Photoperiod differentially modulates photic and nonphotic phase response curves of hamsters

Circadian pacemakers respond to light pulses with phase adjustments that allow for daily synchronization to 24-h light-dark cycles. In Syrian hamsters, Mesocricetus auratus, light-induced phase shifts are larger after entrainment to short daylengths (e.g., 10 h light:14 h dark) vs. long daylengths (e.g., 14 h light:10 h dark). The present study assessed whether photoperiodic modulation of phase resetting magnitude extends to nonphotic perturbations of the circadian rhythm and, if so, whether the relationship parallels that of photic responses. Male Syrian hamsters, entrained for 31 days to either short or long daylengths, were transferred to novel wheel running cages for 2 h at times spanning the entire circadian cycle. Phase shifts induced by this stimulus varied with the circadian time of exposure, but the amplitude of the resulting phase response curve was not markedly influenced by photoperiod. Previously reported photoperiodic effects on photic phase resetting were verified under the current paradigm using 15-min light pulses. Photoperiodic modulation of phase resetting magnitude is input specific and may reflect alterations in the transmission of photic stimuli.     

Hsp72 overexpression accelerates the recovery from caerulein-induced pancreatitis

Background and Aims

Heat shock protein (Hsp) 72 is a molecular chaperone which is upregulated in response to a variety of stress situations and has a general cytoprotective function. Increased Hsp72 levels were implicated in protection from acute pancreatitis; a hypothesis which was not tested in a transgenic mouse model yet.

Methods

To analyze the role of Hsp72 during acute pancreatitis, well-characterized transgenic animals overexpressing rat Hsp72 (Hsp72 mice) under the control of the ß-actin promoter were subjected to caerulein- and L-arginine-induced acute pancreatitis. The severity of experimental pancreatitis was determined via serum lipase levels, morphometric evaluation and quantification of pancreatic edema/inflammation.

Results

Hsp72 mice displayed ∼100-times Hsp72 overexpression, but no changes in the remaining chaperones. Robust Hsp72 signal was observed in pancreatic acini, but not in islets or ductal cells. In both models, elevated Hsp72 did not protect from development of acute pancreatitis and the pancreatitis-associated lung injury, but accelerated recovery from caerulein-induced tissue injury (lower lipase levels, edema, inflammation and necrosis 36 h after caerulein administration). The observed protective function of Hsp72 in caerulein-induced pancreatitis is likely due to an attenuated NF-κB signalling.

Conclusions

Hsp72 overexpression accelerates the recovery from acute pancreatitis and may represent a potential treatment strategy.     

Ephedrine accelerates psychomotor recovery from anesthesia in macaque monkeys

Background Ephedrine is used in treatment of hypotension during anesthesia. We investigated its effects on the psychomotor recovery and its potential adverse reactions on cardiorespiratory functions in rhesus monkeys. Methods The monkeys received 50 μg/kg medetomidine, 2.0 mg/kg S‐ketamine with 150 IU hyaluronidase i.m. Pulse rate, blood pressure and saturation of haemoglobin were monitored for 20 minutes. Thereafter, 1 mg/kg of ephedrine or a placebo was administered i.m. and behavioural changes, pulse rate, blood pressure and saturation of haemoglobin were monitored every 5 minutes. Results Ephedrine shortened recovery from anaesthesia from 80.4 ± 25.8 to 14.83 ± 13.70 minutes. Ephedrine also increased oxygen saturation of haemoglobin and systolic blood pressure and caused significant decrease in pulse rate 5 minutes after its administration. Conclusions Ephedrine can be successfully used to accelerate psychomotor recovery after the use of common anesthetic protocols combining dissociative anesthetic agent and alpha 2‐adrenoceptor agonist in primates.     

Slow recovery from perturbations as a generic indicator of a nearby catastrophic shift

The size of the basin of attraction in ecosystems with alternative stable states is often referred to as "ecological resilience." Ecosystems with a low ecological resilience may easily be tipped into an alternative basin of attraction by a stochastic event. Unfortunately, it is very difficult to measure ecological resilience in practice. Here we show that the rate of recovery from small perturbations (sometimes called "engineering resilience") is a remarkably good indicator of ecological resilience. Such recovery rates decrease as a catastrophic regime shift is approached, a phenomenon known in physics as "critical slowing down." We demonstrate the robust occurrence of critical slowing down in six ecological models and outline a possible experimental approach to quantify differences in recovery rates. In all the models we analyzed, critical slowing down becomes apparent quite far from a threshold point, suggesting that it may indeed be of practical use as an early warning signal. Despite the fact that critical slowing down could also indicate other critical transitions, such as a stable system becoming oscillatory, the robustness of the phenomenon makes it a promising indicator of loss of resilience and the risk of upcoming regime shifts in a system.     

Whey protein supplementation accelerates satellite cell proliferation during recovery from eccentric exercise

Human skeletal muscle satellite cells (SCs) are essential for muscle regeneration and remodeling processes in healthy and clinical conditions involving muscle breakdown. However, the potential influence of protein supplementation on post-exercise SC regulation in human skeletal muscle has not been well investigated. In a comparative human study, we investigated the effect of hydrolyzed whey protein supplementation following eccentric exercise on fiber type-specific SC accumulation. Twenty-four young healthy subjects received either hydrolyzed whey protein + carbohydrate (whey, n = 12) or iso-caloric carbohydrate (placebo, n = 12) during post-exercise recovery from 150 maximal unilateral eccentric contractions. Prior to and 24, 48 and 168 h post-exercise, muscle biopsies were obtained from the exercise leg and analyzed for fiber type-specific SC content. Maximal voluntary contraction (MVC) and serum creatine kinase (CK) were evaluated as indices of recovery from muscle damage. In type II fiber-associated SCs, the whey group increased SCs/fiber from 0.05 [0.02; 0.07] to 0.09 [0.06; 0.12] (p < 0.05) and 0.11 [0.06; 0.16] (p < 0.001) at 24 and 48 h, respectively, and exhibited a difference from the placebo group (p < 0.05) at 48 h. The whey group increased SCs/myonuclei from 4?% [2; 5] to 10?% [4; 16] (p?p < 0.001) and muscle soreness and CK increased (p < 0.001), irrespective of supplementation. In conclusion, whey protein supplementation may accelerate SC proliferation as part of the regeneration or remodeling process after high-intensity eccentric exercise.     

Estrogen accelerates the recovery of the lordosis response after its exhaustion induced by cervical probing

Repetitive flank-perineum palpation combined with probing the vaginal cervix in ovariectomized hormonally untreated rats elicited a mean of 4.2 +/- 0.2 (SEM) successive lordosis responses before the response was exhausted. Two days after a single injection of estradiol benzoate (100 micrograms/kg body wt) in ovariectomized rats, a significantly greater number (7.8 +/- 0.2) of lordosis responses could be elicited before the response was exhausted (P less than 0.01). After this exhaustion, recovery of lordosis responsiveness to this stimulation occurred significantly earlier in the estrogen-treated rats (6 hr) than in the oil-treated rats (60 hr) (P less than 0.01). Several possible mechanisms mediating these effects are proposed.     

Minocycline inhibits 5-lipoxygenase expression and accelerates functional recovery in chronic phase of focal cerebral ischemia in rats

AimsWe previously reported that minocycline attenuates acute brain injury and inflammation after focal cerebral ischemia, and this is partly mediated by inhibition of 5-lipoxygenase (5-LOX) expression. Here, we determined the protective effect of minocycline on chronic ischemic brain injury and its relation with the inhibition of 5-LOX expression after focal cerebral ischemia.Main methodsFocal cerebral ischemia was induced by 90 min of middle cerebral artery occlusion followed by reperfusion for 36 days. Minocycline (45 mg/kg) was administered intraperitoneally 2 h and 12 h after ischemia and then every 12 h for 5 days. Sensorimotor function was evaluated 1–28 days after ischemia and cognitive function was determined 30–35 days after ischemia. Thereafter, infarct volume, neuron density, astrogliosis, and 5-LOX expression in the brain were determined.Key findingsMinocycline accelerated the recovery of sensorimotor and cognitive functions, attenuated the loss of neuron density, and inhibited astrogliosis in the boundary zone around the ischemic core, but did not affect infarct volume. Minocycline significantly inhibited the increased 5-LOX expression in the proliferated astrocytes in the boundary zone, and in the macrophages/microglia in the ischemic core.SignificanceMinocycline accelerates functional recovery in the chronic phase of focal cerebral ischemia, which may be partly associated with the reduction of 5-LOX expression.     

ABCA1 promotes the efflux of bacterial LPS from macrophages and accelerates recovery from LPS-induced tolerance

Macrophages play important roles in both lipid metabolism and innate immunity. We show here that macrophage ATP-binding cassette transporter A1 (ABCA1), a transporter known for its ability to promote apolipoprotein-dependent cholesterol efflux, also participates in the removal of an immunostimulatory bacterial lipid, lipopolysaccharide (LPS). Whereas monocytes require an exogenous lipoprotein acceptor to remove cell-associated LPS, macrophages released LPS in the absence of an exogenous acceptor by a mechanism that was driven, in part, by endogenous apolipoprotein E (apoE). Agents that increased ABCA1 expression increased LPS efflux from wild-type but not ABCA1-deficient macrophages. Preexposure of peritoneal macrophages to LPS for 24 h increased the expression of ABCA1 and increased LPS efflux with a requirement for exogenous apolipoproteins due to suppression of endogenous apoE production. In contrast, LPS preconditioning of ABCA1-deficient macrophages significantly decreased LPS efflux and led to prolonged retention of cell-surface LPS. Although the initial response to LPS was similar in wild-type and ABCA1-deficient macrophages, LPS-induced tolerance was greater and more prolonged in macrophages that lacked ABCA1. Our results define a new role for macrophage ABCA1 in removing cell-associated LPS and restoring normal macrophage responsiveness.     

FK506 accelerates functional recovery following nerve grafting in a rat model.

The sometimes dramatic and permanent functional deficits that result from severe peripheral nerve injuries provide compelling incentives to identify exogenous agents that may expedite axonal regrowth and avoid prolonged denervation of end organs. The purpose of this study was to identify, whether the regular systemic administration of tacrolimus (FK506) or cyclosporin A (CsA) would influence the speed and efficiency of nerve regeneration through short nerve grafts. A total of 35 Buffalo rats each received a 2-cm posterior tibial nerve graft and were randomized to one of three experimental groups. Group I animals were left untreated, group II received daily CsA (5 mg/kg intraperitoneally), and group III received daily FK506 (1 mg/kg intraperitoneally). Walking tracks were obtained starting 3 weeks after graft placement and continuing biweekly for the next 7 weeks. FK506-treated animals fully recovered hindlimb function 7 days earlier than CsA-treated animals or untreated control animals. Regenerated nerves from one-half of each treatment group were harvested for histomorphometric analysis at 7 weeks, shortly after recovery was complete in the FK506-treatment group but not in the other two groups, and once again at 10.5 weeks when recovery of function had stabilized in all groups. At 7 weeks, FK506-treated animals had significantly greater fiber density and percentage of neural tissue per nerve and a significantly larger population of mature, myelinated fibers in comparison with either CsA-treated or untreated animals. The authors concluded that the daily, systemic administration of low-dose FK506 facilitates peripheral nerve recovery and regeneration after nerve grafting.     

Hypoglycaemia-insulin test: discordant growth hormone and cortisol response in paediatric patients regarding recovery from hypoglycaemia with or without oral glucose solution

BACKGROUND: Hypoglycaemia-insulin test (HIT) is the 'gold standard' for the diagnosis of adrenal-pituitary-hypothalamic axis disorders. Controversy exists on the convenience of recovery from an insulin-induced hypoglycaemia since this test is not risk-free. OBJECTIVE: To ascertain whether recovery from insulin-induced hypoglycaemia with an oral glucose solution produces a different response of growth hormone (GH) and cortisol at different times of the study compared with spontaneous recovery from hypoglycaemia. PATIENTS AND METHODS: Prospective study of 100 children and adolescents with growth delay who underwent an HIT. Patients were consecutively assigned to two groups of 50. In one group recovery from hypoglycaemia occurred spontaneously and in the other recovery was achieved with an oral glucose solution (20 g of glucose) when glycaemia was under 30 mg/dl. The two groups did not differ in age, sex, pubertal status, weight, height and IGF-I levels. RESULTS: The response of GH at 30, 60, 90 and 120 min and cortisol at 10, 60, 90 and 120 min was lower and statistically significant in patients with recovery from hypoglycaemia with oral glucose solution. GH deficiency was diagnosed more frequently in patients recovered with glucose solutions (94%) compared to those with spontaneous recovery (68%). CONCLUSIONS: Oral glucose solution administration when glycaemia was under 30 mg/dl in HIT produced a lower GH and cortisol response to insulin stimulus and a greater frequency of GH deficit diagnosis.     

Simultaneous enzyme immunoassay of cortisol and dehydroepiandrostone-sulphate from a single serum sample using a transferable solid phase system

An enzyme immunological methodology for the direct and simultaneous estimation of serum cortisol and dehydroepiandrosterone-sulphate (DHEA-S) useful for the biochemical differential diagnosis of Cushing's syndrome has been developed. The combined estimation of both steroids is more economical in time, work and materials than two separate assays. Two solid phases, a microtitre plate and a covering transferable needle lid system were used in the present procedure. Both solid phases are first coated with anti-rabbit IgG and then each with a specific antiserum. Horseradish peroxidase was used as marker enzyme and tetramethylbenzidine as the chromogen for measuring enzyme activity. No extraction or deproteinization steps are involved. The turn around time for 41 samples (in duplicate) is 3 h. The detection limit of the assay is 5 pg/well for cortisol and 10 pg/well for DHEA-S. Results of the present method correlated well (cortisol, r = 0.95; DHEA-S, r = 0.98) with those of commercial radioimmunoassays using iodinated labels. Thus, this technique offers a convenient non-isotopic procedure in the routine clinical laboratory.     

How light-induced charge transfer accelerates the receptor-state recovery of photoactive yellow protein from its signaling state

Stark (electroabsorption) spectra of the M100A mutant of photoactive yellow protein reveal that the neutral, cis cofactor of the pB intermediate undergoes a strikingly large change in the static dipole moment (|Deltamu| = 19 Debye) on photon absorption. The formation of this charge-separated species, in the excited state, precedes the cis --> trans isomerization of the pB cofactor and the regeneration of pG. The large |Deltamu|, reminiscent of that produced on the excitation of pG, we propose, induces twisting of the cis cofactor as a result of translocation of negative charge, from the hydroxyl oxygen, O1, toward the C7-C8 double bond. The biological significance of this photoinduced charge transfer reaction underlies the significantly faster regeneration of pG from pB in vitro, on the absorption of blue light.     

Protein recovery from reversed micellar solutions through contact with a pressurized gas phase.

We describe a new process for the recovery of encapsulated protein from reversed micellar solution in concentrated form. The method involves desolubilization of the protein by decreasing solvent density through gas dissolution. Under appropriate thermodynamic conditions, the micellar water pool can be converted to clathrate hydrates. Protein recovery is facilitated by clathrate hydrate formation, which causes the desolubilized protein to exist in a solid phase, distinct from the micellar supernatant. The process is carried out without any ionic strength or pH modification.     

Acute pre-learning stress and declarative memory: impact of sex,cortisol response and menstrual cycle phase

This study explores the influence of pre-learning stress on performance on declarative memory tasks in healthy young adults in relation to sex and menstrual cycle phase. The sample was composed of 119 students (32 men and 87 women) from 18 to 25 years of age. The women were tested in different hormonal stages (30 in follicular phase, 34 in luteal phase, and 23 using oral contraceptives). The participants were exposed to the Trier Social Stress Test (TSST) or a control condition. Afterwards, their memory performance was measured using a standardized memory test (Rey's Auditory Verbal Learning Test). In the control condition, all groups of women recalled more words than men, but these differences disappeared in the group exposed to TSST because men's performance on the memory test improved, but only to the level of women. In addition, our data suggest that in women the relationship between cortisol and memory can be modulated by sex hormone levels, since in luteal women a negative relationship was found between memory performance and peak cortisol level. These results confirm that sex differences need to be considered in the relationship between pre-learning stress and memory performance.     

Analysis of biochemical phase shift oscillators by a harmonic balancing technique

The use of harmonic balancing techniques for theoretically investigating a large class of biochemical phase shift oscillators is outlined and the accuracy of this approximate technique for large dimension nonlinear chemical systems is considered. It is concluded that for the equations under study these techniques can be successfully employed to both find periodic solutions and to indicate those cases which can not oscillate. The technique is a general one and it is possible to state a step by step procedure for its application. It has a substantial advantage in producing results which are immediately valid for arbitrary dimension. As the accuracy of the method increases with dimension, it complements classical small dimension methods. The results obtained by harmonic balancing analysis are compared with those obtained by studying the local stability properties of the singular points of the differential equation. A general theorem is derived which identifies those special cases where the results of first order harmonic balancing are identical to those of local stability analysis, and a necessary condition for this equivalence is derived. As a concrete example, the n-dimensional Goodwin oscillator is considered where p, the Hill coefficient of the feedback metabolite, is equal to three and four. It is shown that for p = 3 or 4 and n less than or equal to 4 the approximation indicates that it is impossible to construct a set of physically permissible reaction constants such that the system possesses a periodic solution. However for n greater than or equal to 5 it is always possible to find a large domain in the reaction constant space giving stable oscillations. A means of constructing such a parameter set is given. The results obtained here are compared with previously derived results for p = 1 and p = 2.