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音量 4, 問題 1 (2014)

総説

Angiopoietin-2: A Key to Understanding Sepsis and Its Pulmonary Sequelae?

Ji Young Lee and Edmund J. Miller

Sepsis remains a major cause of morbidity and mortality especially in the older individual. In the US alone, sepsis occurs in approximately 750,000 individuals per year and ranks as the tenth leading cause of death. A major complication of sepsis is organ failure, with the lung being one of the first organs to fail. Moreover, sepsis is the most common risk factor for Acute Lung Injury (ALI) and approximately 50% of individuals with sepsis subsequently develop ALI. Despite its importance, the pathophysiology of sepsis remains unclear. Angiopoietin-2 (Ang-2) is a component of pathways involved in endothelial survival and maintenance of a quiescent state of the vascular system. The functional significance of Ang-2 remains to be fully elucidated, but the evidence thus far suggests that it may be key to a better understanding of the vascular dysfunction and associated organ failure that are so devastating in sepsis. However, the assessment of the cellular release of Ang-2 is not without difficulty. In this brief review, we discuss the relevance of Ang-2 to the endothelial dysfunction associated with the severe inflammatory response in sepsis, and why Ang-2 may not be just a biomarker, but may play a critical role in the pathology. In addition, we discuss some of the reasons why particular sepsis models may present confusing data with respect to Ang-2 involvement.

研究論文

The Study of Association between Helicobacter pylori (H. pylori) and Chronic Obstructive Pulmonary Disease (COPD)

Dinesh Deerpaul and Sun Yun Hui

Background: In past years, many studies have been carried out to understand the complex relationship between Helicobacter pylori (H. pylori) infection and Chronic Obstructive Pulmonary Disease (COPD). Few researches have been successful in showing the epidemiologic and serologic evidence for relationship between Helicobacter pylori (H. pylori) infection and Chronic Obstructive Pulmonary Disease (COPD).

Objective: In this study, we aimed to investigate the seroprevalence of Helicobacter pylori in patients with COPD and to determine whether there is an association between H. pylori infection and COPD.

Method: 40 voluntary patients with COPD and 40 healthy control subjects of similar age and sex were taken as subjects in the study. After the consent form was signed by both the study and control groups, every person was questioned in detail and the relevant data were collected from the case history of the COPD patients. H. pylori-specific IgG was measured with a commercially available Elisa kit from venous blood samples of the study and control groups.

Results: H. pylori IgG seropositivity was 57.5% in the patients with COPD and 37.5% in the control subject, which suggests that H. pylori infection has a higher prevalence in COPD patients than non-COPD patients. Further in our study the mean values of forced expiratory volume in one second (FEV1) and Forced Vital Capacity (FVC) were compared between H. pylori seropositive and seronegative COPD patients and non-COPD patients and the p value was not less than 0.05 in any of the comparisons. Finally to see if H. pylori infection has any impact in COPD, the patients with COPD were grouped according to their stages of diseases and compared with H. pylori IgG seropositivity, the prevalence of H. pylori seropositivity did not differ significantly relatively to the stages of COPD i.e. between patients with mild, moderate and severe COPD. Conclusion: The results from our study suggest that there is higher prevalence of H. pylori seropositivity in COPD patients than in non-COPD patients, but we were not able to show and prove if H. pylori infection is related to COPD since our study was carried out in a very small scale and short period of time. To understand the complex relationship between H. pylori infection and COPD, we need much more time and finance, firstly so that we can carry out our study in a larger scale involving much more individuals in our study and control groups and secondly to be able to use more sophisticated and modern technologies to get better and quicker results.

研究論文

Methodology of an Observational Cohort Study for Subjects with Chronic Obstructive Pulmonary Disease in Dusty Areas Near Cement Plants

Yoonki Hong, Jae-Woo Kwon, Sang-Ah Lee, Young Ji Han, Ji Young Moon, Hee Yoeng Kim, Seon-Sook Han, Seung-Joon Lee and Woo Jin Kim

Chronic Obstructive Pulmonary Disease (COPD) occurs in genetically susceptible individuals by chronic exposure to environmental factors. Although cigarette smoking is a major risk factor for this disease, environmental factors including vapor, gas, dust, and fumes can also impact lung function. Emissions from cement plants are known to have negative health effects; however, the effects of cement dust on COPD subjects living near cement plants have not been fully investigated. We plan to conduct a study to observe clinical outcomes of COPD areas near the cement plants in Korea. Here, we present methodology for an observational cohort study. Cement plants are mostly located in the Kangwon and Chungbuk provinces in Korea. COPD subjects in these areas are recruited for medical examinations consisting of a questionnaire of environmental exposure and health habits, symptom severity, pulmonary function testing, and computed tomography. Blood and urine samples are obtained and subjects will be followed up over 10 years. The patient cohort of this study differs from other COPD study populations in that the participants have been living in dusty areas near cement plants; we therefore termed this cohort COPD in dusty area.

総説

The Nervous Mechanism of Sympathetic over Activity Induced by Chronic Intermittent Hypoxia

Qi An and En-Sheng Ji

Hypertension is concerned to be a common complication in Chronic Intermittent Hypoxia (CIH) conditions which mimic the state of Obstructive Sleep Apnoea (OSA) in clinic. Sympathoexcitation is a crucial origin in the process of high blood pressure and the mechanisms involved in the sympathoexicitatory changes after CIH exposure are complex referring to chemoreflex, baroreflex, neurotransmitters, and central nuclei and so on. In this review we predominantly expound the effect of CIH-induced potentiated Carotid Body (CB) chemoreceptor sensitivity to hypoxia stimulation which results in the enhancement of RSNA and Endothelin (ET) is mentioned due to its expression in CB and the fact that ET is thought to be a significant chemoreceptor-excitatory transmitter. Previously studies have shown expression of ET and ET receptors in the CB chemoreceptor glomus cells and vessel system, and CIH obviously increased the expression which indicated a possible effect of ET to the potentiated ventilatory and cardiovascular responses to acute hypoxia probably via increased inward Ca2+ currents, inflammatory response or Acid-Sensitive Ion Channels (ASICs) in chemoafferent neurons in the petrosal ganglion. However we also display the effect of enhanced central respiratory-sympathetic coupling which also participated in the increase in sympathetic activity. The other mechanism introduced in this review is the role of the Nucleus Tractus Solitarius (NTS) after CIH exposure. Neurotransmitters like ET and Glutamate act on the cerebroventricle and the NTS elicit significantly increase of RSNA in CIH group. The sympathetic nerve originated site Rostral Ventrolateral Medulla (RVLM) also makes adaptive changes after CIH to copes the hypoxia stimulation and induces RSNA responses. At last we raise the phenomenon that depressed baroreflex sensitivity emerged after a long time CIH exposure and is involved in the process of sustained high blood pressure.

ミニレビュー

MicroRNAs and Smooth Muscle Cells Phenotypic Switching in PAH

Dongqing Guo, Lida Wu and Yuchun Gu

Smooth muscle cells undergo a switching from contractile phenotype to synthetic phenotype in pulmonary hypertension characterized by excessive proliferation and migration of smooth muscle cells. MicroRNAs are small noncoding RNAs that can negatively regulate gene expression by directly binding with the 3’-UTR of mRNA. Numerous microRNAs have been reported to modulate the smooth muscle cells phenotypic switching and been urged to become possible therapeutic targets for pulmonary hypertension. This review will focus on the roles of microRNAs in regulating smooth muscle cellular phenotypic switching in PAH.

研究論文

Maternal Asthma and Use of Antiasthmatic Drugs in Early Pregnancy and Congenital Malformations in the Offspring

Bengt Källén

Objectives: To investigate the risk of congenital malformations in infants born of women who had used antiasthmatic drugs in early pregnancy.

Methods: Data were obtained from the Swedish Medical Birth Register for 1996-2011. Information on drug use was based on midwife interviews towards the end of the first trimester. Presence of congenital malformations was ascertained from three national health registers. Risk estimates were made with Mantel-Haenszel odds ratios after adjustment for delivery year, maternal age, parity, smoking, and body mass index. Consideration was taken to concomitantly used drugs.

Results: Among more than 1.5 million women who gave birth, 2.9% reported the use of antiasthmatics. These women had characteristics which distinguished them from other women who gave birth and they more often than these used other drugs than antiasthmatics. These differences seemed to affect malformation risk only little. The risk for a major malformation was slightly but significantly increased (odds ratio=1.09, 95% confidence interval 1.03-1.12), specifically this was seen for cardiovascular defects, median cleft palate, and pyloric stenosis. There was no specific association with specific drugs or drug groups, the highest risk estimate was seen for women who used only one drug and notably a short-acting adrenergic or used three or more antiasthmatic drug groups.

Conclusion: The absolute risk for a congenital malformation in infants born of women using antiasthmatics is low and some evidence indicates that it is due to underlying asthma. A good control of asthma seems important and scare of teratogenicity of the common antiasthmatic drugs should not prevent adequate use.

症例報告

Recurrent Pulmonary Hemangioma: A Case Report

Janah H, Bopaka RG, ElKhattabi W, Affif H and Aichane A

Pulmonary Angioma is an extremely rare benign vascular tumor, affecting, in exceptional cases, some adults. The risk of multiple and postoperative recurrence is rare but should not be ignored in order to establish. We report a case of recurrent pulmonary hemangioma, revealed by chest pain and recurrent hemoptysis for a 27 year old woman who has a medical history of right lower lobectomy indicated in front of a proximal tissue process right lower lobe. Subsequently, the patient had extra-pulmonary locations based on the radio-clinical setting: aggressive Angioma in the lumbar vertebra of L3 confirmed via biopsy, skull Angioma and left distal femoral Angioma

研究論文

Prophylactic Administration of Curcumin Abates the Incidence of Hypobaric Hypoxia Induced Pulmonary Edema in Rats: A Molecular Approach

Sarada SK Sagi, Titto Mathew and Himadri Patir

Background and purpose: High Altitude Pulmonary Edema (HAPE) is a severe high altitude illness with serious pulmonary manifestations. The present study reports benefits of prophylactic administration of curcumin in prevention of hypoxia induced pulmonary edema.

Experimental approach: Male Sprague Dawley rats (n=6 per group) were exposed to a stimulated hypobaric hypoxia at 7620 m for 6 h. The groups studied were (I) Normoxia, (II) Hypoxia (6 h), (III) Normoxia+curcumin (50 mg/kg BW) and (IV) Hypoxia+curcumin (50 mg/kg BW). Curcumin at 50 mg/kg BW, given orally 1 h prior to hypoxia exposure was considered from dose dependent studies as the optimum dose, due to significant reduction in the level of lung water content and lung transvascular leakage (p<0.001) as compared to control (6 h hypoxia). Biochemical analysis, vascular leakage studies, differential expression of proteins were determined by ELISA, Western Blotting and Immunohistochemistry. Changes in lung parenchyma were evaluated by histopathology.

Results: Curcumin administration (50 mg/kg BW) to rats, 1 h prior to hypoxic exposure showed a significant decrease in lactate dehydrogenase (LDH), albumin extravasation in broncho-alveolar lavage (BAL) fluid, oxidative stress (ROS and MDA) levels along with concomitant increase in antioxidant status (GSH, GPx and SOD) in lungs of rats compared to control. Curcumin significantly attenuated the IKKαβ , IKBβ there by leading to down regulation of NFκB protein levels and their downstream regulatory genes (pro-inflammatory cytokines and cell adhesion molecules). Further, hypoxia enhanced HIF-1α and VEGF levels in lungs were significantly down regulated by curcumin leading to reduction in vascular leakage in lungs of rats under hypoxia over control (Hypoxia). The histopathological observations provide substantial evidence in reduction of edema and inflammation by curcumin treatment.

Conclusion: These results indicate that, curcumin to be a potent drug against HAPE as it effectively attenuates inflammation as well as fluid influx in the lungs of rats under hypoxia.

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