Neutralinos, Big Bang Nucleosynthesis and 6Li in Low-Metallicity Stars
【综述】朗罕氏细胞组织细胞增生症的神经内分泌表现

【综述】朗罕氏细胞组织细胞增生症的神经内分泌表现《Handbook of Clinical Neurology》杂志2021年8月[181:127-135]刊载希腊的Maria P Yavropoulou, Marina Tsoli, Gregory Kaltsas等撰写的综述《朗罕氏细胞组织细胞增生症的神经内分泌表现。
Neuroendocrine manifestations of Langerhans cell histiocytosis》(10.1016/B978-0-12-820683-6.00009-9 )。
朗罕氏细胞组织细胞增生症(LCH)是一种罕见的炎性髓样肿瘤(inflammatory myeloid neoplasia),可影响人体任何器官或系统。
它通常在儿童期被诊断出来,但也可能影响成人。
最近的研究表明,有相当比例的垂体前叶和后叶功能缺陷的患者的下丘脑-垂体轴(HPA)受累,在大多数情况下是永久性的,需要特定的激素替代方案。
中枢性尿崩症被认为是LCH中HPA受累最常见的异常,可以遇到作为单独的缺陷或伴随其他垂体缺陷。
特别是当垂体受累时,强烈建议对LCH 患者进行完整的垂体激素评估和长期随访。
介绍朗汉氏细胞组织细胞增生症(Langerhans cell histiocytosis ,LCH)是一种罕见的疾病,其特征是,具有与可以潜在地浸润人体的任何器官或组织的正常表皮Langerhans细胞相似的形态特征的,特异性树突状细胞的克隆积累和/或增殖(the clonal accumulation and/or proliferation of specific dendritic cells)。
虽然尚不完全清楚其发病机制,但LCH病变包括具有常见BRAFV600E突变的克隆性CD207+树突状细胞以及炎性成分。
此外,最近的证据支持一种模型,即LCH的出现继发于髓样前体细胞(myeloid precursors)中丝裂原活化蛋白激酶通路(the mitogen-activated protein kinase pathway)的病理性激活。
神经组织XX

•(神经胶质膜)
•神经元 神经胶质细胞
• 分布:神经元胞体附近及轴突周围
•少 • 胞体较小,突起较少;突起末端扩展成扁平薄膜 ,包卷神经元的轴突形成髓鞘
•突 • 功能:是中枢神经系统的髓鞘形成细胞 •胶 •质 •细 •胞
•型 ②参与构成血-脑屏障 •胶 ③分泌神经营养因子
④组织损伤时,细胞增生形成胶质瘢痕
•质 •细 •胞
•原浆性星形胶质细胞 (主要分布于灰质)
•纤维性星形胶质细胞 (主要分布于白质)
•神经元 神经胶质细胞
• 由连续毛细血管内皮、基膜及星型胶质细胞脚板(神经胶质膜)共同 构成的血液与中枢神经组织之间的屏障结构,可以阻止某些物质进入 中枢神经组织,但能允许营养物和代谢产物顺利通过,以维持中枢神 经组织内环境的稳定。
•的 髓鞘 •无 • 一个施万细胞可包含多条轴突 •髓 • 相邻的施万细胞衔接紧密,无郎飞结 •神 •经 •纤 •维
•神经纤维
•CNS
•的 •无
• 轴突外面没有特异性的神经胶质 细胞包裹,轴突裸露地走行于有 髓神经纤维或神经胶质细胞之间
•髓
•神
•经
•纤
•维
神经末梢
nerve ending
神经末梢 nerve ending
•神经末梢
•环 •层 •小 •体
•感受: 压觉和振动觉
•神经末梢
•环 •层 •小 •体
环层小体光镜像
•运动神
•肌•经纤维 •梭
•神经末梢
•被囊
•花枝样感觉 •神经末梢 •环状感觉 •神经末梢 •梭内肌 •细胞核
•梭内肌细胞
•运动神 •经末梢
神内复试名词解释

1.POEMS综合征(以多发性周围神经病(polyneuropathy)、脏器肿大(organomegaly)、内分泌障碍(endocrinopathy)、M 蛋白(monoclonal protein)血症和皮肤病变(skin changes)为主要临床表现)由于浆细胞瘤或浆细胞增生所致多系统损害的一种综合征。
临床表现为进行性多发性周围神经病、肝脾肿大、内分泌紊乱、M蛋白增高和皮肤色素沉着,并可出现全身凹陷性水肿、胸腹水、杵状指和心力衰竭等症状。
鉴别诊断:慢性格林—巴利综合征:主要表现为多发性周围神经病变及脑脊液蛋白的增高,一般不出现皮肤损害及内分泌功能障碍。
无骨骼损害及M蛋白、浆细胞浸润等。
2.10个英语病名:transient ischemic attack(TIA), subarachnoid hemorrhage(SAH), Alzheimer’s disease(AD), herpes simplex virus encephalitis(HSE), multiple sclerosis(MS), Parkinson’s disease(PD), acute myelitis, migraine, neuromyelitis optic(NMO/Devic), epilepsy, acute inflammatory demyelinating polyneuropathy(AIDP) , trigeminal neuralgia, poems syndrome, myasthenia gravis(MG)3.临床见到的记忆深刻的病4.为什么不报北京的学校啊?————————吉林大学学术沉淀厚重,相应的学术氛围比较浓厚。
老师治学态度严谨,医德高尚。
更加注重对学生临床实践。
学生有更多自己思考,自己动手的机会。
从而形成自己的临床诊断思维。
对以后的职业发展有好处。
in my opinion, jilin university has a longer history in neurology. Correspondingly, its academic atmosphere is stronger than those in Beijing.7介入,人多不留你。
中枢神经系统脱髓鞘疾病英文

Clinical research cooperation
要点三
Regular physical examinations
Regular physical examinations are conducted, especially for individuals with a family history, in order to detect potential demyelinating diseases at an early stage.
Transplantation surgery
Transplanting healthy nerve tissue to the damaged area to promote nerve regeneration and repair.
Other treatment methods
Physical therapy
03
Psychological adjustment
Patients should maintain a positive and optimistic attitude, learn to regulate their emotions, and reduce the impact of anxiety and depression on the disease.
Through surgery, the pressure on nerve tissue caused by lesions is reduced, improving nerve function.
Excision surgery
The removal of diseased tissue to eliminate the cause and alleviate symptoms.
大三医学资料神经系统-英文

灰质gray matter皮质cortex 神经核nucleus白质white matter髓质medulla 纤维束fasciculus 神经结ganglion网状结构reticular formation脊髓spinal cord颈膨大cervical enlargem ent腰骶膨大lumbosac ral enlargem ent脊髓圆锥conus medullari终丝filum terminale马尾cauda equina中央管central canal中间带intermedi ate zone灰质连合gray commissu re前索anterior funiculus外侧索lateral funiculus后索posterior funiculus后角posterior horn后角边缘核posterom arginal nucleus胶状质substantia gelatinos后角固有核nucleus proprius胸核nucleus thoracicus前角anterior horn侧角lateral horn中间外侧核intermedi olateral nucleus骶副交感核sacral parasymp athetic nucleus背外侧束dorsolater al fasciculus薄束fasciculus gracilis楔束fasciculus cuneatus脊髓小脑后束posterior spinocere bllar tract脊髓小脑前束anterior spinocere bllar tract脊髓丘脑束spinothal amic tract皮质脊髓束corticospi nal tract端脑Telencep halon间脑Dienceph alon小脑Cerebellu m脑干Brain stem中脑Midbrain 脑桥Pons延髓Medulla oblongat a锥体Pyramid锥体交叉Decussati on of pyramid前外侧沟Anterolat eral橄榄Olive橄榄后沟Retrooliva ry sulcus薄束结节Gracile tubercle楔束结节Cuneate tubercle小脑下脚Inferior cerebellar peduncle脑桥小脑三角Pontocer ebellar triagone小脑中脚Middle cerebellar peduncle延髓脑桥沟Bulbopon tine基底沟Basilar sulcus小脑上脚Superior cerebellar peduncle上髓帆Superior medullary velum中脑Midbrain脚间窝Interpedu ncular fossa上丘Superior colliculus下丘Inferior colliculus菱形窝Rhomboi d fossa正中沟Median sulcus界沟Sulcus limitans髓纹Striae medullare s舌下神经三角Hypoglos sal triangle迷走神经三角Vagal triangle闩Obex脑室ventricle一般躯体运动核General somatic motor nuclei动眼神经核oculomot or滑车神经核trochlear nucleus展神经核abducent nucleus舌下神经核hypogloss al nucleus特殊内脏运动核 Special visceral motor nuclei三叉神经运动核motor nucleus of trigeminal面神经核facial nucleus疑核nucleus ambiguus副神经核 spinal accessory nucleus一般内脏运动核General visceral motor nuclei动眼神经副核accessory oculomot or上泌涎核superior salivatory nucleus下泌涎核 inferior salivatory nucleus迷走神经背核 dorsal nucleus of vagus一般、特殊内脏感觉核Visceral sensory nuclei ( general and special )孤束核nucleus of solitary tract一般躯体感觉核General somatic sensory nuclei三叉神经中脑核mesencep halic nucleusof trigeminal三叉神经脑桥核pontine nucleus of trigeminal三叉神经脊束核spinal nucleus of trigeminal特殊躯体感觉核Special somatic sensory nuclei蜗神经核cochlear nuclei前庭神经核vestibular nuclei薄束核gracile nucleus楔束核cuneate nucleus下橄榄核inferior olivary nucleus脑桥核pontine nucleus红核red nucleus黑质substantia nigra上丘superior colliculus下丘inferior colliculus内侧丘系Medial lemniscus脊髓丘脑束Spinothal amic tract三叉丘系Trigemina l lemniscus外侧丘系Lateral lemniscus脑桥被盖Tegment um of基底部Basis Pontis延髓内侧综合征medical medullary syndrome延髓外侧综合征lateral medullary syndrome脑桥基底部综合征basal pontine syndrome脑桥背部综合征dorsal pontine syndrome大脑脚底综合征peduncul ar syndrome本尼迪克特综合征Benedikt syndrome小脑Cerebellu m小脑半球cerebellar hemisphe re小脑蚓vermis小脑扁桃体Tonsil of cerebellu m前叶anterior lobe后叶posterior lobe绒球小结叶flocculon odular小脑脚Cerebellar peduncles小脑皮质cerebellar cortex原小脑Archicere bellum旧小脑Paleocere bellum新小脑Neocereb ellum间脑Dienceph alon背侧丘脑Dorsal thalamus后丘脑Metathala mus上丘脑Epithalam us底丘脑Subthala mus下丘脑Hypothal amus视交叉optic chiasma灰结节tuber cinereum漏斗Infundibul um垂体hypophys is乳头体mamillary body视上核Supraopti c nucleus室旁核Paraventri cular nucleus第三脑室Third ventricle端脑Telencep halon大脑皮质Cerebral cortex沟Sulcus 回Gyrus胼胝体Corpus callosum大脑纵裂Cerebral longitudin al fissure大脑横裂Cerebral transverse fissure中央沟Central sulcus外侧沟Lateral sulcus顶枕沟Parietooc cipital sulcus额叶Frontal lobe顶叶Parietal lobe枕叶Occipital lobe颞叶Temporal lobe岛叶Insular lobe中央前沟Precentral sulcus中央前回Precentral gyrus额上沟Superior frontal sulcus额下沟Inferior frontal sulcus额上、中、下回Superior, middle and inferioe frontal Gyri顶内沟Intraparie tal sulcus中央旁小叶paracentr al lobule海马Hippoca mpus边缘叶Limbic lobe侧脑室lateral ventricle基底核basal nuclei尾状核caudate nucleus豆状核lenticular nucleus杏仁体amygdalo id连合纤维Commiss ural fibers联络纤维associatio n fibers投射纤维Projecting fibers内囊internal capsule隔区septal area硬脊膜spinal dura mater硬膜外隙epidural space硬膜下隙subdural space脊髓蛛网膜spinal arachnoid mater软脊膜spinal pia mater蛛网膜下隙subarach noid终池Terminal cistern硬脑膜Cerebral dural mater脑蛛网膜Cerebral arachnoid mater软脑膜Cerebral pia mater大脑镰cerebral falx小脑幕tentorium of cerebellu m小脑镰cerebellar falx鞍隔diaphrag ma sellae上矢状窦Superior sagittal sinus下矢状窦Inferior sagittal sinus直窦Straight sinus窦汇Confluenc e of sinus横窦Transvers e sinus乙状窦Sigmoid sinus岩上窦superior petrosal sinuses岩下窦inferior petrosal sinuses海绵窦Cavernou s sinus蛛网膜粒Arachnoi d granulatio颈内动脉internal carotid artery大脑前动脉anterior cerebral artery大脑中动脉middle cerebral artery脉络丛前动脉anterior choroidal artery椎动脉vertebral artery基底动脉basilar artery大脑后动脉posterior cerebral artery脑脊液cerebrosp inal fluid (CSF)神经元Neuron 神经胶质细胞Glial cell无髓鞘神经纤维Unmyelin ated nerve fiber有髓鞘神经纤维Myelinate d nerve fiber顺向轴浆运输Anterogra de axoplasmi c transport逆向轴浆运输Retrograd e axoplasmi c transport电突触Electrical synapse化学性突触Chemical synapse兴奋性突触后电位Excitatory postsyna ptic potential, EPSP抑制性突触后电位Inhibitory postsyna ptic potential, IPSP突触的可塑性Synaptic plasticity习惯化Habituati on敏感化Sensitizati on长时程增强Long-time potentiati on, LTP长时程抑制Long-time depressio n, LTD神经调质Neuromo dulator乙酰胆碱Acetylcho line, ACh胆碱能神经元Cholinerg ic neuron胆碱能纤维Cholinerg ic fiber非条件反射Unconditi oned reflex条件反射Condition ed reflex单线式联系Single line connectio辅散式联系Divergent connectio n聚合式联系Converge nt connectio n连锁式Chain connectio n环 式Recurrent connectio n外感受器Exterocep tors内感受器Enterocep tors本体感觉Proprioce ption触-压觉Touch-pressure sensation温度觉Warm/col d sensation内脏痛Visceral pain牵涉痛Referred pain特异感觉接替核Specific sensory relay nucleus感觉联络核Associate d nucleus简化眼Reduced eye老视presbyopi a瞳孔近反射Near reflex of the pupil瞳孔的对光反射Pupillary light眼球会聚Converge nce近视Myopia远视Hyperopi a散光Antigmati sm视杆Rod 视锥细胞Cone视紫红质Rhodopsi n视敏度Visual acuity视野Visual field听阈Hearing threshold听域Hearing span气传导Air conductio n骨传导Bone conductio n耳蜗微音器电位 cochlear micropho nic potential, CM半规管Semicircul ar canals椭圆囊Utricle 球囊Saccule眼震颤Nystagm us反射运动Reflex motor activity随意运动Voluntary motor activity节律性运动Rhythmic motor activity运动单位Motor unit脊髓休克Spinal shock姿势反射Postural reflex屈肌反射Flexor reflex对侧伸肌反射Crossed extensor reflex牵张反射Stretch reflex腱反射Tendon reflex肌紧张Muscle tonus肌梭Muscle spindle反牵张反射Inverse stretch reflex去大脑僵直Decerebr ate Rigidity易化区Inhibitory area抑制区Facilitator y area状态反射Attitudina l reflex迷路紧张反射Tonic labyrinthi ne reflex颈紧张反射Tonic neck reflex翻正反射Righting reflex巴宾斯基征Babinski sign震颤麻痹Parkinson ’s disease舞蹈病Huntingto n’s disease自主神经系统Autonomi c Nervous System(A NS)非联合型学习non-associativ e learning联合型学习associativ e learning习惯化habituatio n敏感化sensitizati on经典条件反射condition ed reflex操作式条件反射operant conditioni ng遗忘症amnesia长时程增强long-term potentiati on , LTP长时程减弱long-term depressio n,LTD鬼影细胞ghost cell单纯性神经元萎缩simple neuronal atrophy中央性尼氏小体溶解central chromatol ysisWaller变性waller degenera tion噬神经细胞现象neuronop hagia小胶质细胞结节microglial node格子细胞gitter cell 卫星现象satellitosis流行性脑脊髓膜炎Epidemic cerebrosp inal meningiti流行性脑脊髓膜炎Epidemic cerebrosp inal meningiti流行性乙型脑炎Epidemic encephali tis B阿尔茨海默病Alzheimer disease老年斑senile plaque神经原纤维缠节neurofibri llary tangles,NFTs帕金森病Parkinson 's disease,P D镇静催眠药Sedative-hypnotic Drugs地西泮diazepam苯二氮卓类benzodia zepine drugs, BZD巴比妥类barbiturat es水合氯醛chloral hydrate唑吡坦zolpidem 佐匹克隆zopiclone右佐匹克隆eszopiclo ne抗癫痫药Antiepilep tic Drugs抗惊厥药Anticonvu lsive Drugs苯妥英钠Phynotoni n Sodium卡马西平Carbmaze pine苯巴比妥Phenobar bital乙琥胺Ethosuxi mide丙戊酸钠,德巴金Sodium Valproate硫酸镁Magnesiu m Sulfate抗帕金森病药物Anti-Parkinson Drugs左旋多巴Levodopa ( L-dopa)溴隐亭Bromocri ptine卡比多巴carbidopa苯海索Trihexyph enidyl阿尔茨海默病治疗药物Drugs for Alzheimer ’s Disease多奈哌齐donepezil 他克林tacrine利斯的明,卡巴拉汀,艾斯能Rivastigmi ne加兰他敏Galantami ne石杉碱甲,双益平Huperzin e A美金刚,易倍申Memantin e占诺美林Xanomeli ne吡拉西坦,脑复康Piracetam抗精神失常药Agents Against Psychiatri c氯丙嗪chlorpro mazine氟西汀fluoxetine碳酸锂lithium carbonate三环类抗抑郁药Tricyclic Antidepre ssants (TCAs)米帕明,丙米嗪Imipramin e选择性5-HT再摄取抑制药 SSRIs黛力新Deanxit 丁螺环酮Buspirone 氯氮平Clozapine奥氮平Olanzapin e利培酮,维思通Risperido ne卡马西平Carbamaz epine镇痛药Opioid Analgesic s吗啡morphine地芬诺酯,苯乙哌啶Diphenox ylate可待因,甲基吗啡Codeine 哌替啶Pethidine 度冷丁Dolantin美沙酮Methado ne芬太尼Fentanyl喷他佐辛,镇痛新Pentazoci ne布托啡诺Butorpha nol纳洛酮Naloxone解热镇痛抗炎药Nonsteroi dal Anti-inflammat ory Drugs阿司匹林aspirin 对乙酰氨基酚, 扑热息痛Acetamin ophen布洛芬Ibuprofen吲哚美辛Indometh acin吡罗昔康Piroxicam局部麻醉药Local Anestheti cs普鲁卡因Procaine 利多卡因Lidocaine丁卡因Tetracain e布比卡因Bupivacai ne全身麻醉药General Anestheti cs吸入性麻醉药Inhaled anesthetic s静脉麻醉药Intraveno us anesthetic s最小肺泡浓度Minimum alveolarconcentra tion, MAC 恩氟烷Enflurane 异氟烷Isoflurane硫喷妥钠Pentothal Sodium 丙泊酚Propofol 氯胺酮,K粉Ketamine 麻醉前给药Premedic ation基础麻醉Basalanesthesia诱导麻醉Inductionofanesthesia低温麻醉Hypothermalanesthesia控制性降压Controlledhypotensi on神经安定镇痛术Neurolept analgesia Neurolog yIntroduc tionNeuroexa m略头痛Headache头晕Dizziness 癫痫Seizure肌无力Myasthenia 昏迷Coma 痴呆Dementi a步态障碍gaitdisorder 偏头痛Migraine紧张性头痛Tension type headach e(TTH)丛集性头痛Cluster headach e良性阵发性位置性眩晕Benign Paroxys mal Positiona l Vertigo (BPPV)前庭神经原炎Vestibula r neuroniti s(VN)后循环缺血Post-cycle ischemia( PCI)偏头痛眩晕症Migraino us vertigo( MV)自动症Automati sm短暂性脑缺血发作Transient Ischemic Attacks, TIA格林巴利综合症Guillain-Barrésyndrom e谵妄delirium 模糊vague嗜睡Somnole nce昏睡Stupor。
医学神经系统小脑间脑和大脑

内囊通过的投射纤维
上行: 丘脑皮质束(内囊后肢) 视辐射(内囊后部) 听辐射(内囊后部) 其它
下行: 皮质脊髓束(内囊后肢) 皮质脑干束(内囊膝部) 皮质桥束: 额桥束(前肢) 定、枕桥束(后肢) 其它
梭形细胞
大脑皮质 分层及神 经元类型
颗粒细胞
大脑皮质 分层及神 经元类型
Martinotti 氏细胞
大脑皮质 分层及神 经元类型
水平细胞
2、大脑皮质的分层
新皮质分为6层:
分子层:
I
外颗粒层:
II
外锥体层:
III
内颗粒层:
IV
内锥体层:
V
多形层或梭形细胞层: VI
传入层 传出层
古皮质(海马)只分为3层: 分子层、锥体细胞层、多形层
1. 室床; 2. 起层; 3. 锥体细胞层; 4. 放射层; 5. 腔隙分子层
3、大脑皮质的功能分区
Brodmann —— 52个区
额叶皮质:躯体运动、头眼运动、发育和语言
以及高级思维活动
(1)躯体运动区:
第一运动区(4区):中央前回、旁中央小叶前部
组成锥体束(30%)
6区:
中央前回前上部、额上回后上部
小脑(小)球
二、小脑的核团
小脑中央核
顶 核 —— 接受蚓部皮质的纤维
球状核 栓状核
接受中间部皮质的纤维
齿状核 —— 接受外侧部皮质的纤维
三、小脑的纤维联系
(1) 既接受来自运动中枢的信息,也接受与 运动有关的大量感觉信息;
(2) 上述信息主要汇聚到Puikinje细胞, Puikinje细胞的活动又主要通过小脑核 影响脊髓、脑干和大脑皮质的运动功能;
加拿大发现调控肥胖和焦虑生物途径

加拿大发现调控肥胖和焦虑生物途径--> 近日,来自加拿大的科学家在著名国际期刊Neuron发表了一项最新研究进展,他们发现了一条新的调控焦虑和肥胖的生物途径,同时发现一种用于临床治疗肥胖的药物或可用于对抗焦虑症。
研究人员指出,肥胖和焦虑正逐渐成为社会性大问题,而之前研究发现遭受代谢和肥胖相关疾病困扰的病人通常也会出现情绪紊乱和焦虑,因此了解肥胖与焦虑之间的生物学联系,或对协同治疗肥胖和焦虑具有重要意义。
他们在之前研究LMO4基因对大脑发育的影响时发现,该基因在小鼠大脑特定部位缺失会导致小鼠出现焦虑和肥胖症状。
而在本文中,他们结合了之前的研究发现,进一步证明PTP1B在联系LMO4,焦虑,肥胖和内源性大麻素系统的分子机制中发挥了重要作用。
Trodusquemine是一种用于调节食欲,减轻体重的临床药物,同时还对乳腺癌治疗具有潜在作用。
研究人员应用这种药物特异性抑制PTP1B活性,结果发现小鼠的焦虑和肥胖症状均得到改善。
综上所述,目前关于焦虑症的治疗方法存在成瘾问题和其他副作用,而这项研究发现的方法能够让大脑通过调节PTP1B活性自行修复,或对协同治疗肥胖和焦虑具有重要意义。
对与那些因肥胖而焦虑的小伙伴们,这或许是个不错的好消息。
上海市疾病预防控制中心最新慢性病及其危险因素监测报告显示,从2007年至2013年,上海居民超重和肥胖率均呈上升趋势,由原来的34%上升为42%。
其中,上海成人(18岁)男性总超重率达38.6%,总肥胖率达10.6%,成人女性总超重率已达26%,总肥胖率为9.1%。
值得注意的是,在45岁之前,上海女性的超重或肥胖率仅为男性一半;45岁之后,女性肥胖率显著升高,超过男性。
“超重和肥胖导致癌症的发生存在10年滞后期,但在未来10-20年后,超重和肥胖将导致相应癌症增长。
”上海市疾控中心肿瘤防治科主任郑莹介绍。
女性更易因肥胖致癌昨日,在市疾控中心举行的2015年女性健康论坛活动上,郑莹指出,2013年美国医学会正式认定肥胖是一种疾病,而超重与肥胖作为威胁健康的危险因素一直是医学研究热点。
2型糖尿病进程中小鼠下丘脑室旁核和视上核nesfatin`-1表达

2型糖尿病进程中小鼠下丘脑室旁核和视上核nesfatin`-1表达2型糖尿病是一种常见的慢性代谢性疾病,其特征为血糖调节功能异常。
随着生活水平的不断提高,2型糖尿病患者数量逐渐增多,对于这一疾病的病理机制研究成为了当前医学领域的热点之一。
糖尿病的发生和发展受到多种因素的影响,其中包括神经内分泌系统的失衡。
下丘脑室旁核和视上核是一对非常重要的神经核,它们分别参与血糖调节和食欲调控。
近年来的研究表明,nesfatin-1是一种新的食欲调控因子,它在调节食欲和体重的过程中发挥着重要的作用。
研究2型糖尿病进程中小鼠下丘脑室旁核和视上核nesfatin-1表达的变化,对于揭示糖尿病的病理机制具有重要的意义。
为了深入研究这一问题,我们开展了相关实验。
我们使用了小鼠模型建立了2型糖尿病模型,然后通过免疫组化和原位杂交等技术手段,对小鼠下丘脑室旁核和视上核的nesfatin-1表达进行了观察和分析。
实验结果显示,在2型糖尿病小鼠模型中,下丘脑室旁核和视上核的nesfatin-1表达水平发生了显著变化。
具体来说,在2型糖尿病小鼠模型中,下丘脑室旁核的nesfatin-1表达水平明显下降,而视上核的nesfatin-1表达水平明显上升。
这些结果表明,2型糖尿病可能通过影响下丘脑室旁核和视上核的nesfatin-1表达来影响食欲和体重调节,进而加重糖尿病的发展。
我们还发现,下丘脑室旁核和视上核的nesfatin-1表达水平与2型糖尿病的临床参数呈现一定的相关性。
具体来说,下丘脑室旁核的nesfatin-1表达水平与血糖、胰岛素和胰岛素抵抗指标呈负相关,而视上核的nesfatin-1表达水平与这些指标呈正相关。
这些结果表明,下丘脑室旁核和视上核的nesfatin-1表达可能参与了2型糖尿病的发生和发展过程,具有一定的临床预测价值。
我们的研究结果揭示了2型糖尿病进程中小鼠下丘脑室旁核和视上核nesfatin-1表达的变化规律,为进一步揭示糖尿病的病理机制提供了重要的实验依据。
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a r X i v :a s t r o -p h /0405583v 2 22 N o v 2004Neutralinos,Big Bang Nucleosynthesis and 6Li in Low-Metallicity StarsKarsten JedamzikLaboratoire de Physique Math´e mathique et Th´e orique, C.N.R.S.,Universit´e de Montpellier II,34095Montpellier Cedex 5,FranceThe synthesis of 6Li during the epoch of Big Bang nucleosynthesis (BBN)due to residual anni-hilation of dark matter particles is considered.By comparing the predicted 6Li to observations ofthis isotope in low-metallicity stars,generic constraints on s-wave dark matter annihilation rates into quarks,gauge bosons,and Higgs bosons are derived.It may be shown that,for example,wino dark matter in anomaly-mediated SUSY breaking scenarios with masses m χ<∼250GeV orlight neutralinos with m χ<∼20GeV annihilating into light quarks are,taken face value,ruled out.These constraints may only be circumvented if significant 6Li depletion has occurred in all three low-metallicity stars in which this isotope has been observed to date.In general,scenarios invoking non-thermally generated neutralinos with enhanced annihilation rates for a putative explanation of cosmic ray positron or galactic center as well as diffuse background gamma-ray signals by present-day neutralino annihilation will have to face a stringent 6Li overproduction problem.On the other hand,it is possible that 6Li as observed in low-metallicity stars is entirely due to residual dark matter annihilation during BBN,even for neutralinos undergoing a standard thermal freeze-out.The nature of the ubiquitous cosmological dark mat-ter is one of the outstanding questions in cosmology.Though there exist a multitude of proposed candidates,much consideration has been given to the supersymmet-ric (SUSY)neutralino,provided it is the lightest super-symmetric particle (LSP).SUSY extensions of the stan-dard model are particularly successful in overcoming a number of shortfalls of the standard model,such as the hierarchy problem and grand unification.Neutralinos are appealing since neutral,likely stable,and endowed with annihilation/scattering cross sections which (a)makes it likely have the right cosmological abundance and (b)makes it be detectable in the not-to-distant future by either direct-(e.g.scattering in cryogenic detectors)or indirect-(e.g.observation of positrons or γ-rays due to residual neutralino annihilation in the Galaxy)detection means [1].In general,the post-freeze-out number-to-radiation en-tropy n χ/s of a stable and initially abundant particle subject to self-annihilation is given byY fχ=(n +1)H g f H2SUSY theories,may be easily formed after an inflation-ary epoch of the Universe.As they are made of squarks,and are unstable in SUGRA and AMSB,their R-parity and baryon-number conserving evaporation at late times T D <∼1GeV may not only generate many LSP’s but also the observed cosmic baryon asymmetry.The thus gener-ated LSP’s may undergo further self-annihilation to reach an asymptotic final abundance dependent on T D [10].Similarly,in AMSB scenarios,gravitinos are typicallyheavy m ˜G >∼50TeV,such that their decay occurs before BBN.In such scenarios,which circumvent the gravitinoproblem,neutralinos are produced in ˜G(and/or mod-uli)decays well after the conventional thermal freeze-out of neutralinos from equilibrium [4,5].When additional substantial non-thermal injection of neutralinos at T D occurs,their final present day abundance may still be calculated via Eq.(1)and Eq.(2)with x f given byx f =max[x D ,x tf ](3)where x D =m χ/T D ,and x tf quantifies the appropriate freeze-out temperature during thermal freeze-out [11],and where it has been implicitly assumed that the pre-annihilation neutralino abundance exceeds that of Eq.(1)and Eq.(2).LSP abundance estimates may also be changed (i.e.increased)when compared to the standard evolution of the Universe,when additional degrees of free-dom are present in the early Universe.This may be,for example,due to the existence of a quintessence field in the stage of kination,or quite generally,due to extra de-grees of freedom g H (with g S unchanged)contributing to the Hubble expansion [12].There are currently no limits on g H at high T other than those from the (much later)epoch at BBN T <∼1MeV.Though the post-freeze-out Y fχstays essentially un-changed,residual χannihilations occur up to the present day and may have considerable impact on the process of Big Bang nucleosynthesis (BBN).The effects of resid-ual annihilation of χ’s during BBN have been considered some time ago [13,14].Nevertheless,whereas earlier studies were based on the isotopes 2H and 4He ,it has been pointed out that 6Li production during electromag-netic [15,16]or hadronic [15,17,18,19]energy injection during BBN is particularly efficient [20].The isotope of 6Li may be produced via non-thermal reactions (subject to energy threshold),such as 3H(α,n )6Li or 3He(α,p )6Li.Energetic 3H and 3He are readily produced via nuclear 4He spallation by energetic nucleons or 4He photodisin-tegration.Since the photodisintegration of 4He is only efficient for T <∼0.3keV particular importance in the an-nihilation case is due to hadronic spallation.This is be-cause residual annihilation is stronger at earlier times.Resulting 6Li abundances are given formally by a time integraln 6Li d t n p,n n p,nn 6d t=σvm χ2(5)with ρχneutralino density,(b)the generated energeticprotons p and neutrons n per annihilation,(c)the pro-duced energetic mass-three nuclei per generated ener-getic nucleon,and (d)the produced 6Li per energetic mass-three nucleus,respectively.Here the first factor is determined by the annihilation rate under the assump-tion that χis the dark matter whereas the second fac-tor may be obtained assuming a particular χannihila-tion channel and computing the energetic nucleon spec-trum via a hadronic flux tube Monte Carlo code such as PYTHIA [21].Concerning the third and fourth fac-tors I have recently presented first [18]results and a first description of a newly developed Monte-Carlo code de-scribing the cascading of energetic nucleons and nuclei on background thermal nucleons,nuclei,and electromag-netically interacting particles which allows me to evalu-ate Eq.(4).This code includes,Coulomb and Thom-son stopping of fast charged nucleons and nuclei,elastic-and inelastic-nucleon-nucleon scattering and elastic-and break-up-processes in nucleon-4He scattering.Of all mass three nuclei produced a small fraction react on 4He to form 6Li.The probability to do so,may be approxi-mated byP 6Li = n 6d E i E iE thd E1l nuc (d E/d x )C(6)a convolution over the initial energy distribution of mass-three nuclei,d n 3/d E i ,-the probability that a mass-three nucleus during it’s passage through energy space due to the dominant multiple Coulomb interactions with energy loss per unit length d E/d x undergoes a reaction to form 6Li (where l 6Li =1/(σ6Li n 4He )is the mean free path to-wards formation of 6Li)-while,the exponential factor,not having undergone already another nuclear interac-tion (mean free path due to all nuclear interactions is l nuc )[22].Compared to the Coulomb losses other nu-clear interactions in Eq.(6)are typically not very impor-tant,except for charge exchange between the mirror nu-clei 3H(p,n )3He and to a lesser degree elastic p-3H and p-3He scattering.in only a narrow temperature range between several keV and ≈20keV.Nevertheless,though the freshly synthesized energetic 6Li typically survives almost completely p -spallation [23]it may only survive 6Li(p,α)3He thermal reactions (after it’s rapid thermal-ization)when T <∼10keV.It has been realized [13,19]that in the above-given temperature window Coulomb losses loose some of their efficiency (by roughly a factor 3-10)for energetic 3-nuclei with velocities below the elec-tron thermal velocities (but still above the lithium forma-tion reaction thresholds of 8.39and 7.05MeV for 3H and310-1210-1110-10FIG.1:Final 6Li yield functions defined via Eq.(7)as a function of neutralino mass for various annihilation channels as labeled in the key.The 1-σrange of the 6Li abundance in HD84937is also shown.3He,respectively).I have computed the energy transfer of a fast charged nucleon or nucleus due to Coulomb in-teractions with an electron-positron plasma at tempera-ture T ,explicitly accounting for a thermal average and accounting for higher order terms.Details on this cal-culation will be presented elsewhere.Since 6Li synthe-sis during/after BBN is dominated during those epoch where (a)the annihilation rate Eq.(5)is still large,(b)synthesized 6Li survives the thermal 6Li(p,α)3He reac-tion,and (c)d E/d x |C is at it’s minimum,the bulk of the 6Li is synthesized at T ≈10keV and an exact eval-uation of d E/d x |C is paramount to an evaluation of 6Li abundances.I have thus computed the 6Li yield for annihilating par-ticles and under the assumption of specific annihilationchannels such as into u ¯u ,d ¯d ,s ¯s ,b ¯b ,or t ¯tquark-antiquark pairs,as well as W −W +or ZZ gauge bosons [24].The re-sults of these computations for varying neutralino masses m χare shown in Fig. 1.Here the annihilation-channel dependent yield functions Y i 6Li are defined via the equa-tionn 6Li0.1126 2i b i Y i 6Li (7)where the b i are branching ratios into channel i andm χ,100is the neutralino mass in units of 100GeV.Eq.(7)is remarkable as it allows a quite general evaluation of the final 6Li abundance,independent of the nature of the annihilating particle,as well as applicable for essen-tially all relevant σv and m χ.Note that the Y 6Li ’s for leptonic channels,which are not shown,are essentially zero due to the absence of injected nucleons.Annihi-lation into Higgs bosons,on the other hand,yield Y 6Li only somewhat smaller than those shown in Fig.1,since Higgs bosons typically decay into heavy quarks or mas-10-2610-2510-2410-23101001000M x (GeV)<σv> (cm 3/s)δg/g = 104δg/g = 102T D = 100 MeVT D = 5 GeVstandard thermal freeze-outFIG.2:Annihilation-channel dependent constraints on the s-wave annihilation rate due to possible 6Li overproduction as a function of neutralino mass.For simplicity,only the u ¯u ,b ¯b and W −W +channels are shown with heavy lines and linestyles as indicated in Fig.1.Constraints on other quark-and gauge boson-annihilation channels are virtually identical to those shown as may be verified by inspection of Fig.1.Anni-hilation rates above the lines are ruled out.Also shown are the annihilation rates required [34]to produce Ωχh 2=0.1126during standard thermal freeze-out (solid line)or during ther-mal freeze-out when extra degrees of freedom (contributing to the Hubble expansion during freeze-out)are present (theupper two solid lines with δg f H /g fH as labeled).The dotted di-agonal lines correspond to the required σv for post thermal freeze-out non-thermal generation of Ωχh 2=0.1126at tem-peratures,from top to bottom,0.1,0.2,0.5,1,2,and 5GeV,respectively.Here the QCD phase transition has been as-sumed to occur at 200MeV.The curved dotted line shows the annihilation rate in case of AMSB winos [5].sive gauge bosons.A simple scaling with σv was possi-ble due to the linearity in the 6Li production and destruc-tion mechanisms.Note that though for fixed dark matterdensity d Ann /d t ∼m −2χa scaling in Eq.(7)with m −1.5χhas been adopted.This is due to higher mass χpro-ducing more energetic primary nucleons which,in turn,produce a larger number of secondary p and n ,yieldinga final n 6Li /n H ∼m −1.5χ.Fig.1also shows the one-sigma range 6Li/H ≈8.47±3.10×10−12[26]of the observationally best determined 6Li/H-ratio in a low-metallicity star,i.e.in HD84937,which has been analyzed by several groups [26,28].6Li detections have been currently claimed in three low-metallicity [Z]<∼−2[26,28,29]and two higher metal-licity stars [Z]∼−0.6[30]with their abundances coin-cidentally all in the same range,reminiscent of a unique cosmic abundance.In principle,6Li may be depleted in stars,in practice,however,those low [Z ]stars which show 6Li have normal “Spite”-plateau 7Li abundances,and as this latter isotope would,in most circumstances,be depleted as well,substantial 6Li depletion seems un-410-2710-2610-2510-2410-23101001000M x (GeV)<σv> (cm 3/s)FIG.3:S-wave annihilation rate required to produce within the 2−σlimits the 6Li abundance of HD84937.The heavy lines indicate the central value of HD84937,whereas lighter lines the 2−σranges.For simplicity only the u ¯u (solid)and W −W +(dotted)channels are shown with results for other channels similar (cf.Fig.1).likely [31].The origin of the 6Li at [Z]<∼−2is somewhat mysterious as only with considerable difficulty explained by traditional galactic cosmic ray spallation and fusion reactions [32].It is thus conceivable that 6Li at low [Z ]is,in fact,entirely of primordial origin,though other al-ternative origins have also been proposed [33].In the absence of stellar 6Li depletion the efficient pro-duction of 6Li due to annihilating neutralinos may be used to constrain the properties of the dark matter par-ticle itself.Fig.2shows annihilation-channel dependent limits on the s-wave annihilation χχcross section of a dark matter particle,representing a convolution of the results in Fig.1with Eq.(7).Here the two-sigma up-per limit on 6Li in HD84937has been adopted such that dark matter particles above the diagonal lines in the up-per part of the figure are ruled out due to 6Li overpro-duction.For reference,the figure also shows annihilation cross sections required to obtain the WMAP abundance given (a)standard thermal freeze-out [34](b)thermal freeze-out when additional degrees of freedom are presentδg fH/g f H >0as,for example due to a quintessence field and (c)via late generation below the thermal freeze-out temperature due to,for example,decay of gravitinos or evaporation of Q-balls.Furthermore,the figure shows the predicted LSP wino σv into W +W −in AMSB sce-narios as given in Ref.[5]It is evident that possible 6Li overproduction imposes stringent constraints on dark matter particle proper-ties.As evident from Fig.2,light neutralinos with mass m χ<∼20GeV annihilating into light quarks are ruled out at two-sigma.AMSB winos may only be consistent with the 6Li abundance when m χ>∼250GeV.When the dark matter particle is the first excited Kaluza-Klein modeB (1)[36]of the U (1)Y gauge boson,it may not be lighter than m KK <∼200GeV due to its efficient annihi-lation into right-handed up-type te-time gen-eration of dark matter χ’s is disallowed for all tempera-tures below 200MeV unless the dark matter particle is fairly heavy m χ>∼400GeV or annihilation does not occur into hadronic or gauge (and higgs)boson channels.Fi-nally,a substantially increased Hubble rate during ther-mal freeze-out is for all but the heaviest neutralinos ob-servationally disallowed.These limits may be circum-vented in case substantial stellar 6Li depletion occurred which,nevertheless,would require a coincidentally sim-ilar amount of depletion in all three 6Li-rich observed stars to date.Limits of this sort are also important in light of scenarios which invoke neutralino annihilation as putative explanations of,for example,the observed cosmic positron excess at ∼10−30GeV [37,38]as de-termined by HEAT,or the galactic-center [39,40,41],or extragalactic diffuse [42],gamma-ray fluxes as deter-mined by EGRET,VERITAS,or CANGAROO.In order to explain anomalous components of such signals such as bumps in the spectrum a signal boost (enhancement)factor B s of the order ∼50−103[43,44]is essentially always required.Considering the most recent N-body simulations on substructures and halo profiles [45],such B s seems only unlikely due to clumpy halos or singular halo profiles though,in principle,one could envision it due to an enhanced σv with respect to it’s standard thermal freeze-out value.Nevertheless,already modest particle-physics motivated boost-factors of the order of ∼1−10will have to face a potential 6Li overproduction problem.Last but not least,it is possible that the entire ob-served 6Li at low metallicity may be due to the residual annihilation of a dark matter particle.Fig.3shows the mass-dependent annihilation rate required to produce a 6Li abundance within the 2σranges of those observed in HD84937.It is seen that this may be accomplished even by a standard thermal freeze-out with dominant s-wave component annihilation into light quarks,provided the neutralino mass is within the approximate range of 20−80GeV [34].The observed amount of 6Li may be produced for even larger mass neutralinos when either coannihilation effects or annihilation on poles occur in the thermal freeze-out case or neutralinos are generated non-thermally.Coincidentally,the recently proposed specific dark matter neutralinos [46]and Kaluza-Klein particles [47]which could explain the claimed bump in the extra-galactic γ-ray background and/or the positron excess as observed by HEAT would have just the right properties to yield 6Li abundances as observed in low-[Z]stars.Such annihilation is also associated with some,albeit small,amount of observationally favored 7Li deple-tion [18].It is intriguing that the observed abundances of 6Li in low-metallicity stars may be entirely a product of dark matter annihilation.I acknowledge discussions with Eric Nuss.[1]for a recent reviews cf.G.Bertone, D.Hooperand J.Silk,arXiv:hep-ph/0404175; C.Munoz, arXiv:hep-ph/0309346.[2]D.N.Spergel et al.,Astrophys.J.Suppl.148,175(2003)[3]D.G.Cerdeno and C.Munoz,arXiv:hep-ph/0405057,and references therein.[4]T.Gherghetta,G.F.Giudice and J.D.Wells,Nucl.Phys.B559,27(1999)[5]T.Moroi and L.Randall,Nucl.Phys.B570,455(2000)[6]P.Ullio,JHEP0106,053(2001).[7]H.Baer and J.O’Farrill,JCAP0404,005(2004)[arXiv:hep-ph/0312350]and references therein.[8]A.Bottino,N.Fornengo and S.Scopel,Phys.Rev.D67,063519(2003)[9]for a review cf.to K.Enqvist and A.Mazumdar,Phys.Rept.380,99(2003)[10]K.Enqvist and J.McDonald,Phys.Lett.B440,59(1998);M.Fujii and K.Hamaguchi,Phys.Rev.D66, 083501(2002);M.Fujii and M.Ibe,Phys.Rev.D69, 035006(2004).[11]Here x tf=ln(A)−(n+1/2)ln(ln(A))with A≈0.038(n+1)M pl Mχσ0gχ/(g f H)1/2where M pl is the(non-reduced)Planck mass and gχis the statistical weight of the freez-ing out particle.[12]P.Salati,Phys.Lett.B571,121(2003);F.Rosati,Phys.Lett.B570,5(2003);S.Profumo and P.Ullio,JCAP 0311,006(2003);R.Catena,N.Fornengo,A.Masiero, M.Pietroni and F.Rosati,arXiv:astro-ph/0403614.[13]M.H.Reno and D.Seckel,Phys.Rev.D37,3441(1988)[14]J.A.Frieman,E.W.Kolb and M.S.Turner,Phys.Rev.D41,3080(1990).[15]S.Dimopoulos,R.Esmailzadeh,L.J.Hall andG.D.Starkman,Astrophys.J.330,545(1988).[16]K.Jedamzik,Phys.Rev.Lett.84,3248(2000).[17]M.Y.Khlopov,Y.L.Levitan,E.V.Sedelnikov,andI.M.Sobol,Phys.Atom.Nucl.bf57,1393(1994).[18]K.Jedamzik,Phys.Rev.D063524(2004),arXiv:astro-ph/0402344.[19]M.Kawasaki,K.Kohri and T.Moroi,arXiv:astro-ph/0402490.[20]Limits based on2H are typically more than an order ofmagnitude weaker.[21]T.Sj¨o strand,P.Ed´e n,C.Friberg,L.L¨o nnblad,G.Miu,S.Mrenna and E.Norrbin,Computer Physics Commun.135238(2001);www.thep.lu.se/torbjorn/Pythia.html [22]Note that though Eq.(6)incorrectly approximates massthree nuclei during p-3H(3He)elastic scattering to loose most of their energy,in the Monte-Carlo analysis this problem is treated properly.[23]Note,thisfinding is in stark contrast with the result ofthe recent paper Ref.[19],which makes me suspect that the authors of the latter analysis have not included a thermal average over electron velocities in the computa-tion of d E/d x|C.[24]The calculations assumeΩb h2≈0.0218.Furthermore thesmall amount of standard thermal6Li production via D(α,γ)6Li[25]has been conservatively neglected.An-nihilation products have been forced in PYTHIA to be on-shell.The post-annihilation“initial”state is therefore two on-shell primaries with each energy mχ.[25]K.M.Nollett,M.Lemoine,and D.N.Schramm,Phys.Rev.C561144(1997)[26]R.Cayrel,M.Spite, F.Spite, E.Vangioni-Flam,M.Cass´e,and J.Audouze,Astron.&Astrophys.343 923(1999).[27]S.G.Ryan,T.C.Beers,K.A.Olive,B.D.Fields andJ.E.Norris,Astrophys.J.Lett.530,L57(2000) [28]V.V.Smith,mbert,and P.E.Nissen,Astro-phys.J.408262(1993);506405(1998);L.M.Hobbs and J.A.Thorburn,Astrophys.J.491772(1997); [29]P.E.Nissen,M.Asplund,V.Hill,and S.D’Odorico,Astr.&Astrophys.357L49(2000)[30]P.E.Nissen,mbert,F.Primas,and V.V.Smith,Astr.&Astrophys.348211(1999)[31]Note that results of analysis of the observational data aretypically given as6Li/7Li ratios.Conversion to a6Li/H-ratio requires thus a7Li/H ratio.This latter value is given for HD84937in Ref.[26]at7Li/H≈1.63×10−10, agrees with other7Li/H ratios on the Spite-plateau[27] but not with that predicted from standard BBN for Ωb h2≈0.0218,which is about a factor3larger.In case the observed value of7Li is due to a significant factor ∼3stellar depletion,a factor>∼3stellar depletion of6Li is predicted.In this case,observational constraints based on6Li abundances are relaxed.On the other hand,the re-sulting uncomfortably large pre-depletion6Li abundance seems unattainable within the context of galactic cosmic ray nucleosynthesis,arguing for an origin of6Li which is likely primordial or at the least pre-galactic.[32]E.Vangioni-Flam,M.Cass´e,R.Cayrel,J.Audouze,M.Spite,and F.Spite,New Astron.4245(1999);B. D.Fields and K. A.Olive,New Astron.4255(1999);R.Ramaty,S.T.Scully,R.E.Lingenfelter andB.Kozlovsky,Astrophys.J.534,747(2000);A.Alib´e s,bay,and R.Canal,Astrophys.J.571,326(2002).[33]T.K.Suzuki and S.Inoue,Astrophys.J.573168(2002)[34]Here it is implicitly assumed that the dominant annihi-lation component is s-wave.Moreover,effects of coanni-hilation and annihilation on poles[35]are not taken into account in the estimate.Given the same thermal freeze-outΩm these latter effects have the potential to either reduce,or increase,the effective annihilation rate rele-vant during the BBN era.An increase by a factor up to ∼4may be due to,a significantly suppressed NLSP-LSP, and NLSP-NLSP annihilation rate with respect to the LSP-LSP annihilation rate,in the coannihilation case, since coannihilation only plays a role during freeze-out.Even larger enhancement factors are conceivable due to different thermal broadening of pole annihilation during the respective eras of LSP freeze-out and BBN.This may occur for fairly small decay width,Γ<∼T f of the interme-diate particle produced on the pole,as here a thermal av-eraging reduction of σv at T f>∼Γbut not at T BBN≪Γmay result.[35]K.Griest and D.Seckel,Phys.Rev.D43,3191(1991).[36]G.Servant and T.M.P.Tait,Nucl.Phys.B650,391(2003)[37]E.A.Baltz,J.Edsjo,K.Freese and P.Gondolo,Phys.Rev.D65,063511(2002),and references therein. 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