowering effect that persisted for 72 h. This change could be related to the elevated insulin concentrations during OGTT.     

Abscisic acid content at defined levels of bud dormancy and frost tolerance in two contrasting populations of Picea abies grown in a phytotron

Seedlings of a southern (Romanian) and a northern (Swedish) population of Picea abies were cultivated under continuous light and 20°C for 10 weeks. To arrest growth, induce terminal bud dormancy and promote frost tolerance the seedlings were then exposed to 16 h nights for 12 weeks, with gradually lower temperature during the last 6 weeks. Samples for estimating the abscisic acid content of the needles were taken just before the onset of the night treatment, at day 3 of the treatment, and then with one, and later 2 week, intervals. From the second week onwards (third week for frost tolerance) bud dormancy and frost tolerance were assessed at the same time as abscisic acid (ABA) determinations. Phosphate-buffered saline extracts were purified on mini-columns (in some cases immunoaffinity colums) and quantified by HPLC. The degree of dormancy was estimated by transferring the seedlings to growth conditions and determining the number of days until growth was resumed. The frost tolerance of the needles exposed to –10°C and –20°C was classified in 6 classes. The frost tolerance of the terminal buds was estimated as the number of seedlings that showed some growth after 6 weeks in growth conditions. The night treatment rapidly induced terminal bud dormancy in both populations, but the release of dormancy occurred earlier in the northern population. The needles and the terminal buds became highly frost tolerant more rapidly in the northern than in the southern population and before the temperature decrease. The degree of dormancy began to decline before full frost tolerance was obtained in the southern population and this decline continued in both populations, while frost tolerance remained at a high level. The southern population showed a transient peak in ABA content at day 3. Although the ABA content of the northern population was lower than in the southern before the 16-h night treatment, it increased in the northern population during the treatment period, in particular after the temperature decrease.     

Effect of 6-week endurance training on hemodynamic and neurohormonal responses to lower body negative pressure (LBNP) in healthy young men.

Endurance training is considered as a factor impairing orthostatic tolerance although an improvement and lack of effect have been also reported. The mechanisms of the changes and their relation to initial tolerance of orthostasis are not clear. In the present study, effect of moderate running training on hemodynamic and neurohormonal changes during LBNP, a laboratory test simulating orthostasis, was investigated in subjects with high (HT) and low (LT) tolerance of LBNP. Twenty four male, healthy subjects were submitted to graded LBNP (-15, -30 and -50 mmHg) before and after training. During each test heart rate (HR), stroke volume (SV) and blood pressure, plasma catecholamines, ACTH, adrenomedullin, atrial natriuretic peptide, and renin activity were determined. Basing on initial test, 13 subjects who withstood LBNP at -50 mmHg for 10 min were allocated into HT group and 11 subjects who earlier showed presyncopal symptoms to LT group. Training improved LBNP tolerance in six LT subjects. This was associated with attenuated rate of HR increase and SV decline (before training, at -30 mmHg deltaHR was 21 +/- 4 beats/min and deltaSV - -36+/- 8 ml while after training the respective values were 8 +/- 4 beats/min and -11+/- 6 ml). No differences in hemodynamic response were found in HT subjects and those from LT group whose LBNP tolerance was unchanged. In neither group training affected neurohormonal changes except inhibition of plasma ACTH rise in subjects with improvement of LBNP tolerance. It is concluded that some subjects with low orthostatic tolerance may benefit from moderate training due to improvement of cardiac function regulation.     

Impact of Thermal History on Tolerance of Meloidogyne hapla Second-stage Juveniles to External Freezing

Low temperature induced physiological changes that increased the ability of second-stage juveniles of Meloidogyne hapla to survive external freezing. Second-stage juveniles in polyethylene glycol solution were exposed to -4 , 0, 4, or 24 C, and then their survival was determined after ice-induced freezing of the suspensions at - 4 C for 24 hours. Survival was greatest for juveniles exposed to 4 C before freezing. Some juveniles were killed by exposure to - 4 C before freezing of the suspensions. The percentage of juveniles surviving freezing increased from about 30% to 80% within 12 hours of exposure to 4 C. This tolerance of external freezing was lost during subsequent exposure to 24 C. Longer exposures, of 1 to 15 days, to low temperature did not increase the percentage surviving external freezing, as compared to the 12-hour exposure, but reduced the tolerance of external freezing lost during subsequent exposure to 24 C for 48 hours.     

Nitrazepam: lastingly effective but trouble on withdrawal.

The sleep of 10 volunteers with an average age of 57 years was recorded electrophysiologically before, during, and after nitrazepam 5 mg nightly for 10 weeks. Sleep was longer and less broken on the drug and no tolerance was obvious after two months'' use. Withdrawal of the drug, however, caused sleep to be temporarily worse than before the drug had been taken. Slow-wave sleep was reduced by nitrazepam, but the accompanying secretion of growth hormone was not impaired.     

天敌昆虫耐冷藏力研究进展

低温冷藏是延长天敌昆虫货架期的有效方法之一.昆虫的存活率、生殖力、田间寄生(捕食)力等是评估天敌昆虫耐冷藏力的重要指标.昆虫耐冷藏力受冷藏前、冷藏中和冷藏后的各种外源(非生物)因子和内源(生物)因子的影响.这些因子主要包括温度、湿度、光周期、氧浓度、冷藏持续时间、冷藏前的预处理、冷藏过程中的温度处理(混合低温)等外源因子和虫体能量物质的储备、繁殖方式、年龄/龄期、滞育(休眠)状态、营养等内源因子.本文对影响天敌昆虫耐冷藏性的内源因子和外源因子的种类以及产生这些影响的生理学机制等进行了综述,以期为天敌昆虫低温储藏技术研究和生产方案的制定提供依据.     

The effect of endotoxin and endotoxin tolerance on inflammation induced by mycobacterial adjuvant

Peptidoglycan, the substance in mycobacteria thought to be responsible for inducing adjuvant arthritis, and endotoxin (lipopolysaccharide or LPS) share many inflammatory properties. Since repeated administration of LPS produces tolerance, i.e., resistance to the toxic and inflammatory effects of LPS, we tested whether LPS and/or LPS tolerance might influence inflammation due to mycobacterial adjuvant. Male Sprague-Dawley rats were injected with Escherichia coli LPS or saline intraperitoneally and then challenged with 100 micrograms killed Mycobacteria butyricum (adjuvant) in the footpad. A single dose of 100 micrograms LPS three or 24 hours before adjuvant markedly, but transiently, reduced the local footpad swelling that begins within hours of the adjuvant injection and histologically resembles a sterile abscess. Animals that received multiple doses of LPS and were therefore tolerant or animals that received LPS 72 hours before adjuvant demonstrated adjuvant-induced footpad swelling nearly equal to controls. The anti-inflammatory effect of LPS was transient since footpad swelling in all groups was nearly comparable six days after the adjuvant injection and LPS failed to inhibit consistently the arthritis that develops two or more weeks after adjuvant injection. These studies establish that LPS can markedly inhibit the prodrome of adjuvant arthritis (footpad swelling due to M. butyricum), that inhibition of this prodrome does not prevent the subsequent development of arthritis, and that LPS tolerance diminishes this anti-inflammatory effect of LPS.     

Effects of a 6-mo endurance-training program on venous compliance and maximal lower body negative pressure in older men and women.

Aging and chronic exercise training influence leg venous compliance. Venous compliance affects responses to an orthostatic stress. The extent to which exercise training in a previously sedentary older population will affect venous compliance and tolerance to the simulated orthostatic stress of maximal lower body negative pressure (LBNP) is unknown. The purpose of this investigation is to determine the influence of a 6-mo endurance-training program on calf venous compliance and responses and tolerance to maximal LBNP in older men and women. Twenty participants (exercise group: n = 10, 5 men, 5 women; control group: n = 10, 6 men, 4 women; all >60 yr) underwent graded LBNP to presyncope or 4 min at -100 mmHg before and after a 6-mo endurance-training program. Utilizing venous occlusion plethysmography, calf venous compliance was determined in both groups using the first derivative of the pressure-volume relation during cuff pressure reduction before training, at 3 mo, and at the end of the training program. The exercise group improved their fitness with the 6-mo endurance-training program, whereas the control group did not change (14 +/- 3 vs. <1 +/- 2%; P < 0.05). LBNP tolerance did not differ between groups or across trials (P = 0.47). Venous compliance was not different between groups or trials, either initially or after 3 mo of endurance training, but tended to be greater in the exercise group after 6 mo of training (P = 0.08). These data suggest that a 6-mo endurance-training program may improve venous compliance without affecting tolerance to maximal LBNP in older participants.     

Effects of d-amphetamine on the behavior of pigeons exposed to the peak procedure

The effects of d-amphetamine on pigeons' key-pecking under the peak interval (PI) procedure were investigated in two experiments. In experiment I the effects of doses of d-amphetamine from 0.75 to 3.0 mg/kg on responding under PI 30 and 45 s were studied for 10 successive days. Reductions in peak time and wait time were observed at both PI values and an increase in the width was found at PI 30 s. There was no evidence of tolerance. In experiment II, pigeons exposed to a PI 45 s schedule were administered doses of D-amphetamine of 1.5 and 3.0 mg/kg for 30 successive days. Reductions in peak time and wait time were found here. Evidence of tolerance was found in wait time, peak time and width of the distribution at the higher dose. In both experiments a rate-dependent effect of the drug was found in the portion of each peak trial before the time that food was delivered on reinforced trials; this effect was weaker after the customary time of food delivery. The rate-dependent effect for responses before food time, combined with little effect of the drug on responses after food time, is shown by simulation to be sufficient to account for the reduction in peak time, without the need to appeal to an internal clock mechanism.     

Influence of acute and chronic administration of benzylamine on glucose tolerance in diabetic and obese mice fed on very high-fat diet

The combination of vanadate plus benzylamine has been reported to stimulate glucose transport in rodent adipocytes and to mimic other insulin actions in diverse studies. However, benzylamine alone activates glucose uptake in human fat cells and increases glucose tolerance in rabbits. The aim of this work was to unravel the benzylamine antihyperglycemic action and to test whether its chronic oral administration could restore the defective glucose handling of mice rendered slightly obese and diabetic by very high-fat diet (VHFD). When VHFD mice were i.p. injected with benzylamine at 0.7 to 700 micromol/kg before glucose tolerance test, they exhibited reduced hyperglycemic response without alteration of insulin secretion. Whole body glucose turnover, as assessed by the glucose isotopic dilution technique, was unchanged in mice perfused with benzylamine (total dose of 75 micromol/kg). However, their in vivo glycogen synthesis rate was increased. Benzylamine appeared therefore to directly facilitate glucose utilisation in peripheral tissues. When given chronically at 2000 or 4000 micromol/kg/d in drinking water, benzylamine elicited a slight reduction of water consumption but did not change body weight or adiposity and did not modify oxidative stress markers. Benzylamine treatment improved glucose tolerance but failed to normalize the elevated glucose fasting plasma levels of VHFD mice. There was no influence of benzylamine ingestion on lipolytic activity, basal and insulin-stimulated glucose uptake, and on inflammatory adipokine expression in adipocytes. The improvement of glucose tolerance and the lack of adverse effects on adipocyte metabolism, reported here in VHFD mice allow to consider orally given benzylamine as a potential antidiabetic strategy which deserves to be further studied in other diabetic models.     

Prevention by the MER tubercle bacillus fraction of immunosuppression induced by cancer chemotherapeutic agents

Summary Contact hypersensitivity (CH) to 2,4-dinitro-1-fluorobenzene (DNFB) was induced in guinea pigs and mice by DNFB skin application. Development of CH was suppressed in both species either by cyclophosphamide (CY) treatment after sensitization or by single intravenous injection of dinitrobenzene-sulfonate (DNBS) before sensitization (hapten-induced tolerance). Additional treatment schedules were employed in guinea pigs, with the following results: Suppression of CH by injection of DNBS concomitant with sensitization; abrogation of hapten-induced tolerance by administration of CY before sensitization; and potentiation of CH skin reactivity by administration of CY before sensitization.Pretreatment by two injections of the methanol extraction residue (MER) tubercle bacillus fraction restored significantly the ability of CY treated animals to respond to DNFB sensitization. In contrast, administration of MER either by one injection before sensitization, concomitant with DNFB, or after sensitization did not prevent immunosuppression by CY.MER treatment was not effective in reversing hapten-induced tolerance in mice, and had only an occasional effect on this process in guinea pigs. Abrogation of hapten-induced tolerance and potentiation of DNFB sensitization by CY in guinea pigs were also not influenced by MER treatment.Supported by Contract NO1-CM-12127 from the NCI and by research grants from Concern Foundation, Inc., the Lautenberg Endowment, the National Council for Research and Development, Israel, and the GSF Munich, Germany, and the Leukemia Research Foundation, Inc.     

Short term increases in the cold tolerance of red osier dogwood stems induced by application of cysteine

Bark tissues of Cornus stolonifera stems, treated with cysteine at 24 hours after treatment, survived exposure to −11 C (the tissue temperature) with little or no injury. An initiation of increase in the cold tolerance was usually observed when plants were treated with cysteine at 12 hours after treatment. Neither plants at 36 or 48 hours after treatment nor plants 12 hours before treatment had shown increases in the cold tolerance. They were killed below −5 C, which was the survival temperature of untreated control plants. Two weeks or more of short day induction before cysteine application were required for a significant effect of short term 5 C increase in the cold tolerance.     

A method for the rapid development of opiate tolerance in the guinea pig ileum

The rate and degree of in vitro tolerance development to morphine, normorphine and d,1-methadone were assessed on the excised guinea pig ileum. Agonists in fixed concentrations at 1/4, 1/2, 1 and 2 x IC50 were incubated with the tissue for 1, 2 or 4 hours. The degree of tolerance development was expressed as a ratio of the IC50 after and before incubation. A high degree of tolerance developed to all three agonists and the effect could be prevented by co-incubation with naloxone. Tolerance development was stereo-specific; levorphanol and 1-methadone developed much higher degrees of tolerance than their respective d-isomers. Furthermore, under the same conditions, subsensitivity to acetylcholine, norepinephrine, and adenosine monophosphate did not develop. The in vitro tolerance was accompanied by physical dependence development as evidenced by the fact that naloxone elicited muscular contracture in the tolerant ileum. cAMP enhanced the development of tolerance to normorphine and cycloheximide could reduce this phenomenon. It is concluded that the procedure may facilitate studies on the mechanisms involved in the development of opiate tolerance and physical dependence.