Effect of Lonicerae japonicae Flos Carbonisata-Derived Carbon Dots on Rat Models of Fever and Hypothermia Induced by Lipopolysaccharide.

INTRODUCTION: A correlation is established between the efficacy of Chinese herbal medicine and its charcoal drugs. Lonicerae japonicae Flos (LJF) is commonly used to treat fever, carbuncle, and tumors, among others. LJF Carbonisatas (LJFC) is preferred for detoxifying and relieving dysentery and its related symptoms. However, the mechanisms underlying the effects of LJFC remain unknown. AIM: The aim of this study was to explore the effects of LJFC-derived carbon dots (LJFC-CDs) on lipopolysaccharide (LPS)-induced fever and hypothermia rat models. METHODS: LJFC-CDs were characterized using transmission electron microscopy, high-resolution transmission electron microscopy, Fourier-transform infrared, ultraviolet, fluorescence, X-ray photoelectron spectroscopy, X-ray diffraction and high-performance liquid chromatography. The anti-inflammatory effects of LJFC-CDs were evaluated and confirmed using rat models of LPS-induced fever or hypothermia. RESULTS: The LJFC-CDs ranged from 1.0 to 10.0 nm in diameter, with a yield of 0.5%. LJFC-CDs alleviated LPS-induced inflammation, as demonstrated by the expression of tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 and the recovery of normal body temperature. CONCLUSION: LJFC-CDs may have an anti-inflammatory effect and a potential to alleviate fever and hypothermia caused by inflammation.

Antidepressant Potential of Lotus corniculatus L. subsp. corniculatus: An Ethnobotany Based Approach.

As a Turkish traditional medicinal plant, aerial parts of Lotus corniculatus L. subsp. corniculatus (Fabaceae) are used as a painkiller, antihemoroidal, diuretic and sedative. In this study, the antidepressant potential of the plant has been attempted to clarify. Extracts with water, n-Hexane, ethyl acetate, and methanol were prepared respectively from the aerial parts. Antidepressant activity of the extracts were researched by using three different in vivo test models namely a tail suspension test, antagonism of tetrabenazine-induced hypothermia, ptosis, and suppression of locomotor activity and forced swimming test on male BALB/c mice and in vitro monoamine oxidase (MAO)-A and B inhibition assays. The results were evaluated through comparing with control and reference groups, and then active compounds of the active extract have been determined. Bioassay-guided fractionation of active fraction led to the isolation of three compounds and structures of the compounds were elucidated by spectroscopic methods. The data of this study demonstrate that the MeOH extract of the aerial parts of the plant showed remarkable in vivo antidepressant effect and the isolated compounds medicarpin-3-O-glucoside, gossypetin-3-O-glucoside and naringenin-7-O-glucoside (prunin) from the active sub-fractions could be responsible for the activity. Further mechanistic and toxicity studies are planned to develop new antidepressant-acting drugs.

Effects of a methanol extract of Ficus platyphylla stem bark on a two-way active avoidance task and on body core temperature.

Preparations of Ficus platyphylla are used in Nigeria's folk medicine to manage a variety of diseases, including insomnia, psychoses, depression, epilepsy, pain, and inflammation. In this study, we examined the effects of the standardised methanol extract of F. platyphylla stem bark (FP) on two-way active avoidance learning and body core temperature to complement earlier studies on the neuroleptic potential of this medicinal plant, which is already in common use. The extract did not interfere with the acquisition and consolidation of the conditioned avoidance reaction (CAR), but did diminish the retrieval of CAR. The extract dose-dependently reduced body core temperature; this was significantly ameliorated by the use of amphetamine. The results confirmed the neuroleptic-like efficacy of FP, probably via the modulation of dopaminergic neurons.

Discovery of new antidepressant agents: In vivo study on Anthemis wiedemanniana Fisch. & Mey.

ETHNOPHARMACOLOGICAL RELEVANCE: Many of the currently available antidepressants have serious adverse effects and are also expensive. Traditional medicines are major sources of original drugs, and their role in effective treatment is remarkable. In Turkish folk medicine, decoctions and infusions are prepared from the flowers of Anthemis wiedemanniana Fisch. & Mey. They exert antispasmodic and sedative effects and are also used for treating urinary inflammations. The present study was designed to evaluate the antidepressant activity of A. wiedemanniana, which is used against central nervous system disorders in Turkish folk medicine. MATERIALS AND METHODS: n-Hexane, ethyl acetate, and methanol (MeOH) extracts were prepared from the flowers of the plant. The antidepressant potentials of these extracts were evaluated in mouse models using the forced swimming test, tail suspension test, and antagonism of tetrabenazine-induced ptosis, hypothermia, and suppression of locomotor activity. The results were compared with those in control and reference groups, and active constituents of the plant were determined. The MeOH extract of A. wiedemanniana was subjected to various chromatographic separation techniques, leading to the isolation and identification of the active component(s). RESULTS: After confirmation of the antidepressant activity, the MeOH extract was subjected to successive solvent partitioning using solvents of increasing polarity, yielding four subextracts. Each subextract was tested on the same biological activity models. Fraction B was found to have the highest activity and subjected to further chromatographic separation. Isolated germacronolide-type sesquiterpene lactones were elucidated as tatridin A (1) and tanachin (1-epi-tatridin B) (2), which were responsible for the antidepressant activity of the flowers. CONCLUSIONS: This study explored the antidepressant potential of A. wiedemanniana. Using bioassay-guided fractionation and isolation techniques, tatridin A and tanachin (1-epi-tatridin B) were determined as the main active components of the flowers. Further antidepressant mechanistic studies should be conducted for exploring the activity of these compounds against depression. This study can be an important step in the discovery of newer antidepressants.

Involvement of serotonergic, noradrenergic and dopaminergic systems in the antidepressant-like effect of ginsenoside Rb1, a major active ingredient of Panax ginseng C.A. Meyer.

ETHNOPHARMACOLOGY RELEVANCE: Ginsenoside Rb1, a 20 (S)-protopanaxadiol, is a major active ingredient of Panax ginseng C.A. Meyer, which as the King of Chinese herbs, has been wildly used for the treatment of central nervous system diseases. Previous studies have shown that 20 (S)-protopanaxadiol possesses a novel antidepressant-like effect in the treatment of depression, whereas ginsenoside Rb1 in depression has been rarely reported. AIM OF THE REVIEW: The present study was to investigate the antidepressant-like effect of ginsenoside Rb1 and its relevant mechanisms. MATERIALS AND METHODS: The whole experiment was divided into two parts: one part we examined the antidepressant-like effect of ginsenoside Rb1 with open-field test (OFT), tail suspension test (TST), forced swim test (FST), 5-HTP induced head-twitch and reserpine response in mice, another part we used chronic unpredicted mild stress (CUMS) model to further explore the antidepressant-like effect of ginsenoside Rb1 with caffeine, fluoxetine and p-Chlorophenylalanine (PCPA) in rats. Furthermore, the levels of monoamine neurotransmitters of NE, 5-HT, DA and their metabolites 5-HIAA, DOPAC, HVA were all measured by ELISA kits after the CUMS protocol. RESULTS: Our data indicated that 7 days treatment with ginsenoside Rb1 (4, 8, 10mg/kg, p.o.) significantly decreased immobility time in the FST and TST in mice, and played important roles in mice which were induced by 5-HTP (200mg/kg, i.p.) and reserpine (4mg/kg, i.p.). On the basis of CUMS model, 21 days treatment with ginsenoside Rb1 not only had effective interactions with caffeine (5mg/kg, i.p.), fluoxetine (1mg/kg, i.p.) and PCPA (100mg/kg, i.p.), but also significantly up-regulated the 5-HT, 5-HIAA, NE and DA levels in CUMS rats' brain, whereas HVA and DOPAC had no significant difference. Moreover, there was no alteration in spontaneous locomotion in any experimental group. CONCLUSIONS: These results suggest that ginsenoside Rb1 exhibits significant antidepressant-like effect in behavioral tests, chronic animal model and drug interactions, its mechanisms mainly mediated by central neurotransmitters of serotonergic, noradrenergic and dopaminergic systems.

Ginger Extract-Loaded Solid Dispersion System with Enhanced Oral Absorption and Antihypothermic Action.

The aim of this study is to enhance the antihypothermic action of ginger extract (GE) employing a solid dispersion (SD) approach. The prepared SD of GE (GE/SD) was characterized in terms of physicochemical and pharmacokinetic properties. The antihypothermic action of GE samples was evaluated in a rat model of hypothermia. GE/SD exhibited improved dissolution behavior of the major active ingredients in GE, 6-gingerol (6G) and 8-gingerol (8G), with levels of dissolution 12- and 31-fold higher than that of GE, respectively. Even after storage under accelerated conditions, limited degradations of 6G and 8G were observed in GE/SD, although 6G and 8G were slightly degraded in GE. After oral administration of GE (300 mg/kg) and GE/SD (100 mg of GE/kg), the relative bioavailabilities of 6G and 8G in GE/SD were 5.0- and 5.8-fold higher than those in GE, respectively. Orally administered GE/SD (30 mg of GE/kg) inhibited ethanol-evoked hypothermia because of improved oral absorption of 6G and 8G. From these observations, the SD approach might be efficacious for enhancing the nutraceutical potentials of GE.

Antidepressant-like effects of the Radix Bupleuri and Radix Paeoniae Alba drug pair.

The Radix Bupleuri and Radix Paeoniae Alba drug pair plays a pivotal role in Xiaoyaosan, a famous Chinese herbal preparation that is popular in clinical medicine. To investigate the antidepressant-like effects and potential mechanism of action of the Radix Bupleuri and Radix Paeoniae Alba drug pair, we carried out the forced swim test (FST) and tail suspension test (TST), as the mouse models of depression; and the open field test (OFT) to exclude false-positive results. Subsequently, ptosis and hypothermia induced by reserpine were assessed. Finally, the concentrations of monoamine neurotransmitters and their metabolites, namely epinephrine (NE), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in the hippocampal and cortical tissues of mice were detected with HPLC with electrochemical detector. The Radix Bupleuri and Radix Paeoniae Alba (1:1) drug pair at low, medium, and high doses decreased immobility time in both the FST and TST, and counteracted hypothermia induced by reserpine in mice. After the administration of reserpine, the concentrations of 5-HT and NE in the hippocampal and cortical tissues were decreased; however, pre-treatment with the Radix Bupleuri and Radix Paeoniae Alba drug pair significantly elevated the concentrations of 5-HT and NE in the hippocampal and cortical tissues. The results suggested that, compared with single dose of fluoxetine and the drugs used individually, the Radix Bupleuri and Radix Paeoniae Alba drug pair had an excellent antidepressant-like effect. These data revealed a possible mechanism of action, as the regulation of the central monoaminergic neurotransmitter system in the hippocampal and cortical tissues.

[Restoration of respiratory function of an organism after cold oppressions without warming].

In experiments on rats studied influence of intravenous introduction NazdTA on respiratory function of rats after the full termination of breath at deep hypothermia. It is shown that such method without warming application it is possible to lower on 1.5-2.0 degrees C a temperature threshold of approach full a cold paralysis of respiratory function of an organism. It confirms the hypothesis put forward earlier about an important role of infringement of balance of ions of calcium in cytoplasm of cells in development of a pathology of an organism at deep hypothermia. The received results can be used at resuscitation of victims accidental hypothermia.

Lithium attenuates lipopolysaccharide-induced hypothermia in rats.

BACKGROUND: Changes in body temperature are common features among patients with sepsis and septic shock. Similarly, systemic administration of bacterial endotoxin (lipopolysaccharide, LPS) to rats leads to an initial hypothermia followed by elevation in body temperature. These changes in body temperature are accompanied by increased levels of prostaglandin E2 (PGE2) in the hypothalamus. OBJECTIVE: This study examined the effects of lithium and SB216763 - two different glycogen synthase kinase (GSK)-3 inhibitors - on LPS-induced changes in body temperature and hypothalamic PGE2 levels in endotoxemic rats. MATERIALS AND METHODS: Endotoxemia was induced by intraperitoneal injection of LPS (10 mg/kg). Lithium (100 mg/kg) and SB216763 (5 mg/kg) were administered at 2 h before LPS. Body temperature and mortality were monitored during 48 h after LPS injection. In another protocol, rats were sacrificed at 2 h post LPS injection and then, blood, liver and hypothalamus were extracted for inflammatory mediators determination. RESULTS: Lithium but not SB216763 significantly reduced LPS-induced hypothermia, while both compounds did not alter the subsequent elevation in body temperature. Moreover, only lithium significantly reduced hypothalamic PGE2 levels. On the other hand, both compounds significantly reduced plasma, hepatic and hypothalamic tumor necrosis factor-α and decreased plasma PGE2 levels. Both compounds did not alter LPS-induced mortality. CONCLUSIONS: These results suggest that the attenuation of LPS-induced hypothermia by lithium may derive from its reduction of hypothalamic PGE2 levels.

[Experimental evaluation of actoprotective activity of nitrogen-containing heterocyclic compounds derivatives in extreme conditions].

In experiments on nonlinear male mice the ability of new derivatives of nitrogen-containing heterocyclic compounds to increase the physical working capacity in conditions of hyperthermia, hypothermia and acute normobaric hypoxia and hypercapnia has been investigated. It is established, that pyridine derivative IBHF-11 has more expressed positive action in the said conditions. It provided increase of the working capacity of animals at all kinds of extreme influence, and the value of positive action was comparable, and in conditions of acute normobaric hypoxia and hypercapnia exceeded those at the reference products bemitil and bromantan.

Fuzi-Lizhong pill compensates hypothyroid-hypothermia via ghrelin release.

ETHNOPHARMACOLOGICAL RELEVANCE: Fuzi-Lizhong pill (FLZ) is a traditional Chinese medicine for treating patients with Spleen Yang deficient syndrome. Ghrelin, a peptide with 28 amino acid residues, plays multiple roles in thermogenesis. This study aims to explore FLZ regulating ghrelin to compensate hypothermia in rats with hypothyroid and indigestion. MATERIALS AND METHODS: In litter-matched rats, hypothermia was developed with both thyroidectomy at d1 and interscapular brown adipose (IBA) removal at d42, indigestion was induced with both high fat diet and fasting-feeding cycle from d56; the littermates with hypothermia and indigestion were administrated with FLZ from d70. Adaptive thermogenesis, thyroid hormones, metabolites, ghrelin dynamics were measured at d98. RESULTS: The results showed that plasma ghrelin levels were inversely correlated with the gastric ghrelin levels and adaptive thermogenesis in rats undergone both thyroidectomy and IBA removal. Fatty diet and FLZ enhanced the increase of plasma ghrelin of hypothyroid rats. These were supported by the changes of plasma thyroid related hormones, plasma metabolites, gastric ghrelin mRNA and protein, and the effects of fatty diet or FLZ. CONCLUSIONS: Our results suggest that more ghrelin release compensate chronic hypothermia in rats with both hypothyroidism and indigestion. It could explain the mechanisms of FLZ in relieving chronic hypothermia.

Antidepressant-like effect of ethanol extract from Zuojin Pill, containing two herbal drugs of Rhizoma Coptidis and Fructus Evodiae, is explained by modulating the monoaminergic neurotransmitter system in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Zuojin Pill (ZJP), a traditional Chinese medicinal decoction, contains two herbal drugs: Coptis chinensis Franch. and Evodia rutaecarpa (Juss.) Benth. in the ratio of 6:1 (w/w). Previous pharmacological studies have shown that two herbs in ZJP have the antagonistic effects on catecholamine secretion in bovine adrenal medullary cells. Furthermore, the alkaloids from the two herbs in ZJP may provide a protective effect for depression in individuals with a low expressing 5-HTT allele by increasing receptor concentration in serotonergic neurons. However, antidepressant effect has not been reported before and has not been fully clarified. AIM OF THE STUDY: The present study aimed to investigate the antidepressant potential of ethanol extract from ZJP and its monoaminergic mechanism in mice. MATERIALS AND METHODS: Seven alkaloids were determined from the ethanol extract of ZJP using High Performance Liquid Chromatography (HPLC) with the gradient mobile phase. The ethanol extract from ZJP was used to evaluate the antidepressant potential in mice. Mouse models of depression including the tail suspension test (TST) and the forced swim test (FST) were used to evaluate the effects of the ethanol extract from ZJP. A possible mechanism was explored in the tests of antagonism of reserpine-induced ptosis and hypothermia, and 5-HTP induced head twitch response in mice. The contents of monoamine neurotransmitters including norepinephrine (NE), serotonin (5-hydroxytryptamine or 5-HT) in hippocampus of mice and NE, 5-HT, dopamine (DA) in striatum of mice were determined by HPLC system with Electrochemical Detector (ECD). RESULTS: The results showed that intragastric administration of the ethanol extract from ZJP (5, 10, 20mg/kg) or fluoxetine (7.5mg/kg) significantly reduced the duration of immobility in TST and FST. However, the effect was not dose-dependent. Ethanol extract from ZJP (5, 10, 20mg/kg) also increased the accumulative number of the 5-HTP-induced head twitch response in mice. The mice were treated with the ethanol extract from ZJP (5, 10, 20mg/kg) or fluoxetine (7.5mg/kg), which could antagonize reserpine-induced ptosis and hypothermia, moreover, both of them could elevate the contents of NE, 5-HT in hippocampus as well as NE, 5-HT, DA in striatum significantly. CONCLUSION: These results indicate that the ethanol extract from ZJP produced antidepressant-like effect and the possible mechanism, at least in part, is via the central monoaminergic neurotransmitter system and 5-HT plays a major role.

Oily nanosuspension for long-acting intramuscular delivery of curcumin didecanoate prodrug: preparation, characterization and in vivo evaluation.

The objective of this study was to prepare the nanocrystals of curcumin didecanoate (CurDD) by wet ball milling and to investigate the comparative pharmacokinetics of oily nano- and micro-suspensions after intramuscular (i.m.) administration to rats. Upon optimizing the wet ball milling parameters, CurDD nanocrystals were produced with median particle size of ~500 nm and the freeze-dried nanocrystals were readily dispersed in peanut oil to form stable nanosuspensions. Although the nanosuspension appeared to exhibit slower clearance from the injection site after i.m. injection, compared to microsuspension (~5 µm), a significantly higher maximum plasma curcumin concentration (69.0 ng/ml) was observed for the former than that for the latter (18.5 ng/ml). In addition, the nanosuspension provided significant higher plasma curcumin concentrations and brain CurDD contents for at least 15 days than the microsuspension, except for the initial times. A single i.m. injection of nanosuspension appeared to achieve reversal effect on reserpine-induced hypothermia for at least 13 days. This study demonstrates that CurDD nanosuspension may act as a long-acting i.m. injectable for sustained delivery of curcumin, potentially applicable to elicit a long-lasting antidepressant effect.

[Resuscitation of vital activity in intensively cooled animals by physiological methods without rewarming].

White rat males (Wistar) were cooled in the water (9-10 °C) to the stop breathing (at rectal temperature 14.7 ± 0.5°, brain 16.0 ± 0.3 °C). After the removal of water animals were injected 0.5% solution disodium salt ethylenediaminetetraacetic acid (Na2EDTA) intravenously, which reduced the concentration of Ca2+ in the blood. Breathing rats were resumed after 4-8 min after administration Na2EDTA. Then one group of rats was cooled to the temperature of the body 12.2 ± 0.7 (brain 14.9 ± 0.3 °C). At such a low temperatures the breath of rats was long-term (2-3 hours) supported at the level of 12 ± 3 cycle/min. The second group of rats was not additionally cooled after the resumption of breathing. The same dose of Na2EDTA caused the rise of the respiratory rate to a higher level--29 ± 4 cycles/min at a temperature in the rectum and the brain 15-16°. Apparently, the process of accumulation of Ca2+ in the cytoplasm of the respiratory center's cells was slowed after the Na2EDTA injection to hypothermal rats in the bloodstream. It is assumed that the Na2EDTA injection under the hypothermia conditions was activated the cell's protection mechanisms from cold damage. The obtained results and the literature data allowed to conclude that nonhibernators are able to maintain basic life functions under significant reduction in the body temperature.

Persistent hypothermia after intrathecal morphine: case report and literature review.

PURPOSE: To describe a case of persistent hypothermia following spinal anesthesia with intrathecal morphine. CLINICAL FEATURES: Following elective right total knee arthroplasty under spinal anesthesia with isobaric 0.5% bupivacaine 11 mg, fentanyl 15 µg, and preservative-free morphine 150 µg, a 57-yr-old female (93.5 kg, 151 cm) developed postoperative hypothermia with a nadir rectal temperature of 33.6°C four hours after surgery. At times, her temperature could not be measured by tympanic, temporal arterial, oral, axillary, or rectal routes. In spite of the low temperature, the patient complained of feeling hot and was diaphoretic without shivering. With the exception of her temperature, her vital signs were normal postoperatively, and aside from hyperglycemia, complete blood count, electrolytes, thyroid-stimulating hormone, serum cortisol, troponin, and twelve-lead electrocardiogram were normal. Her temperature did not respond to warming efforts with a forced-air warming blanket, infusion of warmed intravenous crystalloid, and hourly bladder irrigation with warm saline through an indwelling urinary catheter. Normothermia returned after she received a small dose of sublingual lorazepam eight hours after surgery. The remainder of her postoperative stay was uneventful. CONCLUSION: Patients undergoing spinal anesthesia with intrathecal morphine may develop postoperative hypothermia that is resistant to warming measures. This complication may be treated successfully with lorazepam.

Antidepressant-like effects of L-theanine in the forced swim and tail suspension tests in mice.

L-theanine (γ-glutamylethylamide), an amino acid component of green tea, has been shown to reduce mental and physical stress, and to improve memory function. In this study, the antidepressant effect of L-theanine was investigated in mice using the forced swim test, tail suspension test, open-field test and reserpine test. L-theanine produced an antidepressant-like effect, since the administration of L-theanine at doses of 1, 4 and 20 mg/kg for 10 successive days significantly reduced the immobility time in both the forced swim test and tail suspension test, compared with the control group, without accompanying changes in ambulation in the open-field test. Moreover, L-theanine significantly antagonized reserpine-induced ptosis and hypothermia. Taken together, these results indicate that L-theanine possessed an antidepressant-like effect in mice, which may be mediated by the central monoaminergic neurotransmitter system.

Respiration restitution in rats following its termination in immersion hypothermia.

Rats were cooled in water until attaining profound hypothermia and respiratory arrest. After removal from water, 0.5% solution of Na2EDTA was administered intravenously. This led to a drop of blood [Ca2+] by 20-30% from the baseline and promoted recovery of respiration following its arrest lasting 10.3±1.4 min. By the 30th minute of Na2EDTA administration, respiration rate increased to 32.3±5.2 cycles per minute and respiration amplitude reached 68±4% of the baseline level. This effect was observed without special warming of the rats. It was concluded that the period during which the organism maintains viability in respiration arrest and disturbances in respiratory center are still reversible is prolonged under conditions of profound hypothermia.

[Cold pathology and experimental therapy of deep hypothermia].

A complete cold paralysis of respiration and thermoregulation occurs in rats at the temperature in the brain 16.6 +/- 0.3 and in the rectum 15.2 +/- 0.3 degrees C. Under the conditions of room temperature 18-19 degrees C, the respiration never restores, and the animals die. This is believed [6] to be the result of calcium ion Ca2+ accumulation in the cells of respiration and thermoregulation centers. After the arrest of respiration the animals were injected with the solution of disodium salt of ethylenediaminetetraacetic acid (Na2EDTA), which binds calcium ions in the blood and facilitates their removal from the cell (explanations in the text). In 7-9 min after the injection the calcium content in the blood decreased and the respiration began to restore at the temperature of the cold paralysis. Thermoregulation was also restored. All the test animals survived. All the control animals, which were not injected with Na2EDTA, died.

Spontaneous endogenous hypermelatoninemia: a new disease?

Melatonin, a major photoperiod-dependent hormone, regulates circadian rhythms and biological rhythms and acts as a prominent sleep promoter. Symptoms related to hypermelatoninemia have been reported in individuals supplemented with melatonin. However, spontaneous endogenous hypermelatoninemia has not been reported previously. A 6-year-old girl previously diagnosed with Shapiro's syndrome was admitted to our hospital on several occasions during a 1-year period with complaints of altered consciousness, syncope, hypothermia and episodes of sweating. The episodes occurred daily and during sleep and lasted for 1-6 h. During these episodes, she sweated profusely and felt faint and her skin was pale and cool. Other complaints included recurrent abdominal pain, urge incontinence and myopia. She was shown to have hypermelatoninemia (>1,000 pg/ml, normal range 0-150 pg/ml) during these episodes. The duration of her attacks decreased with phototherapy and she was successfully treated with propranolol. To our knowledge, this is the first case of hypermelatoninemia without any detectable organic pathology. We did not determine the exact mechanism of hypermelatoninemia in this patient; however, it might have been related to irregular control of pinealocytes by the suprachiasmatic nucleus or related pathways. Hypermelatoninemia should be considered in patients with spontaneous periodic hypothermia and hyperhidrosis, and also in patients with Shapiro's syndrome.