Melatonin Augments the Effects of Fluoxetine on Depression-Like Behavior and Hippocampal BDNF-TrkB Signaling / 神经科学通报·英文版

Depression is a debilitating psychiatric disorder with a huge socioeconomic burden, and its treatment relies on antidepressants including selective serotonin reuptake inhibitors (SSRIs). Recently, the melatonergic system that is closely associated with the serotonergic system has been implicated in the pathophysiology and treatment of depression. However, it remains unknown whether combined treatment with SSRI and melatonin has synergistic antidepressant effects. In this study, we applied a sub-chronic restraint stress paradigm, and evaluated the potential antidepressant effects of combined fluoxetine and melatonin in adult male mice. Sub-chronic restraint stress (6 h/day for 10 days) induced depression-like behavior as shown by deteriorated fur state, increased latency to groom in the splash test, and increased immobility time in the forced-swim test. Repeated administration of either fluoxetine or melatonin at 10 mg/kg during stress exposure failed to prevent depression-like phenotypes. However, combined treatment with fluoxetine and melatonin at the selected dose attenuated stress-induced behavioral abnormalities. Moreover, we found that the antidepressant effects of combined treatment were associated with the normalization of brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) signaling in the hippocampus, but not in the prefrontal cortex. Our findings suggest that combined fluoxetine and melatonin treatment exerts synergistic antidepressant effects possibly by restoring hippocampal BDNF-TrkB signaling.

Nutritional status in acute stage ischemic stroke and its relation to disease severity and prognosis of patients / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the nutritional status in acute stage ischemic stroke and its relation to disease severity and prognosis of patients.</p><p><b>METHODS</b>Fifty patients with ischemic stroke were admitted in hospital within 48 h after onset. National Institute of Health stroke scale (NIHSS) was used to assess the severity of stroke. Physical index and laboratory index were measured on d1, d7 and d14 after admission. Physical index included body weight, body mass index, triceps skin folds, upper arm circumference and arm muscle circumference. Laboratory index included prealbumin, high sensitivity C-reactive protein (hs-CRP), complement C3 and cortisol. The severity of metabolic disturbance was expressed as the difference of biochemical indexes between the d7 and d1. All cases were followed up for 6 months. The prognosis of stroke was evaluated with modified Rankin (mRankin) scores.</p><p><b>RESULTS</b>No significant changes of physical indexes were found between d7 and d1. The levels of prealbumin and complement C3 on d7 after admission were significantly decreased compared to d1 (198.8 mg/L±20.3 mg/L vs 286.7 mg/L±23.8 mg/L and 0.6 g/L±0.1 g/L vs 1.0 g/L±0.1 g/L, respectively, both P<0.05). The levels of hs-CRP and cortisol at d7 were significantly increased compared to d1 (495.2 nmol/L±39.5 nmol/L vs 24.1 mg/L±5.2 mg/L and 396.4 nmol/L±41.3 nmol/L vs 5.1 mg/L±1.2 mg/L, respectively, both P<0.05). On d14 after admission hs-CRP (13.2 mg/L±4.5 mg/L) and cortisol levels (463.4 nmol/L±32.1 nmol/L) were still significantly higher than d1 (both P<0.05). However, there were no difference in prealbumin (259.2 mg/L±22.8 mg/L) and complement C3 (0.8 g/L±0.2 g/L) levels between d1 and d14 after admission. Correlation analysis revealed that the NIHSS scores and mRankin scores were correlated with nutrition metabolism disturbances (P<0.05).</p><p><b>CONCLUSION</b>Nutrition metabolism disturbances in patients with acute ischemic stroke are related to the disease duration, the severity and prognosis of stroke.</p>

Effects of thioperamide on seizure development and memory impairment induced by pentylenetetrazole-kindling epilepsy in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Histamine H(3) receptor antagonists have been considered as potential drugs to treat central nervous system diseases. However, whether these drugs can inhibit epileptogenesis remains unclear. This study aimed to investigate the effects of thioperamide, a selective and potent histamine H(3) receptor antagonist, on the seizure development and memory impairment induced by pentylenetetrazole (PTZ)-kindling epilepsy in rats.</p><p><b>METHODS</b>Chemical kindling was elicited by repeated intraperitoneal (ip) injections of a subconvulsant dose of PTZ (35 mg/kg) once every 48 hours for 12 times, and seizure activity of kindling was recorded for 30 minutes. Control rats were ip injected with saline instead of PTZ. Morris water maze was used to evaluate the spatial memory. Phosphorylated cyclic adenosine monophosphate response element binding protein (p-CREB) was tested by Western blotting in hippocampus.</p><p><b>RESULTS</b>Intracerebroventricular (icv) injections with thioperamide (10 µg, 20 µg) 30 minutes before every PTZ injections, significantly prolonged the onset of PTZ-kindling and inhibited the seizure stages. PTZ-kindling seizures led to the impairment of spatial memory in rats, and thioperamide ameliorated the impairment of spatial learning and memory. Compared to non-kindling rats, there was a significant decrease in p-CREB level in hippocampus of the PTZ-kindling rats, which was reversed by thioperamide.</p><p><b>CONCLUSIONS</b>Thioperamide plays a protective role in seizure development and cognitive impairment of PTZ-induced kindling in rats. The protection of thioperamide in cognitive impairment is possibly associated with the enhancement of CREB-dependent transcription.</p>

Effects of Wuling mycelia on pentylenetetrazole-induced epilepsy in rats / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effects and mechanisms of Wuling mycelia on seizure development and learning ability induced by pentylenetetrazole-kindling epilepsy in rats.</p><p><b>METHODS</b>SD rats were randomly divided into four groups: pentylenetetrazole-kindling model group (model group), low dose Wuling mycelia (0.3 g*kg(-1)) group (LD-WM group), high dose Wuling mycelia (0.6 g*kg(-1)) group (HD-WM group) and control group. The rats were intraperitoneal injected with a subconvulsive dose (35 mg*kg(-1)) of pentylenetetrazole (saline in control group) every 48 h for 12 times. Wuling mycelia was intragastrically applied 30 min before pentylenetetrazole injection. An 8-arm radial maze ( 4 arms baited) was used to measure the learning ability. Histamine was measured by chemical fluorometric enzyme immunoassay.</p><p><b>RESULTS</b>Compared with the model group, the kindling stage of LD-WM group degraded significantly after 7th injection, the latency to the onset of myoclonic jerks (LTMJ) and the latency to the onset of generalized seizures (LTGS) prolonged after the 6th and 7th injection, respectively (P<0.05). The kindling stage of HD-WM group also degraded markedly after the 6th to 8th injection, and the LTMJ and the LTGS extended after the 8th to 9th and 6th injection, respectively (P<0.05). Compared with the control group, the frequency of working memory error (WME) and reference memory error (RME) of the model group in the 8-arm radial maze increased through 3-d training (P<0.05). The memory tests showed that the impairment induced by pentylenetetrazole was partially reversed by Wuling mycelia. Compared with the control group, brain histamine contents (hippocampus, cortex, thalamus and hypothalamus) were significantly lower in model group (P<0.05). But compared with the model group, hippocampal histamine contents in LD-WM group and hippocampal, thalamic and hypothalamic histamine contents in HD-WM group were elevated (P<0.05).</p><p><b>CONCLUSION</b>Wuling mycelia can delay the kindling and ameliorate the ability of learning in rats with pentylenetetrazole-induced epilepsy and the enhancement of neuronal histamine activity may be one of possible mechanisms.</p>

Effects of statins on the liver: clinical analysis of patients with ischemic stroke / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Statins are one of the most common agents prescribed for ischemic stroke patients, but their side effects on the liver are worrisome to both physicians and patients. This study aimed to analyze the features and related factors of the hepatic side effects of statins in patients with ischemic stroke.</p><p><b>METHODS</b>Four hundred and eighty-one patients with ischemic stroke who had been treated with statins at our department from July 1, 2008 to June 30, 2009 were investigated retrospectively. Liver function, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), within 6 months after they began to use statins and related factors were analyzed.</p><p><b>RESULTS</b>The incidence of mild ALT and AST elevation, less than three times the upper limit of normal, and the incidence of moderate elevation, ALT and AST levels 3-10 times the upper limit of normal, in ischemic stroke patients who had been treated with statins were 2.3% and 2.1%, respectively. These incidences were higher than in patients with common hyperlipidemia or coronary heart disease. The relatively high incidence was associated with older age (≥ 65 years) and chronic liver diseases, and was not related to the type of stroke, gender, and reduction of low-density lipoprotein. The levels of ALT and AST normalized after withdrawal of statins or lowering the dosage. None of the patients developed hepatic failure.</p><p><b>CONCLUSIONS</b>Asymptomatic elevation of ALT and AST after administration of statins is more likely to occur in ischemic stroke patients than in others, and the elevation is related to age and chronic liver diseases. However, statins are still safe for ischemic stroke patients.</p>

Comparison of midazolam and propofol as conscious sedation in oocyte retrieval of IVE-ET / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To compare the efficacy and safety of midazolam combined with fentanyl and propofol combined with fentanyl as conscious sedation in oocyte retrieval of in vitro fertilization and embryo transplantation (IVF-ET).</p><p><b>METHODS</b>Eighty patients receiving IVE-ET were randomly divided into midazolam combined with fentanyl group (midazolam group) and propofol combined with fentanyl group (propofol group). Antalgic effects, circulation status (blood pressure, heart rate), respiration status (rate, oxygen saturation and respiration depression) during operation, nausea and vomiting, and amnestic effects after operation were compared.</p><p><b>RESULT</b>No differences of antalgic effects and circulation status between two groups were observed. Percentages of respiration depression,vomiting and amnesia of midazolam group were 5.0 %, 10.0 % and 25%, respectively, and those of propofol group were 25%, 27.5% and 7.5%, respectively, which had statistical significance.</p><p><b>CONCLUSION</b>As conscious sedation, midazolam combined with fentanyl is better than propofol combined with fentanyl in oocyte retrieval of IVF-ET.</p>

Study of Fufang Haishe capsule against cell apoptosis / 中国中药杂志

<p><b>OBJECTIVE</b>To study mechanismt of Fufang Haishe capsule for dementia by observing the effect of it on PC-12 cell apoptosis, which was induced by beta-amyloid protein (Abl-42).</p><p><b>METHOD</b>Nerve growth factor (NGF) was used to cultivate the PC-12 cells. Fufang Haishe capsule at different concentrations was added into the culture medium so as to identify the nontoxic concentrations with MTT. To analyze the PC-12 cell apoptosis respectively by MTT assay, Flow cytometry (FCM technique) with different concentrations of Fufang Haishe capsule (0.01, 0.1, 1, 5 mg x mL(-1)), adding Ab or not Western blot was used to detect apoptosis which was measured on the implementation of caspase-9 and caspase-3 activity.</p><p><b>RESULT</b>Fufang Haishe capsule could significantly inhibit the apoptosis of PC-12 cells induced by Abeta with increased colorimetric MTT asay ( compare among the control group and concentration 0, 0.01, 0.1, 1 and 5 mg x mL(-1) group, which is the same below: 1.75 +/- 0.12, 0.73 +/- 0.35, 0.79 +/- 0.11, 0.83 +/- 0.07, 1.31 +/- 0.07, 1.80 +/- 0.38, P < 0.01) and the decreased apoptosis rate of the cells which was analysed by flow cytometry (1.93 +/- 0.41)%, (46.17 +/- 4.08)%, (35.35 +/- 4.63)%, (28.62 +/- 3.81)%, (15.13 +/- 3.15)%, (7.84 +/- 1.76)%, P < 0.01. In addition, Fufang Haishe capsule inhibited the activity of caspase-9 and caspase-3 of PC-12 cells which was induced by Abeta.</p><p><b>CONCLUSION</b>Fufang Haishe capsule significantly inhibite apoptosis of PC-12 cells induced by Abeta. The mechanism might be that Fufang Haishe capsule decrease the activity of the apoptosis implementing protein,caspase-9 and caspase-3.</p>

Effects of endogenous histamine on memory impairment induced by pentylenetetrazole-kindled epilepsy in rats / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the mechanisms of memory impairment induced by pentylenetetrazole (PTZ)-kindled epilepsy in rats and the effects of endogenous histamine.</p><p><b>METHODS</b>Rats were injected i. p with a subconvulsive dose of PTZ every 48 h until fully kindled. Memory was tested by shuttle box with passive avoidance. Brain histamine was measured spectrofluorometrically. Neurons of hippocampus were investigated with HE stain.</p><p><b>RESULT</b>PTZ-kindled epilepsy caused memory impairment in rats, i .e. latency of passive avoidance was shortened in shuttle box. Pretreatment of histidine, the precursor of histamine, showed an ameliorating effect on memory impairment induced by epilepsy. Decreased histamine contents in the hippocampus, thalamus and hypothalamus were observed after fully kindled in rat. In addition, intact neurons of the CA1 and CA3 regions in hippocampus decreased to 72.7 % and 78.9 % compared with those in control group.</p><p><b>CONCLUSION</b>PTZ-kindled epilepsy causes memory impairment, and it might be due to a decrease of brain histamine and loss of hippocampal neurons induced by epilepsy.</p>

Mechanisms of the effect of brain histamine on chronic epilepsy induced by pentylenetetrazole / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the mechanisms of histamine on chronic epilepsy induced by pentylenetetrazole (PTZ).</p><p><b>METHODS</b>To induce chemical kindling, a subconvulsive dose (35mg/kg) of PTZ was ip injected every 48 h in rats. Behavior changes were observed for 30 min after every injection of PTZ.</p><p><b>RESULT</b>Ip injection of histidine or icv injection of clobenpropit inhibited the development of kindling induced by PTZ, presenting prolonged latency for myoclonic jerks and clonic generalized seizures and depressed seizure stages in a dose-dependent manner. H(3)receptor agonist, immepip, and histidine decarboxylase, alpha-fluoromethylhistidine reversed the ameliorating effect of clobenpropit on seizure development in a dose-dependent manner.</p><p><b>CONCLUSION</b>Brain histamine plays an important role in protection against myoclonic jerks and clonic generalized clonic seizures and its action may be via H(3)receptor.</p>

Influence of chronic epilepsy on spatial memory retrieval in rats / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the influence of chronic epilepsy on spatial memory retrieval in rats, and to evaluate the effects of TAK-147, an acetylcholinesterase inhibitor, and histidine, the precursor of histamine, on the amnesia induced by epilepsy.</p><p><b>METHODS</b>After successfully trained in the 8-arm (4-arm baited) radial maze, the rats were ip injected with a subconvulsive dose of pentylenetetrazole (PTZ) every 48 h until fully kindled. Memory retrieval was tested at the same maze.</p><p><b>RESULT</b>Impairment of memory retrieval was in a steady state 1 to 18 days after fully kindled, the ability of memory retrieval returned to the control level 31 days after fully kindled. TAK-147 showed an ameliorating effect on memory impairment induced by epilepsy, including reference and working memory in a dose-dependent manner. Histidine only ameliorated reference but not working memory.</p><p><b>CONCLUSION</b>PTZ-kindled seizure impair spatial memory retrieval, which it might be due to a decrease of brain acetylcholine and histamine induced by epilepsy.</p>

Effects between the first-and second-generation histamine H1-antagonists on seizure development of pentylenetetrazole-induced kindling in rats / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effects and the mechanisms of the first-generation histamine H(1)-antagonist diphenhydramine and the second-generation histamine H(1)- antagonist fexofenadine on seizure development of pentylenetetrazole (PTZ)-induced kindling in rats.</p><p><b>METHODS</b>The first-or second-generation histamine H(1)-antagonists and/or histidine were ip injected in rats every 48 h, followed by a subconvulsive dose of PTZ (35 mg/kg). Then the behavioral changes were observed for 30 min after every injection of PTZ. The histamine content of brain was measured spectrofluorometrically.</p><p><b>RESULT</b>Compared with the control group, diphenhydramine (5 mg/kg) significantly augmented the severity of seizure development of PTZ-induced kindling, whereas fexofenadine (5 mg/kg) had no marked influence. The effects of diphenhydramine were antagonized by histidine, the precursor of histamine.</p><p><b>CONCLUSION</b>Seizure development of PTZ-induced kindling is promoted by the first-but not the second generation histamine H(1)-antagonists via the blockade of brain histamine H(1)-receptor.</p>