Nanofocusing of X-ray free-electron laser using wavefront-corrected multilayer focusing mirrors.

A method of fabricating multilayer focusing mirrors that can focus X-rays down to 10 nm or less was established in this study. The wavefront aberration induced by multilayer Kirkpatrick-Baez mirror optics was measured using a single grating interferometer at a photon energy of 9.1 keV at SPring-8 Angstrom Compact Free Electron Laser (SACLA), and the mirror shape was then directly corrected by employing a differential deposition method. The accuracies of these processes were carefully investigated, considering the accuracy required for diffraction-limited focusing. The wavefront produced by the corrected multilayer focusing mirrors was characterized again in the same manner, revealing that the root mean square of the wavefront aberration was improved from 2.7 (3.3) rad to 0.52 (0.82) rad in the vertical (horizontal) direction. A wave-optical simulator indicated that these wavefront-corrected multilayer focusing mirrors are capable of achieving sub-10-nm X-ray focusing.

Towards ultrafast dynamics with split-pulse X-ray photon correlation spectroscopy at free electron laser sources.

One of the important challenges in condensed matter science is to understand ultrafast, atomic-scale fluctuations that dictate dynamic processes in equilibrium and non-equilibrium materials. Here, we report an important step towards reaching that goal by using a state-of-the-art perfect crystal based split-and-delay system, capable of splitting individual X-ray pulses and introducing femtosecond to nanosecond time delays. We show the results of an ultrafast hard X-ray photon correlation spectroscopy experiment at LCLS where split X-ray pulses were used to measure the dynamics of gold nanoparticles suspended in hexane. We show how reliable speckle contrast values can be extracted even from very low intensity free electron laser (FEL) speckle patterns by applying maximum likelihood fitting, thus demonstrating the potential of a split-and-delay approach for dynamics measurements at FEL sources. This will enable the characterization of equilibrium and, importantly also reversible non-equilibrium processes in atomically disordered materials.

Effect of Lipopolysaccharide on the Progression of Non-Alcoholic Fatty Liver Disease in High Caloric Diet-Fed Mice.

The incidence of non-alcoholic steatohepatitis (NASH) is increasing. Because gut microbiota have been highlighted as one of the key factors in the pathogenesis of metabolic syndrome, we investigated the involvement of the bacterial component in the progression of non-alcoholic fatty liver (NAFL) to NASH. C57BL/6 mice were fed with maintenance food (MF, groups A and B) or a high caloric diet (HCD, groups C and D) for 1 month. Mice were then divided into four groups: Groups A and C were inoculated with PBS, while groups B and D were inoculated with lipopolysaccharide (LPS) plus complete Freund's adjuvant (CFA). The inoculations were performed a total of 3 times over 3 months. At 6 months, while hepatic steatosis was observed in groups C and D, cellular infiltration and fibrosis were less evident in group C than in group D. Inflammatory cytokines were upregulated in groups B and D. 16S rRNA pyrosequencing of whole colon homogenates containing faeces showed that certain bacterial groups, such as Bacteroidaceae, Peptostreptococcaceae and Erysipelotrichaceae, were increased in groups C and D. Although loading of bacterial components (LPS) resulted in hepatic inflammation in both MF- and HCD-fed mice, HCD feeding was more crucial in the progression of NAFL during the triggering phase.

Hypoxia-induced hypothermia mediated by GABA in the rostral parapyramidal area of the medulla oblongata.

Hypoxia evokes a regulated decrease in the body core temperature (Tc) in a variety of animals. The neuronal mechanisms of this response include, at least in part, glutamatergic activation in the lateral preoptic area (LPO) of the hypothalamus. As the sympathetic premotor neurons in the medulla oblongata constitute a cardinal relay station in the descending neuronal pathway from the hypothalamus for thermoregulation, their inhibition can also be critically involved in the mechanisms of the hypoxia-induced hypothermia. Here, I examined the hypothesis that hypoxia-induced hypothermia is mediated by glutamate-responsive neurons in the LPO that activate GABAergic transmission in the rostral raphe pallidus (rRPa) and neighboring parapyramidal region (PPy) of the medulla oblongata in urethane-chloralose-anesthetized, neuromuscularly blocked, artificially ventilated rats. Unilateral microinjection of GABA (15nmol) into the rRPa and PPy regions elicited a prompt increase in tail skin temperature (Ts) and decreases in Tc, oxygen consumption rate (VO2), and heart rate. Next, when the GABAA receptor blocker bicuculline methiodide (bicuculline methiodide (BMI), 10pmol) alone was microinjected into the rRPa, it elicited unexpected contradictory responses: simultaneous increases in Ts, VO2 and heart rate and a decrease in Tc. Then, when BMI was microinjected bilaterally into the PPy, no direct effect on Ts was seen; and thermogenic and tachycardic responses were slight. However, pretreatment of the PPy with BMI, but not vehicle saline, greatly attenuated the hypothermic responses evoked by hypoxic (10%O2-90%N2, 5min) ventilation or bilateral microinjections of glutamate (5nmol, each side) into the LPO. The results suggest that hypoxia-induced hypothermia was mediated, at least in part, by the activation of GABAA receptors in the PPy.

Thermoregulatory responses elicited by microinjection of L-glutamate and its interaction with thermogenic effects of GABA and prostaglandin E2 in the preoptic area.

The aim of the present study was to investigate the thermoregulatory effects of neuronal activation with sodium L-glutamate (glutamate) in the preoptic area (POA) of the hypothalamus and to examine its possible interaction with the thermogenic effects of GABA and prostaglandin E(2) (PGE(2)). Unilateral microinjection of glutamate (5 nmol) into the lateral POA or its vicinity elicited a prompt increase in tail skin temperature and simultaneous decreases in the O(2) consumption rate (VO(2)), heart rate, and colonic temperature in urethane-chloralose-anesthetized rats. A central subpopulation of these sites at around the level of bregma was also responsive to the thermogenic and tachycardic effects of GABA (30 nmol). Although the microinjection of GABA into nearby sites elicited no direct effect, it greatly attenuated the hypothermic effects of glutamate subsequently administered to the same site. These results suggest that activation of the lateral POA elicited heat-loss responses and that its central part provided a tonic inhibitory drive toward heat production and tail vasoconstriction. On the other hand, the microinjection of glutamate elicited initial small decreases and subsequent large increases in VO(2) and heart rate in the rostromedial POA. However, no thermoregulatory response was elicited by the microinjection of glutamate at sites where the microinjection of PGE(2) (35 fmol) elicited thermogenic, tachycardic and hyperthermic responses. These results may suggest that the rostromedial POA contained two glutamate-responsive cell groups that had opposite influences on thermoregulation and that the locus that was highly sensitive to the thermogenic effect of PGE(2) was unreactive to glutamate. Collectively, activation of neurons in the lateral POA and rostromedial POA evoked distinct thermoregulatory responses.

Hypoxia-induced hypothermia mediated by the glutamatergic transmission in the lateral preoptic area.

Hypoxia evokes a regulated decrease in the body core temperature, which response is mediated, at least in part, by noradrenaline (NA) and nitric oxide (NO) in the rostromedial preoptic area (POA) of the hypothalamus. In the accompanying paper, it was shown that glutamatergic activation of the lateral POA also evokes hypothermic responses. Here, I tested the hypothesis that the glutamatergic transmission in the lateral POA is critically involved in the neural mechanism of hypoxia-induced hypothermia. Hypoxic ventilation (10% O(2)-90% N(2), 5 min) as well as a single microinjection of NA (50 pmol) or the NO donor sodium nitroprusside (8.4 nmol) into the rostromedial POA evoked an increase in the tail skin temperature and a decrease in the colonic temperature in urethane-chloralose-anesthetized, neuromuscularly blocked, artificially ventilated rats. All of these responses were greatly attenuated by pretreatment with multiple microinjections of kynurenic acid (10 nmol, four locations), a nonselective glutamate receptor antagonist, but not by those with saline solution, in the bilateral rostral and central parts of the lateral POA. These results suggest that the NA- and NO-sensitive structure in the rostromedial POA activated the glutamatergic transmission in the lateral POA to mediate hypoxia-induced hypothermia.

Hypoxia-induced hypothermia mediated by noradrenaline and nitric oxide in the rostromedial preoptic area.

Central nitric oxide (NO) has an important role in hypothermia induced by hypoxia as well as in that elicited by noradrenaline (NA) microinjected into the rostromedial preoptic area (POA) of the hypothalamus. Here, I tested the hypothesis that activation of adrenoceptors and NO in the rostromedial POA is involved in hypoxia-induced hypothermia in urethane-chloralose-anesthetized, neuromuscularly blocked, artificially ventilated rats. Hypoxic ventilation (10% O2-90% N2, 5 min) evoked an increase in the tail skin temperature and a decrease in the colonic temperature, though these changes occurred at 30 s to 7 min after returning the rats to ventilation with room air. These responses were eliminated by prior bilateral transection of the carotid sinus nerves, but not by bilateral cervical vagotomy, suggesting the involvement of activated carotid chemoreceptors in the hypoxic ventilation-induced hypothermia. Such responses were also greatly attenuated by the microinjection of an NO synthase (NOS) inhibitor, NG-monomethyl-L-arginine (L-NMMA, 25 nmol), but not by that of its inactive enantiomer, NG-monomethyl-D-arginine (D-NMMA, 25 nmol), into the NA-sensitive, hypothermia-inducing site in the rostromedial POA. Pretreatment with the α1-adrenoceptor blocker prazosin (50 pmol), but not vehicle saline, also greatly attenuated the hypoxic ventilation-induced heat loss responses. These results suggest that this hypoxia-induced hypothermia was mediated, at least in part, by activation of α1-adrenoceptors and NOS in the rostromedial POA.

Nitric oxide mediates noradrenaline-induced hypothermic responses and opposes prostaglandin E2-induced fever in the rostromedial preoptic area.

Noradrenaline (NA) microinjected into the rostromedial preoptic area (POA) elicits heat loss responses and opposes prostaglandin E(2)-induced fever. Here, I tested the hypothesis that local synthesis and release of nitric oxide (NO) mediates the NA-induced effects. The unilateral microinjection of the NO donor sodium nitroprusside (SNP, 8.4 nmol), but not that of saline solution, into the NA-sensitive site elicited an increase in tail skin temperature and decreases in the whole-body O(2) consumption rate, heart rate, and colonic temperature simultaneously in urethane-chloralose-anesthetized rats. Pretreatment with SNP greatly attenuated the thermogenic, tachycardic, and hyperthermic effects of prostaglandin E(2) (140 fmol) microinjected into the same site. Furthermore, the NA-induced hypothermic responses were largely blocked by a prior microinjection of an NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA, 5 nmol), but not by that of its inactive enantiomer, N(G)-monomethyl-D-arginine (D-NMMA, 5 nmol), at the same site. These results suggest that the hypothermic and antipyretic effects of NA are mediated by NO in the rostromedial POA.

[Coronary artery fistula into the right atrium complicated by atrial futter; report of a case].

A 62-years-old woman with uncommon atrial flutter underwent the catheter ablation therapy. In the catheter ablation therapy and subsequent coronary angiography, a coronary artery fistula into the right atrium was found. A giant aneurysm formed in the junctional region between the coronary artery fistula and right atrium. The giant aneurysm might have been a course of uncommon atrial flutter. We ligated the coronary artery fistula to prevent the giant aneurysm rupture. Any events have not been observed after catheter ablation and ligation.

Heat loss responses and blockade of prostaglandin E2-induced thermogenesis elicited by alpha1-adrenergic activation in the rostromedial preoptic area.

The unilateral microinjection of noradrenaline (NA), but not vehicle solution, into the rostromedial preoptic area (POA) elicited simultaneous increases in cutaneous temperatures of the tail and sole of the foot and decreases in the whole-body O(2) consumption rate, heart rate, and colonic temperature in urethane-chloralose-anesthetized rats, suggesting a coordinate increase in heat loss and decrease in heat production. The magnitude of these responses increased dose-dependently over the range of 1-100 pmol, except for the metabolic and bradycardic responses. Similar hypothermic responses were elicited by the microinjection of 40 pmol methoxamine (an alpha(1)-adrenergic agonist), but not by that of clonidine (an alpha(2)-agonist) or isoproterenol (a beta-agonist). Sites at which microinjection of NA elicited hypothermic responses were in the vicinity of the organum vasculosum of the lamina terminalis including the median preoptic nucleus, whereas no thermal or metabolic response was elicited when NA was microinjected into the lateral POA or caudal part of the medial POA. The microinjection of 130 fmol prostaglandin (PG) E(2) into the NA-sensitive site always elicited thermogenic, tachycardic, and hyperthermic responses. Furthermore, the PGE(2)-induced febrile responses were greatly attenuated by prior administration of NA at the same site. These results demonstrate that NA in the rostromedial POA exerts alpha(1)-adrenoceptor-mediated hypothermic effects and opposes PGE(2)-induced fever.

Increased fat:carbohydrate oxidation ratio in Il1ra (-/-) mice on a high-fat diet is associated with increased sympathetic tone.

AIMS/HYPOTHESIS: Proinflammatory cytokines, including IL-1, exert pleiotropic effects on the neuro-immuno-endocrine system. Previously, we showed that mice with knockout of the gene encoding IL-1 receptor antagonist (Il1ra (-/-), also known as Il1rn (-/-)) have a lean phenotype. The present study was designed to analyse the mechanisms leading to this lean phenotype. METHODS: Il1ra (-/-) mice were fed a high-fat diet following weaning. Energy expenditure, body temperature, heart rate, blood parameters, urinary catecholamines and adipose tissue were analysed. RESULTS: Il1ra (-/-) mice exhibited resistance to obesity induced by a high-fat diet; this resistance was associated with increased energy expenditure and a decreased respiratory quotient, indicating that the ratio of fat:carbohydrate metabolism in Il1ra (-/-) mice is greater than in controls. Activity level in Il1ra (-/-) mice was significantly decreased and body temperature was significantly increased, compared with wild-type (WT) mice. Inguinal white adipose tissues in Il1ra (-/-) mice express increased levels of Ucp1 and mitochondrial respiratory chain genes compared with WT mice. Histological analysis of adipose tissue in Il1ra (-/-) mice revealed that brown adipose tissue is hyperactive and inguinal white adipose tissue contains smaller cells, which exhibit the distinctive multilocular appearance of brown adipocytes. Urinary epinephrine and norepinephrine excretion in Il1ra (-/-) mice was significantly increased compared with WT mice, suggesting that Il1ra (-/-) mice have increased sympathetic tone. Consistent with this, heart rate in Il1ra (-/-) mice was also significantly increased. CONCLUSIONS/INTERPRETATION: Our results show that Il1ra (-/-) mice have increased energy expenditure, fat:carbohydrate oxidation ratio, body temperature, heart rate and catecholamine production. All of these observations are consistent with an enhanced sympathetic tone.

Ventromedial hypothalamus lesions induce jejunal epithelial cell hyperplasia through an increase in gene expression of cyclooxygenase.

BACKGROUND: We demonstrated that ventromedial hypothalamus (VMH) lesions facilitate DNA synthesis, which reflects cell proliferation in abdominal organs, including the liver, pancreas, stomach, small intestine and large intestine, all of which are amply innervated by the vagal nerve. OBJECTIVE: To investigate which area DNA synthesis facilitates and what factors contribute to cell proliferation in the small intestine in VMH-lesioned rats. DESIGN: At 7 days after VMH lesions or sham operations, a segment of rat jejunum was taken for histological examination. A part of the jejunum was also removed from VMH-lesioned and sham-operated rats after 3 days and examined for 5-bromo-2'-deoxyuridine (BrdU) incorporation. At 6, 12 and 24 h after VMH lesions, the proximal intestine was removed from individual rats, from the pylorus to the mid-jejunum. Total RNA was extracted from these tissues of each rat, and the levels of epidermal growth factor (EGF) and transforming growth factor (TGF)-alpha mRNA were determined using reverse-transcription polymerase chain reaction. Cyclooxygenase (COX)-1 and -2 mRNA levels were determined using Northern blotting. RESULTS: : Jejunal villi in VMH-lesioned rats were markedly enlarged compared to those of sham-operated rats and jejunal crypts in VMH-lesioned rats more markedly incorporated BrdU. Northern blot analysis revealed an increase in COX-1 mRNA after 6, 12 and 24 h in the jejunum of VMH-lesioned rats. COX-2 mRNA was decreased 6 and 12 h after VMH lesioning; however, it was significantly increased 24 h after VMH lesions in comparison to sham-operated rats. The levels of EGF and TGF-alpha mRNA were unchanged in VMH lesioned rats. CONCLUSION: VMH lesions induced enlargement of jejunal villi and increased the gene expression of COX-1 in the small intestine. Prostaglandins, probably E(2), induced by COX-1 may be one candidate factor responsible for the cell proliferation of the small intestinal epithelium in these rats.

Direct imaging of the InSb001-c8 x 2 surface: evidence for large anisotropy of the reconstruction.

We have observed the InSb(001)-c(8 x 2) surface by using high-resolution transmission electron microscopy in the profile-imaging geometry. All images observed at temperatures up to 420 degrees C agree well with the c(8 x 2) model reported by Kumpf et al. [Phys. Rev. Lett. 86, 3586 (2001)]]. 1/30 sec real-time observations at 420 degrees C evidence that a part of the subsurface and surface layers (called a gull-type segment) undergo switching to and from a bulk configuration. The finding is suggestive of large anisotropy in the mean square displacement of the c(8 x 2) surface.

Energy expenditure by intracerebroventricular administration of orexin to anesthetized rats.

Orexin-A and -B are hypothalamic neuropeptides that have been implicated in stimulating food intake and maintaining arousal. Because food intake is closely related to the control of energy homeostasis, we examined the effects of intracerebroventricular administration of orexins on O2 consumption (VO2), an index of energy expenditure, body temperature, skin temperature and heart rate (HR) in urethane-anesthetized rats. VO2 increased significantly after an orexin-A injection, and this increase was accompanied by a significant tachycardiac response. Orexin-B also increased VO2 and HR, although orexin-A was approximately 30 times more potent in eliciting these responses than orexin-B. The effects of orexin-A were dose dependent over the range of 1 pmol(-1) x nmol, whereas an injection of the saline vehicle had no effect. These findings suggest that centrally acting orexin-A functions to increase energy expenditure.

Thermogenesis induced by intravenous infusion of hypertonic solutions in the rat.

1. Intravenous administration of 20-60 % glucose, 3.2-9.7 % NaCl or 20 % mannitol solutions (1.66 ml kg(-1)) for 5 min increased oxygen consumption in urethane-anaesthetized rats, whereas administration of physiological saline had no effect. Administration of 7.7-18.3 % urea slightly increased the oxygen consumption, but the increase was significantly smaller than that measured after the administration of other hypertonic solutions. The magnitude of the thermogenic effect correlated with the osmolality of the applied solutions. These results suggest that the thermogenesis was caused mainly by changes in osmolality rather than by a specific action of the different solute molecules. 2. Neither pretreatment with the ganglion blocker hexamethonium (20 mg kg(-1), I.P.) or the beta-adrenergic antagonist propranolol (10 mg kg(-1), I.P.), nor bilateral cervical vagotomy or bilateral adrenalectomy had any effect on the osmotically induced thermogenesis. Therefore, the autonomic nervous system and the adrenal gland were not involved in this metabolic response. 3. In response to osmotic stimulation, the temperature of the skeletal muscle increased significantly, whereas that of brown adipose tissue did not change and that of the colon and liver decreased. Accordingly, the site of osmotic thermogenesis is probably in the skeletal muscle, although osmotic stimulation was not accompanied by electromyographic activity and was not blocked by pretreatment with muscle relaxants such as dantrolene sodium or pancuronium bromide, or with the Na(+)-Cl(-) co-transport inhibitor bumetanide. 4. The increases in plasma osmolality observed after the administration of 20 % (1.3 osmol kg(-1)) glucose and 4.1 % (1.3 osmol kg(-1)) NaCl were 4.50 +/- 0.88 and 5.57 +/- 0.71 mosmol kg(-1), respectively. Since the slight increase in osmolality is well within the physiological range of changes that occur after food ingestion, diet-induced thermogenesis may have a component that is mediated by an increase in plasma osmolality, which results from the prandial increase in circulating nutrients.

A model for Sec incorporation with the regions upstream of the UGA Sec codon to play a key role.

For eukaryotic selenoprotein mRNAs, it has been proposed that the SECIS element in the 3'-UTR is required for recognition of UGA as a Sec codon. Some proteins which bind to SECIS (SBP) have been reported. However, it is not clear how the SECIS element in the 3'-UTR can mediate Sec insertion far at the in-frame UGA Sec codons. The idea that there must be a signal near the UGA Sec codon is still being considered. Therefore, we searched for a protein which binds to an RNA sequence surrounding the UGA Sec codon on human GPx mRNA. We found a protein, prepared from bovine brain microsomes, which strongly bound to the RNA fragment upstream of the UGA Sec codon but not to the RNA sequence downstream of the UGA codon. This protein also bound to the SECIS sequence in the 3'-UTR of human GPx, and this binding to SECIS was competed with the RNA fragment upstream of the UGA Sec codon. We also obtained the similar results with the RNA fragments of type I iodothyronine 5'-deiodinase (5'DI) mRNAs. Comparison of such RNA fragments with SECIS fragments revealed similarities in the region upstream of the in-frame UGA Sec codon of several Se-protein mRNAs. The study thus favors a novel model of Sec incorporation at the UGA Sec codon that involves the regions upstream of the UGA codon of mRNAs of mammalian selenoproteins. This model explains that the stem-loop structure covering the UGA codon is recognized by SBP and how the UGA Sec codon escapes from attack by eRF.

Different origin of hypertriglyceridemia induced by a high-fat and a high-sucrose diet in ventromedial hypothalamic-lesioned obese and normal rats.

OBJECTIVE: To clarify the mechanism by which plasma triacylglycerol is affected by a high fat or a sucrose diet. DESIGN: Two sets of six groups each having six rats were prepared-(1) ventromedial hypothalamic (VMH)-lesioned rats fed a standard diet; (2) sham VMH-lesioned rats fed a standard diet; (3) VMH-lesioned rats fed a high-fat diet; (4) sham VMH-lesioned rats fed a high-fat diet; (5) VMH-lesioned rats fed a high-sucrose diet; and (6) sham VMH-lesioned rats fed a high-sucrose diet. After VMH lesions and sham operations, the rats were provided standard, high-fat and high sucrose diets for 2 weeks. Two weeks later, blood samples were collected after overnight fast to determine plasma triacylglycerol (TAG), hepatic triacylglycerol secretion rate (TGSR), fractional catabolic rate (FCR) of triacylglycerol and postheparin plasma lipoprotein lipase (LPL), plasma glucose, insulin and leptin. RESULTS: Values of TAG, TGSR, FCR and LPL in VMH-lesioned obese rats were all greater than those in sham-operated rats, regardless of the diet fed. In sham-operated rats, high-fat diet fed rats showed higher TAG with similar TGSR, higher LPL and lower FCR than those of standard diet fed rats. High-sucrose diet fed rats showed significantly higher TAG with higher TGSR, higher LPL and lower FCR than those of standard diet fed rats. Moreover, high-sucrose diet fed rats showed higher TAG with higher TGSR, lower LPL and higher FCR than those of high-fat diet fed rats. In VMH-lesioned rats, high-fat diet fed rats showed higher TAG with similar TGSR, higher LPL and lower FCR than those of standard diet fed rats. High-sucrose diet fed rats showed markedly higher TAG with notably higher TGSR, higher LPL and lower FCR than those of standard diet fed rats. High-sucrose diet fed rats showed still higher TAG with markedly higher TGSR, similar LPL and higher FCR than those of high-fat diet fed rats. CONCLUSIONS: The mechanism by which TAG metabolism is affected by a high-fat or a high-sucrose diet differed; a high-fat diet increased plasma TAG level by lowering removal of TAG without increase in hepatic TAG secretion in sham-operated (normal) rats. A high-sucrose diet, in contrast, induced much higher plasma TAG levels by both increased hepatic TAG secretion and decreased removal of TAG. The effects of a high-fat or a high-sucrose diet were similar but exaggerated in VMH lesioned animals.

Thermogenesis induced by osmotic stimulation of the intestines in the rat.

Infusion of 5-20% glucose, 1.8-3.6% NaCl, 20% methylglucose, 20% fructose, or 5-10% solutions of various amino acids (10 ml x kg(-1)) into the duodenum induced dose-dependent thermogenesis in urethane-anaesthetized rats. In contrast, infusion of 0.9% NaCl, distilled water, or safflower oil had no effect on the metabolic rate. Infusion of 7.2% urea induced a small and transient increase in the metabolic rate. These results suggested that the thermogenesis was caused mainly by changes in osmolality rather than by a specific action of the different solute molecules. The respiratory exchange ratio increased after the infusion of glucose, fructose, glycine, or serine, did not change after the infusion of NaCl, methylglucose, safflower oil, or distilled water, and decreased after infusion of arginine. Therefore, there was no relationship between substrate utilization and the occurrence of thermogenesis. Intestinal infusion of 3.6% NaCl elevated the plasma osmolality, with a plateau increase of approximately 20 mosmol x kg(-1). However, intravenous infusion of the same amount of NaCl induced a significantly smaller thermogenic response, although it elevated the plasma osmolality with a time course and magnitude similar to those obtained after the intestinal infusion. Infusion of NaCl into the hepatic portal vein or the peritoneal cavity also produced a significantly small thermogenic response. These results suggested an intestinal or mesenteric location for osmoreceptors. To test for possible stimulation of intestinal osmoreceptors after intake of a normal meal, we measured the osmolality of the intestinal contents. The osmolality of the duodeno-jejunal contents was 600-800 mosmol kg-1, whereas the plasma osmolality was 306 +/- 1 mosmol x kg(-1), which suggests that the intestinal osmoreceptors are stimulated after meals and are involved in diet-induced thermogenesis.

Lack of integrative control of body temperature after capsaicin administration.

BACKGROUND: Body temperature is usually regulated by opposing controls of heat production and heat loss. However, systemic administration of capsaicin, the pungent ingredient of hot peppers, facilitated heat production and heat loss simultaneously in rats. We recently found that the capsaicin-induced heat loss and heat production occur simultaneously and that the biphasic change in body temperature is a sum of transient heat loss and long-lasting heat production. Moreover, suppression of the heat loss response did not affect capsaicin-induced heat production and suppression of heat production did not affect capsaicin-induced heat loss. These observations suggest the independent peripheral mechanisms of capsaicin-induced thermal responses. Thus, the capsaicin-induced thermal responses apparently lack an integrated control. METHODS: Male Wistar rats were maintained at an ambient temperature of 24 +/- 1 degrees C on a 12 h on-off lighting schedule at least for two weeks before the experiments. They were anesthetized with urethane (1.5 g/kg, i.p.) and placed on a heating pad, which was kept between 29 and 30 degrees C. Skin temperature(Ts) was measured with a small thermistor, which was taped to the dorsal surface of the rat's tail, to assess vasoactive changes indirectly. Colonic temperature(Tc) was measured with another thermistor inserted about 60 mm into the anus. O2 consumption was measured by the open-circuit method, and values were corrected for metabolic body size (kg0.75). Capsaicin (Sigma) was dissolved in a solution comprising 80% saline, 10% Tween 80, and 10% ethanol, and injected subcutaneously at a dose of 5 mg/kg. Each rat received a single injection of capsaicin because repeated administration of capsaicin renders an animal insensitive to the subsequent administration of capsaicin. Laminectomy was performed at the level of the first and second cervical vertebrae to expose the cervical spinal cord for sectioning. The brain was transected at 4-mm rostral from the interaural line with an L-shaped knife. RESULTS: After administration of capsaicin, O2 consumption increased from 13.5 +/- 0.4 mL/min/kg0.75 at 0 min to a peak of 15.9 +/- 0.4 mL/min/kg0.75 at 71 min and gradually declined but remained higher than the basal value until the end of the 4-h observation period. Ts also immediately increased from 27.7 +/- 0.2 degrees C to 31.9 +/- 0.3 degrees C at 39 min, and it returned to the baseline level within 90 min after the capsaicin administration. Tc initially decreased from 37.1 +/- 0.1 degrees C to 36.8 +/- 0.2 degrees C at 43 min and then gradually increased over the baseline level and remained at 37.6 +/- 0.2 degrees C until the end of the experiment. In spinalized rats, the capsaicin-induced increases in O2 consumption was largely attenuated, while the basal O2 consumption was similar to that of control rats. The basal Ts of spinalized rats was 32.4 +/- 0.3 degrees C, which was higher than that of control rats. Capsaicin increased Ts by less than 1 degree C, and Tc did not change after the capsaicin administration. O2 consumption of decerebrated rats was statistically higher than that of control rats after the injection of capsaicin. However, capsaicin did not increase Ts, showing a lack of a vasodilatory response. Decerebration between the hypothalamus and midbrain prevented the capsaicin-induced heat loss but not the heat production response. CONCLUSION: These results show that the capsaicin-induced heat production and heat loss are controlled separately by the brainstem and by the forebrain, respectively, and suggest that the body temperature regulation is performed without an integrative center.