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Brain energetics and tolerance to anoxia in deep hypothermia.

The remarkable time-resolution enhancement by deep lethargic hypothermia (15 degrees C rectal temperature, "cold narcosis," "anesthesia by internal cold") of metabolic events in the rat brain after oxygen deprivation has been exploited to monitor metabolic changes by in vivo (31)P-NMR. A correlation was established between the bioenergetic status of the brain and physiological descriptors of tolerance (survival and revival times) determined in parallel experiments with large series of animals. Spectral peak integrals were transformed into absolute concentrations by comparison to biochemically determined time series of data obtained in freeze-trapping experiments conducted under identical conditions. Serial spectra were used to reconstruct the time-course kinetics of intracellular brain pH and of concentration changes of inorganic phosphate, phosphocreatine, ATP, and ADP. Both the biochemical and NMR time series of data were simultaneously fitted by a set of exponential kinetic equations accounting for relationships imposed by the Lohmann and adenylate kinase reactions. Depletion profiles were then computed for a number of descriptors of brain energy status (energy charge, phosphorylation potential, total adenylate, and primary energy stores expressed as the sum of high-energy phosphate-bond equivalents). The results contribute to the understanding of the role of brain energetics in tolerance to oxygen deprivation.

Adenosine Diphosphate↗

Sex differences and hormonal influences on response to cold pressor pain in humans.

UNLABELLED: Although most studies show that women have higher subjective pain ratings in response to painful stimuli, there is less consistency across studies with regard to the influence of gonadal hormones on pain responsivity. The present study evaluated sex differences in response to cold pressor pain in normally menstruating women (NMW), women maintained on oral contraceptives (OCW), and men. Testing occurred during 5 phases of the menstrual cycle. All participants completed 10 sessions (2 sessions per phase). During the cold pressor test, participants immersed the forearm into water maintained at 4 degrees C, and pain threshold and tolerance were measured. Subjective ratings of pain, physiologic indices, and plasma levels of estradiol and progesterone were also assessed. Both estradiol and progesterone levels varied as a function of menstrual cycle phase in NMW and were significantly higher in NMW compared with OCW and men. There were no significant differences in pain threshold or tolerance for any of the groups as a function of menstrual cycle phase. There were no significant differences in pain tolerance between groups. However, pain threshold was higher in NMW compared with OCW and men. When the data were reanalyzed across consecutive sessions, a significant sex-by-day interaction was observed for both threshold and tolerance. Specifically, pain threshold and tolerance were similar for NMW, OCW, and men, but these latencies changed at different rates across session days. Pain threshold remained relatively constant for both OCW and men, but it increased across days for NMW. Pain tolerance remained stable across sessions in OCW, a slow consistent increase was observed for men, whereas a sharper increase, followed by an asymptote, was observed for NMW. These results suggest that circulating gonadal hormones might mediate adaptation to cold pressor pain. PERSPECTIVE: The present study supports the notion that differences in pain perception between the sexes and among menstrual cycle phases are subtle. However, normally menstruating women exhibited an increase in pain tolerance and threshold over repeated stimulation, whereas men exhibited a shallow increase in pain threshold only, suggesting a sex difference in the adaptation to painful stimuli in men and women.

Adult↗

Metallothionein-null mice exhibit reduced tolerance to ultraviolet B injury in vivo.

Events that induce expression of the metallothionein (MT) gene, such as injection of cadmium chloride, cold stress or topical application of 1,25-dihydroxyvitamin D3, can deplete the number of ultraviolet (UV) B-induced sunburn cells (SBC) in mouse skin in vivo. MT-null mouse skin explants exhibit reduced tolerance to UVB injury in vitro. However, the in vivo response of MT-null mice to UVB injury has not been investigated. In the present study, we investigated the role of the MT gene on UVB injury in vivo. MT-null mice that are deficient in MT-I and MT-II genes were studied and compared with homozygous wild-type mice. Mouse dorsal skin was irradiated with 0.05, 0.70 and 1.40 J/cm2 UVB. The thickness of the dorsal skin was measured with a spring micrometer before and 24 h after UVB irradiation. In addition, SBC were counted 24 h after UVB irradiation. No significant difference was found in the change of skin thickness between MT-null mice and control mice irradiated with low-dose UVB (0.05 J/cm2) (Student's t-test, t = 1.519, P = 0.167). At higher doses (0.70 and 1.40 J/cm2), the skin of MT-null mice became much thicker than that of control mice (Student's t-test, t = 6.576, P < 0.01 and t = 3.142, P = 0.007, respectively). More SBC were detected in MT-null mice skin irradiated with the highest dose of UVB (1.40 J/cm2) (Student's t-test, t = 4.258, P < 0.01). These results suggest that the MT gene in mice has a photoprotective role in vivo.

Animals↗

Tolerance of aversive stimuli in relation to life change.

This study investigated the relation between an individual's tendency to tolerate and/or report discomfort and the amount of life change experienced by that individual. The role of attention in this relation was also examined and manipulated through instruction. Eighty college freshman were selected and divided into three groups (high, medium, low) as a function of scores obtained on the College Schedule of Recent Experience (CSRE). Participants were asked to experience two known discomforting stimuli, the cold pressor and loud broad-band noise. Dependent measures included participant's tolerance time, report of discomfort, and amount of attention paid to each of the stimuli. Results indicated that "high"-life change groups tolerated the two discomforting stimuli significantly less than either the "low"- or the "medium"-life change groups. Neither discomfort ratings nor attention was significantly different across groups. Findings are discussed in relation to epidemiological studies of the life change and illness relation.

Adolescent↗

The hot but not the cold minimal model allows precise assessment of insulin sensitivity in NIDDM subjects.

Assessment of insulin sensitivity in subjects with non-insulin-dependent diabetes mellitus (NIDDM) is of paramount importance but intrinsically difficult. The standard (hereafter cold) minimal model, in conjunction with an insulin-modified protocol, has been recently proposed, but the estimates of insulin sensitivity showed poor precision (Saad et al. Diabetes 43: 1114-1121, 1994). We propose the tracer (hereafter hot) minimal model as a highly reliable method to estimate insulin sensitivity (SI*) and fractional glucose clearance (SG*), reflecting glucose disposal only, in NIDDM subjects. A [6,6- 2H2] glucose-labeled insulin-modified intravenous glucose tolerance test was performed in seven NIDDM subjects. In particular, SI* was 1.07 +/- 0.34 x10(-4)min(-1).microU-1.ml estimated with an average precision (mean coefficient of variation of 12%, range 4-22%), whereas the cold minimal model SI was 0.96 +/- 0.26 x 10(-4) min-1. microU-1.ml (mean coefficient of variation of 105%, range 3-353%). Another advantage of the hot indexes with respect to the cold indexes is their ability to reflect glucose and insulin effect on glucose disposal only, and not also on hepatic glucose production. Finally, we also studied by simulation the effect of glucose urinary loss on cold and hot minimal model indexes; only cold glucose effectiveness (SG) was significantly affected, resulting in a mean approximately 40% lower. The hot minimal model appears therefore more reliable than the cold model for assessing glucose tolerance in NIDDM subjects. In particular its ability to dissect disposal from production processes, coupled with the very good precision of the estimated metabolic indexes, supports the clinical use of this method in NIDDM subjects.

Blood Glucose↗

The hypoalgesic effect of tramadol in relation to CYP2D6.

Tramadol inhibits norepinephrine reuptake, stimulates serotonin release, and acts with mu-opioid receptors by way of its metabolite (+)-M1. Formation of M1 seems to depend on the genetic polymorphic CYP2D6. The analgesic effect of 2 mg/kg tramadol was evaluated in 15 extensive and 12 poor metabolizers of sparteine in two parallel, randomized, double-blind, placebo-controlled crossover studies that used experimental pain models. In extensive metabolizers, tramadol increased pressure pain detection (p = 0.03) and tolerance (p = 0.06) thresholds, as well as thresholds for eliciting nociceptive reflexes, after single (p = 0.0002) and repeated (p = 0.06) stimulation of the sural nerve. Peak pain and pain area in the cold pressor test were reduced (p = 0.0006 and 0.0009). In poor metabolizers, only thresholds to pressure pain tolerance (p = 0.02) and nociceptive reflexes after single stimulation (p = 0.04) were increased and the reflex threshold was less increased in poor metabolizers than in extensive metabolizers (p = 0.02). The serum concentration of (+)-M1 2 to 10 hours after tramadol ranged from 10 to 100 ng/L in extensive metabolizers, whereas in poor metabolizers serum concentrations of (+)-M1 were below or around the detection limit of 3 ng/ml. It is concluded that formation of (+)-M1 by way of CYP2D6 is important for the effect of tramadol on experimental pain.

Adult↗

Influence of ozone on cold acclimation in sugar maple seedlings.

During summer 1994, sugar maple (Acer saccharum Marsh.) seedlings were grown in open-top chambers supplied with air containing near ambient ozone concentration (control, low O(3)) or three times the ambient ozone concentration (high O(3)). The rate of CO(2) assimilation was significantly reduced by chronic exposure to a high concentration of ozone during the summer. During fall, seedlings were removed from the open-top chambers and acclimated to cold under natural conditions. In both species during cold acclimation, the starch concentration decreased, whereas the sucrose concentration increased. There was no treatment effect on the freezing tolerance of roots, even though roots in the high-O(3) treatment accumulated higher concentrations of the cryoprotective oligosaccharides raffinose and stachyose than control roots. Cold acclimation occurred earlier and stachyose concentration of stems was higher in high-O(3)-treated seedlings than in low-O(3)-treated seedlings. Cold acclimation was associated with an earlier accumulation of ABA in the xylem sap of high-O(3)-treated seedlings compared with low-O(3)-treated seedlings.

Journal Article↗

Absence of dermal ridge patterns: genetic heterogeneity.

An apparently new form of complete absence of dermal ridge patterns was transmitted as an autosomal dominant trait through five generations in an Irish-American family. Affected individuals lacked dermatoglyphic patterns, sweat pores, and ability to sweat in the volar areas of the fingertips, palms, and soles. They also had congenital milia and blisters on the fingertips and soles at birth, abnormal nails, single transverse palmar creases, increased heat tolerance, and painful fissures in adult life around the fingernails in cold weather.

Dermatoglyphics↗

The moderating effect of anxiety sensitivity on caffeine-induced hypoalgesia in healthy women.

RATIONALE: Caffeine is an analgesic adjuvant, but also has panicogenic properties. Anxiety sensitivity is a trait vulnerability factor related to negative responses to pain, and is known to moderate negative psychological responses to caffeine. OBJECTIVES: The current study sought to investigate whether anxiety sensitivity moderates the effect caffeine has on the pain responses of healthy women. METHODS: Caffeine (250 mg) was administered to women pre-selected as high, medium or low in anxiety sensitivity. Measures of arousal and mood were taken before and after drug administration. The cold pressor pain task was used to induce pain. Pain threshold, tolerance, sensory and affective pain responses were also recorded. RESULTS: Caffeine increased systolic blood pressure and mood. Additionally, those low in anxiety sensitivity exhibited caffeine-induced improvement in negative mood (less depressed) and caffeine-related hypoalgesia. CONCLUSIONS: These results suggest that the analgesic effects of caffeine may depend on anxiety sensitivity status, and that the fear of bodily sensations should be considered in pain management programmes.

Adolescent↗

Right-left asymmetry in tonic pain perception and its modification by simultaneous contralateral noxious stimulation.

Administration of the cold pressor test (I test) in normal healthy subjects revealed lateralization of pain perception with the right hand showing higher threshold and tolerance, as well as lower pain scores on Graphic Rating Scale, PPI and MPQ. To find out whether this lateralization persists, the cold pressor test was given while the contralateral hand was simultaneously exposed to non-noxious stimulus (II test) or noxious stimulus (III test). Reversal of laterality to the left hand was observed in the III test in 40% of the subjects for pain threshold. The mechanism of diffuse noxious controls and attentional focus to the noxious stimulus that is more intense, are suggested for the observed changes in laterality when two concurrent noxious stimuli are present.

Adolescent↗

Prospective comparison of continuous femoral nerve block with nonstimulating catheter placement versus stimulating catheter-guided perineural placement in volunteers.

BACKGROUND AND OBJECTIVES: Stimulating catheter-guided perineural placement may potentially increase the success rate and quality of continuous femoral nerve block as compared with a nonstimulating catheter technique. These hypotheses have not been rigorously tested. METHODS: Twenty volunteers underwent placement of bilateral femoral nerve catheters in this prospective, randomized, double-blind study. For each side, a stimulating needle was advanced until quadriceps contractions were obtained at < or =0.5 mA. On one side, a stimulating catheter was advanced 4 to 5 cm beyond the needle tip while eliciting quadriceps contractions via the catheter. If quadriceps contractions decreased or disappeared, the catheter position was adjusted until quadriceps contractions could be elicited at < or =0.5 mA. On the contralateral side, an identical catheter was advanced 4 to 5 cm beyond the needle tip without attempts to elicit quadriceps contractions via the catheter. After bolus injection of 10 mL lidocaine 1%, ropivacaine 0.2% at 10 mL/h was continuously infused through both catheters for 4 hours. Success of femoral block was defined as loss of sensation to cold and pinprick stimuli. Quality of successful block was determined by tolerance to transcutaneous electrical stimulation and force dynamometry of quadriceps strength. RESULTS: Block success was 100% via the stimulating catheters versus 85% via the nonstimulating catheters (P =.07). Overall tolerance to transcutaneous electrical stimulation (P =.009) and overall depth of motor block (P =.03) was significantly higher in the stimulating catheter-guided femoral nerve blocks. CONCLUSIONS: In this volunteer study, there was no statistically significant difference in block success between the two techniques. However, stimulating catheter-guided placement provided an increased overall quality of continuous femoral perineural blockade. Further studies are needed to verify these observations in the clinical setting.

Adolescent↗

Molecular responses to drought and cold stress.

A variety of plant genes are induced by drought and cold stress, and they are thought to be involved in the stress tolerance of the plant. At least five signal transduction pathways control these genes: two are dependent on abscisic acid (ABA), and the others are ABA-independent. A novel cis-acting element involved in one of the ABA-independent signal transduction pathways has been identified. In addition, a number of genes for protein kinases and transcription factors thought to be involved in the stress signal transduction cascades have been shown to be induced by environmental stresses.

Abscisic Acid↗

Fructans in crested wheatgrass leaves.

Crested wheatgrass is an important cool-season grass that has become naturalized in many semiarid regions of the western U.S. It provides ground cover and reduces soil erosion caused by water and wind. Additionally, crested wheatgrass produces important forage for livestock and wildlife on 6 to 8 million hectars of western rangeland. It is well adapted to semiarid cold desert regions because of its cool temperature growth and drought tolerance. Understanding the biosynthesis of fructans in crested wheatgrass is important because of their likely role in both cool temperature growth and drought tolerance. Recent research described a major gene (6-SFT) in crested wheatgrass that is involved in fructan biosynthesis. 1-kestotriose, the major DP3 fructan in crested wheatgrass, serves as the substrate for the two major DP4 fructans, 1&6-kestotetraose and 1,1-kestotetraose. The three major DP5 fructans are 1&6,1-kestopentaose, 1,1&6-kestopentaose and 1,1,1-kestopentaose. The major DP6 fructan is 1&6, 1&6-kestohexaose. We postulate that 1&6,1&6-kestohexaose is synthesized from the addition of a fructose to 1&6, 1-kestopentaose. This paper provides structures of the various DP 3, 4, 5 and 6 fructan types produced by crested wheatgrass and provides suggested biosynthetic pathways for all major fructan linkage types present.

Agropyron↗

Regulation of the cardiorespiratory system of common carp (Cyprinus carpio) during severe hypoxia at three seasonal acclimation temperatures.

Little is known of the cardiorespiratory control mechanisms utilized by hypoxia-tolerant teleost fish to tolerate prolonged periods (h) of near anoxic exposure. Here, we report on the cardiorespiratory control mechanisms of the common carp Cyprinus carpio L. during normoxia and prolonged, severe hypoxic (<0.3 mg O(2) L(-1)) exposure at acclimation temperatures of 5 degrees C, 10 degrees C, and 15 degrees C. Through serial intra-arterial injections of alpha - and beta -adrenergic, cholinergic, and purinergic antagonists while measuring cardiac output (Q), heart rate (f(H)), ventral aortic blood pressure, and respiration rate, we established that autonomic cardiovascular and respiratory control was preserved during severe hypoxia at all three acclimation temperatures and contributed to downregulation of cardiorespiratory activity. Specifically, inhibitory cholinergic tone mediated up to 76% reductions in f(H) and Q during hypoxia, whereas the accompanying arterial hypotension was attenuated by an upregulation of an alpha -adrenergically mediated peripheral vasoconstriction. Despite the overall cardiac downregulation, a large, stimulatory cardiac beta -adrenergic tone was present during prolonged, severe hypoxia, possibly to protect the heart from attendant acidotic conditions. Purinergic blockade, following alpha -adrenergic and cholinergic antagonists, showed that the hypoxic ventilatory depression, which reversed the 2.3- to 7.7-fold increases in respiration rate that occurred with the onset of hypoxia, was a result of purinergic inhibition at all three acclimation temperatures. In contrast, purinergic inhibition of cardiac activity during hypoxia might be important only at 5 degrees C. Finally, given that cardiac power output was reduced 72%-87% during prolonged, severe hypoxia and that glycolysis yields approximately 94% less ATP per mole glucose than oxidative phosphorylation, it seems unlikely that the common carp sufficiently reduces its cardiac energy demand to a level to preclude activation of a partial Pasteur effect. This means that glycogen stores will be used and waste products will accumulate at faster rates, a finding that may help explain why the common carp cannot tolerate such extended periods of severe hypoxia (weeks to months) at cold acclimation temperatures as the freshwater turtle, which is able to reduce its cardiac energy demand to a level that does not require a Pasteur effect and also blunts autonomic cardiovascular control.

Acclimatization↗

Comparison of the analgesic potency of xenon and nitrous oxide in humans evaluated by experimental pain.

We have compared the analgesic potency of MAC-equivalent concentrations of xenon (10, 20, 30 and 40%) and nitrous oxide (15, 30, 45 and 60%) in humans using a multimodal experimental pain testing and assessment technique. We tested 12 healthy volunteers in a randomized, single-blind, crossover study. The following experimental pain tests were used: nociceptive reflex to repeated stimuli; pain tolerance to maximal effort tourniquet ischaemia; electrical stimulation; mechanical pressure; and cold. Reaction time was also measured. Xenon and nitrous oxide produced analgesia to ischaemic, electrical and mechanical stimulation, but not to cold pain. There was no difference in MAC-equivalent concentrations of xenon and nitrous oxide. Both increased reaction time in a similar manner. Xenon and nitrous oxide evoked nausea and vomiting in a large number of volunteers.

Adult↗