转化生长因子β_3对早产大鼠肺表面活性物质蛋白质基因表达的影响及机理

为研究转化生长因子β３（ＴＧＦ－β３）对发育期肺表面活性物质蛋白质（ＳＰｓ）基因表达的影响。利用孕１９天早产大鼠肺组织块及肺Ⅱ型细胞培养，检测ＳＰｓ（ＳＰ－Ａ、ＳＰ－Ｂ和ＳＰ－Ｃ）基因表达。结果：单纯使用ＴＧＦ－β３对ＳＰ－Ａ、ＳＰ－Ｂ、ＳＰ－Ｃ基因表达无明显影响，但ＴＧＦ－β３可明显抑制１００ｎｍｏｌ／ｍｌ地塞米松增加ＳＰ－Ｂ、ＳＰ－Ｃ基因表达的效应，随ＴＧＦ－β３浓度增加抑制显著。ＴＧＦ－β３并非直接作用于肺Ⅱ型上皮细胞，而是以成纤维细胞为介导产生抑制效应。ＴＧＦ－β３对地塞米松增加ＳＰ－Ａ基因表达无影响。提示：ＴＧＦ－β３对肺发育期ＳＰｓ基因表达有抑制作用，糖皮质激素预防新生儿呼吸窘迫综合征效果不理想可能与ＴＧＦ－β３作用有关。     

肺表面活性物质的免疫作用

越来越多的研究揭示肺表面活性物质(PS)在肺部免疫防御作用中具有重要地位。PS中亲水性的相关蛋白(SP)-A和SP-D的免疫调节作用最为显著，在肺部起到趋化、调理吞噬和促杀菌的作用，参与调节细胞因子和炎症介质的合成和释放，对淋巴细胞的增殖和肺部过敏反应也有影响。对于疏水性的SP-B、SP-C和磷脂的免疫调节多是通过对替代性PS的研究进行的，目前认为磷脂对肺部的免疫调节以抑制为主，SP-B和SP-C主要调节PS的表面活性，免疫作用不明显，这方面的研究也很少。     

肺表面活性物质的免疫作用

越来越多的研究揭示肺表面活性物质(PS)在肺部免疫防御作用中具有重要地位。PS中亲水性的相关蛋白(SP)A和SPD的免疫调节作用最为显著,在肺部起到趋化、调理吞噬和促杀菌的作用,参与调节细胞因子和炎症介质的合成和释放,对淋巴细胞的增殖和肺部过敏反应也有影响。对于疏水性的SPB、SPC和磷脂的免疫调节多是通过对替代性PS的研究进行的,目前认为磷脂对肺部的免疫调节以抑制为主,SPB和SPC主要调节PS的表面活性,免疫作用不明显,这方面的研究也很少。     

肺表面活性物质相关蛋白与临床肺疾病

肺表面活性物质是由Ⅱ型细胞产生的磷脂蛋白复合体,有四种肺表面活性物质相关蛋白(SP).根据它们与磷脂的结合可分为亲水性和疏水性两种,亲水性SP属于C型凝集素家族,基因定位及结构均与其他C型凝集素相似,主要参与宿主防御反应、免疫调节等;疏水性SP由于其结构特征,能够降低肺表面张力,提高肺顺应性.SP参与多种临床疾病的过程,在各种疾病中的变化各不相同.SP基因的各种变异也影响个体对肺部疾病的易感性和对治疗的反应.本文对SP与临床肺疾病作一综述,利于正确认识它们之间的关系.     

肺表面活性物质在重症呼吸道疾病中的应用

肺表面活性物质治疗新生儿呼吸窘迫综合征取得成功，关于用药剂量、药物选择及预防用药有新的见解，其它呼吸疾病，如成人呼吸窘迫综合征，重症肺炎及胎粪吸入综合征等的发病过程涉及肺表面活性物质数量、成分及功能的病理改变，实验研究的结果提示：活性物质治疗这些疾病有效。临床试用肺表面活性物质制剂治疗成人呼吸窘迫综合征、肺炎和胎粪吸入综合征也取得了可喜的进展。     

肺表面活性物质治疗病毒性肺炎的实验研究

为探讨重症肺炎时肺表面活性物质（ＳＡＭ）的变化及外源性肺表面活性剂替代治疗对肺功能的影响，采用随机对照实验方法，对重症仙台病毒肺炎大鼠肺灌洗液内总磷脂和卵磷脂含量及ＳＡＭ替代治疗对动脉血氧分压的影响进行了观察。结果：肺炎大鼠肺灌洗液中总磷脂和卵磷脂含量与正常大鼠比较差异无显著意义。治疗组大鼠气管内注入ＳＡＭ后３０分钟，氧分压与治疗前比较明显上升，４５和６０分钟时ＰＯ２仍保持在较高水平，与盐水对照组和未治疗组比较差异均有显著意义。提示：重症病毒性肺炎时肺表面活性物质无明显数量变化，肺表面活性剂替代治疗能有效地改善肺氧合功能。     

高氧对早产鼠肺表面活性物质及其蛋白基因表达的影响

肺表面活性物质 (ＰＳ)是由磷酯和肺表面活性物质蛋白(ＳＰ)组成 ,虽然磷脂对ＰＳ功能致关重要 ,但只有在ＳＰ同时存在时 ,才能有效发挥其降低表面张力的生理功能[1 ] 。本研究利用高氧早产鼠肺损伤模型 ,探讨了高氧对ＰＳ代谢和ＳＰ基因表达的影响。材料及方法1.高氧暴露实验 :高氧暴露实验的详细过程按参考文献 [2 ]介绍的方法进行。动物于高氧暴露 7ｄ后处死 ,采用双相薄层层析法 (2Ｄ ＴＬＣ)进行了肺组织总磷酯 (ＴＰＬ)、卵磷酯 (ＰＣ)、溶血卵磷酯 (ＬＰＣ)、鞘磷酯 (ＳＰＨ)、磷酯酰甘油 (ＰＧ)、磷酯酰氨酸 (ＰＳ)、磷酯酰肌醇 (Ｐ…     

肺表面活性物质在重症呼吸道疾病中的应用

肺表面活性物质治疗新生儿呼吸窘迫综合征取得成功，关于用药剂量、药物选择及预防用药有新的见解。其它呼吸道疾病，如成人呼吸窘迫综合征、重症肺炎及胎粪吸入综合征等的发病过程涉及肺表面活性物质数量、成分及功能的病理改变。实验研究的结果提示：活性物质治疗这些疾病有效。临床试用肺表面活性物质制剂治疗成人呼吸窘迫综合征、肺炎和胎粪吸入综合征也取得了可喜的进展。     

肺表面活性物质临床治疗的现状

肺表面活性物质成功用于临床后，已有多种ＰＳ制剂用于治疗新生儿ＲＤＳ，这些制剂原料来源，不断工艺不尽相同，用药剂量差别也较大，但在给药方法，时间及次数较为一致，其改善气体交换、降低呼吸机条件效果极其明显，而治疗最终效果如降低患儿病死率，发病率却相差甚远。     

The importance of different immunosuppressive regimens in the development of posttransplant diabetes mellitus

Solid-organ transplantation is the optimal long-term treatment for most patients with end-stage organ failure. After solid-organ transplantation, short-term graft survival significantly improved (1). However, due to chronic allograft nephropathy and death with functioning graft, long-term survival has not prolonged remarkably (2). Posttransplant immunosuppressive medications consist of one of the calcineurin inhibitors in combination with mycophenolate mofetil (MMF) or azathioprine (Aza) and steroids. All of them have different adverse effects, among which posttransplant diabetes mellitus (PTDM) is an independent risk factor for cardiovascular (CV) events and infections causing the death of many transplant patients and it may directly contribute to graft failure (3). According to the criteria of the American Diabetes Association (4), diabetes mellitus (DM) is defined by symptoms of diabetes (polyuria and polydipsia and weight loss) plus casual plasma glucose concentration ≥ 11.1 mmol/L or fasting plasma glucose (FPG) ≥ 7.0 mmol/L or 2-h plasma glucose level ≥ 11.1 mmol/L following oral glucose tolerance test (OGTT). This metabolic disorder occurring as a complication of organ transplantation has been recognized for many years. PTDM, which is a combination of decreased insulin secretion and increased insulin resistance, develops in 4.9/15.9% of liver transplant patients, in 4.7/11.5% of kidney recipients, and in 15/17.5% of heart and lung transplants [cyclosporine A (CyA)/tacrolimus (Tac)-based regimen, respectively] (5). Risk factors of PTDM can be divided into non-modifiable and modifiable ones (6), among which the most prominent is the immunosuppressive therapy being responsible for 74% of PTDM development (7). Emphasizing the importance of the PTDM, numerous studies have determined the long-term outcome. On the basis of these studies, graft and patient survival is tendentiously (8) or significantly (9, 10) decreased for those developing PTDM.     

GENETICS OF CARNEY COMPLEX AND RELATED FAMILIAL LENTIGINOSES, AND OTHER MULTIPLE TUMOR SYNDROMES

Carney complex is a multiple endocrine neoplasia (MEN) syndrome that affects the adrenal cortex, the pituitary and thyroid glands, and the gonads. The complex is also associated with skin and mucosa pigmentation abnormalities and myxoid and other neoplasms of mesenchymal and neural crest origin. Thus, this syndrome also belongs to another group of genetic disorders, the lentiginoses (or lentigenoses), which include the Peutz-Jeghers, LEOPARD, arterial dissections and lentiginosis, and Laugier-Hunziker syndromes, Cowden disease and Ruvalcaba-Myhre-Smith (Bannayan-Zonana) syndrome and the centrofacial, benign patterned and segmental lentiginoses, all of which can be associated with a variety of developmental defects. The inheritance of Carney complex, just like that of the other MENs and the lentiginoses, is autosomal dominant. Genetic loci or genes have been identified for Carney complex, Peutz-Jeghers and Ruvalcaba-Myhre-Smith syndromes, but not for other lentiginoses. Elucidation of the molecular defects responsible for these disorders is expected to shed light on aspects of early neural crest differentiation, the regulation of pigmentation, the development of autonomous endocrine function, and endocrine and nonendocrine tumorigenesis.     

All you ever wanted to know about infant formulas (but were afraid to ask)

The World Health organisation recommends breast feeding infants for the first six months of life. When this breast feeding does not occur either through parental choice or medical need, infant formulas will be required. There is a bewildering array of formulas on the UK market for many different requirements. When faced with an unsettled infant many parents (and health care professionals) will experiment with the infant formula available and often attend the paediatric clinic looking for help and advice. It is therefore essential that paediatricians understand what milks are available and what the key differences between different products are. This review attempts to provide a simple guide through many of the formulations currently available in the UK; and offers advice for the dietary management of the child with extra calorie requirements, infants with cow's milk protein allergy, gastro oesophageal reflux disease, apparent unresolved hunger and infantile colic. Whatever the underlying condition, there is likely to be an infant formula that is suitable in this generation of ever expanding formulations.     

Differential effects of inhaled budesonide on serum osteocalcin in children and adolescents with asthma

In recent years, measurement of serum osteocalcin has been introduced for assessment of bone turnover in patients treated with exogeneous glucocorticoids. Studies in children with asthma on inhaled glucocorticoids, however, have shown inconsistent results. The aim of the present study is to assess bone turnover in prepubertal children and in adolescents with asthma treated with inhaled budesonide using three different osteocalcin assays: the Pharmacia Osteocalcin CAP FEIA, the CIS OSTK-PR and CIS IRMA ELSA-OSTEO assays. Two studies were conducted: 1) a randomised double blind two-period crossover study of 22 prepubertal children aged 5-12 years. In one period 800 μg budesonide was given once in the morning, in the other 400 μg was given twice daily; 2) a randomised double blind placebo controlled two period crossover study of inhaled budesonide 400 μg twice daily in fourteen 13-16 year old adolescents with pubertal stages II-V. In both studies, treatment periods were of four weeks duration, and blood samples were collected at the last day of each period. In the prepubertal children none of the osteocalcin assays detected any statistically significant differences between any of the periods. In the adolescent group reduced levels of osteocalcin were seen during budesonide treatment. The suppression reached statistical significance with the CAP FEIA (P = 0.03) and the OSTK-PR (P =0.01) assays, but not with the ELSA-OSTEO assay (P = 0.06). Correlation analyses showed statistically significant correlation coefficients varying between 0.58 and 0.91 (P=0.03 and P < 0.0001, respectively). The effect of inhaled glucocorticoids on serum osteocalcin may depend on the assay applied, and inhaled glucocorticoids have differential effects in children and adolescents.     

Représentations émotionnelles de la maladie chez 22 enfants drépanocytaires

Background

The emotional and psychological impact of chronical disease among children is considerable. The aim of this study was to explore the emotional representations of sickle cell children followed up at Bordeaux University Hospital in both qualitative and quantitative ways.

Methods

Prospective observational study, conducted from February to May 2010 among 22 sickle cell children (SS, SC and Sβ) followed at Bordeaux University Hospital and among their parents. A questionnaire evaluating depressive symptoms and emotional representations was proposed to children and to their parents separately, measuring their child's emotions. Children were asked to draw themselves during sickle cell crisis and without any painful episode, in order to illustrate their perception of their disease.

Results

Emotional and psychological impact on sickle cell children was important in this study. Eighty-six percent of children have commonly had negative feelings such as sadness, anger or fear. Thirty-six percent of them had depressive symptoms. Parents largely underestimated this impact. Drawings and answers to the questionnaire emphasized an important lack of disease understanding, social consequences, and depressive affects.

Conclusion

Psychological and emotional difficulties in sickle cell children should be identified and supported. Resources for psychological and educational support are necessary to improve the quality of life of sickle cell patients in France.     

Limiting light-induced lipid peroxidation and vitamin loss in infant parenteral nutrition by adding multivitamin preparations to Intralipid

Parenteral lipids are susceptible to light-induced peroxidation, particularly under phototherapy. Ascorbic acid is protective. The aim of this study was to investigate whether dark delivery tubing and/or coadministration of multivitamin preparations could prevent peroxidation of Intralipid without undue vitamin loss. In experiments carried out on the benchtop, lipid peroxidation occurred in ambient light and was more extensive under phototherapy. Dark tubing decreased peroxide formation, but only by about 65%. In simulated clinical conditions in which solutions were pumped through standard clear or dark minibore plastic tubing, Intralipid accumulated lipid peroxides as measured by the FOX assay (280 µM) or as triglyceride hydroperoxides (52 µM). Multivitamin preparations (MVIP or completely, and were fully protective when used with dark tubing. There was loss of riboflavin (65% from Soluvit and 35% from MVIP) in clear tubing but this was decreased to 18% and 11%, respectively, in dark tubing. Ascorbate loss was 20% (MVIP) and 50% (Soluvit) and only slightly less in dark tubing. Ascorbate loss was also seen in the absence of Intralipid and is due to riboflavin-induced photo-oxidation.Conclusion: Multivitamin preparations protect Intralipid against light-induced formation of lipid hydroperoxides, and administering multivitamins with Intralipid via dark delivery tubing provides a practical way of preventing peroxidation of the lipid while limiting vitamin loss. This procedure should be considered for routine use as well as with phototherapy. Soluvit/Vitlipid) inhibited peroxide formation almost     

SociaBillyQuizz,un jeu pour l’entraînement aux habiletés sociales chez l’enfant et l’adolescent : étude exploratoire

Background

The SociaBillyQuizz is a therapeutic game designed for social skills training groups with children and adolescents. Using an entertaining method, this media requests several dimensions: exposure, cognition, communication skills, imagination, emotional expression and sign decoding. In this preliminary study, the setting includes two groups of six adolescents, one with social anxiety disorder and the other with Asperger syndrome.

Objective

To evaluate, in an exploratory study, the effects of a therapeutic device involving this game for these two clinically different groups of adolescents.

Methods

During 26 of 1 hour weekly sessions, two adolescents groups participate to a program including the SociaBillyQuizz and cognitive behavioral therapies. The groups are moderated by two therapists. The SociaBillyQuizz is a board game for two to six players; its goal is to collect points by answering instructions from the different thematic cards. There are four thematic cards: action cards (players have to do something), brainstorming cards (players have to use their imagination and demonstrate cognitive flexibility), interview cards (players have to express themselves about what they think or feel) and mystery cards (unexpected instructions). According to the groups’ clinical characteristics, some aims are specifically highlighted. In the anxiety disorder group, the cognitive dimension is privileged and in the Asperger syndrome group, we emphasise the pretend, cognitive flexibility and theory of mind. The effects are measured by the Rathus Assertiveness Schedule and the Fear Avoidance Hierarchy (FAH) for the social anxiety disorder group and by the Faux Pas Recognition Test and the Social Responsiveness Scale (parent version) for the Asperger group.

Results

These assessment tools indicate, for both groups, a significant increase of the scores corroborating the observed clinical effects. For eleven of the twelve adolescents, a clinical interview 6 months after the retest shows a continuity of therapeutic benefit.

Discussion

These early results suggest that a social skills training device featuring the SociaBillyQuizz produces clinical improvements in these two groups of adolescents. In future researches, with control group and more complete follow-up, nature and effectiveness of its contribution should be specified.

Conclusion

In this preliminary study, the SociaBillyQuizz appears to be an interesting therapeutic tool that can increase implication, motivation, participation and cohesiveness of the group. It also makes easier the cognitive-behavioural-strategies learning.     

Les effets de l’incarcération chez les mineurs

Aim of this study

In this article we wish to question the effects of incarceration on minors. The history of prison reveals that it is the work of a humanist and philanthropic discourse that ensued from the effects of revolutionary ideas. However, from the moment of its reform – that transformed it from a place of confinement to a penal institution – it has only demonstrated its dysfunctional aspect. Our objective is to initiate a reflection on the effects of incarceration, whether it be collective or individual and in particular when it involves adolescents.

Genotype/phenotype association in Indian congenital aniridia

The developmental birth eye disorder of iris is known as aniridia. Heterozygous PAX6 gene, which causes human aniridia and small eye in mice, is located on chromosome 11p13. The variability had been documented between the affected individuals within the families, is due to genotypic variation. Haploinsufficiency renders PAX6 allele non-functional or amorphic, however it presents hypomorphic or neomorphic alleles. India is not a well-studied ethnic group, hence the focus on congenital aniridia gene analysis supports the literature and the phenotypic association were analysed both in sporadic as well as familial. The consistent association of truncating PAX6 mutations with the phenotype is owing to non-sense-mediated decay (NMD). It is presumed that the genetic impact of increased homozygosity and heterozygocity in Indian counter part arises as the consequence of consanguineous marriages. The real fact involved in congenital aniridia with other related phenotypes with PAX6 mutations are still controversial.     

Bilateral nephrectomy, peritoneal dialysis and subsequent cadaveric renal transplantation for treatment of renal failure due to polycystic kidney disease requiring continuous ventilation

We report here on a newborn with end-stage renal failure due to autosomal recessive polycystic kidney disease, also causing ventilation-requiring respiratory distress. Peritoneal dialysis was able to keep the newborn alive but not wean it from the respirator. After removal of both huge kidneys, dialysis became more effective and allowed the neonate to be extubated only 5 days later. It was decided to register the baby for a pediatric cadaveric kidney transplant when it reached 6 kg/body wt or to perform a living related transplant if no such kidney became available and the baby grew to 7 kg/body wt. At the age of 9 months and a weight of 6 kg a cadaveric kidney from a 20-month-old donor became available and was transplanted extraperitoneally. Prophylactic immunosuppression included cyclosporin, mycophenolate mofetil and steroids. Pneumonia on post-operative day 10 required respiratory care for several days and acute rejection requiring peritoneal dialysis. Both complications were controlled with antibiotics and conversion from cyclosporin to tacrolimus and a temporary increase in steroids. Thirteen months later the child is alive and well with a serum creatinine of 0.6 mg%. From this experience we would recommend early removal of both polycystic kidneys causing end-stage renal failure and respiratory insufficiency, starting peritoneal dialysis and performing a renal transplant as soon as possible. This therapeutic strategy seems appropriate for this complex situation.