Transient Temperature Increase Research Articles

Acute experimental endotoxemia induces visceral hypersensitivity and altered pain evaluation in healthy humans

Growing evidence suggests that systemic immune activation plays a role in the pathophysiology of pain in functional bowel disorders. By implementing a randomized crossover study with an injection of endotoxin or saline, we aimed to test the hypothesis that endotoxin-induced systemic inflammation increases visceral pain sensitivity in humans. Eleven healthy men (mean±standard error of the mean age 26.6±1.1 years) received an intravenous injection of either lipopolysaccharide (LPS; 0.4ng/kg) or saline on 2 otherwise identical study days. Blood samples were collected 15min before and 1, 2, 3, 4, and 6h after injection to characterize changes in immune parameters including proinflammatory cytokines. Rectal sensory and pain thresholds and subjective pain ratings were assessed with barostat rectal distensions 2h after injection. LPS administration induced an acute inflammatory response indicated by transient increases in tumor necrosis factor alpha, interleukin 6, and body temperature (all P<.001). The LPS-induced immune activation increased sensitivity to rectal distensions as reflected by significantly decreased visceral sensory and pain thresholds (both P<.05) compared to saline control. Visceral stimuli were rated as more unpleasant (P<.05) and inducing increased urge to defecate (P<.01). Pain thresholds correlated with interleukin 6 at +1h (r=0.60, P<.05) and +3h (r=0.67, P<.05) within the LPS condition. This report is novel in that it demonstrates that a transient systemic immune activation results in decreased visceral sensory and pain thresholds and altered subjective pain ratings. Our results support the relevance of inflammatory processes in the pathophysiology of visceral hyperalgesia and underscore the need for studies to further elucidate immune-to-brain communication pathways in gastrointestinal disorders.

Transient Receptor Potential Melastatin 8 (TRPM8) Channels are Involved in Body Temperature Regulation

BackgroundTransient receptor potential cation channel subfamily M member 8 (TRPM8) is activated by cold temperature in vitro and has been demonstrated to act as a ‘cold temperature sensor’ in vivo. Although it is known that agonists of this ‘cold temperature sensor’, such as menthol and icilin, cause a transient increase in body temperature (Tb), it is not known if TRPM8 plays a role in Tb regulation. Since TRPM8 has been considered as a potential target for chronic pain therapeutics, we have investigated the role of TRPM8 in Tb regulation.ResultsWe characterized five chemically distinct compounds (AMG0635, AMG2850, AMG8788, AMG9678, and Compound 496) as potent and selective antagonists of TRPM8 and tested their effects on Tb in rats and mice implanted with radiotelemetry probes. All five antagonists used in the study caused a transient decrease in Tb (maximum decrease of 0.98°C). Since thermoregulation is a homeostatic process that maintains Tb about 37°C, we further evaluated whether repeated administration of an antagonist attenuated the decrease in Tb. Indeed, repeated daily administration of AMG9678 for four consecutive days showed a reduction in the magnitude of the Tb decrease Day 2 onwards.ConclusionsThe data reported here demonstrate that TRPM8 channels play a role in Tb regulation. Further, a reduction of magnitude in Tb decrease after repeated dosing of an antagonist suggests that TRPM8’s role in Tb maintenance may not pose an issue for developing TRPM8 antagonists as therapeutics.

Extreme Thermal Transient Stress Analysis with Pre-Stress in a Metal Matrix Composite Power Package

This paper culminates several years of development of a SiC MOSFET-based solid-state circuit breaker power module designed and fabricated for aluminum-based composite metal-ceramic packaging. The aluminum composite structure was used for high temperature thermal management &amp;gt;350°C and high reliability. Testing of the final module surpassed 750 total cycles. The module was optimized for four dies, 4.1mm × 4.1 mm each for SiC or GaN. The electrically loading per die was 48 A for 5 ms with a di/dt of 2.1 kA/us (23 ns opening time). An internal snubber increased the response to 390 ns. The die absorbed ∼4.6 J causing a transient junction temperature increase of ∼245 °C. Two ambient temperatures were used in testing and set at 25 °C and 105 °C. The maximum junction temperature was conservatively projected to reach 350 °C during the 5 ms pulse. Electrical, thermal and mechanical design and testing results are presented.

Optoacoustic Imaging: An Emerging Modality for the Gastrointestinal Tract

Optoacoustic Imaging: An Emerging Modality for the Gastrointestinal Tract

Pandemic (H1N1) 2009 Virus in Swine Herds, China

To the Editor: During March and early April 2009, a new swine-origin influenza A (H1N1) virus emerged in Mexico and the United States; this virus subsequently spread across the globe by human-to-human transmission at an unprecedented rate. Pandemic (H1N1) 2009 virus also affected pigs. On May 2, 2009, the Canadian Food Inspection Agency notified the World Organisation for Animal Health that the novel influenza A virus had been confirmed on a pig farm in Alberta, Canada. Infection of pigs with pandemic (H1N1) 2009 virus has been observed in multiple countries (1). In this study, we report transmission of pandemic (H1N1) 2009 virus from humans to pigs in the People’s Republic of China. During August 2009–April 2010, swine influenza virus surveillance was conducted in the provinces of central and eastern China, including Henan, Hubei, Hunan, Jiangxi, and Anhui. A total of 1,021 samples, comprising tracheal mucus swabs and lungs, from pigs on 30 farms, were collected, and dozens of swine influenza viruses, H1N1, H1N2, H3N8, H9, and H10 subtypes, were isolated. Eight isolates were subtype H1N1, including 4 novel pandemic (H1N1) 2009 viruses: A/swine/Nanchang/3/2010 (H1N1) (GenBank accession nos. {type:entrez-nucleotide,attrs:{text:JF275917,term_id:321496099,term_text:JF275917}}JF275917–24), A/swine/Nanchang/5/2010 (H1N1) (GenBank accession nos. {type:entrez-nucleotide,attrs:{text:JF275933,term_id:321496135,term_text:JF275933}}JF275933–40) and A/swine/Nanchang/6/2010 (H1N1) (GenBank accession nos. {type:entrez-nucleotide,attrs:{text:JF275941,term_id:321496153,term_text:JF275941}}JF275941–48), which were isolated from tracheal mucus, and A/swine/Nanchang/F9/2010 (H1N1) (GenBank accession nos. {type:entrez-nucleotide,attrs:{text:JF275925,term_id:321496117,term_text:JF275925}}JF275925–32), isolated from the lung. Pigs from which the novel viruses were isolated showed mild respiratory signs, including depression, cough, and transient increase in body temperature. Compared with the sequence of A/California/04/2009 (H1N1), genomic sequencing of the 4 pandemic viruses showed 15 common point mutations, such as polymerase basic protein 2, T588I; polymerase acidic protein, A70V, P224S, D547E; hemagglutinin, P100S, D103E, S145P, T214A, S220T, I338V; nucleocapsid protein, V100I, H289Y; neuraminidase, V106I, N248D; and nonstructural protein, I123V. Recent studies have shown that the novel pandemic (H1N1) 2009 human influenza viruses were almost avirulent for mice (50% mouse lethal dose >106 PFU for A/CA/04/09 [2,3]). In this study, mice were anesthetized with ketamine/xylazine, as described (4) and 50 μL of phosphate-buffered saline containing the indicated doses (105 50% egg infectious dose) of the 4 viruses were instilled into anesthetized mice through nostrils. Interestingly, the 4 pandemic (H1N1) 2009 viruses isolated from pigs could cause systemic infection on mice. All mice had extensive loss of body weight, and some of the infected mice died within 2 weeks postinfection (data not shown). To detect whether the 4 isolated pandemic (H1N1) 2009 viruses could cause clinical diseases in pigs and what kinds of pathologic damage could be induced in infected pigs, pigs were intratracheally challenged with the 4 pandemic (H1N1) 2009 viruses at a dose of 107 50% egg infectious dose and monitored for clinical signs and pathologic changes. Clinical signs in pigs were mild, and no deaths occurred. Except for slightly labored breathing, no infected pigs showed dominant signs, such as cough, nasal discharge, facial edema, and dyspnea. Body temperatures of infected pigs started to increase at 2 days postinfection (dpi), peaked ≈3 dpi at 41.5°C, and returned to the initial temperature by 5 dpi. We observed necrosis of the tracheal wall and pneumonia foci in the 4 pandemic (H1N1) 2009 virus–infected pigs. Hematoxylin and eosin–stained sections of the trachea from the infected pigs showed mild necrotizing tracheitis. The necrotic epithelial cells were present in the lumen, and a mixed inflammatory cell infiltrate was present throughout (Figure). In the lung, we also observed alveolar septal edema and interstitial inflammatory cell infiltrates, as well as histologic changes, including alveolar epithelial hyperplasia, a mixed inflammatory infiltrate, and interstitium broadening (Figure). Additionally, immunohistochemical analysis for the distribution of viral antigens showed positive staining in bronchial epithelial cells and alveolar pneumocytes. Figure Hematoxylin and eosin–stained trachea and lung controls and samples from pigs infected with pandemic (H1N1) 2009 virus. A) Control trachea sample; B) mixed inflammatory cell infiltrate present throughout trachea sample from infected pig. C) Control ... Previous studies showed that pandemic (H1N1) 2009 may have become established in swine populations in Canada, Norway, and Hong Kong (1,5–8). The human-to-pig transmission of pandemic (H1N1) 2009 may substantially affect virus evolution and subsequent epidemiology. Although the pandemic was mild, the virus could develop further reassortment in swine and gain virulence. On the other hand, subtype H5N1 and H9N2 viruses have become established in pigs, so the introduction of pandemic (H1N1) 2009 virus to pigs has provided the possibility for the incorporation of avian virus genes into mammalian-adapted viruses. That transmission could occur from humans to pigs and vice versa is especially troublesome. Given the possible production of novel viruses of potential threat to public health, we should emphasize influenza surveillance in pigs and establishment of the genetic basis of the viral genome for rapidly identifying such reassortment events.

In Vivo Pharmacology and Toxicology Evaluation of Polyethylene Glycol-Conjugated Interferon β-1a

Human interferon (IFN) β has well established beneficial effects in treating relapsing forms of multiple sclerosis, but current first-line treatment requires frequent (from daily to weekly) parenteral administration. A 20-kDa polyethylene glycol (PEG)-conjugated IFN β-1a (PEG-IFN β-1a) is being developed to decrease the frequency of administration and improve patient convenience and compliance. We present pharmacokinetic (PK) and pharmacodynamic (PD) parameters, immunogenicity, and safety of PEG-IFN β-1a in Rhesus monkeys in support of a phase 1 clinical trial. Two single-dose PK/PD studies and one 5-week repeat-dose toxicity study compliant with good laboratory practice were conducted. The PK of IFN β-1a and PEG-IFN β-1a were modeled with a two-compartment model, and the link between drug concentration and neopterin response (PD marker) was described with an indirect stimulatory model. PEG-IFN β-1a showed greater exposure, longer half-life, lower clearance, and reduced volume of distribution than unmodified IFN β-1a. Consistent with the pharmacology of type I IFNs, PEG-IFN β-1a resulted in the elevation of neopterin concentration, a transient body temperature increase, and a reversible lymphocyte count decrease. As expected, neutralizing antibodies to PEG-IFN β-1a formed in almost all monkeys after 5 weeks of treatment, which resulted in significantly reduced drug exposure and abrogation of neopterin induction. There were no drug-related adverse effects at doses up to 100 μg/kg (11 MIU/kg) given subcutaneously or intramuscularly once weekly for 5 weeks. The no-observed-adverse-effect level was determined to be 100 μg/kg (11 MIU/kg), the highest dose tested.

Effect of a single intrauterine administration of recombinant bovine interferon-τ on day 7 of the estrous cycle on the luteal phase length and blood profile in dairy cows

This study tested the effect of recombinant bovine interferon-tau (rboIFN-τ) on the length of estrous cycle, luteal lifespan and side effects of rboIFN-τ in the cow. A normal estrous cycle in six non-lactating cycling Holstein cows was observed (non-treated cycle), and either 2.0mg of liposomalized rboIFN-τ (treated cycle) or bovine serum albumin (BSA; placebo cycle) was infused in the uterus on day 7 of the estrous cycle (day 0=day of ovulation). Rectal temperature, heart rate and respiratory rate were recorded and blood samples were collected before and after the treatments. The length of the estrous cycle and corpus luteum lifespan in rboIFN-τ treated cycles were not significantly different from those of the non-treated and placebo cycles. In contrast, the rboIFN-τ treatment caused a transient increase in rectal temperature and a decrease in the number of peripheral lymphocytes and neutrophils after the treatment.

Methamphetamine causes sustained depression in cerebral blood flow

The use prevalence of the highly addictive psychostimulant methamphetamine (MA) has been steadily increasing over the past decade. MA abuse has been associated with both transient and permanent alterations in cerebral blood flow (CBF), hemorrhage, cerebrovascular accidents and death. To understand MA-induced changes in CBF, we exposed C56BL/6 mice to an acute bolus of MA (5mg/kg MA, delivered IP). This elicited a biphasic CBF response, characterized by an initial transient increase (~5minutes) followed by a prolonged decrease (~30minutes) of approximately 25% relative to baseline CBF—as measured by laser Doppler flowmetry over the somatosensory cortex. To assess if this was due to catecholamine derived vasoconstriction, phentolamine, an α-adrenergic antagonist was administered prior to MA treatment. This reduced the initial increase in CBF but failed to prevent the subsequent, sustained decrease in CBF. Consistent with prior reports, MA caused a transient increase in mean arterial blood pressure, body temperature and respiratory rate. Elevated respiratory rate resulted in hypocapnia. When respiratory rate was controlled by artificially ventilating mice, blood PaCO2 levels after MA exposure remained unchanged from physiologic levels, and the MA-induced decrease in CBF was abolished. In vivo two-photon imaging of cerebral blood vessels revealed sustained MA-induced vasoconstriction of pial arterioles, consistent with laser Doppler flowmetry data. These findings show that even a single, acute exposure to MA can result in profound changes in CBF, with potentially deleterious consequences for brain function.

Body temperature patterns during hibernation in a free-living Alaska marmot (Marmota broweri)

Marmota broweri is endemic to arctic Alaska. We implanted data loggers into one free-living subadult female in August 2007 to record body temperature (Tb). Seasonal heterothermy lasted for 224 days (10 September to 21 April). Midwinter torpor bout length (mean ± SD) was 13.91 ± 3.56 days and duration of interbout euthermy was 18.43 ± 2.55 hr. Unlike other marmot species, torpor entry during midwinter was consistently characterized by two distinct cooling rates differing by about 10-fold and separated by a transient temperature increase. Minimum hibernaculum temperature was − 14.97 °C in February (7 month mean: − 7.33 °C). Minimum Tb was 1.01 °C when defending a 15.5 °C thermal gradient. At least six animals emerged from the hibernaculum suggesting that communal hibernation may be a strategy to reduce metabolic costs while maintaining above-freezing Tb.

Effects of Temperature on Laser-Induced Shape Modification of Silver Nanoparticles Embedded in Glass

The influence of temperature on the laser-induced shape modification and dissolution of silver nanoparticles in glass is investigated theoretically and experimentally. Both the local transient temperature increase in close vicinity to a nanoparticle after laser pulse excitation and effects of permanent heating of the whole sample are discussed. It is shown that the heat-affected zone reaching transiently temperatures above 500 K around a nanoparticle should be limited to a few nanometers to enable the intended transformation of initially spherical nanoparticles to prolate shapes with high aspect ratio by irradiation with a few hundred laser pulses. Already relatively small temperature increase of the sample prior to or during irradiation, provided by external sample heating or temperature accumulation in the focal volume at high laser repetition rates, causes partial destruction of the nanoparticles due to increased diffusion length of the emitted Ag cations.

Inverse modelling of thermal conductivity from temperature measurements at the Prototype Repository, Äspö HRL

The Prototype Repository, at the Äspö HRL (Hard Rock Laboratory), is a demonstration project for the deposition of spent nuclear fuel, and provides a full-scale reference for testing predictive models relating to a spent nuclear fuel repository, both its individual components as well as the complete system. The final layout involves six deposition holes, four in an inner section and two in an outer, each fitted with an electrically heated canister. The access tunnel is backfilled with a mixture of bentonite and crushed rock. In 2001, the inner section was completed and monitoring of the heating process started. Temperature measurements in the rock mass are performed at 37 different points. In this paper, the measured thermal response in the surrounding rock is analysed by inverse modelling of the thermal conductivity of the rock mass. A three-dimensional finite difference model of the prototype repository (canisters, buffers, tunnel, etc.) is used to calculate the transient temperature increase due to the heat generation in the canisters. The value of a homogeneous rock thermal conductivity is chosen to obtain the best fit with measured data for each of the 37 temperature sensor points. The evaluation period for the fitting procedure is varied in order to study sensitivity to different time-scales. Measurements of thermal properties have been conducted within the prototype repository prior to the full-scale test. The thermal properties were predicted based on both field and laboratory measurements. These predictions are verified by comparison with thermal conductivity values calculated through inverse modelling.

Experimental Infection of Pigs with the Human 1918 Pandemic Influenza Virus

Swine influenza was first recognized as a disease entity during the 1918 "Spanish flu" pandemic. The aim of this work was to determine the virulence of a plasmid-derived human 1918 pandemic H1N1 influenza virus (reconstructed 1918, or 1918/rec, virus) in swine using a plasmid-derived A/swine/Iowa/15/1930 H1N1 virus (1930/rec virus), representing the first isolated influenza virus, as a reference. Four-week-old piglets were inoculated intratracheally with either the 1930/rec or the 1918/rec virus or intranasally with the 1918/rec virus. A transient increase in temperature and mild respiratory signs developed postinoculation in all virus-inoculated groups. In contrast to other mammalian hosts (mice, ferrets, and macaques) where infection with the 1918/rec virus was lethal, the pigs did not develop severe respiratory distress or become moribund. Virus titers in the lower respiratory tract as well as macro- and microscopic lesions at 3 and 5 days postinfection (dpi) were comparable between the 1930/rec and 1918/rec virus-inoculated animals. In contrast to the 1930/rec virus-infected animals, at 7 dpi prominent lung lesions were present in only the 1918/rec virus-infected animals, and all the piglets developed antibodies at 7 dpi. Presented data support the hypothesis that the 1918 pandemic influenza virus was able to infect and replicate in swine, causing a respiratory disease, and that the virus was likely introduced into the pig population during the 1918 pandemic, resulting in the current lineage of the classical H1N1 swine influenza viruses.

Remittance at a single wavelength of 390 nm to quantify epidermal melanin concentration

Objective quantification of epidermal melanin concentration (EMC) should be useful in laser dermatology to determine the individual maximum safe radiant exposure (IMSRE). We propose a single-wavelength remittance measurement at 390 nm as an alternative optical method to determine EMC and IMSRE. Remittance spectra (360 to 740 nm), melanin index (MI) measurements and the transient radiometric temperature increase, DeltaT(t), upon skin irradiation with an Alexandrite laser (755 nm, 3-ms pulse duration, 6 Jcm(2)) were measured on 749 skin spots (arm and calf) on 23 volunteers (skin phototypes I to IV). Due to the shallow penetration depth and independence of blood oxygen saturation (isosbestic point), remittance at 390 nm appears to provide better estimates for EMC and IMSRE than MI.

Constraints on the transient climate response from observed global temperature and ocean heat uptake

Projections of future transient global temperature increase in climate models for a known forcing depend on the strength of the atmospheric feedbacks and the rate of transient ocean heat uptake. A Bayesian framework and an intermediate complexity climate model are used to calculate a probability density function (PDF) of the transient climate response (TCR), constrained by observations of global surface warming and ocean heat uptake. The PDF constrained by observations is wider than the TCR range of current climate models, and has a slightly lower mean. Uncertainties in the observed ocean warming are shown to potentially affect the TCR. It is proposed, however, that even if models were found to overestimate ocean heat uptake, correcting that bias would lead to revisions in surface temperature projections over the twenty‐first century that are smaller than the uncertainties introduced by poorly quantified atmospheric feedbacks.

Rapid response of a hydrologic system to volcanic activity: Masaya volcano, Nicaragua

Hydrologic systems change in response to volcanic activity, and in turn may be sensitive indicators of volcanic activity. Here we investigate the coupled nature of magmatic and hydrologic systems using continuous multichannel time series of soil temperature collected on the flanks of Masaya volcano, Nicaragua, one of the most active volcanoes in Central America. The soil temperatures were measured in a low-temperature fumarole field located 3.5 km down the flanks of the volcano. Analysis of these time series reveals that they respond extremely rapidly, on a time scale of minutes, to changes in volcanic activity also manifested at the summit vent. These rapid temperature changes are caused by increased flow of water vapor through flank fumaroles during volcanism. The soil temperature response, ~5 °C, is repetitive and complex, with as many as 13 pulses during a single volcanic episode. Analysis of the frequency spectrum of these temperature time series shows that these anomalies are characterized by broad frequency content during volcanic activity. They are thus easily distinguished from seasonal trends, diurnal variations, or individual rainfall events, which triggered rapid transient increases in temperature during 5% of events. We suggest that the mechanism responsible for the distinctive temperature signals is rapid change in pore pressure in response to magmatism, a response that can be enhanced by meteoric water infiltration. Monitoring of distal fumaroles can therefore provide insight into coupled volcanic-hydrologic-meteorologic systems, and has potential as an inexpensive monitoring tool.

Assessment of Laser Transmission Mirror Materials for ITER Edge Thomson Scattering Diagnostics

An assessment of in-vessel metallic mirror materials for the transmission of the laser beam used in the ITER edge Thomson scattering diagnostics is reported. The transient temperature increase due to the laser pulse irradiation on the laser transmission mirror is calculated by a one-dimensional heat conduction equation. Candidate mirror materials are discussed based on a comparison between the numerical calculation and current data relevant to the laser-induced damage threshold (LIDT). Gold, silver, and copper are considered promising because of its high reflectivity. The LIDT is evaluated considering multi-pulse effects and used to determine the necessary size for the laser transmission mirror for the ITER edge Thomson scattering diagnostics.

Repeated Administration of Vanilloid Receptor TRPV1 Antagonists Attenuates Hyperthermia Elicited by TRPV1 Blockade

Capsaicin, the active ingredient in some pain-relieving creams, is an agonist of a nonselective cation channel known as the transient receptor potential vanilloid type 1 (TRPV1). The pain-relieving mechanism of capsaicin includes desensitization of the channel, suggesting that TRPV1 antagonism may be a viable pain therapy approach. In agreement with the above notion, several TRPV1 antagonists have been reported to act as antihyperalgesics. Here, we report the in vitro and in vivo characterization of a novel and selective TRPV1 antagonist, N-(4-[6-(4-trifluoromethyl-phenyl)-pyrimidin-4-yloxy]-benzothiazol-2-yl)-acetamide I (AMG 517), and compare its pharmacology with that of a closely related analog, tert-butyl-2-(6-([2-(acetylamino)-1,3-benzothiazol-4-yl]oxy)pyrimidin-4-yl)-5-(trifluoromethyl)phenylcarbamate (AMG8163). Both AMG 517 and AMG8163 potently and completely antagonized capsaicin, proton, and heat activation of TRPV1 in vitro and blocked capsaicin-induced flinch in rats in vivo. To support initial clinical investigations, AMG 517 was evaluated in a comprehensive panel of toxicology studies that included in vivo assessments in rodents, dogs, and monkeys. The toxicology studies indicated that AMG 517 was generally well tolerated; however, transient increases in body temperature (hyperthermia) were observed in all species after AMG 517 dosing. To further investigate this effect, we tested and showed that the antipyretic, acetaminophen, suppressed the hyperthermia caused by TRPV1 blockade. We also showed that repeated administration of TRPV1 antagonists attenuated the hyperthermia response, whereas the efficacy in capsaicin-induced flinch model was maintained. In conclusion, these studies suggest that the transient hyperthermia elicited by TRPV1 blockade may be manageable in the development of TRPV1 antagonists as therapeutic agents. However, the impact of TRPV1 antagonist-induced hyperthermia on their clinical utility is still unknown.

Thermoregulatory Control of Feeding and Sleep in Premature Infants*

The aim of the present study was to test the thermoregulatory feeding control hypothesis in sleeping, premature infants. In premature infants, the energy supply from food intake is crucial for (in order of importance): organ operation, body homeothermia, and optimal growth. The Himms-Hagen model of thermoregulatory feeding control involving activation of heat production by brown adipose tissue (BAT) was formulated on the basis of work in (awake) rats. This hypothesis has also been put forward for the human neonate, which can also use BAT to produce metabolic heat. According to the model, feeding episodes occur during a transient increase in body temperature. Feeding is initiated by a dip in blood glucose concentration after sugar uptake by activated BAT. In 14 neonates (bottle-fed on demand), food intake always took place during an increase in skin temperature (+0.19 +/- 0.21 degrees C). Awakening occurred 18 +/- 17 minutes after the minimum skin temperature level had been reached. When feeding time was imposed, feeding was not necessarily situated during an increase in skin temperature, and the sleep duration after food intake increased significantly (+43%). This could be considered as an adaptive response to the short-term sleep deprivation and/or stress elicited by an imposed feeding rhythm. The validity of the model supports the use of on-demand feeding in neonatal care units, in accordance with the infant's physiological body temperature oscillations.

Effect of subdiaphragmatic vagotomy on the noradrenergic and HPA axis activation induced by intraperitoneal interleukin-1 administration in rats

The vagus nerve is thought to participate in signal transduction from the immune system to the CNS. The role of the vagus in the physiological, behavioral and neurochemical responses to intraperitoneally (ip) injected interleukin-1β (IL-1β) was studied using awake subdiaphragmatically vagotomized rats. The rats were injected ip with saline and IL-1β (1 μg/rat) in random order. For the next 2–4 h, they were monitored for locomotor activity, body temperature via abdominally implanted telethermometers, hypothalamic norepinephrine (NE) secretion using in vivo microdialysis and blood sampled via intravenous catheters to determine concentrations of ACTH and corticosterone to assess hypothalamo–pituitary–adrenocortical (HPA) axis activation. Saline injections were followed by transient increases in locomotor activity, body temperature, dialysate NE and plasma concentrations of ACTH and corticosterone. These responses were not significantly altered by vagotomy. IL-1β injections resulted in short-lived increases in shivering and longer decreases in locomotor activity, as well as a delayed modest fever. IL-1β also induced prolonged elevations of hypothalamic microdialysate NE, as well as plasma ACTH and corticosterone. Similar responses were observed regardless of the order of the saline and IL-1β injections. Subdiaphragmatic vagotomy prevented the IL-1-induced increases in body temperature and the increase in dialysate NE, and markedly attenuated the increases in plasma ACTH and corticosterone. The results indicate close temporal relationships between the apparent release of NE and the increase in body temperature and the HPA activation. This together with the effects of vagotomy suggests that the activation of NE in turn increases body temperature and activates the HPA axis. However, because IL-1β induces a limited HPA activation in subdiaphragmatically vagotomized rats, the vagus nerve does not appear to be the only route by which ip IL-1β can activate the HPA axis. It is suggested that IL-1β-induced vagal activation of hypothalamic NE is the major mechanism of HPA activation at low doses of IL-1β. However, IL-1β can also exert direct effects on IL-1 receptors on cerebral blood vessels, activating cyclooxygenases and hence synthesis of prostaglandins which in turn can affect body temperature, behavior and HPA axis activation.

Noninvasive optoacoustic online retinal temperature determination during continuous-wave laser irradiation

The therapeutic effect of most retinal laser treatments is initiated by a transient temperature increase. Although crucial to the effectiveness of the treatment, the temperature course is not exactly known due to individually different tissue properties. We develop an optoacoustic method to determine the retinal temperature increase in real time during continuous-wave (cw) laser irradiation, and perform temperature calculations to interpret the results exemplary for transpupillary thermotherapy (TTT). Porcine globes ex vivo and rabbit eyes in vivo are irradiated with a diode laser (lambda=810 nm, P< or =3 W, phi=2 mm) for 60 s. Simultaneously, pulses from a N2-laser pumped dye laser (lambda=500 nm, tau=3.5 ns, E approximately 5 microJ) are applied on the retina. Following its absorption, an ultrasonic pressure wave is emitted, which is detected by a transducer embedded in a contact lens. Using the previously measured temperature-dependent Gruneisen coefficient of chorioretinal tissue, a temperature raise in porcine eyes of 5.8 degrees C(Wcm2) after 60 s is observed and confirmed by simultaneous measurements with an inserted thermocouple. In a rabbit, we find 1.4 degrees C(Wcm2) with, and 2.2 degrees C(Wcm2) without perfusion at the same location. Coagulation of the rabbit's retina occurs at DeltaT=21 degrees C after 40 s. In conclusion, this optoacoustic method seems feasible for an in vivo real-time determination of temperature, opening the possibility for feedback control retinal laser treatments.