Testosterone effects on pain and brain activation patterns.

BACKGROUND: This study investigated whether pain and pain-related unpleasantness ratings were altered by blood testosterone levels. We also investigated whether activation of brain regions that represent pain intensity [primary somatosensory cortex (S1)] and pain-related unpleasantness [perigenual ACC (pACC) and orbitofrontal cortex (OFC)] were affected by blood testosterone levels. METHODS: Twenty-six healthy men were recruited. Blood testosterone levels were measured before fMRI scanning. The participants were classified into two groups (high vs. low testosterone) according to their blood testosterone level (each group n = 13). The middle finger was immersed in a 50°C water bath (50°C, 30 s, five times) to induce identical noxious stimulation in all participants. RESULTS: The low testosterone group showed statistically significantly higher pain (P = 0.047), unpleasantness (P = 0.047), anxiety (P = 0.015), and fear ratings (P = 0.01) than the high testosterone group. Fear rating increased as pain rating rose and as testosterone level decreased (P < 0.001). When participants received noxious stimulation, the pACC and OFC were more highly activated in the low testosterone group compared to the high testosterone group. Activation of S1, a region related to pain intensity, did not differ between both groups. CONCLUSION: Compared to the high testosterone group, the low testosterone group had significant activation in the pACC and OFC, regions that represent pain-related unpleasantness, but not in S1 that represents pain intensity, leading to higher pain ratings. These findings emphasize the importance of considering the effects of testosterone levels when treating patients.

Intraoperative factors associated with delayed recovery of liver function after hepatectomy: analysis of 1969 living donors.

BACKGROUND: The safety of healthy living donors who are undergoing hepatic resection is a primary concern. We aimed to identify intraoperative anaesthetic and surgical factors associated with delayed recovery of liver function after hepatectomy in living donors. METHODS: We retrospectively analysed 1969 living donors who underwent hepatectomy for living donor liver transplantation. Delayed recovery of hepatic function was defined by increases in international normalised ratio of prothrombin time and concomitant hyperbilirubinaemia on or after post-operative day 5. Univariate and multivariate logistic regression analyses were performed to determine the factors associated with delayed recovery of hepatic function after living donor hepatectomy. RESULTS: Delayed recovery of liver function after donor hepatectomy was observed in 213 (10.8%) donors. Univariate logistic regression analysis showed that sevoflurane anaesthesia, synthetic colloid, donor age, body mass index, fatty change and remnant liver volume were significant factors for prediction of delayed recovery of hepatic function. Multivariate logistic regression analysis showed that independent factors significantly associated with delayed recovery of liver function after donor hepatectomy were sevoflurane anaesthesia (odds ratio = 3.514, P < 0.001), synthetic colloid (odds ratio = 1.045, P = 0.033), donor age (odds ratio = 0.970, P = 0.003), female gender (odds ratio = 1.512, P = 0.014) and remnant liver volume (odds ratio = 0.963, P < 0.001). CONCLUSIONS: Anaesthesia with sevoflurane was an independent factor in predicting delayed recovery of hepatic function after donor hepatectomy. Although synthetic colloid may be associated with delayed recovery of hepatic function after donor hepatectomy, further study is required. These results can provide useful information on perioperative management of living liver donors.

Verification of endotracheal tube placement using electrical stimulation through electrodes placed on the endotracheal tube cuff.

BACKGROUND: Current methods for verification of endotracheal intubation can fail, particularly in emergency settings. We investigated whether a verification method using electrical stimulation through electrodes placed on the endotracheal tube cuff could distinguish endotracheal and esophageal intubations in an experimental setting. METHODS: During three sequential sessions simulating emergency intubation without paralysis, rapid sequence intubation (RSI) with neuromuscular blockade, and intubation during cardiopulmonary resuscitation, eight pigs were intubated with an endotracheal tube fitted with two electrodes exposed on the cuff of the tube, first in the esophagus and next in the trachea or in reverse sequence. Cuff pressure was monitored during a 5-s electrical stimulation (20 mA, 80 Hz, 500 µs), and delta pressure was calculated as the difference between baseline cuff pressure and maximum cuff pressure during the electrical stimulation. RESULTS: Delta pressure was significantly higher in esophageal than in tracheal placements in all three sequential sessions (86.0 [78.3-89.7] vs. 6.5 [2.0-7.9] mmHg, P = 0.001; 16.6 [13.2-22.8] vs. 0.8 [0.3-2.6] mmHg, P = 0.004; 66.1 [60.0-84.7] vs. 2.7 [0.7-9.7] mmHg, P = 0.001). The delta pressure did not overlap between tracheal and esophageal intubations except for the session simulating RSI with neuromuscular blockade, in which one of eight esophageal placements showed a delta pressure within the delta pressure range of tracheal placements. CONCLUSION: Electrical stimulation through electrodes placed on the endotracheal tube cuff produced remarkably greater increases in cuff pressure in esophageal intubations than in tracheal intubations in an experimental setting.

Osteopontin neutralisation abrogates the liver progenitor cell response and fibrogenesis in mice.

BACKGROUND: Chronic liver injury triggers a progenitor cell repair response, and liver fibrosis occurs when repair becomes deregulated. Previously, we reported that reactivation of the hedgehog pathway promotes fibrogenic liver repair. Osteopontin (OPN) is a hedgehog-target, and a cytokine that is highly upregulated in fibrotic tissues, and regulates stem-cell fate. Thus, we hypothesised that OPN may modulate liver progenitor cell response, and thereby, modulate fibrotic outcomes. We further evaluated the impact of OPN-neutralisation on murine liver fibrosis. METHODS: Liver progenitors (603B and bipotential mouse oval liver) were treated with OPN-neutralising aptamers in the presence or absence of transforming growth factor (TGF)-ß, to determine if (and how) OPN modulates liver progenitor function. Effects of OPN-neutralisation (using OPN-aptamers or OPN-neutralising antibodies) on liver progenitor cell response and fibrogenesis were assessed in three models of liver fibrosis (carbon tetrachloride, methionine-choline deficient diet, 3,5,-diethoxycarbonyl-1,4-dihydrocollidine diet) by quantitative real time (qRT) PCR, Sirius-Red staining, hydroxyproline assay, and semiquantitative double-immunohistochemistry. Finally, OPN expression and liver progenitor response were corroborated in liver tissues obtained from patients with chronic liver disease. RESULTS: OPN is overexpressed by liver progenitors in humans and mice. In cultured progenitors, OPN enhances viability and wound healing by modulating TGF-ß signalling. In vivo, OPN-neutralisation attenuates the liver progenitor cell response, reverses epithelial-mesenchymal-transition in Sox9+ cells, and abrogates liver fibrogenesis. CONCLUSIONS: OPN upregulation during liver injury is a conserved repair response, and influences liver progenitor cell function. OPN-neutralisation abrogates the liver progenitor cell response and fibrogenesis in mouse models of liver fibrosis.

Stretchable liquid-crystal blue-phase gels.

Liquid-crystalline polymers are materials of considerable scientific interest and technological value. An important subset of these materials exhibit rubber-like elasticity, combining the optical properties of liquid crystals with the mechanical properties of rubber. Moreover, they exhibit behaviour not seen in either type of material independently, and many of their properties depend crucially on the particular mesophase employed. Such stretchable liquid-crystalline polymers have previously been demonstrated in the nematic, chiral-nematic, and smectic mesophases. Here, we report the fabrication of a stretchable gel of blue phase I, which forms a self-assembled, three-dimensional photonic crystal that remains electro-optically switchable under a moderate applied voltage, and whose optical properties can be manipulated by an applied strain. We also find that, unlike its undistorted counterpart, a mechanically deformed blue phase exhibits a Pockels electro-optic effect, which sets out new theoretical challenges and possibilities for low-voltage electro-optic devices.

Effect of stroke volume variation-directed fluid management on blood loss during living-donor right hepatectomy: a randomised controlled study.

Reducing blood loss is beneficial in living liver donor hepatectomy. Although it has been suggested that maintaining a low central venous pressure is important, it is known that low stroke volume variation may be associated with increased blood loss. Therefore, we compared the effect on blood loss of 40 patients randomly assigned to a high stroke volume variation group (maintaining 10-20% of stroke volume variation) vs 38 patients in a control group (maintaining < 10% stroke volume variation) during living-donor right hepatectomy. Mean (SD) blood loss during donor hepatectomy was significantly lower in the high stroke volume variation group than in the control group: 476 (131) ml vs 836 (341) ml, respectively (p < 0.001). Blood pressure and peri-operative laboratory values did not differ between the two groups. However, in the high stroke volume variation group, central venous pressure values were also significantly lower. We were unable to disentangle the effects of stroke volume variation and central venous pressure, but our results confirm that the two together appear beneficial.

Myofibroblastic cells function as progenitors to regenerate murine livers after partial hepatectomy.

OBJECTIVE: Smoothened (SMO), a coreceptor of the Hedgehog (Hh) pathway, promotes fibrogenic repair of chronic liver injury. We investigated the roles of SMO+ myofibroblast (MF) in liver regeneration by conditional deletion of SMO in α smooth muscle actin (αSMA)+ cells after partial hepatectomy (PH). DESIGN: αSMA-Cre-ER(T2)×SMO/flox mice were treated with vehicle (VEH) or tamoxifen (TMX), and sacrificed 24-96 h post-PH. Regenerating livers were analysed for proliferation, progenitors and fibrosis by qRT-PCR and quantitative immunohistochemistry (IHC). Results were normalised to liver segments resected at PH. For lineage-tracing studies, αSMA-Cre-ER(T2)×ROSA-Stop-flox-yellow fluorescent protein (YFP) mice were treated with VEH or TMX; livers were stained for YFP, and hepatocytes isolated 48 and 72 h post-PH were analysed for YFP by flow cytometric analysis (FACS). RESULTS: Post-PH, VEH-αSMA-SMO mice increased expression of Hh-genes, transiently accumulated MF, fibrosis and liver progenitors, and ultimately exhibited proliferation of hepatocytes and cholangiocytes. In contrast, TMX-αSMA-SMO mice showed loss of whole liver SMO expression, repression of Hh-genes, enhanced accumulation of quiescent HSC but reduced accumulation of MF, fibrosis and progenitors, as well as inhibition of hepatocyte and cholangiocyte proliferation, and reduced recovery of liver weight. In TMX-αSMA-YFP mice, many progenitors, cholangiocytes and up to 25% of hepatocytes were YFP+ by 48-72 h after PH, indicating that liver epithelial cells were derived from αSMA-YFP+ cells. CONCLUSIONS: Hh signalling promotes transition of quiescent hepatic stellate cells to fibrogenic MF, some of which become progenitors that regenerate the liver epithelial compartment after PH. Hence, scarring is a component of successful liver regeneration.

Individual variations in the vascular content of retrodiscal tissue in the temporomandibular joint: a study using histological sections of human foetuses and magnetic resonance images of adults without pathology.

The vascular content of retrodiscal tissue in the temporomandibular joint (TMJ) plays a critical role in joint function, and its morphology is therefore likely relatedto TMJ pain. Using histological sections of human foetuses as well as T2-weighted magnetic resonance images (MRI), we measured the vascular content of retrodiscal tissue. MRI showing no pathology in and around the TMJ were obtained from18 young patients who had been suffering from headache. In 10 small foetuses (12-14 weeks of gestation) as well as 10 larger foetuses (30-37 weeks), the vascular content showed individual variations exceeding 5 times the minimum value (0.24 vs. 0.04 mm2 per 1 mm²), but no difference between foetal stages was evident. In the MRI from young adults, the variation was less than twice the minimum value (13.6 vs. 8.7 mm² per 100 mm²). The vascular density appeared to be lower in adults than in foetuses. In both foetuses and adults, the thickness (anteroposterior length) of the tissue did not correlate with the vascular sectional area. These findings suggest that the considerable inter-individual differences evident in the vascular content of foetal retrodiscal tissue may be reduced during further development.

Blue-phase templated fabrication of three-dimensional nanostructures for photonic applications.

A promising approach to the fabrication of materials with nanoscale features is the transfer of liquid-crystalline structure to polymers. However, this has not been achieved in systems with full three-dimensional periodicity. Here we demonstrate the fabrication of self-assembled three-dimensional nanostructures by polymer templating blue phase I, a chiral liquid crystal with cubic symmetry. Blue phase I was photopolymerized and the remaining liquid crystal removed to create a porous free-standing cast, which retains the chiral three-dimensional structure of the blue phase, yet contains no chiral additive molecules. The cast may in turn be used as a hard template for the fabrication of new materials. By refilling the cast with an achiral nematic liquid crystal, we created templated blue phases that have unprecedented thermal stability in the range -125 to 125 °C, and that act as both mirrorless lasers and switchable electro-optic devices. Blue-phase templated materials will facilitate advances in device architectures for photonics applications in particular.

Viral agents associated with acute gastroenteritis in Seoul, Korea.

BACKGROUND: The present study was carried out to describe the epidemiologic characteristics of viral gastroenteritis and determine the phylogenetic composition of norovirus strains detected in hospitalized children with acute gastroenteritis in Seoul, Korea. METHODS AND RESULTS: In total, 10,603 stool samples were collected from 2004 to 2008 and tested by RT-PCR or ELISA. In 4,170 (39.3%) samples at least one viral pathogen was present. Rotavirus (RoV) (1,864, 17.5%) was found to be the causative agent followed by norovirus (NoV) (1,845, 17.4%), human adenovirus (HAdV) (266, 2.5%), human astrovirus (HAstV) (194, 1.8%), and sapovirus (SV) (1, 0.009%). Five GI genotypes (GI-1, GI-3, GI-4, GI-8, and GI-9) and eight GII genotypes (GII-2, GII-3, GII-4, GII-6, GII-7, GII-12, GII-16, and GII-17) of NoV were identified in acute gastroenteritis patients in 2008. CONCLUSIONS: The genetic characteristics of norovirus and the epidemiologic patterns of a viral pathogen from acute gastroenteritis patients may give potentially effective data for epidemiological studies in Seoul, Korea.

Detection and characterization of enterovirus associated with herpangina and hand, foot, and mouth disease in Seoul, Korea.

BACKGROUND: Human enteroviruses (HEVs) are a major cause of herpangina, HFMD (hand, foot, and mouth disease), and other neurological diseases in Seoul, Korea. METHODS: A total of 56 specimens from hospitalized patients collected from February to December 2009 (37 females and 19 males) in Seoul were tested for HEV from stool, throat swab, and vesicle swab samples taken from patients with herpangina or HFMD using cell culture and RT-PCR in 2009. By the 1D gene, encoding the VP1 capsid protein, seven different HEV genotypes were detected with Coxsackievirus A2, A4, A5, A9, A16 (CA), Coxsackievirus B1 (CB), and Enterovirus 71 (EV71). The most prevalent genotype was CA16 (6, 10.7%), followed by CA2 (4, 7.1%), CA5 (4, 7.1%), EV71 (2, 3.6%), CA4 (1, 1.8%), CA9 (1, 1.8%), and CB1 (1, 1.8%). The 1D gene sequences of two EV71 strains were closely related with one another (98.5% nucleotide similarity) and belonged to the C4 genotype. CONCLUSIONS: It is important to continuously survey the genetic characteristics of EV71 and CA16 from patients, which will provide useful data that aids in our understanding of HFMD infections in Seoul, Korea and may contribute to future control.

Molecular characterization of hepatitis A virus isolated from acute gastroenteritis patients in the Seoul region of Korea.

Hepatitis A virus (HAV) is a major public health problem throughout the world. As a result of declining HAV endemic in Korea, an increasing number of children and adolescents have become susceptible to HAV infection. HAV is related with sanitation conditions of the environment and is transmitted via the fecal-oral route, either through person-to-person contact or by contaminated water and food. The present study has been carried out to determine the phylogenetic analysis and circulating patterns of HAV strains detected from hospitalized patients with acute gastroenteritis (AGE) in the Seoul region of Korea. In total, 2,782 stool specimens from hospitalized patients with AGE collected in October 2006 to September 2007 in Seoul were tested for HAV. A pair comparison of the nucleic acid sequence of a 159-bp base region at the putative VP1/2A junction of 85 Seoul isolates revealed that the most common HAV strain circulating in the region during 2006-2007 was subgenotype IA. HAV phylogenetic studies can provide important information on the genetic characteristics of HAV from AGE patients who may subsequently become the source of infection in Korea.

Investigation of structural transition of dsDNA on various substrates studied by atomic force microscopy.

Structural transition of single dsDNA molecule which is immobilized on 3-aminopropyltriethoxysilane (APTES) treated substrate (APTES/substrate) or alkylthiol treated substrate (alkylthiol/substrate) has been investigated by atomic force microscopy (AFM). The obtained force versus distance (F-D) curves are used to dissect the transition from B-form to S-form, the melting from double stranded (ds) to single stranded (ss) DNA, and its Young's modulus as well as persistence length. The melt from dsDNA to ssDNA is evidenced by fitting with freely jointed chain (FJC) model. FJC fit and Young's modulus or persistence length values when the molecules are fixed on alkylthiol/substrate are more agreeable with other studies than those on APTES. We have clarified the different results of those experiments by analyzing the binding force between DNA molecules and APTES or alkylthiol linkers on the substrate. The DNA binding to APTES linker is much stronger than that on alkylthiol/substrate.

The hedgehog pathway regulates remodelling responses to biliary obstruction in rats.

BACKGROUND: Chronic biliary obstruction provokes fibrosis and accumulation of immature ductular cells. This fibroductular reaction resolves following biliary decompression, suggesting that it may also be involved in the repair of biliary damage. The hedgehog (Hh) pathway becomes activated in liver after bile duct ligation (BDL), and might modulate hepatic remodelling because Hh ligands are potent morphogens. OBJECTIVE: To study the induction of the Hh pathway during progression and resolution of biliary fibrosis, and to clarify whether Hh signalling regulates accumulation of bile duct progenitor cells. DESIGN AND MAIN OUTCOME MEASURES: Livers from rats with BDL were examined by quantitative real-time polymerase chain reaction analysis and immunohistochemistry to identify factors that might stimulate Hh signalling. BDL rats were subjected to Roux-en-Y hepaticojejunostomy (R-Y) to relieve biliary obstruction in order to determine whether these factors and Hh signalling declined as ductular populations and concomitant fibrosis regressed. Cultures of immature ductular cells were treated with putative Hh inducers and Hh ligands to confirm their functional relevance. RESULTS: BDL increased expression of platelet-derived growth factor-BB (PDGF-BB) and sonic hedgehog (Shh), downregulated hedgehog-interacting protein (Hip), activated Hh signalling, and expanded populations of Hh-responsive ductular cells that expressed pancyotkeratin, a liver progenitor cell marker. After R-Y, Hip remained suppressed, expression of PDGF-BB and Shh gradually declined, and populations of hedgehog-responsive ductular cells regressed. In cultured ductular cells, PDGF-BB treatment induced Shh expression, and incubation with Shh inhibited apoptotic activity. CONCLUSIONS: These results identify a mechanism for activation of the Hh pathway during cholestasis and suggest that Hh signalling regulates ductular cell accumulation after biliary injury.

Characterization of the hypothalamic proopiomelanocortin gene and beta-endorphin expression in the hypothalamic arcuate nucleus of mice elicited by inflammatory pain.

We examined proopiomelanocortin (POMC) mRNA and beta-endorphin expression in the hypothalamus of mice after various nociceptive stimuli. The time-course study (10 min, 30 min, 1 h, 2 h, and 10 h) showed that the POMC mRNA level significantly increases from 1 h after s.c. formalin injection and returns to the control level at 10 h. Intrathecal (i.t.) substance P (SP) injection also increases the hypothalamic POMC mRNA level from 1 h to 10 h. However, i.t. glutamate injection did not affect the hypothalamic POMC gene expression at all time points. We found that the POMC mRNA after s.c. formalin injection was located in the arcuate nucleus of the hypothalamus. In the same manner, beta-endorphin immunoreactivity was also increased in the hypothalamic arcuate nucleus. The expression of phosphorylated extracellular signal-regulated protein kinase 1/2 (pERK1/2), phosphorylated calcium/calmodulin-dependent protein kinase-IIalpha (pCaMK-IIalpha) protein and phosphorylated IkappaB (pIkappaB) protein was increased by s.c. formalin injection at various time points. We also found that increased pERK1/2, pCaMKIIalpha and pIkappaB protein after s.c. formalin injection was mainly located in the arcuate nucleus of hypothalamus in which cells containing beta-endorphin after s.c. formalin injection also express pERK1/2, pCaMK-IIalpha and pIkappaB immunoreactivity. In addition, formalin-induced POMC mRNA expression was significantly reduced by 10 min, pretreatment with i.c.v. PD98059 (mitogen-activated protein kinase (MAPK) pathways inhibitor; 6.6 mug) and KN93 (pCaMK-II inhibitor; 20 mug). In conclusion, POMC mRNA expression in the arcuate nucleus of the hypothalamus was increased by inflammatory pain stimuli, in which pERK1/2, pCaMK-IIalpha and NFkappaB may play an important role in the expression of the hypothalamic POMC gene and beta-endorphin expression.

Albumin-bilirubin grade versus MELD score for predicting survival after transjugular intrahepatic portosystemic shunt (TIPS) creation.

OBJECTIVES: The purpose of this study was to compare the albumin-bilirubin (ALBI) grade and model for end-stage liver disease (MELD) scores for predicting survival after transjugular intrahepatic portosystemic shunt (TIPS) creation. MATERIALS AND METHODS: A retrospective study of pre-procedure ALBI and MELD scores was performed in 197 patients who underwent TIPS from 2005 to 2012. There were 140 men and 57 women, with a mean age of 56±11 (SD) (range: 19-90years). The prognostic capability of ALBI and MELD scores were evaluated using competing risks survival analysis. Discriminatory ability was compared between models using the C-index derived from cause specific Cox proportional hazards models. RESULTS: TIPS were created for ascites or hydrothorax (128 patients), variceal hemorrhage (61 patients), or both (8 patients). Prior to TIPS, 5 patients were ALBI grade 1, 76 were grade 2, and 116 were grade 3. The average pre-TIPS MELD score was 14. Pre-TIPS ALBI score, ALBI grade, and MELD were each significant predictors of 30-day mortality from hepatic failure and overall survival (all P<0.05). Based on the C-index, the MELD score was a better predictor of both 30-day and overall survival (C-index=0.74 and 0.63) than either ALBI score (0.70 and 0.59) or ALBI grade (0.64 and 0.56). In multivariate models, after accounting for MELD score ALBI score provided no additional short- or long-term survival information. CONCLUSION: Although ALBI score and grade were statistically significantly associated with risk of death after TIPS, MELD remains the superior predictor.

Risk factors for biopsy-proven advanced non-alcoholic fatty liver disease in the Veterans Health Administration.

BACKGROUND: With its increasing incidence, nonalcoholic fatty liver disease (NAFLD) is of particular concern in the Veterans Health Administration (VHA). AIMS: To evaluate risk factors for advanced fibrosis in biopsy-proven NAFLD in the VHA, to identify patients at risk for adverse outcomes. METHODS: In randomly selected cases from VHA databases (2005-2015), we performed a retrospective case-control study in adults with biopsy-defined NAFLD or normal liver. RESULTS: Of 2091 patients reviewed, 399 met inclusion criteria. Normal controls (n = 65) had normal liver function. The four NAFLD cohorts included: NAFL steatosis (n = 76), nonalcoholic steatohepatitis (NASH) without fibrosis (n = 68), NAFLD/NASH stage 1-3 fibrosis (n = 82), and NAFLD/NASH cirrhosis (n = 70). NAFLD with hepatocellular carcinoma (HCC) was separately identified (n = 38). Most patients were older White men. NAFLD patients with any fibrosis were on average severely obese (BMI>35 kg/m2 ). Diabetes (54.4%-79.6%) and hypertension (85.8%-100%) were more common in NAFLD with fibrosis or HCC. Across NAFLD, 12.3%-19.5% were enrolled in diet/exercise programs and 0%-2.6% had bariatric surgery. Hispanics exhibited higher rates of NASH (20.6%), while Blacks had low NAFLD rates (1.4%-11.8%), particularly NAFLD cirrhosis and HCC (1.4%-2.6%). Diabetes (OR 11.8, P < .001) and BMI (OR 1.4, P < .001) were the most significant predictors of advanced fibrosis. CONCLUSIONS: In the VHA, diabetes and severe obesity increased risk for advanced fibrosis in NAFLD. Of these patients, only a small proportion (~20%) had enrolled in diet/exercise programs or had bariatric surgery (~2%). These results suggest that providers should focus/tailor interventions to improve outcomes, particularly in those with diabetes and severe obesity.

The effect of single or repeated restraint stress on several signal molecules in paraventricular nucleus, arcuate nucleus and locus coeruleus.

The effect of single or repeated restraint stress on several signal molecules in the hypothalamus was studied in ICR mice. Single restraint stress was induced for 30, 60, and 120 min. A repeated restraint stress was induced for 2 h daily during four consecutive days, and then induced in the same time course on the fifth day. In the immunoblot assay, we observed that the signal molecules c-Fos, phosphorylated extracellular cell-regulated protein kinase (pERK), phosphorylated calcium/calmodulin dependent protein kinase II (pCaMKII) and phosphorylated cyclic-AMP response element binding protein (pCREB) in the hypothalamus were increased by single restraint, and the increased c-Fos and pERK levels were attenuated by repeated restraint stress. However, pCaMKII and pCREB levels were increased by both single and repeated restraint stress. We also observed in the immunohistochemistry study that immunoreactivities (IR) of these signal molecules were changed in paraventricular (PVN) and arcuate nuclei (ArcN) of the hypothalamus in accordance with immunoblot results. Furthermore, in confocal immunofluorescence, the pCaMKII and pCREB up-regulated by repeated restraint stress were co-localized within many neurons of PVN and ArcN. In addition, we found that c-Fos and pCaMKII IR in locus coeruleus (LC) were increased by single restraint, and were attenuated by repeated restraint stress. However, the pERK and pCREB IR were increased by both single and repeated restraint stress. The confocal study revealed that pERK and pCREB up-regulated by repeated restraint stress were co-localized within many neurons of LC. Our results suggest that single and repeated restraint stress differentially triggers the induction and phosphorylation of several signal molecules in the PVN, ArcN, and LC. In addition, single and repeated stress stimuli elicited the brain-region specific changes of signal molecules examined. Furthermore, the upstream signal molecule activating CREB may be also brain-region specific, especially in repeated stress stimuli.

Efficacy of pulsed electromagnetic therapy for chronic lower back pain: a randomized, double-blind, placebo-controlled study.

This randomized, double-blind, placebo-controlled clinical trial studied the effectiveness of pulsed electromagnetic therapy (PEMT) in patients with chronic lower back pain. Active PEMT (n = 17) or placebo treatment (n = 19) was performed three times a week for 3 weeks. Patients were assessed using a numerical rating scale (NRS) and revised Oswestry disability scores for 4 weeks after therapy. PEMT produced significant pain reduction throughout the observation period compared with baseline values. The percentage change in the NRS score from baseline was significantly greater in the PEMT group than the placebo group at all three time-points measured. The mean revised Oswestry disability percentage after 4 weeks was significantly improved from the baseline value in the PEMT group, whereas there were no significant differences in the placebo group. In conclusion, PEMT reduced pain and disability and appears to be a potentially useful therapeutic tool for the conservative management of chronic lower back pain.