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1.
Brasília; CONITEC; maio 2022.
Non-conventional in Portuguese | LILACS, BRISA | ID: biblio-1368825

ABSTRACT

INTRODUÇÃO: Pacientes com fatores de risco como idade avançada, imunodepressão, obesidade e doenças cardiovasculares têm risco aumentado de internação, intubação e morte. De acordo com dados brasileiros, o risco de morte por Covid-19 aumenta com o número de fatores de risco que o paciente apresenta, sendo igual a 17% em pacientes com 2 fatores de risco e 76% na presença de 8 fatores de risco. Além disso, mesmo aqueles pacientes que sobrevivem a uma internação em terapia intensiva frequentemente enfrentam sequelas e representam alto custo para o sistema público. O medicamento nirmatrelvir associado ao ritonavir têm o objetivo de prevenir internações, complicações e morte. Ele é indicado para pacientes com Covid-19 leve a moderada, não hospitalizados, até 5 dias do início dos sintomas. Apesar dos avanços da vacinação no Brasil, evidências sobre a falha vacinal em idosos e imunodeprimidos destacam a importância da disponibilidade de alternativas terapêuticas para


Subject(s)
Humans , Severity of Illness Index , Ritonavir/therapeutic use , Chymases/antagonists & inhibitors , SARS-CoV-2/drug effects , COVID-19/drug therapy , Unified Health System , Brazil , Cost-Benefit Analysis/economics
2.
Chinese Journal of Medical Genetics ; (6): 449-454, 2014.
Article in Chinese | WPRIM | ID: wpr-291755

ABSTRACT

<p><b>OBJECTIVE</b>To assess the association of tag single nucleotide polymorphisms (tag SNPs) of chymase gene (CMA1) with essential hypertension in Yi population from Yunnan, China.</p><p><b>METHODS</b>A case-control study was carried out. Four tag SNPs(rs1956921, rs1800876, rs5244 and rs1885108) were genotyped in 303 patients with essential hypertension and 312 healthy controls using polymerase chain reaction - restriction fragment length polymorphism(PCR-RFLP) method.</p><p><b>RESULTS</b>No significant difference in genotypic and allelic distributions of the four polymorphisms was detected between the two groups(P>0.05), and the same results existed in the females. The frequencies of rs1956921 C allele and a C-T haplotype constructed with rs1956921 and rs5244 were greater in male patients compared with male controls(P<0.01).</p><p><b>CONCLUSION</b>The rs1956921 C allele of the CMA1 gene and the C-T haplotype constructed with rs1956921 and rs5244 may be risk factors for essential hypertension in ethnic Yi males from Yunnan.</p>


Subject(s)
Adult , Female , Humans , Male , Middle Aged , Alleles , Asian People , Ethnology , Genetics , Blood Pressure , China , Ethnology , Chymases , Genetics , Essential Hypertension , Hypertension , Ethnology , Genetics , Polymorphism, Single Nucleotide
3.
Journal of Forensic Medicine ; (6): 117-121, 2014.
Article in Chinese | WPRIM | ID: wpr-983893

ABSTRACT

Fatal anaphylactic shock is common in forensic practice. However, it is difficult to diagnose for lacking specific pathological and morphologic changes in forensic autopsy. The application of some biochemical indicators is of great significance. This paper reviews the biological characteristics of some biochemical indicators and detection methods. The forensic application, problems and prospects of these indicators are also introduced in details. The stable biochemical indicators, IgE, tryptase and chymase, show great potential and advantages in the identification of fatal anaphylactic shock in forensic medicine.


Subject(s)
Humans , Anaphylaxis/metabolism , Autopsy , Biomarkers , Chymases , Forensic Medicine , Tryptases
4.
Allergy, Asthma & Immunology Research ; : 409-414, 2013.
Article in English | WPRIM | ID: wpr-133311

ABSTRACT

PURPOSE: The mast cell plays a pivotal role in the human immune response. Crosslinking of 2 IgE molecules bound to the high affinity IgE receptor (FcepsilonRI) on the surface of the mast cell results in mast cell degranulation and the release of several proinflammatory mediators. Patients with type-I allergy have increased levels of IgE in the blood compared to healthy individuals. METHODS: In a 6-week culture system of stem cells to human mast cells we investigated the effect of the concentration of IgE. The mast cells were cultured with different concentrations of IgE for the last 10 days of the maturation period. It was observed how the IgE concentration affects the histamine release, FcepsilonRI density on the mast cell surface and the concentration of other mediators. RESULTS: A clear correlation between IgE concentration in culture medium and the release of histamine upon activation was observed. It showed a bell-shaped dose response curve, with maximal response around an IgE-concentration of 250 ng/mL. Furthermore, the sensitivity of the mast cells and surface density of FcepsilonRI on mast cell surface was also influenced by the IgE concentration in the culture medium. CONCLUSIONS: IgE in the culture medium during the last 10 days of mast cell maturation influences the release of the preformed mediator histamine after mast cell activation and the density of FcepsilonRI on the mast cell surface. The release of the de novo synthetized mediator prostaglandin D2 and the expression of chymase and tryptase are not influenced by IgE in culture medium.


Subject(s)
Humans , Chymases , Histamine , Histamine Release , Hygiene Hypothesis , Hypersensitivity , Immunoglobulin E , Mast Cells , Prostaglandin D2 , Stem Cells , Tryptases
5.
Allergy, Asthma & Immunology Research ; : 409-414, 2013.
Article in English | WPRIM | ID: wpr-133310

ABSTRACT

PURPOSE: The mast cell plays a pivotal role in the human immune response. Crosslinking of 2 IgE molecules bound to the high affinity IgE receptor (FcepsilonRI) on the surface of the mast cell results in mast cell degranulation and the release of several proinflammatory mediators. Patients with type-I allergy have increased levels of IgE in the blood compared to healthy individuals. METHODS: In a 6-week culture system of stem cells to human mast cells we investigated the effect of the concentration of IgE. The mast cells were cultured with different concentrations of IgE for the last 10 days of the maturation period. It was observed how the IgE concentration affects the histamine release, FcepsilonRI density on the mast cell surface and the concentration of other mediators. RESULTS: A clear correlation between IgE concentration in culture medium and the release of histamine upon activation was observed. It showed a bell-shaped dose response curve, with maximal response around an IgE-concentration of 250 ng/mL. Furthermore, the sensitivity of the mast cells and surface density of FcepsilonRI on mast cell surface was also influenced by the IgE concentration in the culture medium. CONCLUSIONS: IgE in the culture medium during the last 10 days of mast cell maturation influences the release of the preformed mediator histamine after mast cell activation and the density of FcepsilonRI on the mast cell surface. The release of the de novo synthetized mediator prostaglandin D2 and the expression of chymase and tryptase are not influenced by IgE in culture medium.


Subject(s)
Humans , Chymases , Histamine , Histamine Release , Hygiene Hypothesis , Hypersensitivity , Immunoglobulin E , Mast Cells , Prostaglandin D2 , Stem Cells , Tryptases
6.
Journal of Forensic Medicine ; (6): 167-171, 2012.
Article in Chinese | WPRIM | ID: wpr-983729

ABSTRACT

OBJECTIVE@#To explore the application value of serum total IgE, tryptase and chymase in the identification of death caused by drug anaphylactic shock.@*METHODS@#The general information from 235 cases of non-drug anaphylactic shock and 32 cases of drug anaphylactic shock were analyzed. The serum IgE level had been detected in the cases. Ten cases caused by coronary disease and 10 cases caused by sudden manhood death syndrome were selected from non-drug anaphylactic shock cases for the control group. Expressions of tryptase and chymase in the lung and heart were detected using immunohistochemistry method. The number and IOD of positive mast cells were counted.@*RESULTS@#In the drug anaphylactic shock group, the IgE value of 18 samples (56.25%) was significantly higher than the normal upper limit of 120 IU/mL. In the non-drug anaphylactic shock group, the IgE value of 67 samples (28.51%) was higher than 120 IU/mL. The expressions of tryptase and chymase were significantly increased in lung and myocardial tissue in drug anaphylactic shock group (P < 0.05).@*CONCLUSION@#Tryptase and chymase are more superior than that of the serum total IgE in the diagnosis of death caused by drug anaphylactic shock, and are more suitable in forensic practice.


Subject(s)
Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Young Adult , Anaphylaxis/pathology , Autopsy , Case-Control Studies , Cause of Death , Chymases/metabolism , Death, Sudden, Cardiac/pathology , Drug Hypersensitivity , Forensic Pathology , Immunoglobulin E/blood , Immunohistochemistry , Lung/pathology , Myocardium/pathology , Tryptases/metabolism
7.
Acta Pharmaceutica Sinica ; (12): 168-173, 2012.
Article in Chinese | WPRIM | ID: wpr-323063

ABSTRACT

To screen potential hamster chymase 2 inhibitors, a high-throughput screening (HTS) model was established. Recombinant hamster chymase 2 with active form was cloned and expressed in E. coli. The HTS model with total volume of 50 microL in 384-well microplate was based on fluorescence analysis and was proved sensitive as well as specific (Z' = 0.84). A total of 40 080 samples (including 28 060 compounds and 12 020 natural products) were screened, and 613 samples with inhibition greater than 90% were selected for further rescreening. Finally, compounds J16647 and J16648 were identified with high inhibitory activity on chymase 2, and whose IC50 values were 0.823 and 0.690 micromol x L(-1), respectively.


Subject(s)
Animals , Cricetinae , Rats , Chymases , Enzyme Inhibitors , Pharmacology , Escherichia coli , Metabolism , High-Throughput Screening Assays , Methods , Inhibitory Concentration 50 , Structure-Activity Relationship
8.
Diabetes & Metabolism Journal ; : 255-261, 2012.
Article in English | WPRIM | ID: wpr-192550

ABSTRACT

Oxidative stress has been paid increasing attention to as an important causative factor for diabetic vascular complications. Among possible various sources, accumulating evidence has indicated that NAD(P)H oxidase may be the most important source for reactive oxygen species production in diabetic vascular tissues. The mechanisms underlying activation and up-regulation of NAD(P)H oxidase has been supposed to be mediated by high glucose-induced protein kinase C (PKC) activation. In this review article, activation of local renin-angiotensin II system induced by chymase activation is also shown to amplify such a PKC-dependent activation of NAD(P)H oxidase. Additionally, human evidence showing the beneficial effect of antioxidants on diabetic vascular complications. Bilirubin has been recognized as a strong endogenous antioxidant. Here markedly lower prevalence of vascular complications is shown in diabetic patients with Gilbert syndrome, a congenital hyperbilirubinemia, as well as reduced markers of oxidative stress and inflammation. Lastly, statin, angiotensin II receptor blocker, chymase inhibitor, bilirubin and biliverdin, PKC beta isoform inhibitor, and glucagon-like peptide-1 analog, are shown to serve as antioxidants and have some beneficial effect on diabetic vascular complications, via inhibiting PKC-NAD(P)H oxidase activation, supporting the notion that this mechanism may be an effective therapeutic target for preventing diabetic vascular complications.


Subject(s)
Humans , Angiotensin II , Antioxidants , Bilirubin , Biliverdine , Chymases , Diabetic Angiopathies , Gilbert Disease , Glucagon-Like Peptide 1 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Hyperbilirubinemia , Inflammation , NADPH Oxidases , Oxidative Stress , Oxidoreductases , Prevalence , Protein Kinase C , Reactive Oxygen Species , Receptors, Angiotensin , Up-Regulation
9.
Braz. j. med. biol. res ; 44(9): 914-919, Sept. 2011. ilus
Article in English | LILACS | ID: lil-599662

ABSTRACT

The classical renin-angiotensin system (RAS) consists of enzymes and peptides that regulate blood pressure and electrolyte and fluid homeostasis. Angiotensin II (Ang II) is one of the most important and extensively studied components of the RAS. The beneficial effects of angiotensin converting enzyme (ACE) inhibitors in the treatment of hypertension and heart failure, among other diseases, are well known. However, it has been reported that patients chronically treated with effective doses of these inhibitors do not show suppression of Ang II formation, suggesting the involvement of pathways alternative to ACE in the generation of Ang II. Moreover, the finding that the concentration of Ang II is preserved in the kidney, heart and lungs of mice with an ACE deletion indicates the important role of alternative pathways under basal conditions to maintain the levels of Ang II. Our group has characterized the serine protease elastase-2 as an alternative pathway for Ang II generation from Ang I in rats. A role for elastase-2 in the cardiovascular system was suggested by studies performed in heart and conductance and resistance vessels of normotensive and spontaneously hypertensive rats. This mini-review will highlight the pharmacological aspects of the RAS, emphasizing the role of elastase-2, an alternative pathway for Ang II generation.


Subject(s)
Animals , Humans , Mice , Rats , Angiotensin II/biosynthesis , Cardiovascular System/metabolism , Renin-Angiotensin System/physiology , Serine Endopeptidases/physiology , Angiotensin I/biosynthesis , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Chymases/metabolism , Serine Endopeptidases/pharmacology
10.
Chinese Journal of Contemporary Pediatrics ; (12): 814-816, 2011.
Article in Chinese | WPRIM | ID: wpr-272462

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the roles of plasma mast cell carboxypeptidase and chymase in the diagnosis of allergic diseases by measuring the contents of both in children.</p><p><b>METHODS</b>A total of 59 children with allergic diseases and 53 healthy children were recruited into the study. Plasma levels of mast cell carboxypeptidase and chymase were measured using ELISA.</p><p><b>RESULTS</b>The plasma levels of mast cell carboxypeptidase and chymase in children with allergic children were 1.089 ± 0.752 ng/mL and 0.905(0.375-2.318) ng/mL, respectively, which were significantly higher than those in healthy children [0.593 ± 0.380 ng/mL and 0.454 (0.097-1.077) ng/mL respectively; P<0.05]. There was a significantly positive correlation between plasma mast cell carboxypeptidase and chymase levels in children with allergic diseases (r=0.684, P<0.01).</p><p><b>CONCLUSIONS</b>Plasma levels of mast cell carboxypeptidase and chymase increase in children with allergic diseases, suggesting that mast cell carboxypeptidase and chymase may serve as the indexes for the diagnosis of allergic diseases.</p>


Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Carboxypeptidases , Blood , Chymases , Blood , Hypersensitivity , Diagnosis , Mast Cells
11.
Journal of Forensic Medicine ; (6): 164-167, 2009.
Article in Chinese | WPRIM | ID: wpr-983464

ABSTRACT

OBJECTIVE@#To explore the expression of tryptase and chymase in human lung tissue of anaphylactic shock and its value for forensic medicine.@*METHODS@#With ten carbon monoxide poisoning cases as control group, the levels of tryptase and chymase were observed by immunofluorescence and analyzed using the Image Analyze and the Image-pro plus 5.0.2. The positive mast cells were counted and the levels of the tryptase and chymase were calculated respectively.@*RESULTS@#There was a statistically significant difference (P < 0.05) for the tryptase and chymase concentrations in the lung tissue between the anaphylactic shock group and the control group.@*CONCLUSION@#The levels of the tryptase and the chymase expression are greatly increased in human lung tissue of anaphylactic shock, which may provide the morphological evidence and reference for the diagnosis of anaphylactic shock in forensic practice.


Subject(s)
Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Young Adult , Anaphylaxis/pathology , Cadaver , Carbon Monoxide Poisoning/pathology , Chymases/metabolism , Fluoroimmunoassay/methods , Forensic Pathology , Lung/pathology , Mast Cells/enzymology , Staining and Labeling , Tryptases/metabolism
12.
Korean Diabetes Journal ; : 204-214, 2008.
Article in Korean | WPRIM | ID: wpr-229165

ABSTRACT

BACKGROUND: The 26S ubiquitin-proteasome system (UPS) is a principal proteolytic pathway of intracellular molecules regulating apoptosis, cell cycle, cell proliferation or differentiation, inflammation and etc. The recent study suggests that the rs1048990 (C/G) polymorphism of the proteasome subunit alpha type 6 (PSMA6) gene is associated with the increase of the risk of myocardial infarction by the dysregulation of IkappaB degradation. We hypothesized that 26S UPS is important in the development of insulin resistance and type 2 diabetes (T2DM) by controlling the degradation of IkappaB and insulin receptor substances as a substrate. We therefore investigated whether the rs1048990 (C/G) polymorphism of PSMA6 gene and the rs2230087 (G/A) polymorphism of proteasome subunit beta type 5 gene (PSMB5), that is chymotrypsin-like protease determining the rate of proteolysis, are associated with susceptibility to T2DM in Korean subjects. METHODS: We examined the polymorphisms of these genes in 309 diabetic subjects and 170 non-diabetic controls. The polymorphisms of rs1048990 (C/G) and rs2230087 (G/A) were genotyped by real-time PCR. RESULTS: The frequency of the G allele of rs1048990 (C/G) and the A allele of rs2230087 (G/A) polymorphisms was significantly higher in diabetic patients (28% and 13%) compared to that in controls (13% and 1%; P = 0.000 and P = 0.000, respectively). Logistic regression analysis of the rs1048990 (C/G) polymorphism showed that the odds ratio (OR) (adjusted for age, smoking, waist circumference, fasting plasma glucose, systolic blood pressure, HDL-C, triglyceride, and total cholesterol) was 3.93 (95% confidence interval [CI], 2.35-6.59; P = 0.000) for the G allele and 5.09 (95% CI, 2.71-9.57; P = 0.000) for CG and GG genotype when compared with the CC genotype. Logistic regression analysis of the rs2230087 (G/A) polymorphism showed that the adjusted OR was 5.70 (95% CI, 1.63-19.98; P = 0.007) for the A allele and 6.08 (95% CI, 1.66-22.29; P = 0.006) for GA and AA genotype when compared with the GG genotype. In multiple logistic regression analysis with T2DM as the independent Variable rs1048990 (C/G) and rs2230087 (G/A) polymorphisms were the predictor for T2DM. CONCLUSION: We suggest that the G allele of rs1048990 (C/G) polymorphism and the A allele of rs2230087 (G/A) polymorphism may be genetic risk factor to type 2 diabetes mellitus in Korean subjects.


Subject(s)
Humans , Alleles , Apoptosis , Blood Pressure , Cell Cycle , Cell Proliferation , Chymases , Diabetes Mellitus, Type 2 , Fasting , Genotype , Glucose , Inflammation , Insulin Resistance , Logistic Models , Myocardial Infarction , Odds Ratio , Plasma , Proteasome Endopeptidase Complex , Proteolysis , Receptor, Insulin , Risk Factors , Smoke , Smoking , Waist Circumference
13.
Journal of Southern Medical University ; (12): 373-376, 2008.
Article in Chinese | WPRIM | ID: wpr-293373

ABSTRACT

<p><b>OBJECTIVE</b>To analyze alterations in the gene expression profiles of Velcade-treated K562 cells using bioinformatics methods.</p><p><b>METHODS</b>The total RNAs of Velcade-treated and control K562 cells were amplified and labeled with fluorescent dyes. The labeled RNAs were hybridized to Agilent Human 1A Microarray, and the raw expression data were processed with Agilent Feature Extraction Software. GeneSifter and GATHER were used for data analysis of the differentially expressed genes to perform gene ontology classification, KEGG pathway analysis, functional protein association network construction and literature mining.</p><p><b>RESULTS</b>Totally 228 differentially expressed genes were identified in the Velcade-treated K562 cells. including 84 up-regulated and 144 down-regulated genes. Chymase 1 gene had the greatest down-regulation by 10.80 folds (log ratio), and interferon alpha-21 gene was also down-regulated by 2.31 folds. Gene ontology classification suggested enhanced aging and leukocyte activity. KEGG pathway analysis showed significant impact of Velcade on JAK-STAT signaling pathway, cytotoxicity mediated by natural killer cells, and antigen processing and presentation pathways. Protein-protein interaction analysis revealed that ubiquitin-dependent protein catabolism, antigen presentation and immune response, as well as JAK-STAT signaling pathway were the major elements of the protein network. Literature mining showed that the differentially expressed genes were strongly associated with terms such as leukemia, apoptosis, cell cycle, proteasome, inhibitor, aging and IkappaB, etc.</p><p><b>CONCLUSIONS</b>Velcade may inhibit the cell survival pathways such as NF-kappaB and JAK-STAT signaling pathways to enhance the cytotoxicity and inducing tumor cell apoptosis. Velcade might also be involved in antigen processing and presentation, immune response and inflammation. Chymase 1 gene is probably the key target of Velcade.</p>


Subject(s)
Humans , Antineoplastic Agents , Pharmacology , Apoptosis , Boronic Acids , Pharmacology , Bortezomib , Chymases , Genetics , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , K562 Cells , Oligonucleotide Array Sequence Analysis , Methods , Pyrazines , Pharmacology
14.
Chinese Medical Journal ; (24): 1886-1892, 2005.
Article in English | WPRIM | ID: wpr-282868

ABSTRACT

<p><b>BACKGROUND</b>Little is known about the role of dual angiotensin II forming pathways during heart failure. In the present study, the changes of chymase and angiotensin converting enzyme (ACE) expressions in the failing hearts of hamsters were analysed.</p><p><b>METHODS</b>Heart failure was induced by ligation of left anterior descending branch of the coronary artery. Chymase, ACE and angiotensin II type 1 receptor (AT1R) mRNA levels were analysed by reverse transcription polymerase chain reaction (RT-PCR). The activities of chymase and ACE were determined by radioimmunoassay (RIA). Myocardial collagen fibre analysis was performed under optical microscope.</p><p><b>RESULTS</b>Left ventricular systolic pressure (LVSP) and maximum left ventricular developed pressure increase rate (dp/dtmax, mmHg/s) gradually moved lower at 2, 3, 4 and 8 weeks after operation. On the other hand, left ventricular end-diastolic pressure (LVEDP) increased gradually after operation. Compared with the control group (3.55 +/- 0.06, 4.79 +/- 0.70), the heart weight/body weight ratio in operation group had increased significantly at 4 weeks and 8 weeks (4.28 +/- 0.43, 6.17 +/- 0.73) (P < 0.01). Collagen staining showed that the quantity of myocardial collagen fibre increased significantly in the operation group. RT-PCR showed that the chymase mRNA level in the operation group was consistently greater than that in the control group. AT1R mRNA level was also increased significantly at 3 weeks and 4 weeks, both being 1.3 times that of the control group (P < 0.01), whereas ACE mRNA level was not changed. Higher activity of chymase was detected in operation group, being 4, 8, 13 and 19 times that of the control group at 2, 3, 4 and 8 weeks (P < 0.01), respectively. ACE activity was also significantly higher at the same time, being 7, 10, 10 and 3.5 times that of the control (P < 0.01). Angiotensin II (Ang II) level in operation group increased significantly, being 2.5, 2.7, 3.5 and 2 times that of the control group at 2, 3, 4 and 8 weeks, respectively (P < 0.01).</p><p><b>CONCLUSIONS</b>A dual Ang II forming pathway from both ACE and chymase in the hamster hearts plays an important role during the development of heart failure. At the decompensatory stage, the reduction of AngII level may be associated with the decrease of ACE activity.</p>


Subject(s)
Animals , Cricetinae , Male , Angiotensin II , Body Weight , Chymases , Heart Failure , Metabolism , Myocardium , Metabolism , Peptidyl-Dipeptidase A , Genetics , Physiology , RNA, Messenger , Receptor, Angiotensin, Type 1 , Genetics , Reverse Transcriptase Polymerase Chain Reaction , Serine Endopeptidases , Genetics , Physiology , Ventricular Function, Left
15.
Chinese Journal of Epidemiology ; (12): 756-760, 2004.
Article in Chinese | WPRIM | ID: wpr-247480

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the association between insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene and the A/B polymorphism of the chymase (CMA) gene with regression of left ventricular hypertrophy (LVH) in patients with essential hypertension and left ventricular hypertrophy. The study subjects had been participants in along-term trial of therapy with an ACE inhibitor.</p><p><b>METHODS</b>Follow-up data of 157 patients with essential hypertension and left ventricular hypertrophy were collected. DNA fragments of ACE gene and CMA gene were amplified by PCR and analysed by RFLP. LVDd, IVST and LVPWT were measured by Ultrasonic Cardiogram (UCG).</p><p><b>RESULTS</b>(1) When long-term treatment with Benazepril was carried out, the blood pressure was markedly decreased and the heart rate was maintained steadily. (2) Regression of left ventricular hypertrophy was improved. (3) The magnitudes of regression of LVM and LVMI during therapy were greater in the DD group than in the II and ID group. No significant differences of other indices were found in the different genotype groups of ACE. (4) No significant differences of all indices were found in the different genotype groups of CMA. (5) No interaction appeared between the genotypes of the ACE and the genotypes of the CMA.</p><p><b>CONCLUSION</b>Hypertensive patients with DD genotype were more likely to have regression of left ventricular hypertrophy when treated with ACE inhibitors than patients with other ACE genotypes. No evidence was found to support an association between CMA genotype and regression of LVH in those patients.</p>


Subject(s)
Adult , Female , Humans , Male , Angiotensin-Converting Enzyme Inhibitors , Therapeutic Uses , Benzazepines , Therapeutic Uses , Chymases , Follow-Up Studies , Genotype , Hypertension , Drug Therapy , Genetics , Hypertrophy, Left Ventricular , Drug Therapy , Genetics , Peptidyl-Dipeptidase A , Genetics , Polymerase Chain Reaction , Polymorphism, Genetic , Polymorphism, Restriction Fragment Length , Serine Endopeptidases , Genetics
16.
Korean Journal of Pediatrics ; : 1137-1141, 2004.
Article in Korean | WPRIM | ID: wpr-13261

ABSTRACT

Mast cells play a key role in elicitation of the early-phase and late-phase IgE-mediated allergic inflammatory reactions. Mast cells are derived from pluripotent stem cells from the bone marrow. These cells migrate through circulation into connective tissues and mucosal surfaces where they mature. On the cell surfaces, mast cells have high affinity IgE receptor(FcepsilonRI), which react with specific IgE to secrete preformed and newly synthesized mediators within minutes or over a period of hours. For human mast cells, two subtypes have been recognized by the distribution of granular neutral proteases. TC-type mast cells(MCTC) contain tryptase together with chymase, cathepsin-G, and carboxypeptidase, while T-type mast cells(MCT) contain tryptase only. They also produce Th2- type cytokines to persist chronic allergic inflammation in local tissues. Mast cells have been widely studied in the context of allergic reactions and parasite infections, but there is growing evidence that they participate in innate immunity, wound healing, fibrosis, remodelling and autoimmune disease. Much research works are expected to be underwent by the development of in vitro culture system of human mast cells in addition to mast cells obtained from animals, human biopsy or cell lines. In conclusion, it is clear that mast cells are pleiotropic, multipotential and complex. More detailed research remains to be needed for further understanding of biology of mast cells and it will be helpful to develop novel treatment modality in allergic inflammation.


Subject(s)
Animals , Humans , Autoimmune Diseases , Biology , Biopsy , Bone Marrow , Cell Line , Chymases , Connective Tissue , Cytokines , Fibrosis , Hypersensitivity , Immunity, Innate , Immunoglobulin E , Inflammation , Mast Cells , Parasites , Peptide Hydrolases , Pluripotent Stem Cells , Tryptases , Wound Healing
17.
Journal of Veterinary Science ; : 221-226, 2004.
Article in English | WPRIM | ID: wpr-161384

ABSTRACT

Mucosal mast cell-derived chondroitin sulphates (sulphated proteoglycans) were assayed in gut washings and homogenate of FcRgamma-knockout (KO) and wild-type (WT) C57BL/6 mice challenged with Strongyloides venezuelensis in order to assess their possible role in secondary immunity against enteric nematodes. Groups of immune KO and WT mice were challenged by oral gavage with 300 infective larvae (L3). Establishment of infection was assessed by daily faecal analysis to determine the number of eggs per gram of faeces (EPG) and by adult worm recovery on days 5 and 13 post challenge. Mucosal mast cell (MMC) counts were done on days 5 and 13 post challenge while MMC-derived chondroitin sulphates in gut washings (days 1 and 5) and homogenate (day 8) were assayed by high performance liquid chromatography (HPLC). Results showed that patent infection occurred in challenged KO but not WT mice despite significantly higher mastocytosis in jejunal sections of KO than WT mice (p<0.001). Similarly but against prediction, significantly higher concentration of MMC-derived chondroitin sulphates was observed in gut homogenate of KO than WT mice (p<0.05). In contrast, significantly higher concentration of chondroitin sulphates was observed in gut washings of WT than KO mice (p<0.05). These results suggest that MMC in KO mice failed to release sufficient amount of sulphated proteoglycans into the gut lumen as did the WT mice, which may have been part of the hostile environment that prevented the establishment in and eventual expulsion of adult S. venezuelensis from the gut of WT mice following challenge.


Subject(s)
Animals , Male , Mice , Cell Count/veterinary , Chondroitin Sulfates/immunology , Chymases , Feces/parasitology , Intestinal Diseases, Parasitic/immunology , Intestinal Mucosa/cytology , Jejunum/cytology , Mast Cells/immunology , Mice, Inbred C57BL , Mice, Knockout , Parasite Egg Count/veterinary , Receptors, IgG/immunology , Serine Endopeptidases/blood , Specific Pathogen-Free Organisms , Strongyloides/immunology , Strongyloidiasis/immunology
18.
Korean Journal of Pathology ; : 306-313, 2001.
Article in Korean | WPRIM | ID: wpr-80857

ABSTRACT

BACKGROUND: It has been suggested that mast cells are involved in the tumor growth and progression by production of a variety of enzymes and growth factors. They were studied in the 10-dimethyl-1,2 benzanthracene (DMBA)-induced rat mammary tumors, and evaluated in relation with the production of tryptase, chymase, and matrix metalloproteinase (MMP)-2 and MMP-9. METHODS: Preneoplastic and neoplastic breast tissues of Sprague-Dawley female rats were obtained every week after DMBA treatment for 12 weeks. Toluidine blue stain was used for the identification of mast cells. Mast cell tryptase was studied by immunohistochemistry, and chymase by esterase stain. MMP-2 and MMP-9 were measured by Western blotting. RESULTS: The numbers of mast cells in breast cancers were higher than in preneoplastic tissues, and there was a positive correlation between the numbers of tryptase-positive cells and the tumor size. MMP-9 quantity was correlated with the numbers of toluidine blue and chymase positive cells, but not with tryptase-positive cells and tumor size. Both active and inactive forms of MMP-2 and MMP-9 were identified in zymogram. CONCLUSIONS: The mast cells are increased in the DMBA-induced breast cancers, and their tryptase and chymase may play a role in tumor progression with or without participation of MMP-2 and MMP-9.


Subject(s)
Animals , Female , Humans , Rats , 9,10-Dimethyl-1,2-benzanthracene , Blotting, Western , Breast , Chymases , Immunohistochemistry , Intercellular Signaling Peptides and Proteins , Mast Cells , Rats, Sprague-Dawley , Tolonium Chloride , Tryptases
19.
Journal of the Medical Research Institute-Alexandria University. 1998; 19 (1 Supp.): 145-153
in English | IMEMR | ID: emr-105117

ABSTRACT

Inspite of the modem and sophisticated tools for the immunophenotyping of acute leukemias, yet there are still simpler methods for initial categorization of leukamias into lymphoblastic and non lymphoblastic. The aim of the present study was to identify mast cell chymase as a marker of acute myeloblastic leukemia since they originate from a common progenitor cell. Bone marrow spiration smears from leukemic patients and control were stained for chymase. The normal control had weak positive reaction, the acute lymphoblastic leukemia had negative reactions while in patients with acute myeloblastic leukemia, the chymase reaction was strikingly positive and positivity correlated well with the basophilic count in the peripheral blood and bone marrow smears. A very strong reaction was seen in patients with myeloid blast crisis and in those who were resistant to induction chemotherapy. Therefore, the chymase identification method is a very cheap and convenient tool for the cytochemical diagnosis of acute myeloblastic leukemia


Subject(s)
Humans , Male , Female , Chymases/blood , Mast Cells/metabolism , Bone Marrow Cells/cytology , Blast Crisis , Basophils/cytology
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