Möbius syndrome in a patient with α 1 antitrypsin deficiency

ABSTRACT. This case report details the coincidence of Möbius syndrome and α antitrypsin deficiency.     

Interleukin-1α, interleukin-6 and tumor necrosis factor-α levels in children with sepsis and meningitis

BACKGROUND: Cytokines are thought to be important endogenous mediators of the host immune response to infection. The purpose of the present study was to evaluate the utility of serum levels of interleukin (IL)-1alpha, IL-6 and tumor necrosis factor (TNF)-alpha in the prediction and differentiation of sepsis and meningitis in children. METHODS: Blood was collected from 50 children admitted to hospital for suspicion of infection. On the basis of predetermined criteria and investigation, the children were classified into sepsis (n = 30) and meningitis (n = 20) groups, as well as into healthy controls (n = 24) and non-infected sick controls (n = 12). The sepsis group was subdivided according to culture results into S1 (proven sepsis, n = 11) and S2 (clinical sepsis, n = 19). Serum IL-1alpha, IL-6 and TNF-alpha were measured by enzyme-linked immunosorbent assay (ELISA) while C-reactive protein (CRP) was measured by nephelometer. RESULTS: In non-infected sick controls, sepsis and meningitis groups, levels of CRP (P < 0.001, P < 0.05 and P < 0.01, respectively), IL-1alpha (P < 0.001 for all), and IL-6 (P < 0.01, P < 0.001, P < 0.001, respectively) were significantly elevated compared to healthy controls. In sepsis, levels of IL-1alpha increased in the S2 subgroup (P < 0.001) and IL-6 increased in the S1 and S2 subgroups (P < 0.05, P < 0.001, respectively) compared with healthy controls. In meningitis, IL-1alpha had the highest sensitivity and negative predictive value, while IL-6 had the highest specificity and positive predictive value in non-infected sick controls, sepsis and meningitis groups. CONCLUSION: Interleukin-1alpha, IL-6 and CRP are increased in non-infected sick controls, sepsis and meningitis patients but it is not possible to differentiate between them. IL-1alpha had the highest sensitivity in meningitis while IL-6 had the highest specificity in prediction of sepsis and meningitis and their assessment together may improve accuracy in the diagnosis of childhood infection.     

Factors influencing residual pancreatic β cell function in recently diagnosed Type 1 diabetic children

ABSTRACT. Children with type 1 diabetes mellitus usually show partial recovery of pancreatic β cell function after initial stabilization. This partial remission may favourably influence the diabetic state. This study aimed to investigate factors that may influence β cell recovery. Studies were made on 26 newly diagnosed diabetic children.
Residual β cell function was estimated by plasma immunoreactive C-peptide (CPR) values in the fasting state and after meal stimulus. Some residual function was detected in all diabetics studied. C-peptide secreted in response to a meal varied between 0.03–0.415 pmol/ml (0.182 ± 0.144 pmol/ml, mean ± SD).
Statistical analysis of variables hypothesised to relate to β cell function showed significant positive correlations between ΔCPR_max. and age, admission pH, duration of preceding symptoms, and duration of treatment. Significant negative correlations were obtained between ΔCPR_max. and fasting glucose and insulin dosage at resuscitation. No significant correlations were observed between fasting CPR and the parameters mentioned. Multiple regression analysis reinforced the relationship between ΔCPR_max. and age at onset, fasting glucose and admission pH. It is concluded that β cell responsiveness is related to these factors at initial presentation and to quality of control as indicated by fasting blood glucose levels     

心脉隆对窒息新生鼠心肌缺氧诱导因子-1α的影响

目的：心脉隆是从昆虫类美洲大蠊中提取和制备的化合物,主要用于心血管疾病的治疗。该文研究心脉隆对窒息新生鼠心肌缺氧诱导因子-1α(HIF-1α)与血浆内皮素1（ET-1）的影响,探讨心脉隆对心肌缺氧缺血性损伤的保护机制。方法：新生7日龄Sprague-Dawley大鼠随机分为假手术组(n=30)、窒息组(n=30)、心脉隆组(n=30)。每组再分6 h,24 h,72 h 3个时间点,每个时间点各10只,心脉隆组在进行窒息前5 min给予心脉隆注射液5 mg/kg腹腔注射。检测新生鼠心肌的HIF-1α,ET-1,心肌酶CK及心肌组织病理学。结果：窒息组4只鼠死亡,心脉隆组1只鼠死亡。窒息组心肌HIF-1α的表达与血浆ET-1水平于6 h升高,24 h达到高峰,72 h下降,均高于假手术组(P＜0.01);3个时间点均可见心肌缺血,24 h还可见细胞坏死;HIF-1α的表达与血浆ET-1水平呈正相关(r=0.876,P＜0.01)。与窒息组同时间点比较,心脉隆组心肌酶CK、血浆ET-1的水平和心肌HIF-1α的表达均显著减低(P＜0.01),且可见心肌缺血改善,未见细胞坏死。结论：窒息时心肌HIF-1α表达和血浆ET-1,CK水平升高;心脉隆可降低HIF-1α表达,降低血浆ET-1的水平,减轻心肌缺氧缺血性损伤。［中国当代儿科杂志,2009,11（8）：683-686］     

Thymosin α1 in Milk Specimens from Guatemalan Women

ABSTRACT. Thymosin α₁ was determined in milk samples obtained from 67 Guatemalan women 5 days, and 1–3 and 6–18 months postpartum. All the specimens collected 5 days after delivery contained measurable levels (583 ± 304 pg/ml) of thymosin α, but only 33 % of those obtained 1–3 months postpartum and none collected thereafter did. Since thymosin α₁ has been shown to increase T-cell mediated immunity, and to enhance host resistance to infection, it may play an important role in the maturation of mucosal immunity and host resistance in general in the neonate. This study is the first to document the presence of a thymic hormone in early postpartum milk.     

紫绀型先天性心脏病患儿血清VEGF和SDF-1水平与循环EPCs的相关性研究

目的：探讨紫绀型先天性心脏病患儿血清血管内皮生长因子（VEGF）和基质细胞衍生因子（SDF-1）的水平与循环内皮祖细胞（EPCs）数量及功能变化的关系。方法：采用ELISA法检测15例法洛四联症患儿（紫绀组）外周血清SDF-1和VEGF的水平;采用密度梯度离心法分离EPCs体外扩增培养;做免疫荧光鉴定及细胞计数。采用MTT比色法、改良的Boyden小室和黏附能力测定实验,观察EPCs的增殖能力、迁移能力及黏附能力。用回归分析法分析VEGF和SDF-1水平与EPCs数量及功能的相关性。单纯室间隔缺损患儿15例为对照组。结果：紫绀组与对照组相比, VEGF水平增高（201.42±44.74 ng/L vs 113.56±35.62 ng/L）;SDF-1水平增高（3.45±1.07 ng/L vs 1.05±0.99 ng/L,P<0.05）。血清VEGF与SDF-1水平呈正相关（r=0.675,P<0.01）。与对照组相比,紫绀组PEPCs数目明显增多（72.2±9.73）/200倍视野vs （51.2±3.83）/200倍视野,P<0.01; EPCs功能明显增强,其增殖能力、迁移能力及黏附能力明显强于对照组。VEGF,SDF-1的血清水平与EPCs数量及功能变化表现出明显的一致性,相关系数分别为0.8395,0.5491,0.6376和0.7392。结论：紫绀型先天性心脏病外周血EPCs数量及功能较非紫绀组明显增加,同时VEGF和SDF-1血清水平也明显增加,上述变化存在相关性,可能共同影响着患者的一些病理、生理变化。［中国当代儿科杂志,2009,11（4）：267-272］     

Effect of environmental and clinical factors on lung function and respiratory symptoms in adolescents with α1-antitrypsin deficiency

Individuals identified in the Swedish neonatal α₁-antitrypsin (AAT) screening study were followed prospectively from their first to their eighteenth year of life. The aim of this study was to analyse the effect of environmental factors, i.e. active and passive smoking, and of clinical factors on lung function and the occurrence of respiratory symptoms in AAT-deficient adolescents. The study group consisted of 88 protease inhibitor (Pi)ZZ and 40 PiSZ adolescents. Medical history including respiratory symptoms, and active and passive smoking were recorded at each follow-up up to the age of 18 y. Lung function tests were performed at the present check-up. At the age of 18 y, both forced expiratory volume in one second (FEV₁) and FEV₁/vital capacity (VC) were significantly lower in the smoking than in the non-smoking subgroup, and significantly more smokers than non-smokers reported the presence of phlegm. The mean FEV₁/VC ratio was lower for those presently exposed to parental smoking. Multiple linear regression analysis indicated that clinical liver disease in early life, active smoking and parental smoking were independent determinants of FEV₁/VC. The results suggest that marginal deviations in lung function and the symptom of phlegm among AAT-deficient adolescents occur characteristically early in the subgroup of smokers. Parental smoking may contribute to decreased lung function     

The Natural History of Liver Disease in (α1-Antitrypsin Deficient Children

ABSTRACT. During 1972–1974, 200 000 Swedish infants were screened for α₁-antitrypsin deficiency. Of 127 PiZ (Protease inhibitor) children followed from infancy to 12 years of age, four PiZ children with neonatal liver disease have died; two of liver cirrhosis, one was found to have liver cirrhosis at autopsy, having died of aplastic anemia and the fourth died in an accident. Liver microscopy showed a mild increase of periportal fibrous tissue. Another PiZ child died of anaphylactic shock. At 12 years of age, none of the PiZ children have clinical symptoms of liver disease. No PiZ-, PiSZ, PiS- or PiFZ child has had any clinical symptom of liver disease. One PiSZ child died of sudden infant death syndrome. Laboratory analyses from birth through 12 years of age have shown increased S-Bilirubin levels in 11% of the PiZ infants, which normalized within the first half year of life. S-GT was abnormal in about half of the infants, but had normalized when checked at 8 and 12 years of age in all but 6-3% of the PiZ children. The percentage of abnormal S-ALAT test results have decreased from 73% during the first year of life, to about 15% at the age of 12. The range of the abnormal levels also decreased considerably. Abnormal S-GT or S-ALAT levels were found in about 20% of the PiSZ infants, the proportion decreasing to 2% at the age of 12.     

Lactoferrin, C-reactive Protein, α-1-Antitrypsin and Immunoglobulin GA in Cerebrospinal Fluid in Meningitis

ABSTRACT. Cerebrospinal fluid measurements of lactoferrin and α-1-antitrypsin showed significant elevation in bacterial meningitis in children. 8 of 10 lactoferrin values and 6 of 11 α-1-antitrypsin values were above the upper range of controls. Both proteins correlated well with the total number of leukocytes in the cerebrospinal fluid. C-reactive protein, measured by either agglutination or radial immunodiffusion in the cerebrospinal fluid, failed to demonstrate any asefulness in diagnosing bacterial meningitis. Neither elevated serum C-reactive protein in cases of bacterial meningitis, nor sepsis, gave detectable concentrations of C-reactive protein in the cerebrospinal fluid.     

Interleukin-1α and interleukin-1 receptor antagonist in the urine of children with acute pyelonephritis and relation to renal scarring

Urinary concentrations of interleukin-lα (IL-lα) and interleukin-l receptor antagonist (IL-Ira) standardized to urinary creatinine concentrations were studied. The median standardized IL-1α creatinine quotient in children with first-time acute pyelonephritis was 3.6 pg/μmol, but was non-detectable in children with recurrent pyelonephritis, children with non-renal febrile conditions and children convalescent after acute pyelonephritis ( p < 0.05–0.01). IL-lra levels were also significantly higher in children with acute first-time pyelonephritis (median of 239 pglpmol) compared to these three groups of children ( p < 0.01–0.001). The highest urinary 1L-lra levels, however, were found in the healthy controls (median value 1.019; p < 0.001). Both cytokines were higher among children younger than one year compared to older children. The acute IL-lα creatinine quotients were lowest in children with uptake defects on ^99mTC-dimercaptosuccinic acid (DMSA) scintigraphy both during the acute infection (reflecting the acute inflammation) ( p < 0.001) and 1 year after the acute infection (reflecting permanent kidney scarring) ( p < 0.01). In conclusion, persisting high urinary levels of 1L-lα were associated with less renal inflammation and scarring.     

Plasma levels of granulocyte elastase–α1-proteinase inhibitor complex in children with hemolytic uremic syndrome caused by verotoxin-producing Escherichia coli

BACKGROUND: Activated neutrophils play an important role in the pathogenesis of renal injury in humans and in experimental models of hemolytic uremic syndrome (HUS). To evaluate the clinical significance of the circulating granulocyte elastase-alpha1-proteinase inhibitor complex (GEPIC), which is a marker of neutrophil activation, we investigated the plasma concentrations of GEPIC in children with hemolytic uremic syndrome (HUS) associated with verotoxin-producing Escherichia coli (VTEC), VTEC gastroenteritis without HUS and in normal controls. METHODS: Of 22 children (1-19 years of age; mean age 5.5 years) with VTEC infection, nine were diagnosed with HUS. Plasma GEPIC, soluble thrombomodulin (sTM) and thrombin-antithrombin-III complex (TAT) levels were measured by ELISA. RESULTS: The number of polymorphonuclear leukocytes and the levels of plasma GEPIC in patients with HUS were significantly higher than those in non-HUS (9850+/-5091 vs. 5278+/-3327 /microL, P<0.05; 432.1+/-211.7 vs. 188.3+/-117.0 ng/mL, P<0.01) or control subjects (9850+/-5091 vs. 4728+/-1977 /microL, P<0.05; 432.1+/-211.7 vs. 105.9+/-51.1 ng/mL, P<0.001). Furthermore, plasma GEPIC levels showed a positive correlation with sTM (r = 0.522; P<0.01), a marker of endothelial cell injury, and TAT (r = 0.594; P<0.01), a marker of thrombin activity. CONCLUSIONS: These results suggest that an increase in circulating GEPIC levels in patients with VTEC-associated HUS may be related to endothelial injury, which may possibly lead to a more severe episode of this disease.     

缺氧诱导因子-1α在婴幼儿血管瘤及血管畸形中的表达与意义

目的 本研究拟通过检测缺氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)、血管内皮生长因子(vascular endothelial growth factor,VEGF)、细胞增殖核抗原Ki-67、血管内皮标志抗原CD34在婴幼儿血管瘤不同时期、血管畸形和儿童正常皮肤中的表达,探讨缺氧在血管瘤血管生成、细胞增殖中的作用.方法 采用免疫组织化学S-P染色法,检测CD34、HIF-1α、VEGF和Ki-67在小儿血管瘤、血管畸形及正常皮肤组织中的表达,并计算微血管密度(MVD).结果 不同时期血管瘤之间,血管瘤与血管畸形、正常皮肤之间HIF-1α、VEGF、Ki-67、MVD均有显著性差异(P<0.05).血管瘤中HIF-1α表达分别与VEGF、Ki-67、MVD表达呈正相关;而血管畸形HIF-1α与VEGF表达不存在相关关系.结论 缺氧是不同时期血管瘤的普遍现象.HIF-1α能促进血管瘤血管生成.而在血管畸形中可能不存在缺氧的微环境,是"血管内皮细胞生长正常的血管形态异常",因此在血管畸形中不会发生内皮细胞的增殖,也不存在类似血管瘤那样出现增生期和消退期.     

SDF-1及CXCR4在哮喘小鼠肺组织中的表达及布地奈德的干预作用

目的：探讨哮喘小鼠发病过程中基质细胞衍生因子-1（SDF-1）及其受体CXCR4在肺内表达的变化及布地奈德的干预影响。方法：清洁级雄性BALB/c小鼠30只,随机分为对照组、干预组及哮喘组。观察卵蛋白激发及用布地奈德干预后哮喘小鼠气道的病理变化;免疫组织化学染色观察SDF-1表达的变化;RT-PCR法观察CXCR4 mRNA表达的变化。结果：SDF-1及CXCR4 mRNA在对照组中呈低表达,在哮喘组中表达明显增加,使用布地奈德进行干预后SDF-1及CXCR4 mRNA的表达明显降低（0.426±0.052 vs 0.361±0.065;0.829±0.027 vs 0.723±0.094; P<0.05）,且二者表达量均与气道壁厚度呈正相关（r=0.744,P<0.01;r=0.553, P<0.01）。结论：SDF-1及其受体CXCR4可能参与了哮喘小鼠气道重塑过程,布地奈德干预改善哮喘小鼠的气道重塑可能与降低 SDF-1及CXCR的表达有关。［中国当代儿科杂志,2010,12（3）：215-218］     

mTOR/4EBP1/HIF-1α/VEGF信号通路在哮喘小鼠肺组织中的表达及意义

目的探讨哺乳动物雷帕霉素靶蛋白(m TOR)/真核生物始动因子4E结合蛋白1(4EBP1)/缺氧诱导因子-1α(HIF-1α)/血管内皮生长因子(VEGF)信号通路在哮喘小鼠中的表达及意义。方法 40只SPF级6~8周龄雌性Balb/c小鼠随机分为对照组、哮喘组、布地奈德干预组及m TOR抑制剂(雷帕霉素)干预组,每组10只。卵清蛋白致敏激发建立哮喘小鼠模型,各干预组分别在激发前30 min给予雷帕霉素3 mg/kg腹腔注射或布地奈德混悬液1 mg雾化吸入,对照组和哮喘组以生理盐水代替。于末次激发24 h后处死小鼠,收集肺泡灌洗液(BALF),采用ELISA法测定HIF-1α、VEGF水平;取肺组织行苏木精-伊红(HE)染色观察其病理变化;免疫组化染色和Western blot法测定肺组织磷酸化的m TOR及4EBP1(p-m TOR及p-4EBP1)蛋白表达水平。Pearson法分析p-m TOR、p-4EBP1、HIF-1α、VEGF表达的相关性。结果与对照组相比,哮喘组气管及其周围炎性细胞浸润明显,分泌物增多;BALF中HIF-1α、VEGF水平显著升高(P0.01);肺组织p-m TOR、p-4EBP1表达显著增加(P0.01)。与哮喘组相比,各干预组气道炎症浸润明显减轻,分泌物减少;BALF中HIF-1α、VEGF水平明显下降(P0.01);肺组织p-m TOR、p-4EBP1表达显著降低(P0.01)。对照组及两干预组间相比上述指标变化差异均无统计学意义(P0.05)。哮喘组小鼠p-m TOR、p-4EBP1、HIF-1α、VEGF表达水平两两互呈正相关(P0.05),而对照组及两干预组各指标间无相关性(P0.05)。结论哮喘发生时p-m TOR、p-4EBP1、HIF-1α、VEGF可能协同参与了哮喘的发病过程。雷帕霉素能阻断这一过程,可能作为治疗哮喘的新靶点。     

Effect of Long-Term Treatment with Massive Doses of 1α-Hydroxyvitamin D3 on Calcium-Phosphate Balance in Patients with Vitamin D-Dependent Rickets Type II

Three patients with vitamin D-dependent rickets type II were given massive doses of 1α-hydroxyvitamin D₃ for 29 to 36 months and their calcium-phosphate balance was studied during treatment and one month after cesation of treatment. During treatment fasting hypercalciuria was observed in patient 1 and an increased rate of calcium excretion after calcium loading in patients 1 and 2. In these patients, calcium excretion was parallel with the serum 24, 25-dihydroxyvitamin D. These findings suggested that the responsiveness to 1,25-dihydroxyvitamin D improved during long-term treatment of these two patients with vitamin D-dependent rickets type II.     

Analysis of Transferrin and α1-Fetoprotein in Amniotic Fluid and Neonatal Serum: a Possible Means for Indirect Prenatal Diagnosis of the Carbohydrate-deficient Glycoprotein Syndrome

A new type of inborn error of glycoprotein metabolism has recently been identified (CDG syndrome). The disease has systemic manifestations but mainly involves the nervous system. The most striking biochemical abnormality is the presence of secretory glycoproteins that are partially deficient in their carbohydrate moieties, the most pronounced of which is seen in serum transferrin. The basic genetic defect of the syndrome has not yet been identified. This study was carried out in order to provide a basis for indirect prenatal diagnosis by qualitative and quantitative analyses of a corresponding carbohydrate-deficiency in transferrin and also in α¹-fetoprotein in amniotic fluid. On isoelectric focusing both glycoproteins normally showed a carbohydrate (sialic acid (-dependent microheterogeneity in amniotic fluid as well as in neonatal serum which in transferrin differed from adult serum. Reference values of total transferrin (TT) and carbohydrate-deficient isotransferrins (CDT) during gestation were determined. Analysis of the microheterogenity of these glycoproteins by isoelectric focusing or determination of the CDT/TT ratio in amniotic fluid might provide a possibility for prenatal diagnosis of this syndrome. It was also shown that neonatal diagnosis is possible by analysis of serum transferrin.     

Ataxic mutant mice with defects in Ca2+ channel α1A subunit gene: morphological and functional abnormalities in cerebellar cortical neurons

ABSTRACT This review summarizes recent studies in the morphological and functional abnormalities of cerebella in three ataxic mutant mice, i.e. tottering mouse, leaner mouse, and rolling mouse Nagoya (RMN). These mutants carry mutations in the Ca²⁺ channel α_1A subunit gene, and become useful models for human neurological diseases such as episodic ataxia type-2, familial hemiplegic migraine, and spinocerebellar ataxia type-6. All three mutants exhibited altered morphology of the Purkinje cells, ectopic synaptic contacts between granule cell axons (parallel fibers) and Purkinje cell dendritic spines and abnormal expression of tyrosine hydroxylase in Purkinje cells. In leaner mice, Purkinje cell loss was observed in alternating sagittal compartments of the cerebellar cortex corresponding to the Zebrin II-negative zones. The mutated Ca²⁺ channel α_1A subunit was highly expressed in granule and Purkinje cells, and the P-type Ca²⁺ currents in Purkinje cells were selectively reduced in the mutant mice. Therefore, we concluded that altered Ca²⁺ currents through the mutated Ca²⁺ channel α_1A subunit might be involved in the functional and morphological abnormalities in granule and Purkinje cells, and might result in expressions of behavioral phenotypes including ataxia. Increased levels of corticotropin-releasing factor and cholecystokinin in some climbing and mossy fibers were observed in RMN. These neuropeptides modulated the excitability of granule and Purkinje cells, indicating the possible expression of ataxic symptoms.     

维生素A对1型糖尿病患儿残存胰岛β细胞功能的保护作用

目的 探讨维生素A对1型糖尿病（T1DM）残存胰岛β细胞功能的保护作用及其机制。方法 46例T1DM患儿（病程0.5~1年）随机分为干预组（23例）和未干预组（23例）,两组均予以胰岛素治疗,干预组服用维生素A （每日1 500~2 000 IU）,并以25例健康儿童为对照组。计算两组T1DM患儿的每日胰岛素用量,并分别于干预前、干预3个月后检测糖化血红蛋白（HbA1C）、激发后血清C-肽、血清维生素A、血清白细胞介素-17（IL-17）水平。结果 维生素A干预前,干预组和未干预组T1DM患儿的血清维生素A水平均低于对照组（P < 0.01）,其IL-17水平均高于对照组（P < 0.01）。维生素A干预3个月后,干预组血清IL-17水平、每日胰岛素用量低于未干预组（P < 0.05）,激发后C肽水平高于未干预组（P < 0.05）。结论 维生素A可以保护残存胰岛β细胞功能,机制可能与维生素A改善T1DM患儿IL-17的异常分泌有关。