Study on separation and purification process of C1 esterase inhibitor / 中国输血杂志

【Objective】 To study the technology of separating and purifying C1 esterase inhibitor (C1-INH) by using the waste washing liquid as raw materia during the preparation of human prothrombin complex (PCC) l. 【Methods】 C1-INH was isolated and purified by a two-step method of polyethylene glycol (PEG) 4000 precipitation and cation chromatography. The pH of raw materials and the concentration of PEG4000 were adjusted to investigate the optimal conditions of PEG4000 precipitation method. After PEG was precipitated and centrifuged, the supernatant is treated as the loading solution for cation exchange chromatography, using Fractogel EMD SE HiCap(M) gel and CM Sepharose FF gel for ion exchange chromatography. The most suitable gel and separation conditions were selected by comparing the C1-INH antigen yield, activity yield and specific activity. 【Results】 Under the condition of pH 6.1, when the mass fraction of PEG4000 was 14%, the recovery rate of C1 esterase inhibitor was close to 70%, and the removal rate of ceruloplasmin was more than 95% after stirring for 10 minutes. As fractogel EMD SE HiCap(M) gel was used for cation exchange chromatography, when the eluent salt concentration was 0.25 M sodium chloride, the activity yield of C1 esterase inhibitor was greater than 80%, and the specific activity was greater than 5 IU/mg. 【Conclusions】 Using the waste washing liquid as the raw material during the preparation of PCC, the C1 esterase inhibitor with high specific activity can be prepared through PEG precipitation and purification by Fractogel EMD SE HiCap(M) ion exchange chromatography.

Hereditary angioedema caused by C1-esterase inhibitor deficiency: a case report with literature-based analysis

Hereditary angioedema (HAE) caused by C1-esterase inhibitor deficiency is an autosomal-dominant disease caused by a mutation in the C1-inhibitor gene. It is a rare disease that is often worsened during pregnancy and childbirth. HAE, though uncommon but if untreated it may lead to maternal death.  The case report presents the successful management of a 24 years old, G2P1, with hereditary angioedema caused by C1-esterase inhibitor deficiency. This patient was managed with a multidisciplinary approach by an obstetrician, an immunologist, an anaesthesiologist and a pediatrician. She had an uneventful antenatal period, labor was induced. She had precipitate delivery and soon after delivery had a flare up of the disease. It was successfully managed with fresh frozen plasma and close observation.

Three-dimensional Culture of Human Airway Epithelium in Matrigel for Evaluation of Human Rhinovirus C and Bocavirus Infections / 生物医学与环境科学（英文）

OBJECTIVE@#Newly identified human rhinovirus C (HRV-C) and human bocavirus (HBoV) cannot propagate in vitro in traditional cell culture models; thus obtaining knowledge about these viruses and developing related vaccines are difficult. Therefore, it is necessary to develop a novel platform for the propagation of these types of viruses.@*METHODS@#A platform for culturing human airway epithelia in a three-dimensional (3D) pattern using Matrigel as scaffold was developed. The features of 3D culture were identified by immunochemical staining and transmission electron microscopy. Nucleic acid levels of HRV-C and HBoV in 3D cells at designated time points were quantitated by real-time polymerase chain reaction (PCR). Levels of cytokines, whose secretion was induced by the viruses, were measured by ELISA.@*RESULTS@#Properties of bronchial-like tissues, such as the expression of biomarkers CK5, ZO-1, and PCK, and the development of cilium-like protuberances indicative of the human respiration tract, were observed in 3D-cultured human airway epithelial (HAE) cultures, but not in monolayer-cultured cells. Nucleic acid levels of HRV-C and HBoV and levels of virus-induced cytokines were also measured using the 3D culture system.@*CONCLUSION@#Our data provide a preliminary indication that the 3D culture model of primary epithelia using a Matrigel scaffold in vitro can be used to propagate HRV-C and HBoV.

Angioedema hereditario, ponderación de evidencias. parte 2 - tratamiento / Hereditary angioedema, weighting of evidence. Part 2 - Treatment

Desde las observaciones de Quincke y Osler, que refirieron pacientes con una "tumefacción" diferente de las que provocaban habitualmente los mecanismos alérgicos hasta el descubrimiento de un nuevo mediador responsable de esos edemas dolorosos y deformantes, se han sucedido los aportes de los investigadores en el esclarecimiento de la patogenia y el tratamiento del AEH hasta la actualidad, en que el arsenal terapéutico se ve notablemente enriquecido por medicamentos altamente eficaces y específicos. Intentaremos describirlos. (AU)

From the observations of Quincke and Osler, who referred patients with a "swelling" different from those that usually provoked the allergic mechanisms until the discovery of a new mediator responsible for these painful and deforming edemas, have been the contributions of researchers in the Clarification of the pathogenesis and treatment of HAE to date, where the therapeutic arsenal is remarkably enriched by highly effective and specific drugs. We will try to describe them.(AU)

ANGIOEDEMA HEREDITARIO, PONDERACIÓN DE EVIDENCIAS. PARTE 1 / Hereditary angioedema, weighting of evidence. Part 1

A pesar de que el angioedema hereditario es un padecimiento raro, tiene una amplia bibliografía que ratifica que la fisiopatología de esta enfermedad es compleja. La constante investigación de la industria farmacéutica no solo ha aportado nuevos recursos terapéuticos sino que ha logrado despertar un inusitado interés en la comunidad médica, permitiendo que tengamos una mayor comprensión sobre los mecanismos que presiden la aparición de las crisis. El Comité de Angioedema Hereditario de la AAAeIC ha desarrollado una puesta al día sobre esta entidad, que, por las características de sus síntomas, es abordada principalmente por los especialistas en alergia e inmunología clínica(AU)

Although hereditary angioedema is a rare condition, it has a large number of references that confirm that the pathophysiology of this disease is complex. The constant research of the pharmaceutical industry has not only brought new therapeutic resources, but also aroused an unusual interest in the medical community, allowing us to have a better understanding of the mechanisms that perform the onset of crises. The AAA e IC Hereditary Angioedema Committee has developed an update on this entity, which, due to the characteristics of its symptoms, is mainly addressed by specialists in allergy and clinical immunology.(AU)

Type I hereditary angioedema in Taiwan – clinical, biological features and genetic study.

Background: Hereditary angioedema (HAE) is a rare, autosomal dominant inherited disease which is caused by a genetic deficiency of C1 esterase inhibitor (C1 INH). There have only been a few case reports in Taiwan to date. Objective: To describe the clinical features of type I HAE in Taiwanese patients. Methods: Three unrelated Taiwanese families with type I HAE are reported, and one case of a family from a review of PubMed was reviewed. Clinical manifestations, diagnostic examinations, management and genetic studies were analyzed. Results: Including this report, 19 patients had low C1 INH and low C4 levels and were diagnosed with type I HAE. Only 11 (57.9%) patients were symptomatic. Recurrent skin swelling and edema over the four extremities or trunk were reported in all symptomatic patients (100%). 45.5% of the patients recalled laryngeal attacks and one patient died from asphyxia. 18.2% of the patients experienced abdominal symptoms. The age at the beginning of clinical symptoms ranged from 5 to 30 years (mean ± SD: 20.82 ± 7.88 years). The diagnosis tended to be delayed (range from 1 to 39 years; mean ± SD: 8.45 ± 11.04 years). Nine patients had a mutant C1 INH gene, and two patients received long-term prophylaxis with danazol. Conclusion: The prevalence of hereditary angioedema in Taiwan is low. Persons with low levels of C1 INH who were clinically symptomatic accounted for only 57.9% of the cases in our study, which is far lower than previous reports from other countries. Ethnic differences may be the reason for this finding. Further genomic studies are needed to elucidate the genetic penetrance of C1 INH deficiency in Taiwan.

The Efficacy and the Safety of Hae-Un-Dae Spa Therapy for the Treatment of Adult Atopic Dermatitis / 대한피부과학회지

BACKGROUND: Spa therapy is widely used in many countries for the treatment of atopic dermatitis. There have been some reports about the therapeutic efficacies and mechanisms of spa therapy for the treatment of atopic dermatitis (AD) from other countries, but there have been no such reports from Korea. OBJECTIVE: The purpose of this study was to investigate the therapeutic efficacy and the safety of Hae-Un-Dae spa therapy for adult AD patients. METHODS: A total of 15 patients with AD were recruited in this study. The patients were classified into the mild group (n=5) and severe group (n=10) according to their eczema area and severity index (EASI) score at baseline. They had a bath in a Hae-Un-Dae spa three times per week for 4 weeks. To evaluate the therapeutic efficacy, the EASI score, the physician's global assessment (PGA) and the visual analogue scale (VAS) for pruritus were assessed every week. The skin hydration, the skin pH and the transepidermal water loss (TEWL) were also measured weekly to investigate the changes of the skin barrier function during the spa therapy. RESULTS: Compared to baseline, the EASI scores of the total group and the severe group decreased at 2, 3 and 4 weeks. Furthermore, the VAS for pruritus of the total group and the severe group was also decreased. Among the factors of the skin barrier function, the skin pH decreased in the mild group and it increased in the severe group during the spa therapy. Of the 15 patients, one patient experienced exacerbation of symptoms and two patients reported a transient pickling sensation during the spa therapy. CONCLUSION: Our study suggests that Hae-Un-Dae spa therapy could be an effective and safe modality for the management of adult AD, yet more studies should be performed to determine the therapeutic mechanism.

Thr-6Pro missense mutation in human lysosomal acid lipase (LAL) gene in patients with familial hypercholesterolemia in Korea

Lysosomal acid lipase (LAL) plays a central role in the intracellular degradation of neutral lipids derived from plasma lipoproteins. In this study, we investigated the missense mutation within exon 2 of human LAL gene changing of codon -6 of prepeptide from threonine to proline. The Thr-6Pro mutation was detected by the Hae III restriction fragment length polymorphism (RFLP) and single-strand conformation polymorphism (SSCP). We analyzed the mutation in subjects with 221 unrelated randomly selected control samples and 86 patients with familial hypercholesterolemia (FH) in Korea. We observed that mutation is present with high frequency in Korea compared to other populations studied previously. The frequency of PP homozygote in the FH group was observed considerably higher than that of control. However, there was no significant difference of genotype frequency between two groups. These results, together with the fact that plasma lipids and lipoproteins levels between genotypes showed no statistical difference, suggest that the Thr-6Pro mutation in the LAL gene may have no association with the increased risk of FH development.