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Objective:To compare the effects of sodium butyrate(Sob)on aged and young asthmatic mice.Methods:Male C57BL/6 mice aged 24 months(n=18)and 4 months(n=18)were divided using randomly generated numbers into 3 groups: a control group, a model group(treated with ovalbumin, OVA), and a treatment group(OVA+ Sob), with 6 mice in each group.The control group was given normal saline as the blank control.Two days before the OVA challenge, the treatment group was given 1 mg/g Sob by intraperitoneal injections and the OVA+ Sob group and the control group were given normal saline intervention.Endpoint evaluation was performed 1 day after the last challenge.Differences in airway hyperresponsiveness(AHR), pathological manifestations of lung tissue sections stained with hematoxylin eosin(HE), and inflammatory factors in lung tissues were compared between aged and young mice and the effects of Sob on asthmatic mice of different ages were evaluated.Results:Under the stimulation of methacholine(Mch), AHR of the O-OVA group was significantly higher than that of the Y-OVA group(6.250 g/L: 276.28±113.62 vs.103.02±19.55, t=3.368, P=0.026; 12.500 g/L: 457.5±157.29 vs.114.76±20.28, t=4.338, P=0.022; 25.000 g/L: 1113.16±256.98 vs.567.87±187.34, t=3.538, P=0.009). HE staining revealed that, compared with the Y-control group, the O-control group exhibited a reduced area of alveolar cavity, partial lung consolidation, proliferation of interstitial fibrous connective tissues, alveolar epithelial cells and capillary endothelial cells.Compared with its control group, the O-OVA group had significantly elevated levels of eotaxin( P=0.035), IL-17A( P=0.004)and IL-1β( P=0.001), among the inflammatory factors, whereas the Y-OVA group had elevated levels of eotaxin( P=0.001), IL-17A( P=0.001), IL-4( P=0.004), KC( P=0.012)and IL-1β( P<0.001). Compared with the O-OVA group, the Y-OVA group had increased levels of IL-4( Z=2.882, P=0.004)but decreased levels of IL-1β( t=2.728, P=0.020). As for the effects of Sob on asthmatic mice of different ages, AHR of the O-OVA+ Sob group was significantly alleviated with stimulation of 12.500 g/L Mch( P=0.015)and 25 g/L Mch( P=0.014), compared with the O-OVA group.With stimulation of 3.125 g/L Mch, AHR of the Y-OVA+ Sob group was significantly decreased( P=0.021)and levels of IL-4( P=0.004)and IL-1β( P=0.014)were significantly reduced in the Y-OVA+ Sob group, compared with the Y-OVA group. Conclusions:The severity of asthma in aged mice is greater than in young mice, perhaps as a result of different immunophenotypes; The alleviating effects of Sob on inflammatory factors in young asthmatic mice may be related to mild AHR in young asthmatic mice, compared with aged asthmatic mice.
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Narcolepsy is the most common cause of excessive daytime sleepiness (EDS) following obstructive sleep apnea. Its treatment aims to reduce EDS and cataplexy, improve nighttime sleep disturbance, sleep paralysis and sleep-related hallucinations. Pitolisant (a histamine H3 receptor antagonist) and solriamfetol (a norepinephrine reuptake inhibitor) have recently been approved effective for narcolepsy in the United States and the European Union. Pitolisant has proved to be effective for both EDS and cataplexy. Besides being effective on EDS, solriamfetol seems to have advantages in abuse potential and withdrawal syndrome. As potential treatments for EDS and cataplexy associated with narcolepsy, several new drugs are being developed and tested. These new drugs include new hydroxybutyrate preparations (controlled release sodium hydroxybutyrate FT218, low sodium hydroxybutyrate JZP-258), selective norepinephrine reuptake inhibitor (AXS-12), and modafinil combined with astroglial junction protein inhibitor (THN102). This paper reviews the recently approved drugs and potential treatments for narcolepsy.
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Aim To investigate the relationship between amnestic effect of ketamine,propofol or sodium oxybate and NMDA receptor.Methods Amnestic model was established by intraperitoneal injection of ketamine (20 mg?kg~-1),propofol(10 mg?kg~-1) or sodium oxybate(100 mg?kg~-1) respectively in mice before intracerebroventricular injection of NMDA,and then the error times,step down latency and step through latency were observed in the step down test and step through test.Results NMDA by intracerebroventricular injection decreased the error times and increased the step down latency and step through latency of amnestic mice induced by ketamine.It had no significant impact on those of amnestic mice induced by propofol or sodium oxybate.Conclusion NMDA receptor may be an important target for amnestic effect of ketamine,rather than the target for amnestic effect of propofol or sodium oxybate.
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AIM: To investigate the relationship between the protective effect of sodium oxybate on neuronal damage induced by hypoxia reoxygenation and GABA A receptor in primary cultured rat cortical neurons. METHODS: The primary cultured rat cortical neurons were used to make the hypoxia reoxygenation damage model. The morphology of cell was observed. The lactate dehydrogenase (LDH) effluxed into the media as an indicator of neuronal injury was detected after 6 h of the reoxygenation injuries. The malonyldialdehyde (MDA) contents, superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities were determined at the same time. RESULTS: The hypoxia reoxygenation caused neuronal swelling and widespread neuronal degeneration, increased LDH efflux and MDA contents, and decreased SOD and GPX activities. Sodium oxybate assuaged neuron damage, decreased LDH efflux and MDA contents (P
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Objective: To determine the influence of ?-hydroxybutyric sodium (7-OH)on the pharmacokinetics of ketamine infusion in preschool children. Method: Sixteen patients were randomly assigned to group Ⅱ (Ketamine) and group Ⅱ (Ketamine plus ?-OH). After trachea intubation,0.05% ketamine was infused in both groups at 3mg?kg~(-1)?h~(-1) and ?-OH 125mg?kg~(-1) only in group Ⅱ. The plasma concentration of ketamine was measured using high performance liquid chromatography. Pharmacokinetic parameters were calculated using 3P_(87) software composed by Chinese Pharmacologic Society. Result: In both groups,pharmaeokinetics could be descrided as two-compartment open model. The T_(1/2)? and the Cl differ between group Ⅰ and group Ⅱ (P
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The interaction between sodium oxybate and ketamine were studied in conscious animals. Sodium oxybate increased the LD_(50) of ketamine, increased the incidence of sleep caused by ke tamine and prolonged the sleep duration and potentiated analgesic action of ketamine. Sodium Oxybate didn't effect the respiratory and circulatory function in rabbits. The results showed sodium oxybate po tentiated the anesthetic action of ketamine and reduced the side effect of ketamine. So It is suggested that sodium oxybate has the anesthetic synergism with ketamine in animals.
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Objective To investigate the effects of sodium hydroxybutyrate (?-OH) on neuronal apoptosis in neonatal rat cortex induced by hypoxic-ischemic (HI) insult. Methods One-hundred and fifty 7-day old newborn SD rats were randomly assigned to one of S groups ( n = 30 each): sham operation group (A); HI + normal saline (NS) group (B) and three HI + ?-OH groups (C, D, E) . HI was induced by ligation of left common carotid artery followed by 2 h inhalation of hypoxic air (8% O2 92% N2). In sham operation group (A) left common carotid artery was exposed but not ligated and no hypoxic air was inhaled after operation. In group B (HI + NS) NS 0.2 ml?10 g-1 was injected intraperitoneally (IP) t.i.d immediately after HI until the animals were killed; whereas in HI +?-OH groups ?-OH 50 (C) or 100 (D) or 200 (E) mg?kg-1 was injected IP instead of NS. Six animals were killed at 1 h, 3 h, 1 d, 3 d and 7 d in each group and brains were removed. The number of apoptotic neurons in the left cortex was detected using TUNEL staining technique. Results The number of apoptotic neurons at 1 h-7 d after HI was significantly greater in group B, C, D and E than in group A ( sham operation) . The expression of apoptosis positive neurons reached the peak at 1 day after HI. The number of apoptotic neurons at 3 h-3 d was significantly greater in group E (?-OH 200 mg?kg-1) than in group C and D (?-OH 50 and 100 mg?kg-1) . There was no significant difference in the number of apoptotic neurons between group B (HI + NS) and E (HI +?-OH 200 mg?kg-1). Conclusion Sodium hydroxybutyrate 50 and 100 mg?kg-1 can attenuate neuronal apoptosis in neonatal rat cortex induced by hypoxic-ischemic insult.
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AIMTo study the protective effect of sodium oxybate (SO) against focal cerebral ischemia-reperfusion injury in rats, and the relationship between the effects of SO and ?-aminobutyric acid (GABA). METHODSThe reversible middle cerebral artery occlusion (MCAO)model in rats was established to investigate the role of SO. The scores of neurological deficits was detected by Longa EZ method in MCAO rats. The extracellular levels of glutamate (Glu) and GABA in CSF were measured by high performance liquid chromatography-fluorometer (HPLC-FR) method, and the weight of cerebral infraction was detected. RESULTSThe scores of neurological deficits and the weight of cerebral infraction markedly decreased by SO while the ratio of GABA/Glu obviously increased administered SO in MCAO rats. CONCLUSIONSSO could prevent MCAO rats from ischemia-reperfusion injury, the protective effect is related to SO keeping dynamic balance of excition-inhibition, and persisting inhibition-depended effect.