Mutational Spectrum of the CFTR Gene in the Kazakhstan Population

Objective: To study the frequency and spectrum of CFTR gene variants in different ethnic groups of Kazakhstan. Methods: We reviewed the records of 58 patients with cystic fibrosis. All the patients underwent molecular genetic analysis to reveal genotype-phenotype correlations. Results: The median (IQR) age of the patients was 5.4 year (7 months, 18 year); 40% were diagnosed at the age of 5-10 year. The study identified 28 specific variants: p.Phe508del, the variant most common in the European population, was detected in 30 patients (51.7%). Variants other than p.Phe508del were revealed in 31% (21 patients). Conclusions: We found a number of specific variants characteristic of the Kazakhstani population. A pronounced regression of disease symptoms was detected in patients with mild mutations; whereas in patients with severe mutations, therapy produced very little effect.

Comparison of histological characteristics of two experimental mouse abdominal aortic aneurysm models / 西安交通大学学报(医学版)

【Objective】 To compare the histological characteristics of porcine pancreatic elastase （PPE） induced abdominal aortic aneurysms （AAA） and angiotensin Ⅱ （AngⅡ） induced AAA in mice. 【Methods】 In the PPE group， the mouse abdominal aorta segment from the infrarenal abdominal aorta to the iliac artery was isolated and its branch arteries were ligated to avoid leakage during PPE perfusion. We perfused the isolated aorta segment with a PPE solution at a concentration of 1.5 U/mL for 5 min and then closed the abdominal cavity. The diameter of the abdominal aorta was measured before and 14 days after the surgery， and the perfusion segment of the arteries was collected at day 14 after the surgery. The histological characteristics of the aneurysm were analyzed and graded by histological and immunohistochemical methods. In the AngⅡ group， ten apolipoprotein E knockout mice were prepared， and AngⅡ [1 000 ng/(kg·min)] was infused with osmotic pumps for 28 days. The aorta was separated and the aneurysm aorta segment was analyzed. The wild type mice were used as normal health controls. 【Results】 In the PPE group， the diameter of the PPE perfused aorta segments increased and was significantly larger than the basal diameter ［（0.52±0.02） mm vs. （1.23±0.11） mm］ at day 14 after surgery. All the ten mice developed AAA after PPE application. The histological results showed typical pathological features of AAA in PPE perfused mice， such as elastic fiber breakage， smooth muscle exhaustion， and increased inflammation. Six of the ten mice developed aneurysms after AngⅡ infusion （6/10）. The aneurysms/dilatations were mostly in the suprarenal abdominal aorta， but also in the thoracic aorta and aortic arch. The histology analysis showed that the formation of arterial dissection was common after AngⅡ infusion， and the typical vascular “false lumen” was found. The breakage of elastic fibers， the exhaustion of smooth muscle damage， and the inflammatory response were not as typical as the PPE model in AngⅡ perfused animals. 【Conclusion】 The histological characteristics of PPE induced AAA are very typical and well present the inflammatory process in the development of aneurysm. The AngⅡ model is suitable for the study of aneurysms combined with aortic dissection. Both models have their own advantages and can complement each other.

Elastase injection into the cerebellomedullary cistern to induce a model of vertebrobasilar dolichoectasia in mice and evaluation of magnetic resonance angiography / 国际脑血管病杂志

Objective:To investigate the effect of magnetic resonance angiography (MRA) in evaluating the mouse model of vertebrobasilar dolichoectasia (VBD) induced by injection of elastase into cerebellomedullary cistern.Methods:Twenty-four male C57/BL6 mice were selected. The mice in the elastase group ( n=12) were injected in the cerebellomedullary cistern with 2.5 μl of phosphate buffer containing 25 mU elastase, and the mice in the saline control group ( n=12) were injected with the same volume of normal saline. MRA examination of the brains of living mice was performed 2 weeks after modeling. Successful modeling was defined as the basilar artery bending angle ≤170°, or the basilar artery bending length accounts for ≥10%, or the basilar artery deviated from the midline by more than 1 grade, or the percentage increase in artery diameter was ≥25%. Results:In the elastase group and the saline control group, 2 mice and 1 mouse did not wake up normally or died, respectively. The 11 surviving mice in the saline control group had no obvious vertebral artery and basilar artery abnormalities. The success rate of modeling in the 10 surviving mice in the elastase group was 80%, and the difference in the success rate between the two groups was statistically significant ( P<0.05). There were significant differences in mean basilar artery diameter (0.30 mm vs. 0.22 mm; P<0.05), mean basilar artery bending angle (115° vs. 170°; P<0.05), and proportion of mean basilar artery bending length (31% vs. 5%; P<0.05) of the surviving mice between the elastase group and the saline control group. Conclusion:MRA can better evaluate the mouse VBD model induced by elastase injection in the cerebellomedullary cistern.

The study of the mechanism related to abdominal aortic aneurysm formation in elastase-induced aneurysm mice model / 中华胸心血管外科杂志

Objective:To establish a mouse model of the abdominal aortic aneurysm by elastase perfusion and to provide a reference for the study of the mechanism related to abdominal aortic aneurysm formation.Methods:AAAs were induced by porcine pancreatic elastase (PPE) infusion in male C57BL/6 mice. The control group was perfused with normal saline (Saline). The changes in abdominal aortic diameter were compared at 14 days after perfusion. The diameter of the abdominal aorta stained with HE was measured. The destruction of the elastic plate in the abdominal aortic wall was observed by elastic plate staining. TUNEL assay was used to evaluate the apoptosis in aneurysm tissues.Results:Porcine pancreatic elastase (PPE) perfusion successfully established the mouse model of abdominal aortic aneurysm, in which an aneurysm formation rate was 100% at 14 days after the operation. After modelling, the abdominal aorta diameter in the mouse was significantly increased, higher than that in the control group perfused with normal saline ( P<0.05). In the PPE group, the elastic plate of the aortic wall was straightened and thinned, and interrupted. The proportion of TUNEL-positive cells in the PPE group was significantly higher than that in the control group perfused with normal saline ( P<0.05). Conclusion:Elastase perfusion can stably establish the abdominal aortic aneurysm model, and we observe the destruction of the elastic plate in the medial layer of the abdominal aortic wall and the up-regulation of the apoptosis process in the model. It provides a reference to study the pathogenesis of abdominal aortic aneurysm further.

Relação entre genótipo e insuficiência pancreática em crianças e adolescentes com fibrose cística de um centro de referência no Brasil / Relationship between genotype and pancreatic insufficiency in children and adolescents with cystic fibrosis in a referral center in Brazil

Introdução: fibrose cística (FC) é uma doença genética que culmina em alterações na proteína transmembrana CFTR, resultando na produção de muco mais espesso em diversos órgãos, destacando-se os tratos respiratório e digestório. A insuficiência pancreática (IP) acomete até 95% dos pacientes com FC. Objetivos: determinar a frequência de IP através da dosagem de elastase fecal-1 (EF-1) e compará-la com o genótipo de pacientes com FC assistidos em um centro de referência. Metodologia: foi realizado um estudo transversal, incluindo-se pacientes com FC de 0 a 20 anos. Após a inclusão dos sujeitos à pesquisa, foi realizada consulta ao prontuário para a obtenção de dados clinicos e demograficos e amostras de fezes foram obtidas para dosagem da (EF-1). Os pacientes foram submetidos à análise molecular das mutações por métodos convencionais, através da extração do DNA em sangue periférico. Quando duas mutações patológicas não foram identificadas, o sequenciamento de nova geração com utilização da plataforma Illumina HiSeq foi realizado em amostras da mucosa oral. Resultados: foram incluídos 31 pacientes, 17 (54,8%) do sexo feminino, mediana de idade de 10 anos, e apenas um paciente foi classificado como branco. Vinte e dois (70,9%) pacientes apresentaram dosagem de EF-1 inferior a 200 µg/g, compatível com o diagnóstico de IP. Destes, 21 (95,4%) apresentaram dosagem de EF-1 menor ou igual a 15µg/g, caracteristica de IP grave. Todos os pacientes com IP apresentavam duas mutações de classes I a III. Conclusão: a IP foi identificada em 70% dos pacientes, ocorrendo em todos os pacientes com duas mutações de classe I-III.

Introduction: cystic fibrosis (CF) is a genetic disease that culminates in alterations in the CFTR transmembrane protein, resulting in the production of thicker mucus in various organs, especially the respiratory and digestive tract. Pancreatic insufficiency (PI) affects up to 95% of CF patients. Objectives: To determine the frequency of PI by measuring fecal elastase-1 (FE-1) and comparing it with the genotype of CF patients assisted at a referral Center. Methodology: a cross-sectional study was conducted, including patients with CF from 0 to 20 years. After the inclusion of the subjects to the research, medical records were consulted to obtain clinical and demographic data and stool samples were obtained for the measurement of (FE-1). Patients were submitted to molecular analysis of mutations by conventional methods by DNA extraction in peripheral blood. When two pathological mutations were not identified, next-generation sequencing using the Illumina HiSeq platform was performed on oral mucosa samples. Results: thirty one patients were included, 17 (54.8%) female, median age 10 years, and only one patient was classified as white. Twenty-two (70.9%) patients had an FE-1 dosage of less than 200 µg / g, compatible with the diagnosis of pancreatic insufficiency (PI). Of these, 21 (95,4%) had an EF-1 dosage less than or equal to 15µg / g, characteristic of severe PI. All patients with two mutations class I to III were PI. Conclusion: PI was identified in 70% of patients, occurring in all patients with class I-III mutations.

A model of vertebrobasilar dolichoectasia in rats induced by injection of elastase into cisterna magna / 国际脑血管病杂志

Objective To investigate the feasibility of a model of vertebrobasilar dolichoectasia (VBD)in rats induced by injection of elastase into cisterna magna. Methods Forty male SD rats were randomly divided into elastase model group (n = 20) and saline control group (n = 20). The elastase model group was intracisternal injected with 0. 3 μl of elastase at a concentration of 1. 5 U/μl, and the saline control group was injected with 0. 3 μl of normal saline. All the animals were sacrificed at 28 d after model preparation.The degree of VBD was observed in both groups, and conventional HE and elastic fiber stain were performed. The tortuosity index and increased percentage of artery diameter were used to determine whether the model was successful. Results One and three rats died in the saline control group and the elastase model group, respectively. The diameter of the basilar artery in the elastase model group was significantly thicker than that in the saline control group (0. 452 ± 0. 062 mm vs. 0. 284 ± 0. 046 mm; t = 9. 113, P < 0. 001).None of the saline control groups showed morphological characteristics of VBD, and 15 in the elastase model group met the morphological characteristics of VBD. The success rate of model preparation was 88. 2％ (15/17 ). Histopathological examination showed that the structure of the vascular wall of was destroyed, the wall of the blood vessel was thinned, and internal elastic layer was discontinuous in the elastase model group; the saline control group had a clear wall structure, a uniform wall thickness, and a complete continuous elastic layer. Conclusion Injection of elastase into occipital cistern can successfully induce VBD in rats, which can be used to make a rat VBD model.

The expression of trypsin in serum and vital organs of septic rats / 中华内科杂志

Objective Pancreatic enzymes may spread into the injured intestine, bloodstream,and cause the cascade of inflammatory reactions. Our objective was to explore trypsin expression in serum and vital organs in septic rats. Methods Trypsin levels in serum, heart, lung and jejunum were tested and compared between Escherichia coli endotoxin injected rats(SS), SS treated with a protease inhibitor (ulinastatin) and control group(SHAM). The correlations between serum trypsin, intestinal proteins and inflammation indices were assessed.Two components of mucosal barrier, i.e. mucin-2 and E-cadherin,were measured to evaluate the intestinal mucosal barrier function. The levels of tumor necrosis factor alpha (TNFα), interleukin-6(IL-6) and neutrophil elastase(NE) were measured to determine the inflammation indices.Results Compared to SHAM group, trypsin levels in serum[(73.71±9.14) ng/ml vs. (12.12±2.36) ng/ml],heart[(51.60±15.06) ng/ml vs. (6.39±3.53) ng/ml],lung [(54.73±5.57) ng/ml vs. (5.24±3.08) ng/ml] and jejunum(1.19 ± 0.48 vs. 0.40 ± 0.12) were significantly higher in SS group (all P<0.05). The level of serum trypsin had negative correlation with mucin-2 and E-cadherin, and positive correlation with TNFα, IL-6 and NE (all P<0.05). In rats treated with ulinastatin, trypsin levels were significantly decreased compared with those in SS group including in serum [(65.79±4.88)ng/ml]], heart [(26.33±12.03)ng/ml], lung [(28.73±14.46) ng/ml] and jejunum (0.80±0.20) (all P<0.05).Serum TNFα[ (247.34±16.97)ng/L vs. (178.78±40.81)ng/L] revealed similar changes in ulinastatin and SS group, whereas mucin-2(0.58 ± 0.14 vs. 0.89 ± 0.17)and E-cadherin(0.11 ± 0.04 vs. 0.23 ± 0.06)were both significantly elevated after administration of ulinastatin (both P<0.05). Conclusion Serum and tissue trypsin is elevated in septic rats. Protease inhibitor ulinastatin protects intestinal function by reducing inflammatory reaction.

The activation of NLRP3-inflammsome by stimulation of diesel exhaust particles in lung tissues from emphysema model and RAW 264.7 cell line

BACKGROUND/AIMS: Diesel exhaust particles (DEPs) lead to elevation of reactive oxygen species, which can activate the nucleotide-binding oligomerization domain-like receptor (NLR) family members containing the pyrin domain 3 (NLRP3)-inf lammasome. In this study, we elucidated whether NLRP3 -inf lammasome is activated by DEPs and whether antioxidants (N-acetylcysteine [NAC]) could inhibit such activation. METHODS: RAW 264.7 cells and ex vivo lung tissues explants obtained from elastase-induced emphysema animal models were stimulated with cigarette smoking extract (CSE), DEPs, and lipopolysaccharide, and levels of interleukin-1β (IL-1β), caspase-1 and nucleotide-binding oligomerization domain-like receptor (NLR) family members containing the pyrin domain (NLRP3)-inflammasome were assessed by Western blotting and immunohistochemistry. RESULTS: NAC and caspase-1 inhibitor suppressed CSE- and DEP-induced secretion of IL-1β in RAW 264.7 cells. The expression levels of the NLRP3-inflammasome and caspase-1 were upregulated in RAW 264.7 cells by stimulation with CSE and DEPs and were inhibited by NAC. CSE and DEPs increased the secretion of IL-1β in lung tissues from both the normal and elastase-induced emphysema groups. The secretion of IL-1β by CSE and DEPs was increased in the elastin-induced emphysema group more than that in the normal group (CSE: 309 ± 19 pg/mL vs. 151 ± 13 pg/mL, respectively, p < 0.05; DEP: 350 ± 24 pg/mL vs. 281 ± 15 pg/mL, respectively, p < 0.05). NAC inhibited CSE- and DEP-induced IL-1β secretion in both the normal and elastase-induced emphysema groups. NLRP3-inflammasome expression as determined by immunohistochemistry was increased by CSE and DEPs in both the normal and elastin-induced emphysema groups, and was suppressed by NAC. CONCLUSIONS: The NLRP3-inf lammasome is activated by DEPs in ex vivo tissue explants from elastase-induced emphysema animal model, and this activation is inhibited by NAC.

Study on the relationship between the expression of toll-like receptor 9-mRNA and inflammatory factors in patients with acute pancreatitis / 临床外科杂志

Objective To investigate the correlation between the expression of Toll-like receptor 9(TLR9)-mRNA and inflammatory factors in patients with acute pancreatitis(AP).Methods A total of 40 patients with AP diagnosed in our hospital from February 2016 to September 2016 in 24 h were enrolled.EDTAK2 anticoagulant venous blood was collected on day 1,3,5.And pancreatic elastase,proinflammatory cytokines and anti-inflammatory cytokines were detected.Peripheral blood monouclear cells were isolated and the mRNA expression of TLR9 was tested by polymerase chain reaction.The change of TLR9-mRNA in 5 days was analyzed.Results The level of TLR9-mRNA in peripheral blood mononuclear cells of patients with AP at 1,3,5 days were significantly higher than that in the control group,and the difference was statistically significant (P ＜ 0.05).Changes of the TLR9-mRNA expression in peripheral blood mononuclear cells in patients with AP was positively correlated with the levels of pancreatic elastase and proinflammatory cytokines,and the difference was statistically significant (P ＜ 0.05).Conclusion The expression of TLR9-mRNA in peripheral blood mononuclear macrophages was closely related to the up-regulation of inflammatory cytokines in AP patients,suggesting that TLR9 may mediate the occurrence and development of AP.To investigate the correlation between the expression of TLR9-mTLR9-mRNA and inflammatory factors in patients with AP.Methods A total of 40 patients with AP diagnosed in our hospital from February 2016 to September 2016 in 24h were selected.EDTAK2 anticoagulant venous blood was collected on day 1,3,5.And Pancreatic elastase,proinflammatory cytokines and anti-inflammatory cytokines were also detected.EDTAK2 anticoagulant venous blood was collected,tested the above indicators and used them as the benchmark level of the corresponding indicators.Results The levels of TLR9-mRNA in peripheral blood mononuclear cells of patients with AP at 1,3,5 days were significantly higher than in the control group,and the difference was statistically significant (P ＜ 0.05).Changes of TLR9-mRNA expression in peripheral blood mononuclear cells in patients with AP was positively correlated with pancreatic elastase and proinflammatory cytokine,and the difference was statistically significant (P ＜ 0.05).Conclusion The expression of TLR9-mRNA in peripheral blood mononuclear macrophages was closely related to the up regulation of inflammatory cytokines in AP patients,suggesting that TLR9 may mediate the occurrence and development of AP.

Comparison of fccal elastase 1 for exocrine panreatic insufficiency evaluationn between ex-alcoholics and chronic pancreatitis patietts / Comparação da elastase fecal 1 para avaliação de insuficiência pancreática exócrina entre ex-alcoólatras e pacientes com pancreatite crônica

Context Fecal elastase is a noninvasive test for pancreatic insufficiency diagnosis. Objectives Evaluate the usefulness of fecal elastase 1 for the indication of exocrine pancreatic insufficiency among former alcohol addicts and patients with chronic pancreatitis. Methods Forty-three patients with chronic pancreatitis and thirty-three asymptomatic former alcohol addicts entered the study. The levels of fecal elastase 1 were measured using a commercial kit. Pancreatic imaging findings were used to categorize the groups. Results The levels of fecal elastase 1 were significantly lower in the patients than in the former alcohol addicts and in the group with tissue calcifications, duct alterations, or atrophy. With a cutoff level of 100 μg/g, the sensitivity of fecal elastase 1 in chronic pancreatitis was 46.51% and its specificity was 87.88% with a positive predictive value of 83.33% and a negative predictive value of 55.77%. When patients were stratified according to the severity of their pancreatitis, the sensitivity was 6.25% for mild pancreatitis and 70.37% for marked pancreatitis. Conclusion Low level of fecal elastase 1 was associated with marked rather than mild chronic pancreatitis; however, it may be useful to indicate pancreatic exocrine insufficiency in asymptomatic former alcohol addicts. .

Contexto O teste de elastase fecal é um teste não invasivo para diagnosticar insuficiência pancreática. Objetivos Avaliar a utilidade da elastase fecal 1 como indicador de insuficiência pancreática entre ex alcoólatras e pacientes com pancreatite crônica. Métodos Quarenta e três pacientes com pancreatite crônica e 33 ex alcoólatras assintomáticos entraram no estudo. Os níveis de elastase fecal 1 foram medidos usando kit comercial. Os achados de imagem pancreática foram usados para categorizar os grupos. Resultados Os níveis de elastase fecal 1 foram significantemente menores nos pacientes que nos ex alcoólatras e no grupo com calcificações teciduais, alterações de ductos, ou atrofia. A sensibilidade da elastase fecal 1 na pancreatite crônica foi de 46,51% e a especificidade foi de 87,88%, com valor preditivo positivo de 83,33% e valor preditivo negativo de 55,77%. Quando os pacientes foram estratificados segundo a severidade da pancreatite, a sensibilidade foi de 6,25% para pancreatite crônica leve e 70,37% para pancreatite crônica severa. Conclusão Baixo nível de elastase fecal foi associado com pancreatite crônica severa mais do que com a leve; entretanto, pode ser útil para indicar insuficiência pancreática exócrina entre os ex alcoólatras. .

Development of different degrees of elastase-induced emphysema in mice: a randomized controlled experimental study

Introduction: Mouse models of emphysema are important tools for testing different therapeutic strategies. The aim of this study was to develop a mouse model of emphysema induced by different doses of elastase in order to produce different degrees of severity. Methods: Thirty female mice (C57BL/6) were used in this study. Different doses of porcine pancreatic elastase were administered intratracheally once a week for four weeks, as follows: 0.1 U (n=8), 0.15 U (n=7), and 0.2 U (n=7). Control mice (n=8) received 50 microL of sterile saline solution intratracheally. Lung mechanics were analyzed by plethysmography. Mean linear intercept and volume fraction occupied by collagen and elastic fibers were determined. Results: An increase in lung resistance was observed with 0.2 U of elastase [median (P-25-P75): 2.02 (1.67; 2.34) cmH2O.s/mL], as well as a decrease in tidal volume and minute ventilation. Peak expiratory flow increased significantly in the groups treated with 0.15 U and 0.2 U of elastase. Mean linear intercept was higher with 0.15 U and 0.2 U of elastase, with destruction of alveolar walls [median (P-25-P75): 30.31 (26.65-43.13) microm and 49.49 (31.67-57.71) microm respectively]. The volume fraction occupied by collagen and elastic fibers was lower in the group receiving 0.2 U of elastase. Conclusion: Four intratracheal instillations of 0.2 U of elastase once a week induced changes in lung function and histology, producing an experimental model of severe pulmonary emphysema, whereas 0.15 U resulted in only histological changes.

Estudo das alterações morfofuncionais cardíacas secundárias ao enfisema pulmonar induzido por elastase pancreática de porco em ratos diabéticos / Study of morphofunctional cardiac changes secondary to pulmonary emphysema induced by porcine pancreatic elastase in Diabetic Rats

Introdução: A Doença Pulmonar Obstrutiva Crônica (DPOC) está freqüentemente associada a comorbidades crônicas como a doença cardiovascular, o diabetes mellitus e a hipertensão. O presente estudo tem por objetivo investigar as alterações morfológicas e funcionais no coração secundárias ao enfisema pulmonar em ratos diabéticos. Métodos: Ratos Wistar machos adultos (200 ± 20 g, n = 36) foram destinados à avaliação ecocardiográfica, análise morfométrica do coração e pulmões e análise da taxa de sobrevida. O diabetes mellitus foi induzido por aloxana (42 mg/kg, iv) 10 dias antes da indução do enfisema pulmonar por instilação de elastase (0,25 UI/100 g de peso corpóreo). Um grupo de ratos diabéticos recebeu tratamento com insulina NPH (4 UI antes da elastase, seguido de 2 UI/dia, 50 dias). Os experimentos foram realizados 50 dias após a instilação. Resultados: Ratos diabéticos e respectivos controles instilados com elastase apresentaram aumentos similares no diâmetro médio alveolar, cujos valores correlacionam-se positivamente com aumentos na espessura da parede (p=0,0022), na área da cavidade (p=0,0001) e espessura dos cardiomiócitos (p=0,0001) do ventriculo direito (VD). Ratos tornados diabéticos por injeção de aloxana exibiram redução na espessura da parede do ventrículo esquerdo (VE), no septo interventricular (IV) e na espessura dos cardiomiócitos. Estas variáveis morfométricas associaram-se à redução da fração de encurtamento do VE (p < 0,05) e a aumento no tempo de relaxamento isovolumétrico do VE (p < 0,05). A taxa de sobrevida reduziu-se de 80% em ratos diabéticos a 40% em ratos diabéticos instilados com elastase (p < 0,05). Conclusões: O diabetes por aloxana em ratos não modifica a hipertrofia do VD secundária ao enfisema pulmonar, porém induz disfunção ventricular esquerda. A manifestação de ambas as doenças, diabetes mellitus e enfisema pulmonar, reduz substancialmente a taxa de sobrevida, enfatizando a condição de comorbidade na coexistência de...

Background: Chronic Obstructive Pulmonary Disease (COPD) is often associated with chronic comorbid conditions of cardiovascular disease, diabetes mellitus and hypertension. This study aimed to investigate morphological and functional alterations of the heart secondary to chronic emphysema in diabetic rats. Methods: Adult male Wistar rats (200 ± 20 g, n=36) were used for echocardiographic measurements, morphometric analyses of the heart and lungs, and survival rate. Diabetes mellitus was induced by alloxan (42 mg/kg, iv) 10 days before the induction of pulmonary emphysema by the instillation of elastase (0.25 IU/100 g body weight). A group of diabetic rats was treated with NPH insulin (4 IU before elastase, plus 2 IU/day, 50 days). Experiments were performed 50 days after instillation. Results: Both elastase-instilled diabetic rats and matching controls exhibited similar increases in mean alveolar diameter, which are positively correlated with increases in RV wall thickness (p=0.0022), cavity area (p=0.0001), and cardiomyocyte thickness (p=0.0001). Alloxan-diabetic rats demonstrated a reduction in left ventricular (LV) wall, IV septum, and cardiomyocyte thickness, associated with a reduction in LV fractional shortening (p<0.05), and an increase in LViv relaxation time (p < 0.05). Survival rate decreased from 80% in diabetic rats to 40% in elastase-instilled diabetic rats. Conclusions: Alloxan diabetes did not affect RV hypertrophy secondary to chronic emphysema, but induced LV dysfunction. The association of diabetes and emphysema substantially reduced the survival rate, emphasizing the comorbid condition of the coexistence of diabetes and COPD.

Inducing common carotid fusiform aneurysms in rabbit with the porcine pancreatic elastase extravascular digestion method / 中国脑血管病杂志

Objective To investigate the feasibility and effectiveness of inducing rabbit common carotid fusiform aneurysms via the common carotid extravascular digestion method. Methods Sixteen New Zealand white rabbits were randomly assigned into either an experiment group ( n=12 ) or a control group (n=4). Porcine pancreatic elastase 80-400 U were used to incubate and digest 2 to 4 cm segment of artery distal to the origin of right common carotid artery. One week after modeling,intravenous angiography was performed and the length and width of fusiform dilatation of common carotid artery were measured. The fusiform dilated artery was examined with hematoxylin and eosin staining and the vascular morphological changes were observed with scanning electron microscope. Isotonic saline solution was used to incubate common carotid arteries of the 4 New Zealand white rabbits in the control group. After one week,the same method was used to observe the lumen of common carotid artery and intimal changes. Results After the digestion of common carotid artery adventitia,the angiography of 12 New Zealand white rabbits of the experimental group revealed fusiform dilatation of common carotid artery of the 10 model rabbits. The widest diameter of the fusiform artery was 3. 70 ± 0. 32 mm;two rabbits had common carotid artery occlusion. Compared with the control group,the right common carotid artery diameter enlarged significantly in the experimental group (1. 80 ± 0. 16 mm,P<0. 01). The HE staining showed that the lumen widened, adventitia and media reduced. Scanning electron microscope showed intimal inflammatory injury and thrombus attachment. Conclusion Using porcine pancreatic elastase to digest the adventitia of common carotid artery can make fusiform dilatation of common carotid artery in rabbits. Using this method may effectively induce a model of fusiform aneurysm,and it has certain feasibility.

Expression of neutrophil adhesion molecule CD11b and plasma levels of elastase in Patients with anaphylactoid purpura / 中华皮肤科杂志

Objective To explore the expression of neutrophil adhesion molecule CD11b,and plasma level of elastase in patients with anaphylactoid purpura during different clinical phases and their correlation with disease activity.Methods A total of 20 patients with anaphylactoid purpura were recruited into this study,along with 20 normal human controls.Two blood samples were collected from each patients at the first visit(active phase)and after 3～5 weeks of treatment(remission phase).The expression of CD11b was measured by flow cytometry in 12 patients and normal controls,and plasma levels of elastase by ELISA in 20 patients and normal controls.Results Increased CD11b expression and elastase level were noted in patients in active phase compared with those in patients in remission phase(3367.25±434.57 vs 2569.33±411.06.13.98±2.05 vs 4.29±0.80.both P＜0.01).No significant difference was found in CD11b expression between patients in remission phase and normal controls(P＞0.05).while the elastase level was higher in patients in remission phase than in normal controls(4.29±0.80 vs 3.67±0.54.P＜0.05).In active phase of anaphylactoid purpura,the expression of CD11b was positively correlated with the plasma level of elastase(r=0.73,P＜0.01),while no correlation was noticed between them in remission phase(r=0.20,P=0.54).Conclusion Peripheral neutrophils are activated in anaphylactoid purpura,which seems to be more obvious in active phase than in remission phase.

Detection of various component in the trace sample of gingival crevicular fluid / 北京大学学报(医学版)

Objective: To evaluate methods of detecting various component in the trace sample of the gingival crevicular fluid (GCF). Methods: One sample of GCF was collected from four patients with mild or moderate periodontitis. At first, one half (group A)of every sample was measured for interleukin-6 (IL-6) by enzyme-linked immunosorbent assay (ELISA) and then detected for Interleukin-1? (IL-1?) in the same sample .Another half (group B) of the sample was used as control for the measurement of Interleukin-1? (IL-1?). Another sample of GCF was collected from nine patients with abutment and non-abutment because of the distal extension teeth lost resulted from the chronic periodontitis. At first, one half (group C) of the sample was detected for tumor necrosis factor -?(TNF-?) by ELISA and then measured for elastase in the same sample. Another half (group D) of the sample was used as control for the measurement of elastase. Results: There was no significant difference of both the measured value of IL-1? absorbency (group A and B are 0.5?0.4 and 0.5?0.4, respectively, P=0.136)and that of elastase absorbency (group C and D are 1.1?0.6 and 1.1?0.6,respectively, P=0.943) between the original elution and the sample after detection of IL-6 or TNF-? in the test 1 and test 2, respectively. Moreover, the values showed high correlation (r=0.993, P=0.000 in the group A and B; r=0.979, P=0.000 in the group C and D). Conclusion: It is practicable that one sample of GCF can be reused to examine for several components of GCF.

The diagnostic value of serum and fecal pancreatic elastase-1 in patients with pancreatic disease / 대한내과학회지

BACKGROUND: The aims of this study were to evaluate the diagnostic value of pancreatic elastase-1(PE-1) in patients with pancreatic diseases and compare the significance of PE-1 with that of pancreatic exocrine function test by pure pancreatic juice (PPJ) collection. METHODS: For evaluation of PE-1, seventy nine patients with pancreatic diseases were examined. For evaluation of exocrine pancreatic function by PPJ, twenty three patients with Chronic pancreatitis(CP) were examined. PPJ was collected by endoscopic cannulation of main pancreatic duct under the intravenous bolus injection of secretin (0.25 CU/kg body weight) and cholecystokinin (CCK, 40 ng/kg body weight). RESULTS: Pancreatic exocrine functions were significantly decreased in patients with CP showing moderate and severe ductal changes on pancreatogram. The mean concentration of fecal PE-1 was significantly decreased in patients with CP and pancreatic cancer, but not in patients with acute pancreatitis. When we analyzed the PE-1 concentration according to Cambridge classification, the concentration of fecal PE-1 was significantly decreased only in patients with moderate and severe CP. With a cut off of 200 ug fecal PE-1/g, the sensitivity of PE-1 was 25%, 60%, and 100%, respectively, for mild, moderate and severe CP, and the specificity was 88.1%. The mean concentration of serum PE-1 was increased both in patients with acute and chronic pancreatitis, but there was no difference between both group. CONCLUSION: Fecal PE-1 is useful for diagnosis of pancreatic exocrine insufficiency in patients with CP, especially in moderate and severe grade of pancreatic exocrine insufficiency. The diagnostic value of fecal PE-1 was also similar to secretin-CCK test in pancreatic exocrine insufficiency.

Correlation of elastase and ?1-antitrypsin level in gingival crevicular fluid with periodontal inflammation / 实用口腔医学杂志

Objective:To study the correlation of elastase(EA) and ? 1-antitrypsin (? 1-AT) level in gingival crevicular fluid(GCF) of different periodontal status and their roles in periodontal inflammatary pathogenesis. Methods: 62 volunteers aged 45～51 years old were enroled.Their periodental status were examined and grouped into healthy periodontium (H),8 cases,marginal gingivitis (MG),12 cases,mild chronic periodontitis (MCP),20 cases and advanced chronic periodontitis (ACP),22 cases.EA in GCF were measured with a chromogenic low molecular weight substrate reaction and the ? 1-AT with ELISA. Results: Significantly positive correlation was found between GCF-EA activity and clinical periodontal parameters (P