Review of the Evidence for Treatment of Children with Autism with Selective Serotonin Reuptake Inhibitors

PURPOSE.  To review the potential role of serotonin dysregulation in autism and the efficacy of selective serotonin reuptake inhibitors (SSRIs) in treating core deficits and associated symptoms of autism in children. The literature was searched for reports of SSRI use in children with autism. Data are presented from prospective clinical trials that evaluated treatment outcomes.
CONCLUSIONS.  Some SSRIs show moderate success in managing specific behaviors. Only fluoxetine shows evidence of decreasing global autism severity.
PRACTICE IMPLICATION.  Definitive conclusions concerning selection criteria, dosage, safety, and efficacy cannot be drawn given the current state of evidence.     

前列腺中凋亡抑制基因Bcl-2的表达研究

目的　了解前列腺组织中　Ｂｃｌ－２蛋白的表达。方法　采用免疫组化技术，检测　　１１例胎儿、２７例成人和　　６０例增生前列腺中Ｂｃｌ－２蛋白的表达。结果　胎儿前列腺Ｂｃｌ－２蛋白表达于全部胚芽上皮细胞；成人前列腺Ｂｃｌ－２蛋白表达主要定位于腺上皮基底细胞，分泌细胞偶见阳性表达；增生前列腺Ｂｃｌ－２阳性表达主要定位于腺上皮基底细胞，分泌细胞亦见不同程度阳性表达；增生前列腺基底细胞、分必细胞Ｂｃｌ－２阳性表达均高于正常前列腺，差异有显著性；正常前列腺与增生前列腺上皮基底细胞Ｂｃｌ－２阳性表达均高于分泌上皮细胞，差异有显著性。结论　基底细胞层可能为成人前列腺的干细胞层，参与前列腺细胞的生长与增殖；Ｂｃｌ－２基因蛋白可能在调节前列腺上皮的凋亡中具有重要作用；Ｂｃｌ－２基因蛋白在前列腺基底细胞增生中起主要作用，而在分泌细胞中不占主要地位。     

放射复合伤口中Bax和Bc-l2蛋白表达与细胞凋亡的关系研究

目的：研究Bax和Bcl-2蛋白在放射复合伤口愈合中的表达及其与细胞凋亡的关系。方法：用原位末端标记（TUNEL）法检测细胞凋亡,用免疫组织化学方法检测Bax、Bcl-2蛋白表达。结果：（1）与单伤组比较,照射后细胞凋亡的变化具有出现较早、频率较高、消失推迟3个显著特点,可能是导致辐射延迟伤口愈合的重要原因。（2）观察伤口愈合过程中Bax、Bcl-2蛋白表达及其与细胞凋亡的关系,发现随着细胞凋亡的增加,Bax蛋白的表达明显增强,并且与细胞凋亡发生频度具有良好的相应关系。而Bcl-2蛋白水平在细胞凋亡达高峰时呈明显下降趋势;当凋亡明显下降时,Bcl-2蛋白表达增加,并逐渐恢复其正常水平。结论：Bax和Bcl-2蛋白在放射复合伤口愈合细胞凋亡的调控中起着重要作用。     

丙戊酸钠诱导孤独症模型大鼠皮层Bcl-2、Bax的表达

目的探讨Bcl-2、Bax在孤独症发病中的作用。方法孕12.5 d Sprague-Dawley孕鼠腹腔注射丙戊酸钠600 mg/kg建立子代孤独症模型大鼠,对照组注射同等剂量生理盐水。利用尼氏染色、免疫组化和图像分析技术观察比较出生后1 d、7 d、14d、28 d和56 d两组大鼠脑部Bcl-2、Bax表达。结果尼氏染色:出生后1 d、7 d模型组神经元数量较少,出生14 d后剧增,出生后28 d、56 d仍高于对照组。免疫组化:出生后1~14 d两组Bcl-2、Bax表达均显著升高(P<0.001),出生28后表达趋于稳定(P>0.05);与对照组相比,模型组各日龄大鼠Bcl-2表达水平均显著降低(P<0.001);Bax于出生后1 d、7 d表达显著升高(P<0.001),出生后14 d表达显著降低(P<0.001),出生28 d后水平相似(P>0.05)。对照组Bcl-2/Bax值出生后1 d最大,随年龄逐渐减小,出生14后趋近于1。模型组Bcl-2/Bax值出生后7 d最低,14 d最高,28 d后趋于稳定。结论孤独症模型大鼠大脑皮层神经元细胞抗凋亡能力下降,尤其在出生后早期。     

硼替佐米对急性单核细胞白血病细胞株SHI-1诱导凋亡作用及其对Bcl2112、Bcl-2和Bax基因表达影响

本研究探讨蛋白酶抑制剂硼替佐米对急性单核细胞白血病细胞株SHI-1增殖和凋亡的影响及Bcl2112、Bcl-2和Bax基因在其中的作用。用MTT比色法观察硼替佐米对SHI-1细胞的生长抑制作用，用Annexin—V标记、线粒体跨膜电位（△ψm）和DNA凝胶电泳分析细胞凋亡，用RT—PCR方法检测0、6，12和24小时Bcl2112、Bcl-2和Bax基因表达。结果表明，硼替佐米呈时间和剂量依赖性抑制SHI-1细胞生长，24小时和48小时半数抑制浓度分别为54．13nmol／L和5．45nmol／L；硼替佐米能够诱导SHI-1细胞凋亡，在6小时Annexin-V阳性细胞就开始增高并呈时间依赖性，ACm减低，形态学可见明显细胞核凝聚、固缩和碎裂，DNA凝胶电泳显示DNA片段化；RT-PCR显示，Bcl2112表达增高，Bcl-2表达减低，但Bax表达无明显改变。结论：硼替佐米抑制SHI-1细胞增殖，并可能通过上调Bcl2112基因和下调Bcl-2基因，使线粒体膜电位下降而促使SHI-1细胞发生凋亡。     

Bax和Bcl2基因在单纯和放射复合伤口中的表达及与细胞凋亡和愈合延迟的关系

目的：研究Bax,Bcl-2基因在单纯和放射复合伤口愈合中的表达规律及与细胞凋亡和愈合延迟的关系。方法：用原位末端标记法（TUNEL）检测细胞凋亡,用核酸原位杂交方法检测Bax,Bcl-2mRNA表达并定量分析。结果：（1）照射后细胞凋亡出现的频度及延续的时间明显高于单伤组;（2）伤口愈合过程中Bax,Bcl-2表达随着细胞凋亡的增加呈规律性改变;Bax表达明显增强,且与细胞凋亡发生有良好的相应关系;而Bcl-2呈明显下降趋势,结论：Bax和Bcl-2基因在放射复合伤口愈合细胞凋亡的调控和愈合延迟中起重要作用。     

Quantification of Bax and Bcl2 in polymorphonuclear leukocytes from haemodialysis patients: relation to hydrogen peroxide

Background Bax and Bcl2 are two apoptosis‐related molecules that play an important role in determining cell fate following oxidative injury. In the present study, we explored the relation of hydrogen peroxide (H₂O₂) generation by polymorphonuclear cells (PMNs) to the cytosolic expression of Bax and Bcl2 proteins and apoptosis in haemodialysis (HD) patients. Methods Cytosolic generation of H₂O₂ by PMNs from control subjects and HD patients was measured by flow cytometry using the dichlorofluorescin diacetate assay. Bax and Bcl2 expression was detected by flow cytometry using FITC‐conjugated antibodies. Apoptosis was quantified by flow cytometry using propidium iodide nuclear staining. To examine the effect of H₂O₂ on Bcl2 and Bax expression, PMNs from control subjects were briefly exposed to H₂O₂ (0·1–100 µM) for 10 min and then washed and cultured for 6 h, with or without catalase, a H₂O₂ detoxifying molecule. Bcl2 and Bax expression was determined by Western blot analysis. Results Basal H₂O₂ generation by resting PMNs was significantly higher in HD patients compared with control subjects (211 ± 115 vs. 23 ± 5 MFI; P = 0·002). However, PMNs from HD patients did not undergo accelerated programmed cell death compared with control subjects (58 ± 7% vs. 46 ± 5; P = 0·14). Polymorphonuclear cells cytosolic Bcl2 was undetected in control subjects but detected in 25% of HD patients, and Bax was more frequently detected in PMNs from HD patients (75% vs. 67%; P = 0·04). In the HD patients with detectable cytosolic Bax and Bcl2 proteins, the Bax to Bcl2 ratio inversely correlated with H₂O₂ levels (P < 0·0001). Finally, brief exposure of PMNs to 0·1–100 µM of H₂O₂ resulted in a marked increase in Bcl2 expression (P = 0·001), which was prevented by catalase (P = 0·05). There was no apparent effect on Bax expression. Conclusions This study demonstrates that in HD patients, high‐resting cytosolic H₂O₂ production by PMNs is not associated with accelerated in vitro apoptosis, and that the Bax/Bcl2 system may counter‐balance the deleterious effects of reactive oxygen species in human PMNs.     

The Triad of Impairment in Autism Revisited

TOPIC:  The triad of impairment referred to at present in the autism-related literature is a behavioral triad. This paper extends this thinking of the triad of impairment to the triad that underlies the behavioral manifestation. The real triad of impairment.
PURPOSE:  This paper considers the thinking and information processing style of autism and takes the next transitional step in understanding the triad of impairment.
SOURCES USED:  Contemporary literature on autism and information processing.
CONCLUSIONS:  Exceptional pioneering work in the late 1970s gave rise to the concept of the triad of impairments as the central plank of the construct of autism: impaired communication; impaired social skills; and a restricted and repetitive way of being-in-the-world. This clear articulation of the structures of the phenomena allowed a new way for professionals and families to see and understand autism, and to relate to those with autism. Like the evolution of many concepts, this was a transitional idea. The original triad of impairments described the behavioral manifestation; the actual triad of impairments is at the level of cognitive processing. The actual triad of impairment is static and ubiquitous unlike the variable and fluctuating behavioral manifestation. The actual triad of impairment in autism is visual as opposed to linguistic processing, impaired abstraction, and lack of theory of mind. The actual triad is central to all diagnosis that together makes up the autism spectrum.     

Two Terms—One Meaning: The Conundrum of Contemporary Nomenclature in Autism

TOPIC:  Autism as a diagnostic construct in the last decade has undergone a process of rapid evolution in the way that it is operationalized. A by-product of the important conceptual shift is that we have been left with two terms, autistic disorder and Asperger's disorder, that point to the same thing. The existence of two terms that cannot be clearly delineated results in confusion and an added element in an already anxiety-laden mix for all those trying to come to terms with the concept of autism.
PURPOSE:  This paper moves beyond contemporary arguments of whether autistic disorder and Asperger's disorder are different entities and uses a case study to consider the mechanism of the confusion caused, and highlight the importance of referent clarity.
SOURCES:  A review of sources in journals and texts related to the topic is included to complement the progressive review of the case study as the clients move through a 1-hour initial consult.
CONCLUSION:  The current diagnostic criteria are ambiguous posing the risk of confusion to parents, clinicians, and researchers. Nurses have an important role in assisting parents' construction of a unified concept of autism clinically, and through research. This paper moves beyond merely acknowledging the confusion that exists by considering the nature of the confusion, and through sharing the experience of one possible way of navigating it.     

以cDNA为内参标RT-PCR定量检测心肌细胞内p53和Bcl-2基因mRNA表达量的方法研究

目的 :探讨 p5 3和 Bcl 2基因在急性心肌梗死时心肌细胞中 m RNA表达量的检测方法。方法 :用以c DNA为内参标的逆转录聚合酶链反应 (RT PCR)方法检测 p5 3和 Bcl 2基因的 m RNA表达量。结果 :p5 3基因 m RNA表达量〔m RNA/总 RNA(ng/ g)〕依次为 :冠脉结扎后 4小时组 (5 76 4 8.78± 19776 .96 ) ng/ g>结扎后 6小时组 (339.0 6± 10 4 .11) ng/ g>结扎后 3小时组 (16 5 .4 4± 33.36 ) ng/ g>结扎后 2小时组 (88.2 5±16 .6 5 ) ng/ g>未结扎 (0 )组 (3.16± 0 .6 9) ng/ g和结扎后 1小时组 (16 .37± 2 .73) ng/ g、8小时组 (2 3.13±7.0 3) ng/ g、 12小时组 (6 .75± 2 .86 ) ng/ g,P均 <0 .0 5 ;Bcl 2基因 m RNA表达量〔m RNA/ g总 RNA(ng/ g)〕:冠脉结扎后 3小时组 (4.5 3± 1.5 9) ng/ g、 4小时组 (0 .0 2± 0 .0 1) ng/ g和 6小时组 (3.4 6±0 .39) ng/ g<结扎后 2小时组 (5 2 .4 8± 14 .18) ng/ g、8小时组 (5 9.2 4± 2 .91) ng/ g<结扎后 1小时组 (77.2 0±12 .4 8) ng/ g和未结扎 (0小时 )组 (81.77± 9.6 2 ) ng/ g<结扎后 12小时组 (99.6 0± 4 .71) ng/ g,P均 <0 .0 5。该种方法能对不同的样本检出不同量的 m RNA含量 ,其特异性强 ,且能检出 0 .0 2 ng/ g的 m RNA含量 ,敏感性高。结论     

Employment Experiences,Perspectives, and Wishes of Mothers of Children with Autism in the People’s Republic of China

Background The purpose of this study was to examine the experiences with and meaning of employment in the lives of mothers of children with autism in China. Materials and Methods This research used qualitative methods including open‐ended questionnaires and semi‐structured interviews with mothers of children with autism participating in an intervention program in Beijing. Results Mothers find employment outside the home appealing, but they also see their role of mother as requiring being responsible and often making sacrifices. Conclusions Mothers in this study make sacrifices in their own lives, including employment, in order to promote and provide intervention for their children with autism. These families had fewer services available to them than in many developed Western countries, and most services are at a cost to the parents. Considerations that Chinese mothers of children with autism make regarding their own employment situation are unique.     

BclⅠ和HindⅢ位点在家系性血友病A基因诊断的意义

本研究旨在探讨FⅧ基因内含子18的BclⅠ及内含子19的HindⅢ多态性位点在血友病A(haemophiliaA,HA)患者及家系成员的基因诊断与携带者检出中的应用价值。对8个HA患者及其家系成员45人运用聚合酶链反应-限制性片断多态性(polymerase chain reaction restriction fragment length polymorphism,PCR-RFLP)方法对X染色体FⅧ基因内含子18的BclⅠ及内含子19的HindⅢ位点进行多态性分析。应用中国遗传咨询网在线家系图绘制工具PediDraw软件绘制家系图。结果表明,联合检测BclⅠ及HindⅢ位点可对8个HA家系中的5个作出诊断,诊断率约为62.57%,且有2个家系同时伴有2个位点的突变。该8个家系11名可疑携带者中6名可作出携带者诊断,携带者的检出率为54.5%。结论:联合运用BclⅠ及HindⅢ位点进行HA患者家系分析可提高HA患者及携带者的诊断率。     

The Undervalued Role of Over-regulation in Autism: Chaos Theory as a Metaphor and Beyond

TOPIC:  A triad of impairment that consists of impaired communication, impaired social skills and over-regulated behavior characterizes autism. Causality of autism is yet to be identified. Therapy has been devised to apply to the work with children and adolescents with a diagnosis of autism in the domains of impaired communication and impaired social skills. Little attention has been paid to the importance of the over-regulated behavior that forms part of the triad of impairment.
PURPOSE:  This paper considers this point of over-regulation in the triad of impairment in autism through the lens of Chaos theory.
SOURCES:  Contemporary literature on autism and Chaos theory.
CONCLUSIONS:  Implications for nursing practice and research are raised.     

The Effectiveness of Naltrexone in Treating Task Attending, Aggression, Self-Injury, and Stereotypic Mannerisms of Six Young Males with Autism or Pervasive Developmental Disorders

An 8-week trial of 2 mg/kg/day of naltrexone (Trexan, now called ReVia) was conducted with four males with autism and two males with pervasive developmental disorders. Two dependent measures were employed: (a) direct behavioral measurement conducted by blind observers using videotape recordings of periodic learning task sessions, and (b) performance measures of the learning activity. Direct behavior measures revealed one participant's attending-to-task improved while receiving naltrexone. However, two of the participants' rates of self-injury increased, as did one of those participant's rate of aggression. Significant improvement was observed on performance measures of the learning task; however, the improved performance continued during the non-drug return to baseline for the three participants who experienced this additional condition. Discussion is provided relating these findings to previously published results.     

The Link Between Perceptions of Self and of Social Relationships in High-Functioning Children with Autism

This study examined the perception of friendship in high-functioning children with autism (8–17 years old) and the link between perceptions of self and of social relationships in these children. Sixteen typically developing children were matched to sixteen high-functioning children with autism, on chronological age, IQ, gender, and mother's education. Study measures included a friendship picture recognition task and three self-report questionnaires: qualities of friendship, loneliness, and self-perception profile. Main results indicated that even if children with autism more frequently related to the intersubjective qualities of friendship such as affective sharing or intimacy, they perceived their friendship to be as close as did typically developing children. Also, for the group with autism, friendship correlated positively with cognitive competencies and general self-worth and negatively with loneliness. In addition, children with autism perceived their social and athletic competencies as lower compared with typically developing children. Implications of the associations between self-perceptions and perceptions of friendship are discussed.     

The Use of Selective Serotonin Reuptake Inhibitors in Children and Adolescents with Major Depression

TOPIC: Recent warnings about suicidal thoughts and self-injurious behavior in youth treated with selective serotonin reuptake inhibitors raise fundamental questions about the risk-benefit ratio of this class of medications. METHODS: Data from placebo-controlled trials are used to elucidate the potential risks and benefits of the selective serotonin reuptake inhibitors (SSRIs) in children and adolescent with major depression. This analysis forms the basis of clinical recommendations. SOURCES: The review includes the six large-scale, placebo-controlled trials that have been published over the past decade. These data were augmented by information from regulatory hearings in 2003-2004 and selected open-label reports. CONCLUSIONS: Emerging data from several clinical trials show that the SSRIs have modest effects on childhood depression. In addition, SSRI treatment may be associated with behavioral activation, self-harm, and suicidal ideation. Appropriate use of SSRIs in children and adolescents requires careful diagnostic assessment, evaluation of co-occurring conditions, and diligent monitoring, especially within the first weeks of treatment.     

Dopamine (DRD2) and Serotonin (HTR2A, 2C) Receptor Gene Polymorphisms do not influence early response to Risperidone in South Indian Patients with Schizophrenia

Treatment response to antipsychotic drugs is variable and conflicting results have been obtained while studying the influence of DRD2 and HTR2 genetic variants on antipsychotic drug efficacy. To explore further, the present study aimed to assess the influence of DRD2 ‐141 C Ins/Del, Taq1A and HTR2A ‐1438 G/A, 102T/C and HTR2C ‐759 C/T genetic polymorphisms in response to risperidone in patients with schizophrenia. The study was conducted among the n = 320 South Indian patients with schizophrenia who received risperidone treatment (4–8 mg per day) for a minimum of four weeks. Genotyping was done by real‐time PCR. Antipsychotic response was assessed using CGI‐I score in cross‐sectional group, PANSS score in prospective group at baseline and after receiving the risperidone therapy. DRD2 ‐141 C Ins/Del (n = 310, Ins/Ins = 177, Ins/Del+ Del/Del = 133, OR 0.70, 95% CI 0.4–1.2 p 0.2), Taq1A (n = 320, AA = 35, AG = 132, GG = 153, p 0.2), HTR2A ‐1438 G/A (n = 320, AA = 39, AG = 164, GG = 117, p 0.2), HTR2A 102T/C (n = 320, CC = 115, CT = 165, TT = 40, p 0.1) HTR2C ‐759 C/T (females n = 132, CC = 65, CT+TT = 67, OR 1.3, 95% CI 0.6–2.8, p 0.5; males n = 186, C = 120, T = 66, OR 1.2, 95% CI 0.6–2.4, p 0.4) genetic polymorphisms did not show any association with antipsychotic response to risperidone. DRD2 ‐141 C Ins/Del, Taq1A, HTR2A ‐1438 G/A, 102T/C and HTR2C ‐759 C/T genetic variants are not associated with antipsychotic response to risperidone.     

Bcl2在乳腺癌中的研究进展

B细胞淋巴瘤/白血病-2(B cell lymphoma/leukemia2,Bcl2)是一种抗凋亡基因,其高表达与肿瘤发生关系密切。非三阴性乳腺癌中存在Bcl2的高表达,其高表达的机制尚未完全清楚,已发现参与调节的因素有雌激素、COX2、EGFR、BP1及E-钙黏蛋白等。研究发现Bcl2的高表达预示着非三阴性乳腺癌患者较好的预后,可能与Bcl2在乳腺癌细胞中高表达可减缓细胞增殖、肿瘤生长,并减弱其侵袭性有关。Bcl2过表达可拮抗细胞凋亡,减弱乳腺癌对化疗药物的敏感性。Bcl2过表达却可作为乳腺癌对他莫昔芬治疗良好反应性的指标。针对Bcl2的基因治疗是目前肿瘤治疗的研究热点,反义寡核苷酸技术、Bcl2蛋白抑制剂等均可作为下调Bcl2的手段,已有不少体外实验证实了它对乳腺癌细胞凋亡的诱导作用及其逆转化疗耐受性的功能。