Glycemic control in the ICU.

Glycemic control clearly improves outcome in critically ill patients. Remaining questions are how tight the control must be to obtain the most benefit without increasing the risk for severe hypoglycemia, and whether an acuity level exists in which this benefit is not clearly visualized. In other words, is this benefit only seen in severely ill patients? The authors believe that clinical trials with ICU lengths of stay of 3 days or less make showing a clinical benefit difficult. Rather, they believe that clinical benefit is seen in higher acuity patients whose ICU length of stay is directly related to the reversal of the inflammatory systemic response rather than the disease or injury alone. Finally, the issue remains of how to obtain a TGC in the 80 to 110 mg/dL range without achieving a less-than-acceptable incidence of hypoglycemia. The answer may well lie with the introduction of continuous glucose monitors that will allow measurements to be obtained every 15 to 30 minutes without introducing an increased workload to the nursing staff. Many of these devices, such as the Optiscanner, which measures plasma glucose continuously, are on the horizon and should be approved by the FDA in 2008.

[Comparison of the effects of sevoflurane and propofol on changes in leukocyte-count induced by surgical stress].

BACKGROUND: It is well known that surgical stress causes granulocytosis and lymphopenia. However, effects of general anesthetics on changes in leukocyte-count induced by surgical stress are not still clear. METHODS: One hundred and sixteen patients undergoing elective surgery with general anesthesia were enrolled in this retrospective study. Patients were classified into two groups according to anesthetic agents used for maintenance of general anesthesia; sevoflurane group (n = 69) and propofol group (n = 47). Changes in leukocyte-count during surgery were compared between the two groups. RESULTS: In sevoflurane group, lymphocyte-count increased in the early period during surgery, but decreased later. However, lymphocyte-count continued to increase during surgery in propofol group. We found a significant difference in lymphocyte-count during surgery between sevoflurane group and propofol group. On the contrary, granulocyte- and monocyte-count increased during surgery in both groups. There were no significant differences in granulocyte- and monocyte-count during surgery between the two groups. CONCLUSIONS: There were significant differences in effects of sevoflurane and propofol on changes in lymphocyte-count induced by surgical stress. Results of this study imply the efficiency of propofol to prevent lymphopenia, which may play an important role in postoperative immunosuppression caused by surgical stress.

Intracerebroventricularly administered oxytocin attenuated cortisol secretion, but not behavioral responses, during isolation in Holstein steers.

In rodents, intracerebroventricular oxytocin administration attenuated hypothalamo-pituitary-adrenal (HPA) responses and anxiety behavior during stress. We examined the effects of intracerebroventricular injection of oxytocin on isolation-induced stress responses in cattle. In a methodological test, we determined the dosage of oxytocin applied in a main test which did not induce an increase in plasma cortisol concentration or stereotyped behaviors. In a main test, 5 steers aged from 199 to 250 days were assigned to the following three treatments randomly: T1, no isolation after injection of 200 microl of artificial cerebrospinal fluid (aCSF); T2, isolation after aCSF injection; and T3, isolation after 0.5 microg of oxytocin in 200 microl aCSF injection. The isolation was conducted by leaving the experimental steer alone in its stall for one hour while its peers were taken outside. In T2, the isolation induced a rapid increase in plasma cortisol concentration. The maximum %-changes from the pre-isolation value were significantly attenuated by oxytocin injection (T2 vs. T3, p<0.05). The isolation also induced an increase in the frequency (number of occurrences/1 hr isolation) of vocalizations and body orientation changes, and a decrease in the percentage of time spent lying and ruminating. The effect of oxytocin on these behavioral responses to isolation was not apparent. These results indicate that intracerebroventricularly injected oxytocin at low dose attenuated the cortisol response to isolation in steers while the effect on behavior was very small in this experimental condition.

Interspecific associations between circulating antioxidant levels and life-history variation in birds.

Antioxidants play an important role in protecting tissues against aging-associated oxidative damage and are thus prime candidates for relating physiological mechanisms to variation in life histories. We measured total antioxidant capacity, antioxidant response to stress, and levels of uric acid, vitamin E, and four carotenoids in 95 avian species, mostly passerines from Michigan or Panama. We compared antioxidant measures to seven variables related to life histories (clutch size, survival rate, incubation period, nestling period, basal metabolic rate, body mass, and whether the species lived in a tropical or temperate climate). Life-history-related traits varied over at least three statistically independent axes. Higher antioxidant levels were generally characteristic of more rapid development, lower survival rate, smaller body size, larger clutch size, and higher mass-adjusted metabolic rate, but the relationships of particular antioxidants with individual life-history traits showed considerable complexity. Antioxidant-life history associations differed between tropical and temperate species and varied with respect to taxonomic sampling. Vitamin E showed few relationships with life-history traits. Overall, our results partly support the hypothesis that antioxidant levels evolve to mirror free radical production. Clearly, however, the complex patterns of physiological diversification observed here result from the interplay of many factors, likely including not just investment in somatic maintenance but also phylogenetic constraint, diet, and other aspects of ecology.

Cortisol response to acute stress in jundiá Rhamdia quelen acutely exposed to sub-lethal concentrations of agrichemicals.

Exposure to agrichemicals can have deleterious effects on fish, such as disruption of the hypothalamus-pituitary-inter-renal axis (HPI) that could impair the ability of fish to respond to stressors. In this study, fingerlings of the teleost jundiá (Rhamdia quelen) were used to investigate the effects of the commonly used agrichemicals on the fish response to stress. Five common agrichemicals were tested: the fungicide - tebuconazole, the insecticide - methyl-parathion, and the herbicides - atrazine, atrazine+simazine, and glyphosate. Control fishes were not exposed to agrichemicals and standard stressors. In treatments 2-4, the fishes were exposed to sub-lethal concentrations (16.6%, 33.3%, and 50% of the LC(50)) of each agrichemical for 96 h, and at the end of this period, were subjected to an acute stress-handling stimulus by chasing them with a pen net. In treatments 5-7 (16.6%, 33.3%, and 50% of the LC(50)), the fishes were exposed to the same concentrations of the agrichemicals without stress stimulus. Treatment 8 consisted of jundiás not exposed to agrichemicals, but was subjected to an acute stress-handling stimulus. Jundiás exposed to methyl-parathion, atrazine+simazine, and glyphosate presented a decreased capacity in exhibiting an adequate response to cope with stress and in maintaining the homeostasis, with cortisol level lower than that in the control fish (P<0.01). In conclusion, the results of this study clearly demonstrate that the acute exposure to sub-lethal concentrations of methyl-parathion, atrazine+simazine, and glyphosate exert a deleterious effect on the cortisol response to an additional acute stressor in the jundiá fingerlings.

Acute mild footshock alters ethanol drinking and plasma corticosterone levels in C57BL/6J male mice, but not DBA/2J or A/J male mice.

Stress is an often-reported cause for alcohol consumption in humans. Acute intermittent footshock is a frequently used paradigm to produce stress in laboratory animals including mice. The effect produced by intermittent footshock stress on ethanol self-administration has been inconsistent: both increases and decreases in ethanol consumption have been reported. The current set of studies further investigates, in three commonly studied mouse strains, the effect of footshock stress on ethanol self-administration. Furthermore, the effect of footshock on plasma corticosterone levels was determined to investigate potential biochemical correlates. Adult male C57BL/6J, DBA/2J, and A/J mice were allowed to self-administer 10% (wt/vol) ethanol for 12 days in a standard 23-h two-bottle paradigm before receiving either 15 min of mild inescapable footshock or no footshock. Shock intensity was equal to the mean intensity at which each strain vocalized as previously determined. Following footshock, animals had the opportunity to self-administer ethanol for an additional 23 h. Separate animals were subjected to either footshock or no shock prior to collection of plasma for corticosterone. Mild footshock stress altered ethanol self-administration and increased plasma corticosterone levels in C57BL/6J mice. Footshock stress did not alter ethanol self-administration or plasma corticosterone levels in DBA/2J or A/J mice. These data demonstrate that mild footshock stress is a suboptimal method of modeling the stress-induced increases in ethanol consumption often reported by humans.

Physiological responses of over-wintering common carp (Cyprinus carpio) to disturbance by Eurasian otter (Lutra lutra).

Using a tame animal, the impact of otter (Lutra lutra) disturbance on over-wintering carp (Cyprinus carpio) was monitored in two experiments, 133 and 140 days, respectively, over two consecutive winters (November-April). The level of stress in over-wintering carp exposed to various intensities of disturbance by otters was quantified using biological indicators of stress (cortisol, cortisone, indices of nitrogen, carbohydrate, lipid and mineral metabolism and activity of basic blood plasma enzymes) taken from blood plasma of stocked carp at the end of the winter seasons (when the photoperiod was 12 light:12 dark, respectively, 13L:10D). Moreover, condition (Fulton's coefficient of condition and fat content in muscles) and mortality rate of that carp were measured after over-wintering and also after the subsequent vegetation period. The analysis of blood and tissue samples of experimental fish showed changes in nitrogen, carbohydrate and mineral metabolism as well as levels of hormones and fat reserves. Higher response to stress in metabolism of carp with lower intensity of disturbance by otter suggests that high level of disturbance can lead to metabolic adaptation of carp to stress. The effect of stress on the mortality rate of carp during the over-wintering is not clear. Nevertheless, the negative effect of stress on survival, condition and growth rate of carp in the subsequent vegetation period was not observed.

Serum lipids and glucose disturbances at professional drivers exposed to occupational stressors.

The aim of this study is to find association between some groups of occupational stressors and serum lipids and glucose concentrations in professional drivers in road traffic. The study included 417 male professional drivers (162 inter city bus drivers, 36 suburban bus drivers, 33 city bus drivers, 81 truck drivers, 71 official car drivers and 34 professional taxi drivers). Occupational stressors were identified and total occupational stress index score was measured by standardized questionnaire authorized by Karen Belkic. Occupational stressors were divided into seven groups (underload, high demand, strictness, extrinsic time pressure, noxious exposures, avoidance and conflict). Serum glucose and lipids concentrations (total cholesterol, LDL cholesterol, HDL cholesterol and triacylglycerols) were measured in study group of drivers. Maximal total OSI values were achieved in group of professional truck drivers. The highest values of serum glucose, total cholesterol, LDL cholesterol and triacylglycerols and the lowest values of serum HDL cholesterol were found at professional truck drivers. With the increase of occupational stress index, there is an increase of the serum glucose, total cholesterol, LDL cholesterol and triacylglycerols concentration in the exposed group of drivers. Specific analytes thresholds' level of occupational stress index exists.

Behavioral plasticity in rainbow trout (Oncorhynchus mykiss) with divergent coping styles: when doves become hawks.

Consistent and heritable individual differences in reaction to challenges, often referred to as stress coping styles, have been extensively documented in vertebrates. In fish, selection for divergent post-stress plasma cortisol levels in rainbow trout (Oncorhynchus mykiss) has yielded a low (LR) and a high responsive (HR) strain. A suite of behavioural traits is associated with this physiological difference, with LR (proactive) fish feeding more rapidly after transfer to a new environment and being socially dominant over HR (reactive) fish. Following transport from the UK to Norway, a switch in behavioural profile occurred in trout from the 3rd generation; HR fish regained feeding sooner than LR fish in a novel environment and became dominant in size-matched HR-LR pairs. One year after transport, HR fish still fed sooner, but no difference in social dominance was found. Among offspring of transported fish, no differences in feeding were observed, but as in pre-transported 3rd generation fish, HR fish lost fights for social dominance against size-matched LR opponents. Transported fish and their offspring retained their distinctive physiological profile throughout the study; HR fish showed consistently higher post-stress cortisol levels at all sampling points. Altered risk-taking and social dominance immediately after transport may be explained by the fact that HR fish lost more body mass during transport than did LR fish. These data demonstrate that some behavioural components of stress coping styles can be modified by experience, whereas behavioural plasticity is limited by genetic effects determining social position early in life story.

Seasonal changes in adrenocortical responses to acute stress in Eurasian tree sparrow (Passer montanus) on the Tibetan Plateau: comparison with house sparrow (P. domesticus) in North America and with the migratory P. domesticus in Qinghai Province.

Seasonal modulation of the adrenocortical response to stress appears to be ubiquitous in arctic-breeding and temperate-zone-breeding birds, but has not been well investigated in alpine-breeding species at mid-latitude. We examined the adrenocortical response to acute stress (capture, handling and restraint) in populations of Eurasian tree sparrow (Passer montanus) among seasons and migratory house sparrow (P. domesticus bactrianus) in pre-breeding on the Qinghai-Xizang Plateau (the Tibetan Plateau). A population of house sparrow (Passer domesticus domesticus) was also sampled in lowland Phoenix, Arizona during breeding and wintering stages. In Eurasian tree sparrows, baseline corticosterone (CORT) does not differ among life history stages, but stress-induced CORT level (maximal CORT, total and corrected integrated CORT) is significantly higher in late breeding stage than those in early breeding and prebasic molt stages. In house sparrows, stress-induced CORT level does not differ between sites and life history stages, but baseline CORT is significantly lower in pre-breeding from Qinghai compared with those in breeding and wintering stages from Phoenix. Interestingly, both baseline CORT and maximal CORT do not differ between the populations of Eurasian tree sparrow and house sparrow in early/pre-breeding stage although tree sparrow is resident species whereas house sparrow is migratory in Qinghai. Our results suggest that the extreme environment of the Tibetan Plateau does not have significant effects on adrenocortical responses to acute stress in Eurasian tree sparrows and house sparrows, which may be a result of masking by human activities. These invasive human commensals may have a unique HPA axis response to different environments because they can take advantage of human food sources and shelter (i.e. buildings).

Plasma concentrations of substance P and cortisol in beef calves after castration or simulated castration.

OBJECTIVE: To evaluate plasma concentrations of substance P (SP) and cortisol in calves after castration or simulated castration. ANIMALS: 10 Angus-crossbred calves. PROCEDURES: Calves were acclimated for 5 days, assigned to a block on the basis of scrotal circumference, and randomly assigned to a castrated or simulated-castrated (control) group. Blood samples were collected twice before, at the time of (0 hours), and at several times points after castration or simulated castration. Vocalization and attitude scores were determined at time of castration or simulated castration. Plasma concentrations of SP and cortisol were determined by use of competitive and chemiluminescent enzyme immunoassays, respectively. Data were analyzed by use of repeated-measures analysis with a mixed model. RESULTS: Mean +/- SEM cortisol concentration in castrated calves (78.88+/-10.07 nmol/L) was similar to that in uncastrated control calves (73.01+/-10.07 nmol/L). However, mean SP concentration in castrated calves (506.43+/-38.11 pg/mL) was significantly higher than the concentration in control calves (386.42+/-40.09 pg/mL). Mean cortisol concentration in calves with vocalization scores of 0 was not significantly different from the concentration in calves with vocalization scores of 3. However, calves with vocalization scores of 3 had significantly higher SP concentrations, compared with SP concentrations for calves with vocalization scores of 0. CONCLUSIONS AND CLINICAL RELEVANCE: Similar cortisol concentrations were measured in castrated and control calves. A significant increase in plasma concentrations of SP after castration suggested a likely association with nociception. These results may affect assessment of animal well-being in livestock production systems.

Stress, metabolism, and antioxidants in two wild passerine bird species.

Antioxidants protect against free-radical damage, and free radicals, in turn, are thought to underlie aging. Thus, measuring antioxidants may aid field ecologists in understanding the physiological mechanisms that underlie life-history trade-offs. Antioxidant levels are known to vary markedly in response to the stress of capture in many birds. These changes in antioxidants could result from regulation (e.g., by stress-related hormones) or consumption (e.g., by an increase in free radicals due to increased metabolic rate). Here we experimentally test the effect of increased metabolic rate on circulating antioxidant and corticosterone concentrations in two wild passerine bird species, house sparrows (Passer domesticus) and gray catbirds (Dumetella carolinensis). We increased metabolic rate via exposure to low ambient temperatures overnight in captivity and measured circulating antioxidant capacity, uric acid, corticosterone, and oxygen consumption in cold-exposed and control individuals. Both species showed increases rather than decreases in all antioxidant parameters overnight, contradicting a consumption-by-energy-expenditure hypothesis. Both positive and negative correlations between antioxidant response and corticosterone response were occasionally but not consistently present, refuting a generalized regulation-by-corticosterone hypothesis. High baseline uric acid predicted diminished response of corticosterone and all antioxidants. Thus, high uric acid may reflect recent stress, poor condition, or a compensatory response. Relationships among metabolic rate, antioxidants, and corticosterone differed qualitatively between the species.

The efficacy of orally dosed ketamine and ketamine/medetomidine compared with intramuscular ketamine in rhesus macaques (Macaca mulatta) and the effects of dosing route on haematological stress markers.

BACKGROUND: This study compared the efficacy of two orally-dosed (PO) anaesthetic regimens for chemical immobilization in rhesus macaques (Macaca mulatta), versus the standard protocol of intramuscular (TM) ketamine. In addition, the effects of dosing route on haematological stress markers were evaluated. METHODS: Testing was conducted on 18 chronically housed animals. Animals were trained to accept oral dosing and then randomly assigned to one of three drug regimens: (1) ketamine IM, (2) ketamine PO, (3) Ketamine/medetomidine PO. Sedation levels for each regimen were evaluated. RESULTS: Oral dosing alone was not sufficient to achieve a plane of sedation that allowed for safe handling. Serum cortisol and glucose levels were unchanged across groups, although differences were observed in the leukogram profiles. CONCLUSION: The oral dosages used in this study fell short in providing adequate sedation for safe handling for routine veterinary procedures. Leukogram profiles indicated that orally dosed animals experienced a higher level of stress.

Stress alters the cellular and proteomic compartments of bovine bronchoalveolar lavage fluid.

The stresses of transportation, weaning and commingling are associated with an increased incidence of bacterial and viral pneumonia in cattle. Proteins expressed in the epithelial lining fluid (ELF) of the lungs, in conjunction with resident leukocytes, represent the first line of defence against opportunistic pathogens, and stress-induced alterations in their expression may reveal markers of disease susceptibility. Bronchoalveolar lavage fluid was sampled in weaned and transported calves and ELF protein expression was compared to a control group of calves using two-dimensional electrophoresis (2DE). Serum and pulmonary haptoglobin were increased following stress concurrent with the number of blood neutrophils. Using 2DE, significant changes in expression were observed in spots identified by mass spectrometry as annexin A1 and A5, odorant-binding protein (OBP), isocitrate dehydrogenase, fibrinogen, heme-binding protein, alpha-2-HS-glycoprotein, alpha-1-antichymotrypsin and albumin. Quantification of OBP mRNA by real-time RT-PCR and OBP protein by western blot revealed gender-dependent differences in relative OBP expression in response to stress. These findings reveal stress-associated protein changes in pulmonary ELF and suggest a mechanism through which stress alters respiratory disease susceptibility.

Characterization of stress-induced suppression of long-term potentiation in the hippocampal CA1 field of freely moving rats.

Several lines of evidence have shown that exposure to stress impairs long-term potentiation (LTP) in the CA1 field of the hippocampus, but the detailed mechanisms for this effect remain to be clarified. The present study elucidated the synaptic mechanism of stress-induced LTP suppression in conscious, freely moving rats using electrophysiological approaches. Open field stress (i.e., novel environment stress) and elevated platform stress (i.e., uncontrollable stress) were employed. Basal synaptic transmission was significantly reduced during exposure to elevated platform stress but not during exposure to open field stress. LTP induction was blocked by elevated platform stress but not influenced by open field stress. Significant increases in serum corticosterone levels were observed in the elevated platform stress group compared with the open field stress group. Furthermore, LTP suppression induced by elevated platform stress was prevented by pretreatment with an anxiolytic drug diazepam (1 mg/kg, i.p.). These results suggest that stress-induced LTP suppression depends on the relative intensity of the stressor. The inhibitory synaptic response induced by an intense psychological stress, such as elevated platform stress, may be attributable to LTP impairment in the CA1 field of the hippocampus.

Non-precocial grey-faced petrel chicks (Pterodroma macroptera gouldi) show no age-related variation in corticosterone responses to capture and handling.

Development patterns in birds range from precocial species, which hatch chicks largely capable of independent existence, to altricial species, chicks of which are highly dependent on their parents for extended periods. Previous work indicates precocial chicks have a robust corticosterone response from hatching whereas non-precocial and altricial chicks have a small response that increases through development. Grey-faced petrels are characteristic of most burrowing procellariiform seabirds with non-precocial chicks that are unable to locomote and are dependent on adults for food, although chicks have well developed downy plumage and can thermoregulate at or soon after hatching. Initial plasma corticosterone concentrations and corticosterone responses to handling were measured during development in semi-precocial grey-faced petrel (Pterodroma macroptera gouldi) chicks to determine whether they showed a precocial or altricial corticosterone response pattern. Chicks were sampled at six intervals through development from shortly after hatching until close to fledging. Mean corticosterone responses to handling after 30 min were high (115.9+/-10.7 ng/ml) from 2 to 4d after hatching and remained high throughout development (70-110 ng/ml). Contrary to expectations for non-precocial chicks, this pattern of corticosterone responses to handling indicates that grey-faced petrel chicks are able to perceive and respond to potential stressors from hatching, a response previously only demonstrated for precocial birds.

Effect of single or combined climatic and hygienic stress in four layer lines: 2. Endocrine and oxidative stress responses.

Effects of long-term climatic stress (heat exposure), short-term hygienic stress [lipopolysaccharide (LPS)], or combined exposure to these stressors on endocrine and oxidative stress parameters of 4 layer lines (B1, WA, WB, and WF) were investigated. The lines were earlier characterized for natural humoral immune competence and survival rate. Eighty hens per line were randomly divided over 2 identical climate chambers and exposed to constant high temperature (32 degrees C) or a control temperature (21 degrees C) for 23 d. Half of the hens housed in each chamber were i.v. injected with LPS at d 1 after the start of the heat stress period. The effect of heat, LPS, or combined exposure on plasma levels of corticosterone, 3,5,3'-triiodothyronine (T(3)), glucose, uric acid (UA), and TBA reacting substances (TBARS) were investigated. Except for UA, there were no interactions between heat stress and LPS administration. Heat stress enhanced levels of corticosterone, glucose, and TBARS, whereas levels of T(3) and UA were decreased. The T(3) levels, however, were enhanced by LPS administration, whereas levels of UA were decreased. Administration of LPS had no effect on levels of corticosterone and TBARS. Because both stressors caused a reduction in feed intake, it is assumed that changes in most of the plasma levels of the endocrine and oxidative stress parameters are related with the reduction in feed intake. Neither natural humoral immune competence nor survival rate, for which the lines have been characterized, was indicative for the endocrine and oxidative stress responses to different stressors. The present data suggest that hens were able to cope with single or combined heat stress and LPS administration and that heat stress and LPS administration acted like 2 independent stressors. Furthermore, the 4 layer lines differed in response patterns and response levels; line WB was physiologically most sensitive to environmental changes.

Advantages of a selective beta-isoform phosphoinositide 3-kinase antagonist, an anti-thrombotic agent devoid of other cardiovascular actions in the rat.

Phosphoinositide 3-kinase (PI3K) beta has been shown to play a critical role in shear-induced arterial thrombosis. The anti-thrombotic effects of a beta isoform selective PI3K inhibitor, TGX221, were compared to the effects of non-selective PI3K inhibitors (LY294002 and wortmannin) and a PI3K delta inhibitor (IC87114) in the rat. TGX221 (2.5 mg/kg i.v.) abolished cyclic flow reductions in a Folts-like carotid artery stenosis preparation of thrombosis while not changing bleeding time, heart rate, blood pressure or carotid vascular conductance. In contrast, the PI3K non-selective isoform inhibitor, wortmannin (5 mg/kg i.v.) was as effective in abolishing cyclic flow reductions, but caused marked hypotension and carotid vasodilatation. In isolated mesenteric arteries, wortmannin was the most potent relaxant of K+-precontracted vessels (pEC(50)=6.6), while LY294002 and TGX221 were 40-60 fold less potent and IC87114 was without effect. These findings suggest that of the subclass of PI3K isoforms, the beta isoform is critical for the selective development of arterial thrombosis in vivo. The multiple actions of wortmannin are consistent with inhibition of the PI3K-C2alpha and beta isoforms and possibly other actions. Thus, a selective inhibitor of the beta isoform of PI3K offers advantages as a potential therapeutic target for the treatment of thrombosis without unwanted extension of bleeding time or adverse cardiovascular sequelae.