贝氏柯克斯体被单核细胞吞噬及其在单核细胞内生长的初步研究

目的探讨贝氏柯克斯体被单核细胞吞噬及其在单核细胞内生长的规律。方法将泛影葡胺梯度超速离心纯化的I相贝氏柯克斯体(强毒株)与体外培养人单核细胞(THP-1)相互作用,用免疫荧光染色和显微镜检查单核细胞内贝氏柯克斯体。用Gamma射线灭活贝氏柯克斯体作平行实验。结果在4 h内分析单核细胞的吞噬作用,发现单核细胞内灭活贝氏柯克斯体的数量迅速增加,而活立克次体的数量无明显变化。在第1-6d的实验周期内,单核细胞内灭活贝氏柯克斯体数逐渐减少,第5d近于完全消失;而活贝氏柯克斯体的数量从第4d开始逐渐增加。结论单核细胞吞噬活贝氏柯克斯体的效率明显低于对灭活贝氏柯克斯体的吞噬;活贝氏柯克斯体可以在人单核细胞内缓慢生长繁殖,而灭活贝氏柯克斯体则在单核细胞内逐渐被清除。     

Superoxide generation by human monocytes and macrophages.

Intracellular and extracellular superoxide (O2.-) generation by human monocytes and macrophages was quantitated by the nitroblue tetrazolium (NBT) reduction method. Human monocytes reduced 4.4 +/- 0.9 nmoles/10(6) cells/15 minutes with an increase to 12.4 +/- 1.3 during phagocytosis of zymosan. Based on inhibition by superoxide dismutase, superoxide generation of these cells was 1.8 +/- 0.9 nmoles in the resting state and 16.8 +/- 2.8 nmoles with zymosan phagocytosis. Human macrophages obtained by thoracentesis had comparable levels of NBT reduction and O2.-generation. Monocytes from a patient with chronic granulomatous disease demonstrated no increment in O2.-production during phagocytosis. Thus, human monocytes and macrophages appear capable of generating substantial amounts of O2.-during phagocytosis which may play an important role in bactericidal and other cell functions.     

Monocyte Function in Normal Adults

Human blood monocytes were separated by centrifugation over modified Ficoll-Hypaque and by this one-step procedure relatively high proportions (mean 54%) and yields of monocytes were obtained. Yields ranged from 0.22 times 10⁹ to 0.98 times 10⁹/1 of blood and averaged 2 1/2 times the theoretical maximum yield calculated from the blood leucocyte and differential counts. A range of tests of monocyte function are described, namely, adhesion to glass, spreading on glass, chemotaxis under agarose and phagocytosis and killing of Candida albicans. These tests are generally simpler to perform than similar tests previously described and give very reproducible results which compare well with those reported by others. Normal values from 35 healthy Chinese adults are recorded.     

Interferon-β regulates proresolving lipids to promote the resolution of acute airway inflammation

Aberrant immune responses, including hyperresponsiveness to Toll-like receptor (TLR) ligands, underlie acute respiratory distress syndrome (ARDS). Type I interferons confer antiviral activities and could also regulate the inflammatory response, whereas little is known about their actions to resolve aberrant inflammation. Here we report that interferon-β (IFN-β) exerts partially overlapping, but also cooperative actions with aspirin-triggered 15-epi-lipoxin A₄ (15-epi-LXA₄) and 17-epi-resolvin D1 to counter TLR9-generated cues to regulate neutrophil apoptosis and phagocytosis in human neutrophils. In mice, TLR9 activation impairs bacterial clearance, prolongs Escherichia coli–evoked lung injury, and suppresses production of IFN-β and the proresolving lipid mediators 15-epi-LXA₄ and resolvin D1 (RvD1) in the lung. Neutralization of endogenous IFN-β delays pulmonary clearance of E. coli and aggravates mucosal injury. Conversely, treatment of mice with IFN-β accelerates clearance of bacteria, restores neutrophil phagocytosis, promotes neutrophil apoptosis and efferocytosis, and accelerates resolution of airway inflammation with concomitant increases in 15-epi-LXA₄ and RvD1 production in the lungs. Pharmacological blockade of the lipoxin receptor ALX/FPR2 partially prevents IFN-β–mediated resolution. These findings point to a pivotal role of IFN-β in orchestrating timely resolution of neutrophil and TLR9 activation–driven airway inflammation and uncover an IFN-β–initiated resolution program, activation of an ALX/FPR2-centered, proresolving lipids-mediated circuit, for ARDS.

Acute respiratory distress syndrome (ARDS) is a common syndrome associated with high mortality in patients admitted to intensive care units (1). ARDS is characterized by diffuse alveolar damage that develops in patients with known risk factors, most commonly pneumonia, sepsis, or trauma (2, 3). The initial alveolar damage leads to recruitment of neutrophils and monocytes, which further aggravate injury (3). Treatment of the underlying cause and lung-protective ventilation are the main elements of supportive therapy (4, 5). Importantly, no therapies are available to resolve the aberrant immune responses underlying ARDS.Type I interferons, IFN-α and IFN-β, are well established to confer antiviral activities to host cells and could also regulate the inflammatory response. A delayed type I interferon response triggers the generation of proinflammatory cytokines and facilitates the recruitment of monocytes to the lung, resulting in lethal pneumonia in mice infected with SARS-CoV-1 (6) or SARS-CoV-2 (7). Type I interferons break TNF-induced tolerance to Toll-like receptor (TLR) signals on monocytes/macrophages, rendering them hyperresponsive to additional TLR signals concurrent with inflammatory activation (8). For instance, bacterial DNA (CpG DNA) or mitochondrial DNA through TLR9 impairs neutrophil phagocytosis, delays neutrophil apoptosis, and perpetuates inflammation (9, 10). In contrast, IFN-β protects against lethal polymicrobial sepsis through inhibiting IL-1 production and/or induction of IL-10 (11–13). IFN-β produced by macrophages during resolution of bacterial pneumonia facilitates removal of neutrophils from inflamed tissues and reprograms macrophages to a proresolving phenotype, thereby driving inflammatory resolution in mice (14). However, the underlying mechanisms are incompletely understood; albeit these would be essential for implementing precision treatment with IFN-β.Resolution of inflammation is an active process governed by specialized proresolving lipid and protein mediators (SPMs) (15–19). These mediators converge on select receptors, including the pleiotropic lipoxin A₄ receptor/formyl peptide receptor 2 (ALX/FPR2) (20). ALX/FPR2 plays critical roles in host defense and orchestrating inflammatory resolution (20–23). ALX/FPR2 binds multiple lipid ligands, including aspirin-triggered 15-epi-lipoxin A₄ (15-epi-LXA₄) and 17-epi-resolvin D1 (17-epi-RvD1), generated within the inflammatory microenvironment (17, 18). SPMs inhibit neutrophil recruitment, promote neutrophil apoptosis and efferocytosis, and facilitate tissue repair and return to homeostasis (17, 18, 24). Activation of ALX/FPR2 with 15-epi-LXA₄ or 17-epi-RvD1 counters TLR9-generated cues, restores impaired neutrophil function, and enhances timely resolution of airway bacterial infections (9). Since resolution of inflammation is skewed toward a proresolving lipid profile (18, 25, 26), we investigated whether IFN-β can modulate ALX/FPR2-based resolution mechanisms. Here, we report that IFN-β exerts partially overlapping, but also cooperative actions with 17-epi-RvD1 to counter TLR9-generated signals to regulate neutrophil phagocytosis and apoptosis in vitro. In mice, IFN-β facilitates clearance of bacteria, neutrophil apoptosis and efferocytosis, and promotes the resolution of acute airway inflammation, in part, by stimulating generation of proresolving lipids and activation of ALX/FPR2-centered proresolving circuits. Our results uncover a hitherto unrecognized effector mechanism by which IFN-β may facilitate resolution of ARDS.     

Plasmodium falciparum malaria blood stage parasites preferentially inhibit macrophages with high phagocytic activity

Exposure to malaria blood stage antigens results in several defects of macrophages/monocytes one of which is an irreversible reduction of phagocytic activity. In the present study we analysed phagocytic activity of subpopulations of human monocyte-derived-macrophages (MDM) based on the capacity of individual cells to ingest FITC-labelled microbeads. The results demonstrate that malaria infection affected predominantly MDM subpopulations with high level of phagocytosis. This population decreased during parasitaemia, however, during recovery from the infection the highly phagocytic cells replaced the damaged cells. The exposure of MDM cultures to blood stage antigens showed that the highly active macrophages from persons with active malaria infection decreased further, while the population increased during recovery. Furthermore, we observed that while ingestion of a few parasitized RBC (3 schizonts) stimulated phagocytosis, larger amounts or longer exposure periods eventually paralysed the entire phagocytic system. Accordingly, by selectively blocking actively phagocytizing macrophages, the malaria parasite prevents both specific and non-specific immune responses, which are initiated by macrophages as phagocytes and professional antigen presenting cells.     

Inflammatory monocytes and Fcγ receptor IV on osteoclasts are critical for bone destruction during inflammatory arthritis in mice

Destruction of bone tissue by osteoclasts represents a severe pathological phenotype during inflammatory arthritis and results in joint pain and bone malformations. Previous studies have established the essential role of cytokines including TNFα and receptor–ligand interactions, such as the receptor activator of nuclear factor-kappa B–receptor activator of nuclear factor-kappa B ligand interaction for osteoclast formation during joint inflammation. Moreover, autoantibodies contribute to joint inflammation in inflammatory arthritis by triggering cellular fragment crystallizable (Fc)γ receptors (FcγR), resulting in the release of proinflammatory cytokines and chemokines essential for recruitment and activation of innate immune effector cells. In contrast, little is known about the expression pattern and function of different FcγRs during osteoclast differentiation. This would allow osteoclasts to directly interact with autoantibody immune complexes, rather than being influenced indirectly via proinflammatory cytokines released upon immune complex binding to other FcγR-expressing innate immune cells. To address this question, we studied FcγR expression and function on osteoclasts during the steady state and during acute joint inflammation in a model of inflammatory arthritis. Our results suggest that osteoclastogenesis is directly influenced by IgG autoantibody binding to select activating FcγRs on immature osteoclasts, resulting in enhanced osteoclast generation and, ultimately, bone destruction.     

Association between serum cystatin C, monocytes and other inflammatory markers

Background: Cystatin C is a marker of renal function that appears to be associated with inflammation. The aim of the present study was to investigate whether there is any relationship between cystatin C, total and differential leukocyte count and other inflammatory markers. Methods: Cystatin C, creatinine, high sensitivity C‐reactive protein (hs‐CRP), haptoglobin, ferritin, serum albumin, glucose, total cholesterol, HDL and triglycerides together with total and differential leukocyte count were determined in 490 adults (46 ± 16 years, 40% men) who underwent a typical health examination. Glomerular filtration rate was estimated by the simplified Modification of Diet in Renal Disease formula. Anthropometric and lifestyle characteristics were also recorded. Results: After adjustment for demographic risk factors, comorbid health conditions and renal function, a positive and independent relationship of serum cystatin C levels with peripheral monocyte blood count (regression coefficient ± SE: 12 ± 3.38, P < 0.001) and white blood count (0.616 ± 0.278, P= 0.027) was evident. In this multiple linear regression analysis, other inflammatory markers (i.e. hs‐CRP, haptoglobin, ferritin, albumin) did not seem to affect cystatin C blood levels. Conclusion: The results of this study demonstrated that monocytes, which play an important role in chronic inflammation and atherosclerosis, were independently related with cystatin C concentrations. This finding may provide a plausible link for the usefulness of cystatin C in predicting increased cardiovascular risk.     

花生四烯酸细胞色素p450表氧化酶基因对野百合碱诱导的肺动脉高压大鼠IL-6,IL-8的影响

目的观察花生四烯酸色素p450表氧化酶基因CYP2J2过表达对野百合碱（MCT）诱导的肺动脉高压大鼠炎症细胞因子IL-6、IL-8、CRP和TNF-α表达的影响,探讨CYP2J2作用于肺动脉高压的机制。方法 ：选取8周龄250-280gSD大鼠60只随机分为正常对照组（n=30）和模型组（MCT组）（n=30）,模型组注射野百合碱（60mg/kg）造模。三周后分为6组：NS组（n=10）,pCDNA3.1（n=10）,pCDNA3.1-CYP2J2（n=10）,MCT＋NS（n=10）,MCT＋pCDNA3.1（n=10）,MCT＋pCDNA3.1-CYP2J2（n=10）,注射质粒三周后,检测大鼠平均肺动脉压（mPAP）,计算右心肥大指数（RVHl=RV/LV＋S）。ELISA法检测大鼠血清中IL-6、IL-8、CRP和TNF-α水平。RT-PCR检测大鼠肺组织中IL-6和IL-8的mRNA表达。结果 ：模型对照组mPAP、RVHI值、血清IL-6、IL-8、CRP和TNF-α水平及肺组织中IL-6和IL-8的mRNA表达均显著增高,与正常对照组相比有显著性差异（P〈0.01）;pCDNA3.1-CYP2J2治疗组mPAP、RVHI值、血清IL-6、IL-8、CRP和TNF-α水平及肺组织中IL-6和IL-8的mRNA表达均明显下调（P〈0.05）,但仍高于正常对照组（P〈0.05）。结论花生四烯酸色素p450表氧化酶基因可通过抑制MCT诱导大鼠肺动脉高压模型中肺组织炎性细胞因子的表达、下调大鼠炎性细胞因子的分泌达到对肺动脉高压的治疗作用。     

O-去甲基文拉法辛对大鼠肝微粒体细胞色素P450酶含量及CYP2D6、CYP3A4活性的影响

目的研究O-去甲基文拉法辛对大鼠肝微粒体内细胞色素P450(CYP450)含量及CYP2D6、CYP3A4活性的影响。方法生理盐水为对照,大鼠灌胃22.90mg.kg-1.d-1的O-去甲基文拉法辛琥珀酸盐一水合物,连续7d,然后测定其肝微体中CYP450含量及CYP2D6、CYP3A4活性。结果与生理盐水组比较,ODV组CYP450含量和CYP3A4活性无变化(P>0.05),CYP2D6活性明显被抑制(P<0.01)。结论ODV对CYP450含量和CYP3A4活性无影响,但对CYP2D6活性有抑制作用。     

Low-dose azithromycin improves phagocytosis of bacteria by both alveolar and monocyte-derived macrophages in chronic obstructive pulmonary disease subjects

Background and objective: Chronic inflammation and reduced airways integrity in chronic obstructive pulmonary disease (COPD) potentially results from secondary necrosis as a result of impaired phagocytosis of apoptotic material by airway macrophages, and increased bacterial colonization. We have previously shown that administration of low‐dose azithromycin to subjects with COPD improved macrophage phagocytosis of apoptotic airway epithelial cells, reduced inflammation and increased expression of macrophage mannose receptor. Methods: We firstly investigated whether there were defects in the ability of both alveolar (AM) and monocyte‐derived macrophages (MDM) to phagocytose bacteria in COPD, as we have previously reported for phagocytosis of apoptotic cells. We then assessed the effects of administration of low‐dose azithromycin to COPD patients on the ability of AM and MDM to phagocytose bacteria. Azithromycin (250 mg orally daily for 5 days then 2× weekly (total 12 weeks)) was administered to 11 COPD subjects and phagocytosis of fluorescein isothiocyanate‐labelled Escherichia coli assessed by flow cytometry. Results: COPD subjects had a significant defect in the ability of both AM and MDM to phagocytose bacteria that was significantly improved by administration of low‐dose azithromycin Conclusions: The data provide further support for the long‐term use of low dose azithromycin as an attractive adjunct treatment option for COPD. Improved clearance of both apoptotic cells and bacteria in the airway may have a dual effect; reducing the risk of secondary necrosis and release of toxic cell contents that perpetuate inflammation as well as contributing to a reduction in the rate of exacerbations in COPD.     

Direct evidence of monocyte recruitment to inflammatory bowel disease mucosa

Alterations in phenotype and function of intestinal macrophages occur in inflammatory bowel disease (IBD) but it is unclear whether these changes result from the recruitment of circulating monocytes to the intestine or from proliferation of resident intestinal macrophages. We sought to demonstrate the arrival of blood monocytes, the precursors of macrophages, in IBD mucosa. Peripheral blood mononuclear cells were isolated from 23 patients with clinically active intestinal inflammation (13 Crohn's disease, eight ulcerative colitis, two infective colitis), then radiolabelled with ^99mtechnetium (Tc)-stannous colloid (n=13) or ¹¹¹indium (In)-oxine (n=10) before re-injection and abdominal scanning. Four patients had demonstrable intestinal monocyte uptake using [^99mTc]-stannous colloid, while six [¹¹¹In]-oxine-labelled monocyte scans were positive. Uptake sites correlated with actively inflamed regions. Patients demonstrating monocyte uptake had been treated with corticosteroids for a significantly (P < 0.02) shorter duration (median 3 vs 20 days) than those with negative scans. There was no significant difference between positive and negative scans for disease category, clinical or histological disease activity, or radioisotope used. Biopsies of inflamed mucosa from two patients suffering ulcerative colitis who had positive scans showed a high proportion of CD14-positive macrophages, 4–9% of which contained autoradiographic grains. These results demonstrate that blood monocytes are recruited to the mucosa of actively inflamed bowel, and suggest that this process may be inhibited by corticosteroids. Moreover, the phenotype of the recently-arrived monocytes indicates their susceptibility to stimulation by lipopolysaccharide, and suggests a mechanism for the continuing inflammation in the bacterial product-rich milieu of IBD.     

Radiographic resolution of community-acquired bacterial pneumonia in the elderly

OBJECTIVES: To investigate the radiographic clearance of proven community-acquired nontuberculous bacterial pneumonia in nonimmunocompromised older patients to provide working estimates of the rate of radiographic resolution as a function of the patient cumulative comorbidities, extent of initial radiographic involvement, functional status, and causative pathogens. DESIGN: A prospective study. PARTICIPANTS: Seventy-four patients aged 70 and older, consecutively admitted to a hospital for community-acquired bacterial pneumonia. SETTING: A university-affiliated teaching hospital. MEASUREMENTS: Chest radiographs were performed every 3 weeks from the date of admission for a total period of 12 weeks or until all radiographic abnormalities had resolved or returned to baseline. RESULTS: Sixty-four patients (86%) completed the study. The rate of radiographic clearance was estimated at 35.1% within 3 weeks, 60.2% within 6 weeks, and 84.2% within 12 weeks. Radiographic resolution was significantly slower for those with high comorbidity index, bacteremia, multilobar involvement, and enteric gram-negative bacilli pneumonias. Multivariate regression analysis demonstrated that the comorbidity index (relative risk for clearance=0.67 per class index, P<.001) and multilobar disease (relative risk for clearance=0.24 for more than one lobe, P<.001) had independent predictive value (Cox proportional hazards regression model) on the rate of resolution. CONCLUSION: The radiographic resolution of nontuberculous bacterial pneumonia in the elderly should take into account the extent of lobar disease and the burden of underlying illnesses. A waiting period of 12 to 14 weeks is recommended for slowly resolving pneumonia to be considered nonresolving.     

Distinct inflammatory mechanisms mediate early versus late colitis in mice.

BACKGROUND & AIMS: Progression from the acute to chronic phase of inflammatory bowel disease cannot be easily evaluated in patients and has not been characterized in animal models. We report a longitudinal study investigating changes in the mucosal immune response in an experimental model of colitis. METHODS: Severity of colitis, body mass, stool consistency and blood content, serum amyloid A, and tissue histology were examined in interleukin (IL)-10-deficient mice over 35 weeks. The corresponding production of IL-12, IL-18, interferon gamma, tumor necrosis factor alpha, IL-4, and IL-13 by lamina propria mononuclear cells in the inflamed intestine was measured. Administration of neutralizing antibody to IL-12 at distinct times during disease progression permitted evaluation of its therapeutic potential. RESULTS: The clinical manifestations and intestinal inflammation delineated an early phase of colitis (10-24 weeks), characterized by a progressive increase in disease severity, followed by a late phase (>25 weeks), in which chronic inflammation persisted indefinitely. Lamina propria mononuclear cells from mice with early disease synthesized progressively greater quantities of IL-12 and interferon gamma, whereas production of both cytokines dramatically declined and returned to pre-disease levels in the late phase of colitis. Consistent with this pattern, neutralizing antibody to IL-12 reversed early, but not late, disease. In contrast, IL-4 and IL-13 production increased progressively from pre- to early to late disease. CONCLUSIONS: Colitis that develops in IL-10-deficient mice evolves into 2 distinct phases. IL-12 plays a pivotal role in early colitis, whereas its absence and the synthesis of IL-4 and IL-13 in late disease indicate that other immune mechanisms sustain chronic inflammation.     

High resolution CT and bronchial reversibility test for diagnosing COPD

BACKGROUND: COPD is defined by airflow limitation that is not fully reversible and is associated with relevant risk factors. The diagnosis requires that other causes of chronic airflow limitation (CAL) be excluded. We assessed the diagnostic utility of high resolution thoracic CT (HRCT) and bronchodilator reversibility to assist in making a diagnosis of COPD. METHODOLOGY: We investigated 516 consecutive patients whose FEV1/FVC was less than 70% after inhalation of bronchodilator. HRCT was performed on all subjects and a final diagnosis was made only after 3 months of treatment and repeated spirometry. RESULTS: Of 516 cases, 54.3% had COPD, 19.8% had asthma plus emphysema, and 13.2% had chronic asthma. The remaining 12.7% of patients with CAL had diffuse panbronchiolitis, bronchiectasis, bronchiolitis obliterans, or other miscellaneous diseases. In these minor diseases HRCT was essential in making a definitive diagnosis. The sensitivities of emphysema on HRCT and of absence of bronchodilator response for the diagnosis of COPD were 81% and 90%, respectively, and the specificities of the tests were 57% and 37%, respectively. In addition, HRCT revealed considerable heterogeneity of COPD. Emphysema was not recognized on HRCT in 18.6% of COPD patients. HRCT also revealed that 17.5% of COPD patients had other pulmonary complications including lung fibrosis compatible with usual interstitial pneumonia in the lung bases. CONCLUSIONS: HRCT and the bronchial reversibility test had reasonable sensitivities but low specificities for diagnosing COPD. HRCT has some additional advantages in detecting heterogeneity and concomitant lung diseases in COPD.     

Development of magnifying video endoscopes with high resolution

Background: The diagnostic capability of a video‐endoscope has been remarkably enhanced by using a high pixel count charge‐coupled device (CCD) and is getting closer to that of the stereomicroscope as its image quality is improved. From this standpoint, the authors have been developing high‐resolution magnifying video‐endoscopes. Methods: There are two methods available to increase the resolution of a video‐endoscope: (i) use a CCD with large pixel number and (ii) optically magnify the image impinging on the CCD. Since the video‐endoscope using a 410 Kilo (K) pixel count CCD was introduced in 1993, the authors have been developing a video‐endoscope using a large pixel count number CCD in pursuit of obtaining better image quality and resolution. Also, the technological innovations in CCD manufacturing have allowed CCDs to become much smaller in size with higher pixel numbers. As the CCD size decreases, the distal part of a video‐endoscope can be made thinner. With respect to optical magnification, two methods are available, the fixed close‐focusing system and variable focus. Results: With combined use of the variable focus magnification and the electronic magnification, a magnification more than × 100 can be achieved on a 14″ television monitor with higher resolution power and wider depth of field. Conclusions: The images captured by the latest magnifying video‐endoscope prove that the image quality of video‐endoscopy is improving and is approaching the diagnostic capability of the stereomicroscope.     

The effects of autologous platelet gel on inflammatory cytokine response in human peripheral blood mononuclear cells

The potential therapeutic value and versatility of platelet-derived products has recently stimulated the research and interest in the field of regenerative medicine. Platelet gels (PG), generated by thrombin-activated platelets, represent a new biotechnology for stimulation and acceleration of tissue healing and regeneration. However, despite the diffused and successful use of PG in clinical practice, a more detailed knowledge of the cellular and molecular mechanisms involved is required. In the present study, we show that human peripheral blood mononuclear cells (PBMC) co-cultured with PG, in the presence of the inflammatory activator lipopolysaccharide, secreted higher amounts of pro-inflammatory and pro-angiogenic cytokines, such as interleukin (IL)-1β, IL-6 and IL-8. In contrast, the release of the anti-angiogenic cytokines interferon-γ and IL-12 was significantly reduced. In addition the production of the anti-inflammatory cytokine IL-10 was not affected by PG. Finally, hypoxia, a common feature of the healing tissue, potentiated the effects exerted by PG on the release of IL-1β by PBMC. In conclusion, PG treatment reveals a unique capacity of articulating a pro-inflammatory and pro-angiogenic cytokine profile in human PBMC, which may partially explain the clinical success of PG application in a wide range of diseases.     

CYP 450 2C19 polymorphisms in Indian patients with coronary artery disease

Background

Dual antiplatelet therapy is the cornerstone in the management of acute coronary syndromes (ACS) and prevention of stent thrombosis (ST). Genetic polymorphisms in CYP2C19 gene involved in hepatic activation of clopidogrel leads to clopidogrel non-responsiveness and may influence clinical outcomes. These polymorphisms in CYP2C19 gene and their impact on clinical outcome in coronary artery disease (CAD) have not been studied in Indian population.

Methods

We studied 110 consecutive patients (mean age 55.7 ± 10.7 years; 90% male) taking clopidogrel with angiographically proven CAD for various genetic polymorphisms in CYP2C19 gene. Relationship between loss of function mutation and clinical presentation with recurrent ACS including ST was analyzed.

Results

Out of 110 patients, 26 (23.64%) had normal genotype, 52 (47.23%) had loss of function mutation *2 and 39 (35.45%) had a gain of function mutation *17, 7 (6.36%) patients were undefined metabolizers (*2/*17) which were excluded from analyses. Final analyses included 103 patients, with 45 (40.90%) having loss of function. Overall 51 patients had ACS, with 27 developing recurrence while on clopidogrel. The prevalence of loss of function mutation was no different between the group with recurrences and those without recurrences (55.6% vs. 50%, p = 0.7). Two patients developed ST while on clopidogrel; both had loss of function mutation.

Conclusion

CYP2C19 gene polymorphisms are common in Indian population. Loss of function mutation status did not affect the clinical outcomes. A larger study also considering P2Y12 receptor polymorphisms together with platelet activity testing, may be required to establish the role of CYP2C19 gene polymorphisms in clinical practice.     

支气管扩张症高分辨率CT与肺通气功能的相关性

目的 探讨支气管扩张症(简称支扩)高分辨率CT(HRCT)与肺通气功能的相关性.方法 纳入经胸部HRCT诊断的支扩稳定期患者40例.根据CT评分系统对其胸部CT进行评分,并进行肺通气功能检查.结果 CT评分显示,支扩分布范围、扩张程度、管壁厚度分别为:(7.098±4.918)分、(6.540±4.113)分、(4.405±2.477)分.肺通气功能指标:FEV1占预计值%(FEVl%pred)为(56.122±26.335)%,FVC占预计值%(FVC%pred)为(66.857±21.951)%,FEV1/FVC为(64.612±14.890)%.支扩分布范围与FEV1 oApred、FVC%pred、FEV1/FVC均呈明显负相关(r=-0.451～-O.571,P值均<0.01).扩张程度、管壁厚度与FEV1%pred、FVC%pred、FEV1/FVC均无相关性.结论 支扩的分布范围与肺通气功能密切相关.