Ivermectina: ¿Un antiparasitario frente a SARS-CoV-2? / Ivermectin: an antiparasitic drug to fight SARS-CoV-2?

RESUMEN La capacidad de propagación y letalidad del SARS-CoV-2 en todo el mundo motiva la urgente necesidad de desarrollar una estrategia terapéutica apropiada para controlar los casos de COVID-19. El desarrollo de nuevos fármacos frente a este nuevo virus es apremiante debido a su rápida diseminación. Se han propuesto alternativas paralelas empleando fármacos ya disponibles para fines similares. Esta revisión describe el potencial antiviral de la ivermectina, así como sus mecanismos de acción frente a algunos virus, y discute su probable aplicación contra el SARS-CoV-2.

ABSTRACT The global spread and lethality of SARS-CoV-2 prompt the urgent need to develop an appropriate therapeutic strategy to control COVID-19 cases. The development of new drugs to fight this novel virus is urgent due to its rapid spread. Parallel alternatives have been proposed by using drugs already available for similar purposes. This review article describes the antiviral potential of ivermectin as well as its mechanisms of action against some viruses, and discusses its probable use to fight SARS-CoV-2.

Role of nicotinic acetylcholine receptors in vascular cognitive impairment / 中华核医学与分子影像杂志

Nicotinic acetylcholine receptors (nAChRs) play an important role in cognitive function.Vascular cognitive impairment (VCI) seriously affects the health and quality of life.Early diagnosis and timely effective intervention of VCI may delay or even prevent the occurrence of dementia.The development of nAChRs agents and molecular imaging,such as PET/CT or PET/MR,may promote research on the early diagnosis and treatment of VCI.This review summarizes the pathogenesis of VCI,the relationship between nAChRs and VCI,the progress on nAChRs receptor imaging,and the treatment of VCI.

Relationship between α7nAChR signaling pathway and regulatory T cells during vagus nerve stimulation-induced reduction of endotoxin-caused acute lung injury in mice / 中华麻醉学杂志

Objective To evaluate the relationship between α7 nicotinic acetylcholine receptor (α7nAChR) signaling pathway and regulatory T cells (Tregs) during vagus nerve stimulation-induced reduction of endotoxin-caused acute lung injury (ALI) in mice.Methods Clean-grade healthy male C57BL/6 mice,aged 6-8 weeks,weighing 22-25 g,were divided into 5 groups (n=10 each) using a random number table method:control group (group C),group ALI,vagus nerve stimulation group (group VNS),α-BGT group (group α-BGT) and vagus nerve stimulation plus α-BGT group (group VNS + α-BGT).After successful establishment of the model,the vagus nerve was stimulated for 30 s with a stimulus intensity of 0.5 mA,frequency of 20 Hz,an interval of 5 min,60 min in total.Sterile normal saline 100 μl was injected into the trachea,and the vagus nerve was only exposed but not stimulated in group C.In group ALI,the ALI model was established,and the vagus nerve was isolated but not stimulated.In group α-BGT,α-BGT 1 μg/kg was intraperitoneally injected,the ALI model was established 1 h later,and the vagus nerve was isolated but not stimulated.In group VNS+α-BGT,α-BGT 1 μg/kg was intraperitoneally injected,the ALI model was established 1 h later,and the vagus nerve was stimulated at 1 h after the end of establishment.Animals were sacrificed at 72 h after establishing the model,and lungs were removed for determination of lung water content,percentage of Tregs (using flow cytometry),myeloperoxidase (MPO) activity (by colorimetric assay),expression of α7nAChR (by Western blot) and contents of interleukin-10 (IL-10),transforming growth factor-β (TGF-β) and IL-1β (by enzyme-linked immunosorbent assay).Results Compared with group C,the lung water content,MPO activity and IL-1β content were significantly increased in the other four groups,the expression of α7nAChR was significantly down-regulated in ALI,α-BGT and VNS+α-BGT groups,the percentage of Tregs was significantly increased in group VNS,the IL-10 content was significantly decreased in ALI and α-BGT groups and increased in VNS and VNS+α-BGT groups,and TGF-β contents were significantly decreased in ALI,α-BGT and VNS+α-BGT groups and increased in group VNS (P＜0.05).Compared with group ALI,the lung water content,MPO activity and IL-1β content were significantly decreased,the expression of α7nAChR was up-regulated,and the percentage of Tregs and contents of IL-10 and TGF-β were increased in group VNS,and the TGF-β content in group α-BGT and contents of IL-10 and TGF-β in group VNS+α-BGT were significantly increased (P＜0.05).Compared with group VNS,the lung water content,MPO activity and IL-1β content were significantly increased,the expression of α7nAChR was down-regulated,and the percentage of Tregs and contents of IL-10 and TGF-β were decreased in α-BGT and VNS+α-BGT groups (P＜0.05).The contents of IL-1O and TGF-β were significantly higher in group VNS+α-BGT than in group α-BGT (P＜0.05).Conclusion Vagus nerve stimulation can activate α7nAChR signaling pathway and raise the percentage of Tregs,thus reducing ALI in mice.

Toxicidad por neonicotinoides: revisión de tema y reporte de dos casos / Toxicity by neonicotinoids: Two case reports and topic review / Toxicidade por neonicotinóides: revisão do assunto e reporte de dois casos

Las intoxicaciones por plaguicidas son la segunda causa de intoxicación en Colombia. Los neonicotinoides son un nuevo grupo de insecticidas que actúa a través de los receptores nicotínicos. Las principales manifestaciones clínicas que se han asociado con dicha intoxicación son alteraciones neurológicas y autonómicas. En este reporte se presentan dos casos de pacientes que ingirieron tiametoxan e imidacloprid y presentaron compromiso del sensorio y de sus signos vitales, por lo que se acudió a manejo en unidad de cuidados intensivos. El objetivo de este reporte es sensibilizar sobre el creciente uso de estos plaguicidas y la necesidad de identificarlos para hacer un diagnóstico diferencial con otras sustancias, realizar un uso adecuado de ayudas diagnósticas y un manejo inicial pertinente para asegurar la vía área y corregir alteraciones hemodinámicas para prevenir complicaciones.

Pesticide poisoning is the second cause of poisoning in Colombia. Neonicotinoids are a new group of insecticides that act through nicotinic receptors. The main clinical manifestations that have been associated with such poisoning are neurological and autonomic disturbances. In this paper, we present two cases in which two patients ingested thiamethoxan and imidacloprid, showing neurologic compromise and affecting their vital signs, requiring management in the intensive care unit. The aim of this article is to raise awareness about the growing use of such pesticides and identify the need to make a differential diagnosis with other insecticides, making appropriate use of diagnostic aids and appropriate initial management of the airway and correcting the abnormalities in their hemodynamic profile to prevent complications.

As intoxicações por praguicidas são a segunda causa de intoxicação na Colômbia. Os neonicotinóides são um novo grupo de inseticidas que atua através dos receptores nicotínicos. As principais manifestações clínicas que se há associado com dita intoxicação são alterações neurológicas e autonómicas. Neste reporte se apresentam dois casos de pacientes que ingeriram tiametoxan e imidacloprid e apresentaram compromisso do sensório e de seus signos vitais, pelo que se acudiu ao manejo em unidade de tratamentos intensivos. O objetivo deste reporte é sensibilizar sobre o crescente uso destes praguicidas e a necessidade de identificá-los para fazer um diagnóstico diferencial com outras substâncias, realizar um uso adequado de ajudas diagnósticas e um manejo inicial pertinente para assegurar a via área e corrigir alterações hemodinâmicas para prevenir complicações.

Role of α7nAChR in reduction of endotoxin-induced acute lung injury by limb ischemic preconditioning in mice / 中华麻醉学杂志

Objective To evaluate the role of α7 nicotinic acetylcholine receptor (α7nAChR) in reduction of endotoxin-induced acute lung injury (ALI) by limb ischemic preconditioning in mice.Methods Eighty healthy male C57BL/6 mice,aged 8-10 weeks,weighing 22-26 g,were randomly divided into 5 groups (n =16 each) using a random number table:control group (group C),ALI group,limb ischemic preconditioning group (group P),α-bungarotoxin (α-BGT) group,and limb ischemic preconditioning +α-BGT group (group P+α-BGT).Normal saline 100 μl was intratracheally instilled in group C.In group ALI,lipopolysaccharide 5 mg/kg was intratracheally instilled (in normal saline) to establish the model of endotoxin-induced ALI.In group P,the mice were subjected to 6 cycles of 5-min ischemia of the right hindlimb followed by 5-min reperfusion,and then the model of ALI was established.In group α-BGT,α-BGT 1 μg/kg was injected intraperitoneally before establishment of the model.In group P+α-BGT,limb ischemic preconditioning was performed,α-BGT 1 μg/kg was then injected intraperitoneally,and the model of ALI was established.At 24 h after LPS instillation,6 mice were selected from each group and sacrificed,and lungs were removed for microscopic examination and for determination of wet and dry lung weight,myeloperoxidase (MPO) activities,contents of interleukin-lbeta (IL-1β),tumor necrosis factoralpha (TNF-α) and IL-6,and expression of α7nAChR and high mobility group box-1 (HMGB1) in lung tissues.The lung water content was calculated.The survival of the left 10 mice in each group was observed at 7 days after establishment of the model,and the survival rate was calculated.Results Compared with group C,the lung water content,MPO activities,contents of IL-1β,TNF-α and IL-6,and HMGB1 expression were significantly increased,α7nAChR expression was significantly down-regulated,and the 7-day survival rate was significantly decreased in group ALI(P＜0.05).Compared with group ALI,the lung water content,MPO activities,contents of IL-1β,TNF-α and IL-6,and HMGB1 expression were significantly decreased,α7nAChR expression was significantly up-regulated,and the 7-day survival rate was significantly increased in group P (P＜0.05).Compared with group P,the lung water content,MPO activities,contents of IL-1β,TNF-α and IL-6,and HMGB1 expression were significantly increased,α7nAChR expression was significantly down-regulated,and the 7-day survival rate was significantly decreased in group P+α-BGT (P＜0.05).Conclusion The mechanism by which limb ischemic preconditioning inhibits inflammatory responses and reduces endotoxin-induced ALI is related to activation of α7nAChR in mice.

Effect of alpha-7 nicotinic acetylcholine receptor activation on beta-amyloid induced recognition memory impairment. Possible role of neurovascular function

PURPOSE: To evaluate the effects of PHA-543613 (α7-nAChR agonist) and galantamine (acetylcholinesterase inhibitor (AChEI)) on recognition memory and neurovascular coupling (NVC) response in beta-amyloid (Aβ) 25-35-treated mice. METHODS: PHA-543613 (1 mg/kg, i.p.), and galantamine (3 mg/kg, s.c.), effects were tested in Aβ25-35 mice model of AD. α7-nAChR antagonist, methyllycaconitine (MLA) (1 mg/kg, i.p.), was used for evaluation of receptor blockade effects. Recognition memory in animals was assessed by the novel object recognition (NOR) task. NVC response was analyzed by laser-doppler flow meter in barrel cortex by whisker stimulation method. RESULTS: Both, PHA-543613 and galantamine improve recognition memory in Aβ-treated animals. However, the advantageous effects of PHA-543613 were significantly higher than galantamine. Also, pretreatment with MLA reversed both galantamine and PHA-543613 effects on NOR. Impaired NVC response in AD animals was improved by PHA-543613 and galantamine. However, MLA pretreatment disrupts this function. CONCLUSION: Activation of α7-nAChR improved recognition memory possible through enhancement of neurovascular response in Alzheimer's disease in animals.

Progress on the clinical research of fluoro-3(2(S)-2-azetidinylmethoxy) pyridine and Iodo-3-(2(S)-azetidinylmethoxy) pyridine / 中华核医学与分子影像杂志

Neuronal nicotinic acetylcholine receptors (nAChRs) are involved in a spectrum of cognitive functions and related to some psychiatric and neurodegenerative disorders such as AD,PD,autosomal dominant nocturnal frontal lobe epilepsy and schizophrenia.Nuclear medicine imaging of neuronal nAChRs in living human is a relatively new field.Halogenated analogs of 3 (2 (S)-2-azetidinylmethoxy) pyridine (A-85380) are the most widely used brain imaging radiotracers.In this review,the progress on the latest research on SPECT and PET using the analogs of A-85380 is summarized.

Role of hippocampal α7nAChR in sevoflurane-induced deficit in long-term cognitive function in neonatal rats / 中华麻醉学杂志

Objective To investigate the role of hippocampal α7 nicotinic acetylcholine receptor (α7nAChR) in sevoflurane-induced deficit in long-term cognitive function in neonatal rats.Methods Sixty-four male Sprague-Dawley rats,aged 7 days,weighing 10-15 g,were randomly divided into 4 groups (n =16each) using a random number table:control group (group C),sevoflurane anesthesia group (group S),sevoflurane anesthesia + α7nAChR agonist PNU-282987 group (group PS),and α7nAChR inhibitor MLA group (group M).In C and S groups,the rats inhaled 30％ oxygen and 3％ sevoflurane for 6 h,respectively.In group PS,PNU282987 (5 mg/kg) was injected intraperitoneally and 24 h later the rats were exposed to 3％ sevoflurane for 6 h.In group M,MLA 3 mg/kg was injected intrappritoneally and 24 h later the rats inhaled 30％ oxygen for 6 h.Eight rats in each group were randomly chosen and sacrificed immediately after oxygen or sevoflurane inhalation.The hippocampus was renoved for determination of the expression of α7nAChR and NR1,NR2A and NR2B subunitscontaining NMDA receptors in the total protein and membrane protein in hippocampal neurons.When the left rats in each group were raised to 2 months,Y-maze test was performed to detect the cognitive function.Results Compared with group C,the expression of α7nAChR and NR1,NR2A and NR2B subunits-containing NMDA receptors in the membrane protein was significantly down-regulated,and the percentage of spontaneous alternation was decreased in group S,the expression of NRI and NR2A subunits-containing NMDA receptors in the membrane protein was down-regulated (P ＜ 0.05),and no significant change was found in the expression of NR2B subunitscontaining NMDA receptors in the membrane protein and percentage of spontaneous alternation in group PS (P ＞ 0.05),and no significant change was found in the expression of NR1 and NR2A subunits-containing NMDA receptors in the membrane protein (P ＞ 0.05),and the expression of NR2B subunits-containing NMDA receptors in the membrane protein was down-regulated,and the percentage of spontaneous alternation was decreased in group M (P ＜ 0.05).Compared with group S,no significant change was found in the expression of NR1 and NR2A subunits-containing NMDA receptors in the membrane protein (P ＞ 0.05),and the expression of NR2B subunitscontaining NMDA receptors in the membrane protein was significantly up-regulated,and the percentage of spontaneous alternation was increased in PS group (P ＜ 0.05).There was no significant difference in the expression of α7nAChR and NR1,NR2A and NR2B subunits-containing NMDA receptors in the total protein and the number of entries into each arm in Y-maze test between the four groups (P ＞ 0.05).Conclusion The mechanism by which sevoflurane induces deficit in long-term cognitive function may be related to decreased function of hippocampal α7nAChR and inhibition of function of NMDA receptors in neonatal rats.

Roles of PI3K/Akt and JAK/STAT signal transduction pathways in reduction of myocardial ischemia/reperfusion injury by postconditioning with α7nAChR agonist in rats / 中华麻醉学杂志

Objective To evaluate the roles of PI3K/Akt and JAK/STAT signal transduction pathways in reduction of myocardial ischemia/reperfusion (I/R) injury by postconditioning with α subunit-containing nicotinic acetylcholine receptor (α7nAChR) agonist in rats.Methods Sixty Sprague-Dawley rats,weighing 290-320 g,were randomly divided into 4 groups (n =15 each):I/R group,ischemic preconditioning group (IPC group),ischemic postconditioning group (IPOC group) and postconditioning with specific α7nAChR agonist PNU282987 group ( PNU group ).Myocardial I/R was produced by 30 min occlusion of left anterior descending coronary artery followed by 180 min reperfusion in the 4 groups.The animals were subjected to 3 cycles of 5 min myocardial ischemia and 5 min reperfusion before 30 min myocardial ischemia in IPC group.The animals underwent 3 cycles of 10 s myocardial ischemia at 5 s intervals before 180 min reperfusion in group IPOC.PNU282987 2.4 mg/kg was injected intraperitoneally immediately before the reperfusion.At 60 min of reperfusion,5 rats in each group were sacrificed and the hearts were removed to determine the expression of Akt and STAT3 mRNA,phosphorylated Akt (p-Akt) and phosphorylated STAT3 (p-STAT3) in myocardial tissues.The left 10 rats in each group were sacrificed at 180 min of reperfusion and the hearts were removed to measure the infarct size.Results Compared with I/R group,the expression of STAT3 mRNA and p-Akt was significantly up-regulated in IPC group,and the expression of p-Akt and p-STAT3 was significantly up-regulated in IPOC group ( P ＜ 0.05).The infarct size was significantly reduced in IPC,IPOC and PNU groups compared with I/R group ( P ＜ 0.05 ).Conclusion The mechanism by which α7nAChR agonist postconditioning reduces myocardial I/R injury is not related to PI3K/Akt and JAK/STAT signal transduction pathways in rats.

Effect of ketamine on nicotine-induced current in rat superior cervical ganglion neurons / 中华麻醉学杂志

ObjectiveTo investigate the effect of ketamine on nicotine-induced current in rat superior cervical ganglion neurons.MethodsNewborn Wistar rats were used in this study.Neurons were isolated enzymatically from superior cervical ganglia of newborn rats in an aseptic condition and cultured in 90％ DMEM/F12,10％ horse serum containing penicillin 100 μg/ml for 5-7 d.Nicotine-induced current was measured and recorded using whole-cell patch clamp technique.A mixture of nicotine 50 μmol/L and different concentrations of ketamine ( 10,25,50,100 μmol/L) was added to the isolated neurons.The effect of ketamine on nicotine-induced current was evaluated.ResultsNicotine-induced peak current was inhibited by ketamine in a concentration-dependent manner.The time constant of fast and slow desensitizing phase of the nicotine acetylcholine receptor was shortened after being exposed to the mixture of nicotine 50 μmol/L + 50 or 100 μmol/L ketamine as compared to nicotine 50 μmol/L-induced current.The median effective concentration of ketamine inhibiting nicotine-induced current was less than 20 μmol/L.ConclusionKetamine can decrease nicotine-induced current in rat superior cervical ganglion neurons in a concentration-dependent manner indicating that inhibition of sympathetic activity is involved in the mechanism of decrease in BP by ketamine in specific condition.

Effects of sevoflurane and isoflurane on blockade of adult type nicotinic acetylcholine receptors of skeletal muscle of rats by rocuronium / 中华麻醉学杂志

ObjectiveTo investigate the effects of sevotlurane and isoflurane on blockade of adult nicotinic acetylcholine receptor (ε-nAChR) of skeletal muscle of rats by rocuronium.MethodsHEK293 cell line was provided by Molecular Biology Laboratory,Chonqing Medical University and cultured in DMEM liquid culture medium containing 10％ bovine calf serum at 37 ℃in incubator filled with 5％ CO2.ε-nAChR was expressed heterologously in HEK293 cell using liposome transfection technology.The whole cell patch clamp technology was used to establish the concentration-effect curves for inhibition of acetylcholine (ACh)-induced current.The 5％ inhibitory concentration values ( IC5 ),25 ％ inhibitory concentration values ( IC25 ) and 50％ inhibitory concentration values (IC50) for sevoflurane,isoflurane and rocuronium were calculated.Firstly the inhibitory effect of rocuronium at a concentration of IC25 was studied in the presence of sevoflurane and isoflurane at concentrations of IC5,IC25 and IC50.Subsequently the inhibitory effect of rocuronium at concentrations of IC5,IC25 and IC50 was studied in the presence of sevoflurane and isoflurane at a concentration of IC25.Inhibition of ACh-induced current amplitude was recorded.ResultsAt the concentrations of IC5,IC25 and IC50 sevoflurane or isoflurane had synergistical inhibitory effect on the current amplitude of ε-nAChR with rocuronium at the concentrations of IC5 and IC25,while had addition inhibitory effect on the current amplitude of ε-nAChR with rocuronium at the concentration of IC50.The inhibitory effect of sevoflurane at the concentration of IC5 on the current amplitude of ε-nAChR with rocuronium at the concentration of IC25 was weaker than that of isoflurane,while the inhibitory effect of sevoflurane at the concentration of IC50 on the current amplitude of ε-nAChR with rocuronium at the concentration of IC25 was stronger than that of isoflurane.The inhibitory effect of sevoflurane at the concentration of IC25 on the current amplitude of ε-nAChR with rocuronium at the concentration of IC5 was weaker than that of isoflurane.ConclusionEither sevoflurane or isoflurane has synergistical blocking effect on ε-nAChR with low concentration of rocuronium,while has addition blocking effect with high concentration of rocuronium.Potentiation of blocking effect of rocuronium on ε-nAChR by low concentration of sevoflurane is weaker than that by isoflurane,while the potentiation by sevoflurane at high concentration is stronger than that by isoflurane.

Role of alpha4 beta2 neuronal nicotinic acetyicholine receptor in inhibition of synapttc long-term potentiation by isoflurane in rat hippncampal slices / 中华麻醉学杂志

Objective To evaluate the role of alpha4 beta2 neuronal nicotinic acetylcholine receptor in the inhibition of synaptic long-term potentiation (LTP) by isoflurane in the CA1 area of rat hippocampal slices.Methods Hippocampal slices (400 μm thick) were prepared from the brains of adult male SD rats, 2 months old, weighing 200-250 g, anesthetized with ether and decapitated. The slices were incubated in artificial cerebrospinal fluid (aCSF) at room temperature for at least 2 h before use. Seventy slices were randomly divided into 10 groups ( n = 7 each): Ⅰ LTP group in which the slices were perfused with aCSF; Ⅱ , Ⅲ and Ⅳ group in which the slices were perfused with aCSF containing isoflurane 0.125, 0.25 and 0.5 mmol/L respectively (group Ⅰ1-3 );Ⅴ and Ⅵ group in which the slices were perfused with aCSF containing epibatidine 0.1 and 1.0 μmol/L respectively (group E1.2 ); Ⅶ group epibatidine 0.1 μmol/L + isoflurane 0.25 mmol/L (group E1 + I2 ); Ⅷgroup epibatidine 1.0 μmol/L + isoflurane 0.25 mmol/L (group E2 + I2); Ⅸ group DHβE 0.1 μmol/L (group D); Ⅹ group DHβE 0.1 μmol/L + isoflurane 0.125 mmol/L (group D + I1 ). Population spikes (PS) were recorded for at least 30 min before LTP in each group. For LTP induction, high-frequency stimulation (HFS) was applied to the Schaffer collateral-commissural pathway of hippocampus and maintained for 15 min using a stimulating electrode.The changes in PS amplitude were analyzed at 5, 10, 15, 20, 25, 30, 40, 50 and 60 min after HFS in each group. Results Compared with group LTP, the PS amplitude was significantly decreased after HFS in group I1 ,I2, I3 , D, D + I1 and E1 + I2 ( P ＜ 0.05), while increased after HFS in group E1 .2 ( P ＜ 0.05 ), but no significant change was found after HFS in group E2 + I2 ( P ＞ 0.05). The PS amplitude was significantly decreased after HFS in group D + I1 compared with group I1 (P ＜ 0.05). The PS amplitude was significantly increased after HFS in group E1 + I2 and F2 + I2 compared with group I2 ( P ＜ 0.01 ). Conclusion Isoflurane inhibits LTP induction via inhibiting the activation of alpha4 beta2 nicotinic acetylcholine receptor in rat hippocampus.

Effects of postconditioning with α7 nicotinic acetylcholine receptor agonist and ischemia on myocardial ischemia-reperfusion injury in rats / 中华麻醉学杂志

Objective To investigate the effects of postconditioning with α7 nicotinic acetylcholine receptor (α7nAChR) agonist and ischemia on myocardial ischemia-reperfusion (IR) injury in rats. Methods Fifty adult male SD rats weighing 290-320 g were randomly divided into 5 groups ( n = 10 each): Ⅰ sham operation group, Ⅱ IR group, Ⅲ ischemic postconditioning group, Ⅳ α7nAChR agonist postconditioning group and Ⅴpostconditioning with α7nAChR agonist and ischemia group. Myocardial I/R was induced by ligation of anterior descending branch of left coronary artery for 30 min followed by 1 80 min of reperfusion. In group] the anterior descending branch was only exposed but not ligated. In group Ⅲ the hearts were subjected to 3 episodes of 10 second ischemia at 10 second intervals at the end of 30 min ischemia before 180 min reperfusion, Intraperitoneal PNU282987 2.4 mg/kg was injected at the end of 30 min ischemia before 180 min reperfusion in group Ⅳ and Ⅴ .Blood samples were taken from right internal jugular vein at 180 min of reperfusion. Then the rats were killed and hearts removed to determine the concentrations of serum cardiac troponin-I (cTnI), TNF-α and high-mobility group box 1 (HMGB1) by ELISA. The infarction size was measured by Evans blue and triphenyltetrazolium chloride staining. Results The infarction size was significantly larger in the other groups and concentrations of serum cTrI, TNF-α and HMGB1 were significantly higher in group Ⅱ than in group Ⅰ ( P ＜ 0.05). The infarction size was significantly smaller and concentrations of serum cTnI, TNF-α and HMGBI were significantly lower in group Ⅲ, Ⅴ than in group Ⅱ (P ＜ 0.05). The infarction size was significantly smaller in group Ⅴ and concentrations of serum cTnI, TNF-α and HMGB1 were significantly lower in group Ⅳ and Ⅴ than in group Ⅲ (P ＜0.05). The infarction size was significantly smaller and concentrations of serum cTnI, TNF-α and HMGB1 were significantly lower in group Ⅴ than in group Ⅳ ( P ＜ 0.05 ). Conclusion Postconditioning with α7nAChR agonist and ischemia can reduce myocardial I/R injury and the efficacy is better than that of α7nAChR agonist postconditioning or ischemic postconditioning alone.

Clinical and genetic studies in three families with nocturnal frontal lobe epilepsy / 中华神经科杂志

Objective To investigate the clinical,electroencephalogram (EEG) and genetic features of nocturnal frontal lobe epilepsy (NFLE) in the Chinese population.Methods Clinical examination,EEG recording,mutation screenings in transmembrane domains 1-3 of neuronal nicotinic acetylcholine receptor (nAChR) α4 (CHRNA4),β2 (CHRNB2) and α2 (CHRNA2) using PCR amplification and sequencing were carried out on 6 patients and some members in 3 families with NFLE.Results Among 6 patients (5 male) with NFLE,the mean age was (20.5±11.5) years and the mean age at onset was (7.3±5.5) years.Clinical features included seizures of dystonic posturing in 2 patients and seizures of hyperkinetic movements in 4 patients with the maximum frequency of 6 seizures within one night.The ictal and interictal video-EEG (VEEG) of frontal lobes showed epileptic discharges,slow wave activity,normal activity or electrode artifacts.There weren' t abnormity in other clinical examination and neuroimagings.No mutations were identified in the genes screened.Conclusion NFLE is a heterogenetic epilepsy syndrome.

Activation of nicotinic acetylcholine receptor prevents the production of reactive oxygen species in fibrillar beta amyloid peptide (1-42)-stimulated microglia

Recent studies have reported that the "cholinergic anti-inflammatory pathway" regulates peripheral inflammatory responses via alpha7 nicotinic acetylcholine receptors (alpha7 nAChRs) and that acetylcholine and nicotine regulate the expression of proinflammatory mediators such as TNF-alpha and prostaglandin E2 in microglial cultures. In a previous study we showed that ATP released by beta-amyloid-stimulated microglia induced reactive oxygen species (ROS) production, in a process involving the P2X7 receptor (P2X7R), in an autocrine fashion. These observations led us to investigate whether stimulation by nicotine could regulate fibrillar beta amyloid peptide (1-42) (fA beta(1-42))-induced ROS production by modulating ATP efflux-mediated Ca2+ influx through P2X7R. Nicotine inhibited ROS generation in fA beta(1-42)-stimulated microglial cells, and this inhibition was blocked by mecamylamine, a non-selective nAChR antagonist, and a-bungarotoxin, a selective alpha7 nAChR antagonist. Nicotine inhibited NADPH oxidase activation and completely blocked Ca2+ influx in fA beta(1-42)-stimulated microglia. Moreover, ATP release from fA beta(1-42)-stimulated microglia was significantly suppressed by nicotine treatment. In contrast, nicotine did not inhibit 2',3'-O-(4-benzoyl)-benzoyl ATP (BzATP)-induced Ca2+ influx, but inhibited ROS generation in BzATP-stimulated microglia, indicating an inhibitory effect of nicotine on a signaling process downstream of P2X7R. Taken together, these results suggest that the inhibitory effect of nicotine on ROS production in fA beta(1-42)-stimulated microglia is mediated by indirect blockage of ATP release and by directly altering the signaling process downstream from P2X7R.