Serum concentration of alpha-2-macroglobulin, alpha-1-antitrypsin and alpha-1-antichymotrypsin [correction of alpha-2-antichymotrypsin] in patients with Hodgkin's disease.

In twenty four patients diagnosed with Hodgkin's disease we have determined several antiproteases. Our findings have shown the decrease of concentration of alpha-2-macroglobulin and increase of alpha-1-proteinase inhibitor and alpha-1-antichymotrypsin. The observed changes were statistically significant p < 0.001. We did not find any correlation between the concentration of inhibitors and the clinical stage of carcinoma and histopathological data. The determination of the level of antiproteases in patients with cancer disease may be assumed to reflect partly at least the capability of anticancer mechanism in the host.     

Smoking and intermediate alpha1-antitrypsin deficiency and lung function in middle-aged men.

Lung function was evaluated in a representative population sample of 50-year-0ld men living in one Swedish city. Twenty-four smoking and 15 non-smoking men heterozygous for alpha1-antitrypsin deficiency--that is, with the protease-inhibitor (Pi1 phenotype MZ--were carefully matched for weight and smoking habit with Pi M controls. The pulmonary function of non-smoking Pi MZ subjects did not differ from that of non-smoking Pi M controls. In contrast, smoking heterozygotes showed a significant loss of elastic recoil, enlarged residual volumes, and increased closing capacity but no signs of obstructive ventilatory impairment. Most smoking Pi MZ individuals reported mild exertional dyspnoea.     

The role of augmentation therapy in alpha-1 antitrypsin deficiency

Abstract

Background:

Since the recognition of alpha-1 antitrypsin deficiency (A1ATD) in 1963, interest in this condition has increased dramatically. A1ATD is now recognized as the only known genetic condition that leads to emphysema/chronic obstructive pulmonary disease (COPD) in many individuals with the condition. Augmentation therapy with plasma-derived alpha-1 antitrypsin (A1AT) was first introduced in 1987.     

Alpha-1-antitrypsin, immunoglobulins and radiological type in Nigerians with pulmonary tuberculosis

Tuberculin skin test tended to be more intensely reactive in the caseonodular and other groups than the military group. Serum IgA, IgG and IgM and alpha-I-antitrypsin levels were higher in Northern Nigerians with pulmonary tuberculosis than in controls. IgA and IgG levels were higher in miliary tuberculosis than caseonodular and cavitating tuberculosis. The cavitatory lesions in tuberculosis may not result from autodigestion by inflammatory proteases since alpha-I-antitrypsin-the major inhibitor of proteases was not deficient in cavitatory tuberculosis. While an unqualified immunological spectrum of tuberculous disease in our patients has not clearly been demonstrated due to limited facilities, our results show a tendency to this spectrum.     

Experimental and investigational drugs for the treatment of alpha-1 antitrypsin deficiency

ABSTRACT

Introduction: Alpha-1 antitrypsin deficiency (AATD) is most often associated with chronic lung disease, early onset emphysema, and liver disease. The standard of care in lung disease due to AATD is alpha-1 antitrypsin augmentation but there are several new and emerging treatment options under investigation for both lung and liver manifestations.

Areas covered: We review therapeutic approaches to lung and liver disease in alpha-1 antitrypsin deficiency (AATD) and the agents in clinical development according to their mode of action. The focus is on products in clinical trials, but data from pre-clinical studies are described where relevant, particularly where progression to trials appears likely.

Expert opinion: Clinical trials directed at lung and liver disease separately are now taking place. Multimodality treatment may be the future, but this could be limited by treatment costs. The next 5–10 years may reveal new guidance on when to use therapeutics for slowing disease progression with personalized treatment regimes coming to the forefront.     

The promise of gene therapy for the treatment of alpha-1 antitrypsin deficiency

In the last 13 years, three gene therapy trials for the treatment of alpha-1 antitrypsin deficiency have been conducted. The first trial delivered plasmid encoding the alpha-1 antitrypsin cDNA to the nasal epithelium using cationic liposomes. The last two trials delivered recombinant adeno-associated vectors encoding the alpha-1 antitrypsin cDNA by intramuscular injection. In this review, the progress of ongoing clinical trials and new gene therapy technologies is discussed.     

Progression of liver disease in children and adults with lysosomal acid lipase deficiency

Background and objective: Manifestations of the autosomal recessive disorder lysosomal acid lipase deficiency (LAL-D) include hepatomegaly, elevated serum liver enzymes, and progressive liver disease. We report an analysis of time to progression from first clinical manifestation to first documentation of hepatic fibrosis, cirrhosis, or liver transplantation from an observational study of pediatric and adult patients with LAL-D (clinical trial registration: NCT01528917).

Methods: Data were analyzed from 31 patients with available biopsy data and 1 patient without biopsy data who had undergone liver transplantation. Time to first documentation of fibrosis, cirrhosis, or liver transplantation following the first LAL-D clinical manifestation was estimated using Kaplan–Meier analysis.

Results: The median time to an event was 3.1 years.

Conclusions: These findings illustrate the progression of liver damage in LAL-D and the elevated risk for liver transplantation among children and adults with LAL-D.     

Impact of smoking on the concentration and activity of alpha-1-antitrypsin in serum in relation to the urinary excretion of hydroxyproline

The impact of active and passive smoking on the serum levels of alpha 1-AT, the trypsin inhibitory capacity (TIC), the trypsin inhibitory activity (TIA) and the urinary hydroxyproline to creatinine ratio (HOP-ratio) was studied. The subjects used in the study on active smoking were 167 healthy adult men and in the study on passive smoking 189 healthy primary school children. Serum levels of alpha 1-AT in active smokers were significantly higher than those in non-smokers. The TIC as well as the TIA in active smokers decreased with increasing number of cigarettes smoked. The urinary HOP-ratio increased significantly with increasing number of cigarettes smoked. On the other hand, in the case of passive smokers a significant difference was obtained only for the HOP-ratio. The correlations between all markers in active smokers were significant. Less significant correlations were found in the case of passive smokers. These results suggest that the urinary excretion of hydroxyproline can be considered as a marker for the imbalance between proteases and anti-proteases as a result of smoking.     

The associations between serum alpha-1-antitrypsin level and the whole blood contents of trace metals in normal women in reproductive age

The concentration of Alpha-1-Antitrypsin (A-1-AT) in the blood serum was measured by single radial immunodiffusion in 21 healthy women in reproductive age. Simultaneously the whole blood levels of cadmium, lead, copper and zinc were determined by atomic absorption spectrometry. Serum A-1-AT correlated significantly with blood copper (r = 0.55, p less than 0.01). The importance of quantitative relations between "acute phase reactants" in blood serum and the blood trace metals is discussed from the point of view of reproductive medicine.     

儿童先天性心脏病手术前后血浆脑钠肽的变化

目的研究先天性心脏病患儿手术前后血循环脑钠肽（Brainnatriureticpeptide,BNP）的变化,了解不同类型先心病患儿手术对心功能的影响。方法以进行小儿先心病手术的100例患儿作为研究对象,选取同期体检健康儿童26例为对照组。先心病类型分为5个亚组[房间隔缺损组（n=14）、空间隔缺损组（n=63）、法络四联征组（n=10）、动脉导管未闭组（n=9）和肺动脉狭窄组（n=4）],术前1d,术后1、2、7d应用免疫荧光干式定量法测定BNP。结果先心病组术前BNP值与对照组相比差异有统计学意义（P〈0．01）,手术前患儿5组BNP值组间差异无统计学意义（P〉0．05）;5组先心病患儿术前BNP与术后4个时间点间比较差异有统计学意义（P〈0．05）。先心病组各时间点两两比较,差异有统计学意义（P〈0．01）。结论不同先心病类型的患儿之间心功能指标-血循环BNP没有差别,但比健康儿童升高。不同病理类型先心病,术后心功能变化不同。     

慢性乙型肝炎肝纤维化评估中血清miR-122的临床意义

目的 探讨慢性乙型肝炎患者血清miR-122与肝纤维化的相关性及其临床意义.方法 选择慢性乙型肝炎患者96例,检测患者血液生化、乙肝病毒学指标及血清miR-122,行肝脏组织活检术进行纤维化分级,对血清miR-122表达水平与肝纤维化的相关性进行分析.结果 血清miR-122水平与肝纤维化分级呈负相关(r=-0.341,P=0.001).肝脏纤维化分级S3、S4患者血清miR-122水平较肝脏纤维化程度为S0、S1、S2患者miR-122水平低(P＜0.05).结论 在慢性乙型肝炎患者中,低水平的血清miR-122可能预示重度肝脏纤维化.     

血小板反应蛋白-1在大鼠肝纤维化中表达的意义

目的研究血小板反应蛋白-1(TSP-1)在肝纤维化模型大鼠肝组织中的表达,探讨TSP-1在肝纤维化发病机制中的作用。方法选择健康雄性大鼠30只,随机分为正常组10只,模型组20只,选用四氯化碳(CCL4)、饮酒、高脂低蛋白饮食等复合因素诱导肝纤维化模型,造模8周,取两组大鼠肝组织HE染色病理观察、纤维化分级,测定肝脏指数、血清透明质酸(HA)、肝组织羟脯氨酸(Hyp)含量及免疫组化法测定肝组织中TSP-1的表达量。结果复合因素大鼠肝纤维化模型造模成功,肝组织病理显示炎症明显、纤维化形成,模型组大鼠肝脏指数、血清HA肝组织Hyp及TSP-1较正常组显著升高,TSP-1在肝组织的表达量与肝纤维化程度成正比。结论TSP-1在肝纤维化发生发展过程中可能发挥了病理作用。