Leukocyte adhesion deficiency: report of two family related newborn infants

Leukocyte adhesion deficiency type 1 (LAD 1) is an autosomal recessive hereditary disorder resulting from deficiency of CD18, characterized by recurrent bacterial infections. We report two consanguineous patients with Leukocyte adhesion deficiency type 1( LAD1). These two infant boy patients were referred to us, within a short period of time, with the complaints of recurrent infections at the age of 38 and 75 days -old, respectively. Parents of two patients were first cousins and their grandmothers also were first cousins. The history of delayed umbilical cord separation was shown in both patients. Patient 1 had history of omphalitis, conjunctivitis, skin lesion of groin area and abscess formation of vaccination site, and had infective wound of eye-lid at the last admission. Patient 2 had history of omphalitis and soft tissue infection of right wrist at the last admission. Laboratory findings showed marked leukocytosis and low CD18 levels (6.6% in Patient 1 and 2.4 % in Patient 2). In Patient 1 recurrent infections were treated with antibiotic regimens and received bone marrow transplantation but Patient 2 died because of septicemia, generalized edema, ascites and progression to acute renal failure at 4 months of age. Due to considerable rate of consanguineous marriages in parents of Leukocyte adhesion deficiency patients, sequence analysis especially for prenatal diagnosis in subsequent pregnancies and genetic counseling is recommended.     

Haematological and tissue abnormalities in chicks caused by acute and subclinical folate deficiency

1. Haematological, histological and ultrastructural findings in young chicks fed on a purified diet severely deficient in folate are reported. 2. Growth of the birds was greatly depressed and they had a macrocytic anaemia. Other haematological changes included abnormal nuclear formations in erythrocytes, numerous mitoses and hypersegmented granulocytes. 3. Megaloblasts were observed in bone marrow and their fine structure is described for the first time in an avian species. 4. Morphological changes occurred also in the liver. The parenchyma had damaged sinusoidal endothelium, inflammatory cells and no glycogen. Mitochondria were damaged and many were associated with unusual crystalline structures. 5. Chickens fed on a semi-purified diet of low folate content showed no growth depression or clinical signs of deficiency but had abnormal haematological values and morphological changes that resembled those seen in birds fed on the purified diet. 6. These abnormalities responded to dietary supplements of pteroylmonoglutamic acid in a dose-related manner and may be useful in diagnosing subclinical folate deficiency.     

Ellagic acid inhibits IL-1beta-induced cell adhesion molecule expression in human umbilical vein endothelial cells

Expression of cell adhesion molecules by endothelium and the attachment of monocytes to endothelium may play a major role in atherosclerosis. Ellagic acid (EA) is a phenolic compound found in fruits and nuts including raspberries, strawberries, grapes and walnuts. Previous studies have indicated that EA possesses antioxidant activity in vitro. In the present study, we investigated the effects of EA on the formation of intracellular reactive oxygen species, the translocation of NFkappaB and expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 and endothelial leucocyte adhesion molecule (E-selectin) induced by IL-1beta in human umbilical vein endothelial cells (HUVEC). We found that EA significantly reduced the binding of human monocytic cell line, U937, to IL-1beta-treated HUVEC. The production of reactive oxygen species by IL-1beta was dose-dependently suppressed by EA. Supplementation with increasing doses of EA up to 50 micromol/l was most effective in inhibiting the expression of VCAM-1 and E-selectin. Furthermore, the inhibition of IL-1beta-induced adhesion molecule expression by EA was manifested by the suppression of nuclear translocation of p65 and p50. In conclusion, EA inhibits IL-1beta-induced nuclear translocation of p65 and p50, thereby suppressing the expression of VCAM-1 and E-selectin, resulting in decreased monocyte adhesion. Thus, EA has anti-inflammatory properties and may play an important role in the prevention of atherosclerosis.     

Primary liver cell carcinoma as complication of alpha 1-antitrypsin deficiency in a 67 year old man

A 67-year-old male patient with pulmonary emphysema was diagnosed with liver cirrhosis. Further investigations revealed an alpha 1-antitrypsin deficiency caused by a PiZZ mutation. The liver cirrhosis was complicated by the development of a hepatocellular carcinoma. The patient died from the consequences of mesentary vein thrombosis. The protease inhibitor alpha 1-antitrypsin controls the tissue damaging effects of proteases which are produced by granulocytes. In the case of alpha 1-antitrypsin deficiency, progressive damage of the lung tissue occurs, resulting in emphysema. The accumulation of abnormal alpha 1-antitrypsin in hepatocytes can result in cirrhosis, with an increased chance of carcinoma. The deficiency is caused by a mutation in the Pi-gene on chromosome number 14. Although treatment options are at present limited, making an early diagnosis has important implications for the prognosis and intended management with respect to the prevention of complications, both in the patient as well as in first degree relatives (children and siblings).     

Resistance to antimicrobials and combination therapy assessment in neonatal sepsis]

OBJECTIVES: To estimate antibiotic resistance among bacterial strains isolated from patients with neonatal sepsis from January 1994 through December 1998, and to assess the predictive value of the checkerboard method for selecting treatment with combination antibiotic therapy in seriously ill patients. METHODS: The study of strain susceptibility was carried out by microdilution in broth, and the checkerboard method in broth trays was used to assess the efficacy of antibiotic combination therapy. RESULTS: Fifty per cent of the strains of coagulase-negative Staphylococcus spp. and 37% of S. aureus strains, which are the main pathogens involved in neonatal sepsis, were resistant to methycillin. Of these strains, 94.5% were resistant to several antibiotics. Four strains of coagulase-negative Staphylococcus spp. and one strain of Enterococcus faecium were resistant to vancomycin (minimal inhibitory concentration = 128 micro g/mL). We noted a high probability of clinical efficacy (P < 0.01) with antibiotic combinations having a synergistic effect in vitro, whereas antagonic reactions were seen in close association with a highly significant probability of clinical therapeutic failure. DISCUSSION: The main cause of neonatal sepsis in the Neonatal Intensive Care Unit at "América Arias" Hospital in Havana, Cuba, were strains of Staphylococcus resistant to methycillin and other antibiotics. In seriously ill patients (according to policy established at this institution), the first line of treatment is a combination of an aminoglycoside antibiotic and a beta-lactamic antibiotic. This study showed that the clinical efficacy of combination antibiotic therapy is not determined by the resistance pattern of the strain and that good clinical results can be attained, in all likelihood, when a synergistic effect can be shown in vitro.     

脐血CD34+细胞向粒、红细胞和血小板定向诱导分化研究

目的 体外定向诱导脐带血CD34^ 细胞向粒细胞、红细胞和血小板的定向分化。方法 用免疫磁珠分选的方法从脐带血中分离CD34^ 细胞，采用SCF与G-CSF、EPO或TPO联合诱导CD34^ 细胞分别向粒细胞、红细胞或巨核细胞和血小板分化成熟，从形态学、免疫表型和功能等方面鏊定已诱导分化的细胞。结果 粒系诱导培养体系中CD15^ 细胞达81．17％，红系诱导培养体系中GPA^ 细胞达95．35％，巨核系诱导培养体系中CD41^ 细胞达77．82％。且分别具有各系成熟细胞形态。粒细胞具有吞噬功能；血小板样颗粒在凝血酶作用下产生聚集反应。结论 建立了CD34^ 细胞分别向粒细胞、红细胞和血小板诱导分化的培养体系，为细胞治疗、分化过程中基因的调控、外源基因的表达等相关研究奠定了基础。     

Resveratrol blunts tumor necrosis factor-��-induced monocyte adhesion and transmigration

The leukocyte recruitment and transmigration across the endothelial barrier into the vessel wall are crucial steps in atherosclerosis. Leukocyte trafficking on the endothelium is elicited by induction of endothelial adhesion molecules, and its transmigration is mediated by degradation of basement membrane proteins through enzymatic activity of matrix metalloproteinases (MMP). The current study investigated whether resveratrol, a polyphenol present in grapes and red wine, was capable of inhibiting leukocyte adhesion to tumor necrosis factor (TNF)-α-activated endothelium. It was found that resveratrol inhibited the TNF-α-activated endothelial expression of vascular cell adhesion molecule-1 in a dose-dependent manner. In addition, resveratrol hampered THP-1 monocyte adhesion to activated endothelial cells. This study further examined whether resveratrol interfered with transendothelial migration of leukocytes. The MMP-2 gelatinolytic activity of endothelial cells was enhanced by TNF-α, which was attenuated by an addition of ≥25 µM resveratrol. In addition, 25 µM resveratrol mitigated the MMP-9 activity of THP-1 cells, followed by a marked inhibition of transendothelial migration. These results demonstrated that resveratrol suppressed monocyte adhesion and migration induced by TNF-α through modulating expression of adhesion molecules and gelatinolytic activity of MMP. These findings suggest that dietary resveratrol may be therapeutic agent for inhibiting leukocyte recruitment into the subendothelium during inflammatory atherosclerosis.     

Differences in muscular changes in rats with vitamin E and with selenium deficiency

The recti muscles of rats with vitamin E deficiency and with selenium deficiency were examined by electron microscopy and compared. In vitamin E deficiency, the first changes occurred in blood vessels and in the extracellular components. The endothelium contained many vacuoles and less cytoplasmic organelles. The basal lamina of the endothelium appeared thicker. As it progressed, vitamin E deficiency caused abnormal pigment granules, mitochondrial degeneration, decreased numbers and irregular arrangement of muscle fibers, and irregular arrangement of z bands. On the other hand, selenium deficiency caused no abnormal changes in the recti muscles. These results suggest that selenium plays a different role from that of vitamin E which is an antioxidant.     

脐带间充质干细胞移植治疗强直性脊柱炎患者的效果分析

目的探讨脐带间充质干细胞移植治疗强直性脊柱炎患者的临床效果。方法选取我院2016年2月至2019年1月收治的40例强直性脊柱炎患者,随机分为对照组和观察组各20例。对照组采用免疫及生物制剂治疗,观察组采用脐带间充质干细胞移植治疗,对比两组的临床治疗效果。结果观察组治疗总有效率高于对照组(P<0.05)。治疗后,观察组的血沉、细胞间黏附分子、血清TNF-α水平均低于对照组(P<0.05);治疗后1个月、3个月、6个月,观察组的疼痛程度评分、活动指数评分均低于对照组(P<0.05)。结论脐带间充质干细胞移植治疗强直性脊柱炎患者的效果显著,值得临床推广。     

Inhibitory effect of delta-tocotrienol,a HMG CoA reductase inhibitor,on monocyte-endothelial cell adhesion

We have previously shown that alpha-tocotrienol (alpha-T3), a vitamin E analogue and HMG CoA reductase (HMGR) inhibitor, markedly inhibited monocyte-endothelial cell adhesion, a process that was reversed with the addition of mevalonate intermediates involved in protein prenylation. Since delta-T3 and gamma-T3 possess greater HMGR inhibition than alpha-T3, we postulated that these analogues might have a greater effect on protein prenylation, and thus on monocyte adhesion and endothelial adhesion molecule expression in comparison to alpha-T3. Hence, we pursued to investigate the effect of various analogues of tocotrienol (alpha, gamma, delta) on monocytic cell adhesion and expression of adhesion molecules using a human umbilical vein endothelial cell-line, EA.hy926, as the model system. Relative to alpha-T3, delta-T3 displayed a more profound inhibitory effect on monocytic cell adherence using a 15 micromol/L concentration within 24 h (delta: 42 +/- 5%; alpha: 26 +/- 8% vs. control). This inhibitory action was reversed by co-incubation with farnesol and geranylgeraniol, suggesting a role for prenylated proteins in the regulation of monocyte adhesion. To further evaluate the effect of tocotrienols on the vascular endothelium, we measured the surface expression of adhesion molecules. Compared to alpha-T3, delta-T3 markedly inhibited the expression of VCAM-1 (delta: 57 +/- 6%; alpha: 37 +/- 10% vs. control) and E-selection (delta: 36 +/- 3%; alpha: 18 +/- 6% vs. control) in TNF-alpha activated endothelial cells. The above result suggests that delta-T3 is a potent and effective agent for the reduction of cellular adhesion molecule expression and monocytic cell adherence.     

新生儿脐血维生素K1及维生素K缺乏诱导蛋白水平的临床研究

目的 了解不同胎龄新生儿脐血维生素K₁及维生素K缺乏诱导蛋白(PIVKA-Ⅱ)水平,探讨其影响因素,为防治维生素K缺乏性出血及维生素K在临床的合理应用提供依据。方法 选择2016年12月-2017年3月在西安交通大学第一附属医院及陕西省人民医院出生,且尚未预防性注射维生素K₁的新生儿,按随机数字法采集100例新生儿脐血,用高效液相质谱法检测VK₁水平,用ELISA法检测PIVKA-Ⅱ水平,并记录产妇病史及相关异常因素。结果 100例新生儿脐血VK₁水平为(0.293±0.135) ng/ml, PIVKA-Ⅱ水平为(22.479±13.151)AU/ml,脐血VK₁水平与PIVKA-Ⅱ水平呈负相关(r=-0.362,P＜0.001)。孕母不同文化程度、不同居住地以及孕期食用绿色蔬菜的多少不同,其新生儿脐血VK₁水平、PIVKA-Ⅱ水平的差异有统计学意义(P＜0.05),其中孕期食用绿色蔬菜的多少是新生儿脐血VK₁,PIVKA-Ⅱ水平的独立影响因素(P＜0.05)。结论 新生儿的脐血VK₁含量较低,PIVKA-Ⅱ水平高。亚临床及临床VK缺乏率较高,围生期母儿PIVKA-Ⅱ、VK监测很有必要。提高孕母孕期绿色蔬菜摄入和孕母孕期、新生儿期PIVKA-Ⅱ、VK₁的监测,有助于预防和及早发现亚临床及临床VK缺乏。     

母血与脐血中VitA VitC VitD VitE含量及其相关性

目的:探讨母血与脐血血清维生素正常水平值及相互关系。方法:对2002年1月～2003年6月在天坛医院妇产科进行检查的北京市崇文区540例孕产妇配对测定母血、脐血中维生素A、C、D、E浓度,比较其水平并进行相关性分析。结果:脐血与母血比较,维生素A、C、D、E差异有显著性意义,脐血维生素值普遍低于母血。母血与脐血维生素A、C、D、E具有相关性。其中尤以母血维生素A与脐血的相关性大。结论:本次研究测得母血、脐血维生素值均低于正常值。提示孕期应合理补充维生素,定期检测体内维生素的含量,母血与脐血维生素A、C、D、E含量具有相关性,妊娠期补充维生素对提高新生儿体内维生素含量有作用,以提高维生素A最容易见效。     

Differences in the accumulation of ascorbic acid in normal,myeloperoxidase deficient and NADPH-oxidase deficient granulocytes

Granulocytes contain large quantities of ascorbic acid (AA). The uptake mechanism is mainly restricted to the accumulation of the oxidized form, dehydroascorbate (DHA). We investigated the uptake of ascorbic acid and dehydroascorbate of normal, myeloperoxidase (MPO)-deficient, and NADPH-oxidase-deficient granulocytes. The accumulation of ascorbic acid was increased in all types of granulocytes after stimulation with phorbol-myristate-acetate, whereas the NADPH-oxidase-deficient cells showed a decreased uptake compared to normal and MPO-deficient cells. The intracellular concentration of ascorbic acid was further enhanced after incubation of granulocytes with DHA, most prominently in NADPH-oxidase-deficient granulocytes. MPO-deficient granulocytes are not able to produce HOCl after activation. The granulocytes of one individual with total MPO deficiency accumulated ascorbate in higher concentrations than did cells with partial MPO deficiency, indicating that HOCl is of minor importance for the oxidation of ascorbate. Since the ability of MPO-deficient cells to kill microorganisms is pronounced in contrast to NADPH-oxidase-deficient cells, effective mechanisms of compensating for the absence of HOCl must exist. We hypothesize that the enhanced uptake of ascorbic acid combined with an enhanced superoxide anion production may favor the generation of OH radicals via the Fenton reaction.     

Deficient expression of leukocyte adhesion proteins. A new Tunisian case

Leukocyte adhesion deficiency (LAD) is a rare primary immunodeficiency inherited as an autosomal recessive genetic disorder. LAD was suspected in a four days old girl. She was born from healthy first cousins. A family history of a boy who died from omphalitis and sepsis was reported. Our patient had the severe form, she had delayed umbilical cord separation and suffered recurrent infections. She had a deletion of the G at position 1497. The patient received bone marrow transplantation from her HLA-identical mother at age of 14 months. She is now 9 years old and in good health.     

补肾活血法治疗输卵管积水性不孕症的研究进展

输卵管积水是输卵管性不孕症的重要病因,目前西医主要以手术对症治疗积水和辅助生殖技术获得妊娠。中医从整体观念和辨证论治的角度出发,认为输卵管积水性不孕症的基本病机是肾虚血瘀,肾虚为本,血瘀为标。病位在胞宫,故以补肾培元和活血通络为治疗大法。中药内服和外用并举,在改善患者临床症状和提高妊娠率方面均有显著疗效。现代药理学也进一步证实补肾活血中药的明确作用机制,以补肾活血法为代表的中医疗法治疗输卵管积水性不孕症有独特优势。综述补肾活血法与输卵管积水性不孕症的理论探讨及研究进展。     

维生素A在铁缺乏及缺铁性贫血治疗中的作用

近几年研究发现维生素A缺乏与铁缺乏具有显著的相关性,维生素A治疗缺铁性贫血和铁缺乏也取得了较好的临床效果.本文就维生素A缺乏与铁缺乏的相关性和作用机制,以及维生素A治疗缺铁性贫血的临床疗效和研究进展进行了综述,为维生素A用于儿童缺铁性贫血的防治提供依据,同时为降低我国儿童缺铁性贫血及铁缺乏的发病率提供更有效的防治措施.     

Carnosic acid reduces cytokine-induced adhesion molecules expression and monocyte adhesion to endothelial cells

Background  Expression of cell adhesion molecules on the endothelium and the attachment of monocytes to endothelium may play a major role in the early atherogenic process. Aim of the study  We investigated the effects of carnosic acid on the adhesion of U937 cells to IL-1β-treated human umbilical vein endothelial cells (HUVECs), as well as on the expression of adhesion molecules. Results  Our data showed that pretreatment with 10 and 20 μmol/l carnosic acid significantly reduced the number of U937 cells adhering to IL-1β-treated HUVECs. In addition, we found that 20 μmol/l carnosic was more effective than 10 μmol/l carnosic acid at inhibiting expression of cell adhesion molecules (ICAM-1, VCAM-1, and E-selectin), the nuclear translocation of NF-κB subunits p65 and p50, and the production of ROS in IL-1β-stimulated HUVECs. Conclusions  We conclude that carnosic acid inhibits IL-1β-induced ICAM-1, VCAM-1 and E-selectin expression in HUVECs through a mechanism that involves NFκB. We propose that the reduction in binding of human monocytic cell line U937 to IL-1β-treated HUVECs is due to the anti-inflammatory properties of carnosic acid.     

Evaluation of the folacin status in children with regard to the cobalamin and iron status. 2. Incidence and severity of folate deficiency

In a study with 165 children the folate, cobalamin and iron status was investigated by biochemical and haematological methods. On the basis of biologically based borderlines it could be demonstrated, that 15% of the children showed folate deficiency in a progressive state. This means that low serum resp. low erythrocytic folate concentrations correlated with alterations in the blood picture (lobe average of the neutrophilic granulocytes). Especially children in the age of puberty (11-15 years) are to be regarded as vulnerable; 30% of this group show deficiency symptoms whereas in very young children (1-5 years) only in 10% the supply situation is insufficient. The folate status in pupils (6-10 years) is comparable to adults (15% deficient). As cobalamin and iron status may influence folate depending parameters the status of these nutrients was estimated, too. Cobalamin deficiency was not detectable in any case. Though the iron supply situation was not adequate in all cases, interactions with the folate depending parameters could be excluded.