Multimodal, Multidimensional Models of Mouse Brain

Summary:  Naturally occurring mutants and genetically manipulated strains of mice are widely used to model a variety of human diseases. Atlases are an invaluable aid in understanding the impact of such manipulations by providing a standard for comparison and to facilitate the integration of anatomic, genetic, and physiologic observations from multiple subjects and experiments. We have developed digital atlases of the C57BL/6J mouse brain (adult and neonate) as comprehensive frameworks for storing and accessing the myriad types of information about the mouse brain. Along with raw and annotated images, these contain database management systems and a set of tools for comparing information from different techniques and different animals. Each atlas establishes a canonical representation of the mouse brain and provides the tools for the manipulation and analysis of new data. We describe both these atlases and discuss how they may be put to use in organizing and analyzing data from mouse models of epilepsy.     

细菌素产生菌的筛选及其细菌素的分离纯化

从香肠中分离得到一株产细菌素的乳酸片球菌，其发酵液经硫酸铵沉淀，CM—Sephadex C50阳离子交换柱层析后，得到的细菌素样品通过SDS—PAGE证明是一条带，分子量约20．83ku，该细菌素对热及酸碱稳定，易被酶降解而失去活性，对许多革兰氏阳性茵有较强的抑制作用，而对革兰氏阴性茵、酵母和霉没有作用。     

Comparing diffusion-weighted and T2-weighted MR imaging for the quantification of infarct size in a neonatal rat hypoxic–ischemic model at 24 h post-injury

PURPOSE: In a neonatal rat model of hypoxic-ischemic (HI) brain injury, using T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI), we aim to determine the best MRI method of lesion quantification that reflects infarct size. MATERIALS AND METHODS: Twenty 7-day-old rats underwent MRI 24h after HI brain injury was induced. Lesion size relative to whole brain was measured using T2WI and apparent diffusion coefficient (ADC) maps, applying thresholds of 60%, 70% and 80% contralateral control hemisphere mean ADC, and at day 10 post-HI on pathology with TTC staining. Multiple linear regression analysis was used to study the relationships between lesion size at MRI and pathology. RESULTS: Lesion size measurement using all MRI methods significantly correlated with infarct size at pathology; using T2WI, r=0.808 (p<0.001), using 80% ADC, 70% ADC and 60% ADC thresholds, r=0.888 (p<0.001), 0.761, (p<0.001) and 0.569 (p=0.014), respectively. Eighty percent ADC threshold was found to be the only significant independent predictor of final infarct volume (adjusted R(2)=0.775). CONCLUSION: At 24h post-HI, lesion size on DWI, using 80% ADC threshold is the best predictor of final infarct volume. Although T2WI performed less well, it has the advantage of superior spatial resolution and is technically less demanding. These are important considerations for experiments which utilize MRI as a surrogate method for lesion quantification in the neonatal rat HI model.     

Developmental changes in intracellular pH buffering power in smooth muscle

 Intracellular pH (pH_i) is known to modulate contraction. Neonatal tissues can differ from adult tissue in contractile response to stimuli known to alter pH_i e.g. hypoxia. Changes of pH are attenuated by buffering, thus any difference in buffering power (β) between tissues could affect their functional response to pH_i perturbation. Similarly the extent to which any extracellular pH (pH_o) alteration is transmitted into a pH_i change will also influence function. We have therefore determined the intrinsic β and effect of pH_o change on pH_i in neonatal and adult ureteric, uterine and gastric smooth muscles using the pH-sensitive fluorophore carboxy-SNARF. β was found to be similar in the three adult tissues, but there were significant differences between neonatal tissues. In contrast, we found little difference in the amount of pH_i change produced by pH_o change between neonatal and adult tissues from the same smooth muscle, but a difference between smooth muscles. These data highlight significant differences between smooth muscles and their developmental state, which may contribute to different degrees of protection when pH is perturbed. Received: 17 October 1997 / Received after revision: 27 November 1997 / Accepted: 28 November 1997     

Acute toxicity of two pyrethroids,permethrin, and cypermethrin in neonatal and adult rats

The present study aims specifically at obtaining a comparison of the acute toxicity of cypermethrin (CY), a type I pyrethroid, and permethrin (PERM), a type II pyrethroid, administered orally as a single dose to neonatal and adult rats, and at assessing the importance of pyrethroid biotransformation in CY and PERM toxicity through use of drug metabolism inhibitors. Our experiments show that CY is more toxic than PERM to adult and neonatal rats. The sensitivity of neonatal rats both to CY and to PERM toxicity is higher, the younger the animals. CY is much more toxic than PERM in the neonatal rat, compared with the adult. In rats aged 8, 16, and 21 days, pretreatment with piperonil butoxide (PB), a monooxygenase inhibitor, or with tri-o-tolyl phosphate (TOTP), an esterase inhibitor, does not produce significant variations in the lethal effects of CY and PERM. Instead, in the adult rats, a significant increase in CY (X²=5.97;p<0.05) and PERM (X²=4.37;p<0.05) mortality occurred in rats pretreated with esterase inhibitors, whereas no increase in CY and PERM toxicity was found in adult animals pretreated with monooxygenase inhibitor. It was concluded that the higher level of sensitivity of the neonate rat to pyrethroid toxicity is probably due to incomplete development of the enzymes which catalyze the metabolism of pyrethroids in the liver of young animals. It is suggested that ester hydrolysis is an important pyrethroids detoxification reaction in the adult rat.     

Role of noradrenergic hyperactivity in neonatal opiate abstinence

Despite the existence of a well-defined abstinence syndrome in offspring of opiate-dependent mothers, the mechanisms involved in neonatal abstinence remain unclear. The goal of the present study was to determine the contribution of noradrenergic neurons in the opiate abstinence syndrome in neonatal rats (10 days old). First, the ability of the α2-adrenergic agonist, clonidine to attenuate the symptoms of neonatal opiate abstinence precipitated by naloxone was determined. Secondly, the activity of noradrenergic neurons was determined by measuring postmortem levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) in the hypothalamus, hippocampus and cortex in opiate-abstinent pups. Neonatal opiate abstinence was characterized by an increased incidence of wall climbing, tremors and mouthing. Acute treatment with morphine and naloxone in chronic saline-treated pups also produced the tremor, albeit less severe than in pups treated chronically with morphine. Clonidine (0.2 mg/kg) attenuated the expression of tremor and mouthing in neonates, but increased wall climbing. Clonidine elicited wall climbing in opiate-naive neonates. Treatment with morphine followed by naltrexone increased MHPG levels in all of the brain areas examined, irrespective of the chronic treatment, but naltrexone treatment elicited a larger increase in MHPG levels in pups treated chronically with morphine. Acute morphine treatment increased MHPG levels only in the hypothalamus. The results of the present study provide behavioral and neurochemical data supporting the hypothesis that noradrenergic hyperactivity plays a role in neonatal opiate abstinence.     

Surgical Treatment of an Early Epileptic Encephalopathy with Suppression-Bursts and Focal Cortical Dysplasia

Summary: A case of early epileptic encephalopathy (EIEE) with suppression-bursts or Ohtahara's syndrome, associated with focal cortical dysplasia is reported. Infantile spasms and brief tonic unilateral seizures began on the fifth day of life. Interictal EEG demonstrated an asymmetrical "suppression-burst" pattern with no wake or sleep cycling. Seizures were refractory to all antiepileptic drug (AED) and steroid therapy. Magnetic resonance imaging (MRI) showed right frontotemporal cortical thickening. After three weeks of an ineffective medical treatment a preoperative evaluation with single photon emission computed tomography (SPECT) and electrocorticography (ECoG) was performed to characterize epileptogenic focus. Surgical resection of the precentral area was performed at age 1 month. Neuropathologic examinations confirmed diagnosis of focal cortical dysplasia by identifying cytoarchitectural disarray and ectopic neurons located deep in subcortical white matter. During follow-up, 1-year postoperative the child had a single febrile seizure. Neurologic examination showed minor developmental delay and slight left-sided weak ness.     

极低体质量近存活期分娩儿一例的出生后早期管理

近存活期分娩（PVB）儿各组织系统发育极不成熟,易发生各种器官功能损害和并发症,预后常不佳。目前关于PVB儿出生后早期管理的报道不多,诸多尚待解决的问题仍是围产医学所面临的挑战。经有效的新生儿复苏和呼吸循环支持、积极的营养支持和喂养、防治感染、内分泌和代谢性疾病管理、积极处理早产儿相关并发症,以及发育支持护理、家庭参与式护理等一系列个体化管理和精细化护理,四川省医学科学院·四川省人民医院成功救治了1例胎龄23周,出生体质量（BW）为450 g的PVB儿。本文通过总结1例PVB儿的出生后早期管理,并结合文献复习进行归纳总结,以期为提高BW<500 g的PVB儿存活率并获得良好预后提供经验及借鉴。     

妊娠期阻塞性睡眠呼吸暂停筛查的研究进展

阻塞性睡眠呼吸暂停（OSA）是妊娠人群中常见的睡眠呼吸障碍性疾病,不仅与多种不良妊娠结局相关,也可能对母婴远期健康产生重要影响。目前诊断OSA的金标准多导睡眠监测在妊娠人群中难以大规模开展,导致绝大多数妊娠期OSA未能得到及时诊断。寻求其他筛查策略和筛查工具准确识别具有OSA风险的孕妇并进行及时诊治,对于改善不良妊娠结局具有重要意义。本文针对妊娠期OSA患病率、筛查现状、筛查时机、目标人群、筛查工具的研究进展进行综述,以期为妊娠期OSA的筛查提供参考和理论依据。     

A screening programme for microalbuminuria at a diabetes clinic in Apulia,southern Italy

Microalbuminuria is a predictor of renal and cardiovascular disease in both type 1 (insulin-dependent) and type 2 (insulin-independent) diabetes. We report on a screening programme for microalbuminuria at a diabetes clinic in Italy. All diabetic patients without Albustix-positive proteinuria attending the clinic between April and September 1991 were screened. Microalbuminuria was defined as a urinary albumin/creatinine ratio, on an early morning sterile urine sample, >3 in at least two consecutive urine collections. Three hundred and fifty patients, 45 (20 female, 25 female) type 1 and 305 (145 male, 160 female) type 2 diabetics, were examined. The age range was 18–42 years and 36–73 years and duration of diabetes 1–24 and 1–35 years for type 1 and type 2 diabetic patients respectively. Blood pressure, lipids, glycosylated haemoglobin, body mass index and insulin dose, where appropriate, were measured in all patients. Microalbuminuria was found in 8 (22%) of the type 1 diabetics. These patients had a longer duration of diabetes (17.5 vs 7.4 years,P<0.001), higher diastolic blood pressure (86±2.1 vs 76±2.6 mmHg,P<0.05) and an increased total serum cholesterol level (203±23 vs 180±25 mg/dl,P<0.05) compared with diabetic patients with microalbuminuria. Of the type 2 diabetic patients 95 (33%) were found to have microalbuminuria and 210 (69%) nor-moalbumiuria. The prevalence of hypertension (defined blood pressure >140/90 mmHg or antihypertensive treatment) and of dyslipidaemia (defined as total cholesterol >200 and triglycerides >170 or hypolipidaemic treatment) were significantly higher (P<0.001 and 0.01 respectively) in patients with microalbuminuria. This study shows a prevalence of microalbuminuria in type 1 and type 2 diabetic patients similar to that reported in surveys of diabetes clinic outpatients in northern Europe. The association between microalbuminuria and recognized risk factors for cardiovascular and renal disease justifies screening programmes for microalbuminuria for early detection of at-risk diabetic patients and for the implementation of preventive therapeutic measures.