Serum Norepinephrine Levels Research Articles

Housing temperature affects the circadian rhythm of hepatic metabolism and clock genes.

Environmental temperature remarkably impacts on metabolic homeostasis, raising a serious concern about the optimum housing temperature for translational studies. Recent studies suggested that mice should be housed slightly below their thermoneutral temperature (26°C). On the other hand, the external temperature, also known as a zeitgeber, can reset the circadian rhythm. However, whether housing temperature affects the circadian oscillators of the liver remains unknown. Therefore, we have compared the effect of two housing temperatures, namely 21°C (conventional; TC) and 26°C (thermoneutral; TN), on the circadian rhythms in mice. We found that the rhythmicity of food intake showed an advanced phase at TC, while the activity was more robust at TN, with a prolonged period onset. The serum levels of norepinephrine were remarkably induced at TC, but failed to oscillate rhythmically at both temperatures. Likewise, circulating glucose levels were increased but were non-rhythmic under TC. Both total cholesterol and triglycerides levels were induced at TN, but showed an advanced phase under TC. Additionally, the expression of hepatic metabolic genes and clock genes remained rhythmic at both temperatures, with the exception of G6Pase, Fasn, Cpt1a and Cry2, at TN. Nevertheless, the liver histology examination did not show any significant changes in response to housing temperature. Although the non-consistent trends of phase changes in each temperature, our results suggest a non-reductant role of temperature in mouse internal rhythmicity resetting. Thus, the temperature-controlled internal circadian synchronization within organs should be taken into consideration when optimizing housing temperature for mice.

216-OR: O-GlcNAc Transferase in the Ventromedial Hypothalamus Regulates Lipid Metabolism through Fat Depot–Specific Sympathetic Innervation

The ventromedial hypothalamus (VMH) is a primary site that initiates counter-regulatory response and regulates food intake, maintaining glucose and lipid homeostasis. Known as a nutrient sensor and metabolic regulator, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of intracellular proteins is catalyzed by O-GlcNAc transferase (OGT). How O-GlcNAc signaling in the VMH regulates whole-body metabolism remains unknown. Here, using the mouse model with VMH neuron-specific OGT deletion (VOK), we report that OGT is a nutrient sensor in VMH neurons that primarily regulates lipid metabolism. VOK mice show increased body weight and adiposity as well as reduced energy expenditure. OGT deletion in VMH neurons has no significant effects on food intake, physical activity, substrate utilization, glucose tolerance or insulin sensitivity. Lipolysis in subcutaneous and visceral white adipose tissues (WATs) is reduced in VOK mice, indicated by reduced activation of hormone-sensitive lipase (HSL) via cAMP-dependent protein kinase (PKA). In addition, VOK mice have lower serum glucagon and norepinephrine levels and show impaired depot-specific sympathetic innervation to WATs. These data reveal that O-GlcNAc signaling in VMH neurons specifically controls lipid metabolism through depot-specific sympathetic innervation. Disclosure Q. Wang: None. B. Zhang: None. Y. Yang: None. J. Mi: None. G. Tian: None. Q. Ong: None. X. Yang: None. Funding American Diabetes Association (1-19-IBS-119 to X.Y.); National Institutes of Health (R01DK089098, R01DK102648)

Intraoperative dexmedetomidine attenuates norepinephrine levels in patients undergoing transsphenoidal surgery: a randomized, placebo-controlled trial

BackgroundDexmedetomidine has sympatholytic effects. We investigated whether dexmedetomidine could attenuate stress responses in patients undergoing endoscopic transnasal transseptal transsphenoidal surgery.MethodsForty-six patients were randomized to receive a continuous infusion of 0.9% saline (n = 23) or dexmedetomidine (n = 23). Immediately after general anesthesia induction, the dexmedetomidine group received a loading dose of 1 mcg/kg dexmedetomidine over 10 min, followed by a maintenance dose of 0.2–0.7 mcg/kg/h and the control group received 0.9% saline at the same volume until 30 min before the end of surgery. Serum levels of epinephrine, norepinephrine, and glucose were assessed before surgery (T1) and the end of drug infusion (T2). The primary outcome was the change in norepinephrine levels between the two time points.ResultsChanges (T2-T1 values) in perioperative serum norepinephrine levels were significantly greater in the dexmedetomidine group than in the control group (median difference, 56.9 pg/dL; 95% confidence interval, 20.7 to 83.8 pg/dL; P = 0.002). However, epinephrine level changes did not show significant intergroup differences (P = 0.208). Significantly fewer patients in the dexmedetomidine group than in the control group required rescue analgesics at the recovery area (4.3% vs. 30.4%, P = 0.047).ConclusionsIntraoperative dexmedetomidine administration reduced norepinephrine release and rescue analgesic requirement. Dexmedetomidine might be used as an anesthetic adjuvant in patients undergoing transnasal transseptal transsphenoidal surgery.Trial registrationClinical Trial Registry of Korea, identifier: KCT0003366; registration date: 21/11/2018; presenting author: Ji Seon Jeong.

Twelve-month Studies on Perilla Oil Intake in Japanese Adults-Possible Supplement for Mental Health.

Perilla oil (PO), rich in α-linolenic acid (LNA, C18:3, ω-3), is increasingly alleged to have numerous health benefits in humans. However, the current reports detailing the effects of PO on human mental health are not adequate. Therefore, in the current investigation we compared the effects of PO or placebo treatment on the mental condition of healthy adult Japanese volunteers. At baseline and after 12 months of treatment, mental health condition was assessed using the Zung Self-Rating Depression Scale (SDS) and Apathy Scale, and serum biochemical parameters were determined. From baseline to 12 months of intervention, both SDS depression and apathy scores improved significantly in the PO-administered group. Compared to those of control group, serum norepinephrine and serotonin levels after 12 months decreased in the PO-administered group. The enhanced mental state observed in PO-subjects was accompanied by LNA level increases in erythrocyte plasma membranes. Our data demonstrate that PO intake enhances blood LNA levels and may maintain healthy mental conditions in adult subjects.

Relationship Between Serum Norepinephrine Levels at ICU Admission and the Risk of ICU-Acquired Delirium: Secondary Analysis of the Melatonin Evaluation of Lowered Inflammation of ICU Trial.

A secondary analysis of the data of 81 patients enrolled in our previous randomized clinical trial. ICU of an academic hospital. ICU patients in whom the serum levels of catecholamines were measured at ICU admission. None. We evaluated the association between the serum levels of catecholamines measured at ICU admission and the risk of ICU-acquired delirium separately in patients who had received exogenous catecholamines at ICU admission (Ex[+] group) and those who had not received exogenous catecholamines (Ex[-] group). The serum levels of norepinephrine measured at ICU admission were significantly associated with the risk of ICU-acquired delirium in the Ex(-) group (odds ratio, 2.58; 95% CI, 1.02-6.52; p = 0.046), but not in the Ex(+) group (odds ratio, 1.02; 95% CI, 0.88-1.18; p = 0.823). Furthermore, there was a statistically significant interaction effect between the serum levels of norepinephrine and the use/nonuse of exogenous catecholamines at ICU admission in relation to the risk of occurrence of ICU-acquired delirium (p interaction = 0.017). The serum levels of norepinephrine measured at admission were associated with the risk of occurrence of ICU-acquired delirium in patients who had not received exogenous catecholamines at ICU admission, whereas no such association was observed in those who had received exogenous catecholamines previously. Thus, the association between the serum levels of catecholamines measured at admission and the risk of ICU-acquired delirium differed between patients who had/had not received exogenous catecholamines at ICU admission.

Sex specific effect of ATPase inhibitory factor 1 on body weight: studies in high fat diet induced obese mice and genetic association studies in humans

BackgroundBased on the metabolic effect of exogenous ATPase inhibitory factor 1 (IF1) on glucose metabolism, we tested whether IF1 treatment is effective in ameliorating weight gain and whether its effects are sex specific. MethodsHFD-fed C57BL/6 mice were treated with IF1 (5 mg/kg body weight, injected intraperitoneally). The underlying mechanisms of effect of IF1 on body weight were investigated in vitro and in vivo. Associations between genotypes of IF1 and obesity and relevant phenotype were further tested at the population level. ResultsChronic treatment with IF1 significantly decreased body weight gain by regulating food intake of HFD-fed male mice. IF1 activated the AKT/mTORC pathway and modulated the expression of appetite genes in the hypothalamus of HFD-fed male mice and its effect was confirmed in hypothalamic cell lines as well as hypothalamic primary cells. This required the interaction of IF1 with β-F1-ATPase on the plasma membrane of hypothalamic cells, which led to an increase in extracellular ATP production. In addition, IF1 treatment showed sympathetic nerve activation as measured by serum norepinephrine levels and UCP-1 expression in the subcutaneous fat of HFD-fed male mice. Notably, administration of recombinant IF1 to HFD-fed ovariectomized female mice showed remarkable reductions in food intake as well as body weight, which was not observed in wild-type 5-week female mice. Lastly, sex-specific genotype associations of IF1 with obesity prevalence and metabolic traits were demonstrated at the population level in humans. IF1 genetic variant (rs3767303) was significantly associated with lower prevalence of obesity and lower levels of body mass index, waist circumference, hemoglobin A1c, and glucose response area only in male participants. ConclusionIF1 is involved in weight regulation by controlling food intake and potentially sympathetic nerve activation in a sex-specific manner.

The Effect of Natural Ocean Sound Exposure and Ocean-Side Relaxation on Chronic Tinnitus Patients: A Pilot Study in Korea.

Sound therapy is a treatment modality for tinnitus patients by increasing the background neuronal activity in the auditory system and inducing relative alleviation of the tinnitus. This study was performed to evaluate the efficacy of natural ocean sound exposure and ocean-side relaxation in chronic tinnitus patients. We prospectively enrolled all 18 chronic tinnitus patients (≥6 months) from July to November 2018. All patients completed 90 hours of our programs. The improvement in their subjective tinnitus severity, moods, the quality of life, and sleep was serially assessed using several questionnaires at baseline, immediately, and 1 month after the program. Changes in serum stress hormone levels of the patients were also compared between the baseline and immediately after the program. Average total Tinnitus Handicap Questionnaire score and factor 2 (hearing difficulty related to tinnitus) score significantly improved over time (P = .024 and P = .002). Patient's serum cortisol and epinephrine level did not show significant decrease, and serum norepinephrine and serotonin level significantly increased immediately after our program (P < .001 and P < .001). Natural ocean sound exposure and ocean-side relaxation for short-term period has a potential efficacy on chronic tinnitus patients.

Efficacy of electroacupuncture combined with probiotics for depression and chronic diarrhea in patients and effect on serum inflammatory cytokines, NE and BDNF.

Efficacy of electroacupuncture combined with probiotics for depression and chronic diarrhea in patients, and its effect on the levels of serum inflammatory cytokines, norepinephrine (NE) and brain-derived neurotrophic factor (BDNF) were investigated. A total of 104 patients with depression and chronic diarrhea admitted to The First Clinical Faculty, Guangxi University of Traditional Chinese Medicine from July 2014 to June 2018 were randomly divided into the observation group (n=56) and the control group (n=48). The observation group was treated with electroacupuncture combined with probiotics, and the control group was given conventional drugs for depression and chronic diarrhea. The Hamilton Depression Rating Scale (HAM-D) score and the abdominal symptom score were evaluated before treatment and at 3 weeks after treatment. Changes in the levels of serum inflammatory cytokines [interleukin (IL)-6, IL-2 and tumor necrosis factor (TNF)-α] as well as the levels of NE and BDNF in the two groups of patients before and after treatment were determined using radioimmunoassay. Compared with those in the control group, the symptoms of depression and diarrhea in the observation group were remarkably alleviated (p<0.05). After treatment, the serum cytokine levels in the two groups of patients were decreased, and the decreased level of serum inflammatory cytokines in the observation group was not obviously different from that in the control group. Besides, the serum BDNF level in the observation group was also reduced (p<0.05). The overall efficacy of the observation group was superior to that of the control group, showing a statistical difference. Electroacupuncture combined with probiotics brings good efficacy to patients with depression and chronic diarrhea, which is worthy of clinical promotion and development.

An enhanced expression of hypothalamic neuronal nitric oxide synthase in a rat model of simulated transport stress

BackgroundTransport stress not only causes physiological changes but also induces behavioral responses, including anxiety-like and depression-like behavioral responses in animals. The neuronal nitric oxide synthase (nNOS) plays a pivotal role in transport stress. This study aimed to investigate the effects of acute transport stress on the expression of nNOS and the distribution of nNOS-positive neurons in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus in rats and to explore the neuroendocrine mechanism of transport stress.ResultsIn this study, for the first time, we investigated the effects of transport stress on nitric oxide (NO)-NOS in the hypothalamus. After simulated stress, rats exhibited behavioral changes in the open field test (OFT), increased serum corticosterone (CORT) and norepinephrine (NE) levels, and increased NO content in the hypothalamus. In addition, nNOS expression in the hypothalamic PVN was upregulated, and its distribution was altered in stressed rats compared with that of unstressed rats.ConclusionsOur findings indicate that simulated transport stress increases nNOS expression and alters its distribution in the PVN of the rat hypothalamus.

Effects of continuous positive airway pressure therapy on daytime and nighttime arterial blood pressure in patients with severe obstructive sleep apnea and endothelial dysfunction.

A nocturnal non-dipping or rise in blood pressure (BP) is associated with poor cardiovascular outcome. This study aimed to test whether continuous positive airway pressure (CPAP) therapy can reduce nocturnal BP and normalize the 24-h BP profile in patients with severe obstructive sleep apnea (OSA) and erectile dysfunction as a surrogate for endothelial dysfunction (ED). Eighteen consecutive patients with OSA and ED on stable antihypertensive medication (age 55.8 ± 9.5years, body mass index 35.5 ± 3.8kg/m2, apnea-hypopnoea index 66.1 ± 27.4/h) were treated with CPAP for 6months (average daily use 5.8 ± 2.3h). Twenty-four hour BP recordings were performed using a portable monitoring device. Rising was defined as an increase, whereas non-dipping was defined as a fall in nocturnal BP of less than 10% compared to daytime values. Serum noradrenaline levels as markers of sympathetic activity were measured at baseline and at 6month follow up. Compared to baseline, nocturnal systolic and diastolic BP were significantly reduced after CPAP therapy (128.5 ± 14 to 122.9 ± 11mmHg, p = 0.036; 76.2 ± 9 to 70.5 ± 5mmHg, p = 0.007). The frequency of non-dipping and rising nocturnal systolic BP, as well as mean nocturnal heart rate, was reduced after CPAP treatment (73 to 27%, p = 0.039; 20 to 7%, p = 0.625; from 81.5 ± 10 to 74.8 ± 8 beats per minute p = 0.043). Serum levels of noradrenaline were significantly lower after CPAP therapy (398 ± 195ng/l vs. 303 ± 135ng/l, p = 0.032). In patients with severe OSA and clinically apparent ED, CPAP therapy was associated with a decrease in nocturnal BP and serum noradrenaline levels, as well as a normalization of the 24-h BP profile.

Walnut-Derived Peptide PW5 Ameliorates Cognitive Impairments and Alters Gut Microbiota in APP/PS1 Transgenic Mice.

Decreasing β-amyloid (Aβ) accumulation is of significance in finding therapeutic candidates for cognitive impairments in Alzheimer's disease (AD). The aim of this study is to investigate the potency of the active components of walnut protein in decreasing Aβ aggregation and ameliorating cognitive impairments. Cell model of intracellular Aβ42 aggregation is used to explore the active ingredients in walnut protein hydrolysate (WPH). A bioactive peptide (Pro-Pro-Lys-Asn-Trp, PW5) with great anti-Aβ42 aggregation activity identified from the WPH is synthesized for in vitro and in vivo experiments. Using classic APP/PS1 mouse model, it is validated that PW5 exerts its effects on cognitive improvement through reducing Aβ plaques accumulation. Moreover, metabolomic analysis reveals that serum norepinephrine (NE) and isovalerate levels are significantly increased in response to PW5 intervention, with decreased serum levels of acetylcholine (AChe) and valerate, compared with the vehicle-treated APP/PS1 mice. PW5 feeding also improves gut dysbiosis in APP/PS1 transgenic mice by increasing the relative abundance of Firmicutes and decreasing Proteobacteria and Verrucomicrobia as displayed by 16s rRNA analyses. These promising results support the utilization of peptide PW5 as an active ingredient in functional foods or potential drug candidate for the prevention and/or treatment of AD.

Is there a new pathway relationship between melatonin and FEZ1 in experimental rat model of Alzheimer's disease?

Alzheimer's disease (AD) is a progressive neurodegenerative disease. This study was performed to determine the possible relationship between melatonin, which is known to play a role in the neuro-protective mechanism in AD, and fasciculation and elongation protein zeta 1 (FEZ1). Thirty male rats were included and separated into 3 groups (n = 10) as vehicle (artificial cerebrospinal fluid), streptozotocin (STZ) and STZ+melatonin (MLT). Two intracerebroventricular (icv) injections of 3 mg/kg STZ were made 48 hours apart. MLT injections were implemented for 14 days (ip; 10mg/kg/day). The Morris Water Maze (MWM) test was performed and rats were sacrificed to assess FEZ1 gene expression and protein levels from the hippocampus tissues and serum levels of noradrenaline (NA), dopamine and serotonin were determined from the blood samples. It was determined that the FEZ1/β-actin protein ratio in the STZ group was significantly higher than that of the Vehicle group (p < 0.05) and in the MLT‑administered group, the protein levels were decreased to the levels observed in the Vehicle group. Serum NA levels of STZ and STZ+MLT groups were found to be lower than those in the Vehicle group, while no difference was found regarding dopamine and serotonin levels. These findings show that reversal of increased FEZ1 levels in AD-induced rats with melatonin administration is the evidence of the effect of melatonin through FEZ1 in AD (Tab. 2, Fig. 5, Ref. 67). Keywords: FEZ1, Alzheimer's disease, melatonin, rat, microtubules, mitochondria.

Sedative and hypnotic effects of Vaccinium bracteatum Thunb. through the regulation of serotonegic and GABAA-ergic systems: Involvement of 5-HT1A receptor agonistic activity

The present study was conducted to investigate the sedative and hypnotic activities of Vaccinium bracteatum Thunb. fruit (VBFW) in an animal model and to identify the underlying mechanisms of its action.VBFW exhibited sedative effects through a reduction in the locomotor activity in the open field test (OFT). In addition, VBFW significantly reduced the sleep latency and increased total sleep duration in pentobarbital-induced sleeping behaviors in mice. The effects of 4-Chloro-DL-phenylalanine methyl ester hydrochloride (PCPA) were studied in normal and serotonin-depleted mice. Additionally, the changes in the related serum corticosterone (CORT) and neurotransmitter levels were evaluated. Pretreatment with VBFW (50, and 100 mg/kg) produced a significant decrease in the immobility time in the forced swim test (FST), while VBFW 100 plus PCPA treatment attenuated the change in immobility time observed following administration of VBFW alone. However, VBFW plus PCPA treatments did not significantly influence the changes in the locomotor activity that were induced by VBFW alone. The results suggest that VBFW leads to a decrease in the levels of serum CORT and norepinephrine in the hippocampus (HC) region (P < 0.01). Furthermore, PCPA treatment alone decreased serotonin (5-HT) levels in the HC (P < 0.05) and the prefrontal cortex (PFC; P < 0.05), while VBFW plus PCPA significantly increased the 5-HT levels in both the HC and the PFC (P < 0.05). In addition, we also found that VBFW showed a strong agonistic effect at the 5-HT1A receptor by activating 5-HT1A receptor-mediated intracellular Ca2+ and ERK1/2 phosphorylation. Similarly, VBFW (30 and 100 μg/mL) significantly increased the intracellular Cl− influx through its effects on the γ-aminobutyric acid type A receptor (GABAA receptor) subunits (α5, β1, and β2) in primary rat cerebellar granule cells. Moreover, the glutamate decarboxylase (GAD)65/67 protein was upregulated following VBFW treatment (30 and 100 μg/mL). The results of our study indicate that VBFW induces sedative and hypnotic effects by regulating the serotonergic and GABAA-ergic systems, which is possibly associated with 5-HT1A receptor agonistic activity. Additionally, this data suggests that VBFW up-regulates intracellular Cl− and GABAA receptor subunits as well as GAD65/67 protein levels.

Using changes in pro-brain natriuretic peptide of plasma amino-terminal and norepinephrine levels as prognostic and diagnostic factors in hand-foot-and-mouth disease.

We explored the possibility of using the variations in the pro-brain natriuretic peptide (NT-proBNP) of serum amino-terminal and norepinephrine (NE) levels as prognostic as well as diagnostic factors in children suffering from severe hand-foot-and-mouth disease (HFMD). From February 2014 to February 2015, 102 HFMD patients were enrolled in this study. They were divided into the common group (n=55) and the severe group (n=47). During the same period, 30 healthy children were enrolled in the control group. NT-proBNP and NE levels were evaluated in all patients. Our results revealed that NT-proBNP and NE levels in the common group were not evidently different compared with those of the control group. However, these levels in the severe group were significantly higher than other groups. After treatment, NT-proBNP and NE levels in the severe group were lower than those measured before treatment. We suggest that serum level of NT-proBNP can be used as a valuable index to judge the severity of HFMD and to predict the prognosis. We believe that NT-proBNP and NE levels can be added to other HFMD diagnostic tools.

Effect of auricular intradermal needling combined with erjian (HX6,7i) bloodletting on sleep quality and neuroendocrine level in patients with perimenopausal insomnia

To compare the effect differences between auricular intradermal needling combined with erjian (HX6,7i) bloodletting and oral administration of western medicine, and to explore the efficacy of neuroendocrine level in patients with perimenopausal insomnia. Ninety patients were randomized into an observation group and a control group, 45 cases in each one. In the observation group, auricular intradermal needling combined with erjian (HX6,7i) bloodletting were adopted alternately in the two ears. The auricular points were shen (CO10), xin (CO15), gan (CO12), shenmen (TF4), jiaogan (AH6a), neifenmi (CO18) and erjian (HX6,7i). The treatment was required once 3 days on the auricular points of one side alternatively. Oral administration of estazolam (1mg each day) was applied in the control group for 2 courses, 4 weeks as 1 course, once a day. The scores of Pittsburgh sleep quality index (PSQI), the levels of serum estrogen (E2), 5-hydroxy tryptamine (5-HT) and norepinephrine (NE) were valuated in the two groups before and after treatment. After treatment, the total scores of PSQI reduced in the two groups (both P<0.05), and the improvements of sleeping quality, sleeping time, sleeping difficulty, daytime dysfunction and the total PSQI score in the observation group were superior to those in the control group (all P<0.05). There was no significant difference in serum E2 before and after treatment in the two groups，and between the two groups after treatment (all P>0.05). After treatment, 5-HT contents increased and NE levels decreased in the two groups (all P<0.05), with better results in the observation group (both P<0.05). The total effective rate was 95.6% (43/45) in the observation group, which was higher than 82.2% (37/45) in the control group (P<0.05). Auricular intradermal needling combined with erjian (HX6,7i) bloodletting can improve the sleep quality of patients with perimenopausal insomnia, and adjust the neurotransmitter level, which achieves better effect than western medication.

Effects of PDCA on psychological status and quality of life in patients with bladder cancer after transurethral resection of bladder tumor

Objective To investigate the effect of Plan-Do-Check-Action (PDCA) on postoperative psychological status and quality of life in patients with bladder cancer undergoing transurethral resection of bladder tumor (TURBT) . Methods A total of 95 patients with non muscle invasive bladder cancer (NMIBC) undergoing TURBT hospitalized in Army General Hospital from November 2013 to November 2015 were selected and randomly divided into the control group (n=47) and the observation group (n=48) . Patients in the control group received routine nursing care, while patients in the observation group received additional PDCA. The changes of serum norepinephrine (NE) , epinephrine (E) and cortisol (Cor) levels were observed before and after the intervention in two groups. The SAS, SDS and the Self-esteem Scale (SES) were used to evaluate the psychological status of patients. The Simple Quality of Life Scale-36 (SF-36) was applied to evaluate the quality of life of patients. Results The postoperative serum NE, E and Cor levels of patients in the observation group were significantly lower than those in the control group (P<0.01) . At 1 month after the operation, SAS and SDS scores of patients in the observation group were lower than those in the control group, while SES score in the observation group was higher than that of the control group; there were statistically significant differences between two groups (P<0.01) . At 18 months after the operation, SF-36 score of patients in the observation group was significantly higher than that of the control group (P<0.01) . Conclusions PDCA can effectively reduce the postoperative stress reaction of bladder cancer patients after TURBT and improve their psychological status and quality of life, which is worthy of clinical promotion. Key words: Urinary bladder neoplasms; Quality of life; Plan-Do-Check-Action; Transurethral resection of bladder tumor; Psychological status

Food Restriction is Required to Preserve the Antisteatotic Effects of Central Leptin in the Liver of Middle-Aged Rats.

Aging is a significant risk factor for the development of obesity and hepatic steatosis associated with insulin and leptin resistance. Food restriction (FR) is commonly used for reducing body weight (BW), adiposity, and liver steatosis. Thus, this study aimed to determine whether FR in middle-aged rats can recover the central leptin antisteatotic effects observed in the liver in young animals. Two groups of 4-month-old Wistar rats were fed ad libitum (AL) or were on FR for 3 months. At 7 months of age, both groups were centrally treated with rat leptin (0.2 μg/d, 7 days) or saline. Central leptin reduced food intake and BW, but not the hepatic triglyceride content, in 7-month-old rats fed AL. However, in 7-month-old FR rats, leptin did not affect BW but markedly reduced serum leptin, serum and hepatic triglyceride levels, and the expression of hepatic lipogenic genes. In addition, central leptin decreased serum and hepatic endogenous norepinephrine levels of FR rats, exerting a homeostatic effect beyond its antisteatotic actions. These findings suggest that in middle-aged rats, moderate FR is required for both preserving the antisteatotic actions of central leptin and avoiding excessive weight loss.

IL-18 cleavage triggers cardiac inflammation and fibrosis upon β-adrenergic insult.

Rapid over-activation of β-adrenergic receptor (β-AR) upon stress leads to cardiac inflammation, a prevailing factor that underlies heart injury. However, mechanisms by which acute β-AR stimulation induce cardiac inflammation still remain unknown. Here, we set out to identify the crucial role of inflammasome/interleukin (IL)-18 in initiating and maintaining cardiac inflammatory cascades upon β-AR insult. Male C57BL/6 mice were injected with a single dose of β-AR agonist, isoproterenol (ISO, 5 mg/kg body weight) or saline subcutaneously. Cytokine array profiling demonstrated that chemokines dominated the initial cytokines upregulation specifically within the heart upon β-AR insult, which promoted early macrophage infiltration. Further investigation revealed that the rapid inflammasome-dependent activation of IL-18, but not IL-1β, was the critical up-stream regulator for elevated chemokine expression in the myocardium upon ISO induced β1-AR-ROS signalling. Indeed, a positive correlation was observed between the serum levels of norepinephrine and IL-18 in patients with chest pain. Genetic deletion of IL-18 or the up-stream inflammasome component NLRP3 significantly attenuated ISO-induced chemokine expression and macrophage infiltration. In addition, IL-18 neutralizing antibodies selectively abated ISO-induced chemokines, proinflammatory cytokines and adhesion molecules but not growth factors. Moreover, blocking IL-18 early after ISO treatment effectively attenuated cardiac inflammation and fibrosis. Inflammasome-dependent activation of IL-18 within the myocardium upon acute β-AR over-activation triggers cytokine cascades, macrophage infiltration and pathological cardiac remodelling. Blocking IL-18 at the early stage of β-AR insult can successfully prevent inflammatory responses and cardiac injuries.

Suppression of isoproterenol-induced apoptosis in H9c2 cardiomyoblast cells by daidzein through activation of Akt.

Increased serum norepinephrine level is one of pathological processes relating to heart disease (HD). Estrogens are considered as potential therapeutics for the treatment of HD; however, estrogen supplementation shows some side-effects, such as increasing the risk of developing breast, endometrial and ovarian cancers. This study investigated the cardio-protective effects of daidzein (Dai), a selective estrogen receptor modulator (SERM) from soy bean extract, in H9c2 cardiomyoblast cells treated with isoproterenol (ISO), a norepinephrine analog. In this in vitro model, H9c2 cells treated with Dai at different concentrations showed no statistical difference in cell viability. TdT-mediated digoxigenin-dUTP nick-end labeling (TUNEL) data and western blotting results indicated that Dai treated-H9c2 cells recovered from the damage induced by ISO. The recovery effects of Dai on ISO-induced damage were blocked by inhibition of Akt activation through adding Akt inhibitor. On the other hand, the fold changes of phosphorylated Akt (p-Akt)/Akt normalized with the control for con, 0.25, 0.5, 1, 3 and 24 h of treatment were 1, 2, 5, 13, 11 and 10, respectively. In conclusion, Dai ameliorates apoptosis of cardiomyoblasts induced by ISO through Akt signaling pathway.

The Role of Omega-3 Polyunsaturated Fatty Acids in Heart Failure: A Meta-Analysis of Randomised Controlled Trials.

Many new clinical trials about the effect of omega-3 polyunsaturated fatty acids (PUFAs) in heart failure (HF) patients have shown inconsistent results. Therefore, a meta-analysis of randomised controlled trials (RCTs) was performed to determine the benefits of omega-3 PUFAs in HF patients. Articles were obtained from PubMed, EMBASE, and the Cochrane Library. RCTs comparing omega-3 PUFAs with placebo for HF were included. Two reviewers independently extracted the data from the selected publications. The I2 statistic was used to assess heterogeneity. The pooled mean difference and associated 95% confidence intervals were calculated, and a fixed or random-effects model was used for the meta-analysis. A total of nine RCTs involving 800 patients were eligible for inclusion. Compared with patients taking placebo, HF patients who received omega-3 PUFAs experienced decreased brain natriuretic peptide levels and serum norepinephrine levels. Although the left ventricular ejection fraction (LVEF) and clinical outcomes (Tei index, peak oxygen consumption) did not improve, subgroup analysis showed that the LVEF increased in dilated cardiomyopathy (DCM) patients. Overall, omega-3 PUFA supplements might be beneficial in HF patients, especially in DCM patients, but further studies are needed to confirm these benefits.