Repeated Dry Sauna Therapy Improves Quality of Life in Obese Korean People / 가정의학회지

Background@#Dry sauna treatments improve the quality of life for chronic pain, congestive heart failure, and type 2 diabetes patients. This study aimed to determine whether dry sauna therapy improved the quality of life of obese people. @*Methods@#A total of 38 consecutive participants aged over 20 years with a body mass index of ≥25 kg/m2 were recruited for the study. The participants were treated with a 90°C dry sauna for 15 minutes, twice daily for 4 consecutive days. To assess the quality of life, all participants completed the 5 level EQ-5D questionnaires and the EQ-Visual Analog Scale. Study parameters were measured on the same day prior to commencing the sauna sessions in a fasted state and 2 days after the last sauna session. @*Results@#The average age was 62.3±9.5 years; 84.2% of the participants were female. The mean body mass index was 28.5±2.4 kg/m2. Dry sauna significantly improved the mean 5 level EQ-5D index scores from 0.83±0.12 to 0.89±0.11 and increased the mean EQ-Visual Analog Scale from 79.0±15.2 to 91.1±9.7. However, there were no significant changes in body mass index, blood pressure, heart rate, or body composition before and after the 8-session sauna therapy. @*Conclusion@#Dry sauna improved the health-related quality of life of obese patients without adverse events. Further clinical studies in larger study populations are needed to verify these findings and provide concrete evidence for obesity treatment.

The Comparison of Seasonal Ginsenoside Composition Contents in Korean Wild Simulated Ginseng (Panax ginseng) which were Cultivated in Different Areas and Various Ages

The ginsenoside content was compared with wild simulated ginseng (Panax ginseng) collected every season at 11 wild simulated ginseng plantations in Korea. As a result, the total saponin of 7 years old wild simulated ginseng showed the highest content of 4.5% in spring sampling wild simulated ginseng, 2.0% in summer sampling wild simulated ginseng, 1.2% in winter sampling wild simulated ginseng and 1.0% in autumn sampling wild simulated ginseng. And also, the total saponin of 10 years old wild simulated ginseng showed the highest content of 3.9% in spring sampling wild simulated ginseng, summer sampling wild simulated ginseng (1.8%), winter sampling wild simulated ginseng (1.6%) and autumn sampling wild simulated ginseng (0.6%). Therefore, the total saponin of spring sampling wild simulated ginseng was about 4.5 – 6.5 times higher than that of autumn sampling wild simulated ginseng regardless of cultivation period.

Dry sauna therapy is beneficial for patients with low back pain

BACKGROUND: Dry sauna has been very popular as an alternative therapy for promoting health among people who want to improve their health condition without relying on pharmaceuticals. The aim of this study was to investigate whether dry sauna therapy improved quality of life and reduced pain in participants with low back pain.METHODS: Study participants comprised a total of 37 consecutive patients who were over 20 years of age with low back pain. Dry sauna therapy was performed twice per day for 5 consecutive days over the course of 1 week, thus comprising a total of 10 sessions each of 15 min of exposure to a 90℃ dry sauna.RESULTS: The verbal numerical rating scale (VNRS) and Oswestry disability index (ODI) scores were significantly reduced after dry sauna therapy (P < 0.001 for both). VNRS pain scores had a median (range) of 5 (2–8) before dry sauna therapy and 3 (0–8) after dry sauna therapy. ODI scores had a median (range) of 12 (2–24) before dry sauna therapy and 8 (1–17) after dry sauna therapy. The proportion of participants who reported successful treatment (excellent + good) was 70%. No adverse effects were observed related to dry sauna therapy.CONCLUSIONS: Our results suggest that dry sauna therapy may be useful to improve quality of life and reduce pain in patients with low back pain. Therefore, pain physicians can recommend dry sauna therapy as an alternative and complimentary therapy for patients with low back pain.

Cocaine- and Amphetamine-Regulated Transcript (CART) Peptide Plays Critical Role in Psychostimulant-Induced Depression

Cocaine- and amphetamine-regulated transcript (CART) peptide is a widely distributed neurotransmitter expressed in the central nervous systems. Previously, several reports demonstrated that nucleus accumbal-injected CART peptide positively modulated behavioral sensitization induced by psychostimulants and regulated the mesocorticolimbic dopaminergic pathway. It is confirmed that CART peptide exerted inhibitory effect on psychostimulant-enhanced dopamine receptors signaling, Ca2+/calmodulin-dependent kinase signaling and crucial transcription factors expression. Besides modulation of dopamine receptors-related pathways, CART peptide also exhibited elaborated interactions with other neurotransmitter receptors, such as glutamate receptors and γ-aminobutyric acid receptors, which further account for attribution of CART peptide to inhibition of psychostimulant-potentiated locomotor activity. Recently, CART peptide has been shown to have anxiolytic functions on the aversive mood and uncontrolled drug-seeking behaviors following drug withdrawal. Moreover, microinjection of CART peptide has been shown to have an anti-depressant effect, which suggests its potential utility in the mood regulation and avoidance of depression-like behaviors. In this review, we discuss CART pathways in neural circuits and their interactions with neurotransmitters associated with psychostimulant-induced depression.

The Memory-Enhancing Effects of Liquiritigenin by Activation of NMDA Receptors and the CREB Signaling Pathway in Mice

Liquiritigenin (LQ) is a flavonoid that can be isolated from Glycyrrhiza radix. It is frequently used as a tranditional oriental medicine herbal treatment for swelling and injury and for detoxification. However, the effects of LQ on cognitive function have not been fully explored. In this study, we evaluated the memory-enhancing effects of LQ and the underlying mechanisms with a focus on the N-methyl-D-aspartic acid receptor (NMDAR) in mice. Learning and memory ability were evaluated with the Y-maze and passive avoidance tests following administration of LQ. In addition, the expression of NMDAR subunits 1, 2A, and 2B; postsynaptic density-95 (PSD-95); phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII); phosphorylation of extracellular signal-regulated kinase 1/2 (ERK 1/2); and phosphorylation of cAMP response element binding (CREB) proteins were examined by Western blot. In vivo, we found that treatment with LQ significantly improved memory performance in both behavioral tests. In vitro, LQ significantly increased NMDARs in the hippocampus. Furthermore, LQ significantly increased PSD-95 expression as well as CaMKII, ERK, and CREB phosphorylation in the hippocampus. Taken together, our results suggest that LQ has cognition enhancing activities and that these effects are mediated, in part, by activation of the NMDAR and CREB signaling pathways.

Fucoidan attenuates 6-hydroxydopamine-induced neurotoxicity by exerting anti-oxidative and anti-apoptotic actions in SH-SY5Y cells

Parkinson's disease (PD) is an irreversible neurological disorder with related locomotor dysfunction and is haracterized by the selective loss of nigral neurons. PD can be experimentally induced by 6-hydroxydopamine (6-OHDA). It has been reported that reactive oxygen species, which deplete endogenous glutathione (GSH) levels, may play important roles in the dopaminergic cell death characteristic of PD. Fucoidan, a sulfated algal polysaccharide, exhibits anti-inflammatory and anti-oxidant actions. In this study, we investigated whether fucoidan can protect against 6-OHDA-mediated cytotoxicity in SH-SY5Y cells. Cytotoxicity was evaluated by using MTT and LDH assays. Fucoidan alleviated cell damage evoked by 6-OHDA dose-dependently. Fucoidan reduced the number of apoptotic nuclei and the extent of annexin-V-associated apoptosis, as revealed by DAPI staining and flow cytometry. Elevation of lipid peroxidation and caspase-3/7 activities induced by 6-OHDA was attenuated by fucoidan, which also protected against cytotoxicity evoked by buthionine-sulfoximine-mediated GSH depletion. Reduction in the glutathione/glutathione disulfide ratio induced by 6-OHDA was reversed by fucoidan, which also inhibited 6-OHDA-induced disruption of mitochondrial membrane potential. The results indicate that fucoidan may have protective action against 6-OHDA-mediated neurotoxicity by modulating oxidative injury and apoptosis through GSH depletion.

Gintonin, an exogenous ginseng-derived LPA receptor ligand, promotes corneal wound healing

Ginseng gintonin is an exogenous ligand of lysophosphatidic acid (LPA) receptors. Accumulating evidence shows LPA helps in rapid recovery of corneal damage. The aim of this study was to evaluate the therapeutic efficacy of gintonin in a rabbit model of corneal damage. We investigated the signal transduction pathway of gintonin in human corneal epithelium (HCE) cells to elucidate the underlying molecular mechanism. We next evaluated the therapeutic effects of gintonin, using a rabbit model of corneal damage, by undertaking histochemical analysis. Treatment of gintonin to HCE cells induced transient increases of [Ca²⁺](i) in concentration-dependent and reversible manners. Gintonin-mediated mobilization of [Ca²⁺](i) was attenuated by LPA1/3 receptor antagonist Ki16425, phospholipase C inhibitor U73122, inositol 1,4,5-triphosphate receptor antagonist 2-APB, and intracellular Ca²⁺ chelator BAPTA-AM. Gintonin facilitated in vitro wound healing in a concentration-dependent manner. When applied as an eye-drop to rabbits with corneal damage, gintonin rapidly promoted recovery. Histochemical analysis showed gintonin decreased corneal apoptosis and increased corneal cell proliferation. We demonstrated that LPA receptor activation by gintonin is linked to in vitro and in vivo therapeutic effects against corneal damage. Gintonin can be applied as a clinical agent for the rapid healing of corneal damage.

Differential Effects of Quercetin and Quercetin Glycosides on Human α7 Nicotinic Acetylcholine Receptor-Mediated Ion Currents

Quercetin is a flavonoid usually found in fruits and vegetables. Aside from its antioxidative effects, quercetin, like other flavonoids, has a various neuropharmacological actions. Quercetin-3-O-rhamnoside (Rham1), quercetin-3-O-rutinoside (Rutin), and quercetin-3-(2(G)-rhamnosylrutinoside (Rham2) are mono-, di-, and tri-glycosylated forms of quercetin, respectively. In a previous study, we showed that quercetin can enhance α7 nicotinic acetylcholine receptor (α7 nAChR)-mediated ion currents. However, the role of the carbohydrates attached to quercetin in the regulation of α7 nAChR channel activity has not been determined. In the present study, we investigated the effects of quercetin glycosides on the acetylcholine induced peak inward current (I(ACh)) in Xenopus oocytes expressing the α7 nAChR. I(ACh) was measured with a two-electrode voltage clamp technique. In oocytes injected with α7 nAChR copy RNA, quercetin enhanced I(ACh), whereas quercetin glycosides inhibited I(ACh). Quercetin glycosides mediated an inhibition of I(ACh), which increased when they were pre-applied and the inhibitory effects were concentration dependent. The order of I(ACh) inhibition by quercetin glycosides was Rutin≥Rham1>Rham2. Quercetin glycosides-mediated I(ACh) enhancement was not affected by ACh concentration and appeared voltage-independent. Furthermore, quercetin-mediated I(ACh) inhibition can be attenuated when quercetin is co-applied with Rham1 and Rutin, indicating that quercetin glycosides could interfere with quercetin-mediated α7 nAChR regulation and that the number of carbohydrates in the quercetin glycoside plays a key role in the interruption of quercetin action. These results show that quercetin and quercetin glycosides regulate the α7 nAChR in a differential manner.

Quinpirole Increases Melatonin-Augmented Pentobarbital Sleep via Cortical ERK, p38 MAPK, and PKC in Mice

Sleep, which is an essential part of human life, is modulated by neurotransmitter systems, including gamma-aminobutyric acid (GABA) and dopamine signaling. However, the mechanisms that initiate and maintain sleep remain obscure. In this study, we investigated the relationship between melatonin (MT) and dopamine D2-like receptor signaling in pentobarbital-induced sleep and the intracellular mechanisms of sleep maintenance in the cerebral cortex. In mice, pentobarbital-induced sleep was augmented by intraperitoneal administration of 30 mg/kg MT. To investigate the relationship between MT and D2-like receptors, we administered quinpirole, a D2-like receptor agonist, to MT- and pentobarbital-treated mice. Quinpirole (1 mg/kg, i.p.) increased the duration of MT-augmented sleep in mice. In addition, locomotor activity analysis showed that neither MT nor quinpirole produced sedative effects when administered alone. In order to understand the mechanisms underlying quinpirole-augmented sleep, we measured protein levels of mitogen-activated protein kinases (MAPKs) and cortical protein kinases related to MT signaling. Treatment with quinpirole or MT activated extracellular-signal-regulated kinase 1 and 2 (ERK1/2), p38 MAPK, and protein kinase C (PKC) in the cerebral cortex, while protein kinase A (PKA) activation was not altered significantly. Taken together, our results show that quinpirole increases the duration of MT-augmented sleep through ERK1/2, p38 MAPK, and PKC signaling. These findings suggest that modulation of D2-like receptors might enhance the effect of MT on sleep.

Growth Hormone-Releaser Diet Attenuates Cognitive Dysfunction in Klotho Mutant Mice via Insulin-Like Growth Factor-1 Receptor Activation in a Genetic Aging Model

BACKGROUND: It has been recognized that a defect in klotho gene expression accelerates the degeneration of multiple age-sensitive traits. Accumulating evidence indicates that aging is associated with declines in cognitive function and the activity of growth hormone (GH)/insulin-like growth factor-1 (IGF-1). METHODS: In this study, we examined whether a GH-releaser diet could be effective in protecting against cognitive impairment in klotho mutant mice. RESULTS: The GH-releaser diet significantly induced the expression of IGF-1 and IGF-1 receptors in the hippocampus of klotho mutant mice. Klotho mutant mice showed significant memory impairments as compared with wild-type mice. In addition, the klotho mutation significantly decreased the expression of cell survival/antiapoptotic factors, including phospho-Akt (p-Akt)/phospho-glycogen synthase kinase3beta (p-GSK3beta), phospho-extracellular signal-related kinase (p-ERK), and Bcl-2, but significantly increased those of cell death/proapoptotic factors, such as phospho-c-jun N-terminal kinase (p-JNK), Bax, and cleaved caspase-3 in the hippocampus. Treatment with GH-releaser diet significantly attenuated both decreases in the expression of cell survival/antiapoptotic factors and increases in the expression of cell death/proapoptotic factors in the hippocampus of klotho mutant mice. In addition, klotho mutation-induced oxidative stress was significantly attenuated by the GH-releaser diet. Consequently, a GH-releaser diet significantly improved memory function in the klotho mutant mice. GH-releaser diet-mediated actions were significantly reversed by JB-1, an IGF-1 receptor antagonist. CONCLUSION: The results suggest that a GH-releaser diet attenuates oxidative stress, proapoptotic changes and consequent dysfunction in klotho mutant mice by promoting IGF-1 expression and IGF-1 receptor activation.

Neuroprotective effects of resveratrol on 6-hydroxydopamine-induced damage of SH-SY5Y cell line / 대한수의학회지

Parkinson's disease is known to exhibit progressive degeneration of the dopaminergic neurons in the substantia nigra via inhibition of glutathione metabolism. It is well known that 6-Hydroxydopamine (6-OHDA) induces Parkinson's disease-like symptoms, while resveratrol (3,5,4'-trihydroxystilbene) has been shown to have anti-inflammatory and antioxidant effects. In the present study, we investigated the neuroprotective effects of resveratrol, a phytoalexin found in grapes and various plants, on 6-OHDA-induced cell damage to the SH-SY5Y human neuroblastoma cell line. Resveratrol (5 and 10 microM) inhibited 6-OHDA (60 microM)-induced cytotoxicity in SH-SY5Y cells and induced a reduction of the number of apoptotic nuclei caused by 6-OHDA treatment. Additionally, the total apoptotic rate of cells treated with both resveratrol (10 microM) and 6-OHDA (60 microM) was less than that of 6-OHDA treated cells. Resveratrol also dose-dependently (1, 5 and 10 microM) scavenged reactive oxygen species (ROS) induced by 6-OHDA in SH-SY5Y cells and prevented depletion of glutathione in response to the 6-OHDA-induced cytotoxicity in the glutathione assay. Overall, these results indicate that resveratrol exerts a neuroprotective effect against 6-OHDA-induced cytotoxicity of SH-SY5Y cells by scavenging ROS and preserving glutathione.

Involvement of Genetic and Environmental Factors in the Onset of Depression

First, this article provides a brief overview of the previous hypotheses regarding depression and then focuses on involvement of genetic and environmental factors in development of depression. According to epidemiological research, 30~40% of occurrences of bipolar disorder involve a genetic factor. Therefore, environmental factors play a more important role in development of depression. Resilience and resistance to stress are common; therefore, although a certain extent of stress might be received during the embryonic or perinatal period, having a genetic predisposition to mental disorders does not imply that a mental disorder will develop. However, having a genetic predisposition to disorders does weaken resistance to stresses received during puberty, and without the ability to recover, a mental disorder is triggered. The importance of epigenetics in maintaining normal development and biology is reflected by the observation that development of many diseases occurs when the wrong type of epigenetic marks are introduced or are added at the wrong time or in the wrong place. Involvement of genetic and environmental factors in the onset of depression was investigated in relation to epigenetics. When mice with the disrupted in schizophrenia 1 (DISC1) abnormal gene received isolated rearing stress, depression-like abnormal behaviors and decreased gene expression of tyrosine hydroxylase in the frontal cortex by epigenetical suppression via DNA methylation were observed. Decrease of dopamine in the frontal cortex triggers behavioral disorders. Administration of a glucocorticoid receptor antagonist resulted in full recovery from neurological and behavioral disorders. These results suggest a new therapeutic approach to depression.

Esculetin inhibits N-methyl-D-aspartate neurotoxicity via glutathione preservation in primary cortical cultures / 한국실험동물학회지

Recently, loss of endogenous glutathione during N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxic injury, and the resultant overproduction of reactive oxygen species (ROS) through an arachidonic acid cascade process in brain, have been implicated in neuronal damage in various neurodegenerative diseases. Glutathione depletion induced by L-buthionine-(S,R)-sulfoximine (BSO), an inhibitor of glutathione synthesis, is known to cause arachidonic acid-mediated excitotoxicity in primary mixed cortical cultures. The aim of this study was to investigate whether esculetin (6,7-dihydroxycoumarin), an inhibitor of lipoxygenase, protects against neurotoxicity induced by NMDA or BSO. We observed that neurotoxicity induced by NMDA but not kainic acid was attenuated by esculetin. At the same concentration (100 microM), esculetin attenuated the 45Ca2+ uptake elevation induced by NMDA. Free radical-mediated neuronal injury induced by H2O2 and xanthine/xanthine oxidase was concentration-dependently blocked by esculetin. Esculetin (1-30 microM) dose-dependently inhibited BSO-induced neuronal injury. In addition, arachidonate-induced neurotoxicity was completely blocked by esculetin. BSO also reduced glutathione peroxidase (GPx) activity, but did not change glutathione reductase (GR) activity 24 h after treatment. Esculetin dose-dependently increased GR activity, but did not alter GPx activity. These findings suggest that esculetin can contribute to the rescue of neuronal cells from NMDA neurotoxicity and that this protective effect occurs partly through NMDA receptor modulation and the sparing of glutathione depletion.

Exposure to Extremely Low Frequency Magnetic Fields Induces Fos-Related Antigen-Immunoreactivity Via Activation of Dopaminergic D1 Receptor

We previously demonstrated that repeated exposure to extremely low frequency magnetic fields (ELF-MF) increases locomotor activity via stimulation of dopaminergic D1 receptor (J. Pharmacol. Sci., 2007;105:367-371). Since it has been demonstrated that activator protein-1 (AP-1) transcription factors, especially 35-kDa fos-related antigen (FRA), play a key role in the neuronal and behavioral adaptation in response to various stimuli, we examined whether repeated ELF-MF exposure induces FRA-immunoreactivity (FRA-IR) in the striatum and nucleus accumbens (striatal complex) of the mice. Repeated exposure to ELF-MF (0.3 or 2.4 mT, 1 h/day, for consecutive fourteen days) significantly induced hyperlocomotor activity and FRA-IR in the striatal complex in a field intensity-dependent manner. ELF-MF-induced FRA-IR lasted for at least 1 year, while locomotor activity returned near control level 3 months after the final exposure to ELF-MF. Pretreatment with SCH23390, a dopaminergic D1 receptor antagonist, but not with sulpiride, a dopaminergic D2 receptor antagonist, significantly attenuated hyperlocomotor activity and FRA-IR induced by ELF-MF. Our results suggest that repeated exposure to ELF-MF leads to prolonged locomotor stimulation and long-term expression of FRA in the striatal complex of the mice via stimulation of dopaminergic D1 receptor.

Serochemical and Histopathological Observations on the Effect of Malotilate in Chronic Liver Injury Induced by Carbon Tetrachloride with or without Ethanol

An experimental studies were carried out to observe the protective effects of malotilate, a new antihepatotoxic agent, on the chronic hepatic injury induced by CCl4 with or without ethanol. The rats used weighed about 200g were divided into 2 groups, 4 weeks & 8 weeks. Each group was given by orally with malotilate, 100 mg/kg, once a day, and was injected by subcutaneously with CCl4 1.5 mg/kg in a mixture with olive oil twice a week. Aqueous ethanol (20%) was administered in drinking water daily. The serochemical and histopathological studies were carried out in each experimental group. The results were as follows: 1. The chronic liver injuries induced by CCl4 with or without ethanol were significantly ameliorated by normalize serum values GOT, GPT. Alkaline phosphatase, Cholesterol, HDL-Cholesterol, and gamma glutamyl transpeptidase. 2. In Group of 4 weeks, malotilate manifested protective effects by significant inhibition of fatty changes, spotty necrosis and fibrosis in CCl4-intoxicated liver with or without additional ethanol. 3. In group of 8 weeks, malotilate significantly imoproved fatty changes, fibrogenic activity in the group administered with CCl4, followed by ethanol.