The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Volume 207, Issue 2
October
Displaying 1-11 of 11 articles from this issue
Invited Review
Regular Contributions
  • Kazuhisa Matsuda, Yukio Mikami, Kazunori Takeda, Shoji Fukuyama, Shini ...
    2005 Volume 207 Issue 2 Pages 99-107
    Published: 2005
    Released on J-STAGE: September 02, 2005
    JOURNAL FREE ACCESS
    It has recently been recognized that anandamide (arachidonylethanolamide), which is an endogeneous-cannabinoid (endocannabinoid), mediates septic shock. Cannabinoid means a mind-active material in cannabis (marijuana). Anandamide is mainly produced by macrophages. Cannabinoid 1 (CB1) receptor, which is one of the cannabiniod receptors, is also known to mediate hypotensive shock. The role of endocannabinoids in the progression of acute pancreatitis is unclear. The aims of this study are to clarify their relationship and to find a new therapeutic strategy by regulating the endocannabinoid signaling in acute pancreatitis. Male Wistar rats were injected with caerulein intravenously to induce mild edematous pancreatitis or injected with 5% sodium taurocholate to the bilio-pancreatic duct to induce severe necrotizing pancreatitis. The animals in the latter group were also injected with a CB1 receptor antagonist, AM251, or vehicle solution to see if the inhibition of endocannabinoids improves their survival. Plasma anandamide level was measured by the liquid chromatography/tandem mass spectrometry method. In both models of acute pancreatitis, the plasma anandamide levels were increased, and the levels were significantly higher in rats with severe necrotizing pancreatitis than those in rats with mild edematous pancreatitis. The mean arterial pressure and survival rate were significantly improved by the treatment with AM251, despite that the local inflammatory changes in the pancreas and various parameters (white blood cells, hematocrit, serum amylase, and serum interleukin-6) were similar. This is the first report to show that endocannabinoids are involved in the deterioration of acute pancreatitis and that the down-regulation of endocannabinoid signaling may be a new therapeutic strategy for severe acute pancreatitis.
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  • Hiroyasu Yasuda, Tomoko Suzuki, Kiyoshi Zayasu, Satoshi Ishizuka, Hiro ...
    2005 Volume 207 Issue 2 Pages 109-118
    Published: 2005
    Released on J-STAGE: September 02, 2005
    JOURNAL FREE ACCESS
    It is still uncertain how viral respiratory infections cause acute exacerbations of bronchial asthma, although several mechanisms have been proposed. We studied the relationship between the airway narrowing and the inflammatory and bronchospastic factors in peripheral venous blood and urine, in 30 patients with asthma at the exacerbations caused by upper respiratory tract infections (URTIs). Acute exacerbations caused decreases in peak expiratory flow rate (PEFR) in all 30 patients with asthma. Asthma exacerbations caused the rises in serum levels of interleukin-6, soluble intercellular adhesion molecule-1 and eosinophil cationic protein, concentrations of urinary leukotriene E4 and plasma histamine, compared with those in patients with asthma at a stable condition and those in 30 control subjects (p < 0.05). The values of PEFR at the exacerbations correlated with the levels of these factors. Treatment with oral glucocorticoids reversed the decreases in PEFR and the increases in these factors. At the onset of URTIs, rhinovirus and influenza type A virus were identified in 13 and 7 patients, respectively. Each of parainfluenza virus, adenovirus, and enterovirus was identified in one patient. These findings suggest that respiratory viral infections may cause acute asthma exacerbations via the production of mediators that induce inflammation and bronchospasm.
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  • Mustafa Emir, Kanat Ozisik, Kerim Cagli, Pinar Ozisik, Serdar Tuncer, ...
    2005 Volume 207 Issue 2 Pages 119-124
    Published: 2005
    Released on J-STAGE: September 02, 2005
    JOURNAL FREE ACCESS
    Cardiac injury, occurred after traumatic brain injury (TBI), has been recognized for more than a century. Bcl-2 is a key regulatory component of the mitochondrial cell death pathway, and its overexpression is cytoprotective in many cell types. The therapeutic agents, which induce the expression of bcl-2 protein, might provide a new therapy to prevent cardiac myocyte damage following TBI. In this study, we investigated whether methylprednisolone sodium succinate (MPSS) influences the expression of bcl-2 in the heart. Wistar-Albino female rats underwent TBI (300 g/cm) generated by the weight-drop method, and were left untreated (n = 6) or treated with either MPSS (30 mg/kg) (n = 6) or vehicle (albumin solution) (n = 6). The heart was isolated from each animal with TBI. For comparison, the hearts were isolated from sham-operated (n = 6) and control rats (n = 6). The relative expression of bcl-2 mRNA in the heart was quantitated by real-time polymerase chain reaction. We also assessed lipid peroxidation in the heart tissue by determining the concentration of thiobarbituric acid-reactive substances (TBARs) as an indicator of tissue damage. The bcl-2 expression level was significantly higher in the hearts of MPSS-treated rats compared to that of other TBI groups (p < 0.0001). Moreover, TBI increased the lipid peroxidation in the heart, which was significantly reduced by the treatment with MPSS (p < 0.0001). These findings provide evidence for the efficacy of MPSS in protection of cardiac myocytes to achieve optimal heart donation after TBI in heart transplantation.
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  • Sinan Erginel, Irfan Ucgun, Huseyin Yildirim, Muzaffer Metintas, Sebne ...
    2005 Volume 207 Issue 2 Pages 125-132
    Published: 2005
    Released on J-STAGE: September 02, 2005
    JOURNAL FREE ACCESS
    Approximately 20% of mechanically ventilated patients experience post-extubation stridor (PES) and reintubation, which subsequently may lead to an increased risk of morbidity and mortality. The risk of PES development is significantly higher in obese patients. Low air leakage between the endotracheal tube and the trachea, following cuff deflation, may indicate a higher risk for the development of PES. The aim of this study is to identify the relationship between body mass index (BMI) and PES using the cuff-leak test in patients intubated in the respiratory intensive care unit. A total of 67 consecutive intubations on 56 different ventilated patients were included in this study. The mean age was 63.6 ± 12.1 years and 84% of the patients were male. PES developed in seven patients (10.4%). The mean cuff-leak volume was 395 ± 187 ml in non-PES patients and 240 ± 93 ml in PES patients (p = 0.023). The mean BMI was 36 ± 13 kg/m2 in PES patients and 24 ± 7 kg/m2 in non-PES patients (p = 0.046). BMI > 26.5 kg/m2 (OR: 1.2), low cuff-leak volume (< 283 ml) and mechanical ventilation required for more than 5 days (OR: 0.9) were independent variables for PES occurrence. We therefore suggest that non-obese patients, short-term intubated patients and those having a high air leakage around the endotracheal tube could be extubated without much difficulty.
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  • Burhan Kabay, Faruk O. Aytekin, Cagatay Aydin, Atilla Ozer, Nilgun Kab ...
    2005 Volume 207 Issue 2 Pages 133-142
    Published: 2005
    Released on J-STAGE: September 02, 2005
    JOURNAL FREE ACCESS
    To investigate the role of interleukin (IL)-10 gene therapy on the reperfusion-induced lung injury, we utilised the technique of liposomal gene delivery before the induction of intestinal ischemia. Plasmid DNA encoding human IL10 (hIL-10) or empy vector was injected intraperitoneally 24 h before the study. Male Balb/c mice randomized into three groups: Sham operated control (n = 12), empty plasmid vector (n = 12), and hIL-10 gene therapy group (n = 12). The ischemia was generated by selective occlusion of superior mesenteric artery for 60 min and followed by reperfusion for 30 min. Lung tissue neutrophil infiltration was determined by myeloperoxidase assay and neutrophil counts. For the determination of lung tissue microvascular permeability, Evans blue dye injection was made and the lung edema was assesed by wet/dry ratio. hIL-10 protein expression was studied by immunostaining and ELISA. We found that pre-ischemic hIL-10 overexpression attenuated dye extravasation, leukocyte sequestration and reduced pulmonary tissue injury compared to the empty vector-injected control. Our study indicates that pre-ischemic hIL-10 overexpression attenuates lung injury caused by intestinal ischemia-reperfusion.
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  • Kunihiko Hoshi, Shin Kurosawa, Masato Kato, Kohkichi Andoh, Daizoh Sat ...
    2005 Volume 207 Issue 2 Pages 143-148
    Published: 2005
    Released on J-STAGE: September 02, 2005
    JOURNAL FREE ACCESS
    Many studies have suggested that neutrophil elastase (NE) may contribute to multiple organ failure (MOF) and acute injury of lung endothelial cells. It is therefore conceivable that NE inhibitors may improve the outcome of MOF patients. A synthetic NE inhibitor, sivelestat, which was developed and released in Japan, inhibited inflammatory reactions in various animal models. We examined the medical records of patients requiring more than two days of respiratory care in four intensive care units to investigate whether sivelestat contributed to improvement of their conditions. A total of 110 patients were divided into two groups (sivelestat treated group of 57 patients and untreated group of 53 patients). The conditions and age of the patients were similar in both groups. Sivelestat (0.2 mg/kg/hr) was administered continuously for 14 days beginning on the day of the intensive care unit (ICU) admission or for less than 14 days until discharge from the ICU. Hospital mortality differed significantly between the two groups (treated: 19% and untreated: 40%, p < 0.05). The severity of acute lung injury is defined by the ratio of arterial oxygen partial pressure (PaO2)/fraction concentration of oxygen in the inspired air (FiO2). When the PaO2/FiO2 ratio is more than 200 mmHg, the morbidity is lower. In patients with PaO2/FiO2 ratio more than 200 mmHg, the hospital mortality was 33.3% (7/21) in the untreated group and 6.0% (1/18) in the treated group (p = 0.0236). We conclude that administration of sivelestat reduces mortality of critically ill patients.
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  • Hiroaki Nakazawa, Motohiro Nozaki
    2005 Volume 207 Issue 2 Pages 149-155
    Published: 2005
    Released on J-STAGE: September 02, 2005
    JOURNAL FREE ACCESS
    Hypothermia is a common complication in patients with extensive burns, receiving massive volumes of fluid for resuscitation at ambient temperature. It is therefore important to maintain the body temperature of patients with extensive burns. The present study was performed to evaluate the usefulness of warm fluid for burn injury resuscitation. Ten dogs were used in this study. Full-thickness burns, involving 40% of the body surface, were generated in the backs of the animals. In the control group (n = 5), the fluid temperature was maintained at about 23°C, while in other group (n = 5), the temperature of the fluid was maintained at 39°C with a warming device. Cardiac output and urinary output were measured in both groups for up to 24 hours. The cardiac output decreased in all animals during the first two hours following injury. The cardiac dynamics remained depressed in the control group. By contrast, in animals treated with warm fluid, the cardiac output returned to the baseline level within 4 hours of resuscitative measures and then decreased slightly for the subsequent 20 hours. The urinary output was better in animals treated with warm fluid, indicating the improved hemodynamic state in these animals. These results suggested that the hemodynamic state in acute burn shock was ameliorated by the use of warm fluid. Therefore, warmed fluid resuscitation might be useful to perform immediate excision and grafting for the patients with extensive burns in acute burn shock.
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  • Songül Acar Vaizoglu, Sefer Aycan, Levent Akin, Pelin Koçd ...
    2005 Volume 207 Issue 2 Pages 157-163
    Published: 2005
    Released on J-STAGE: September 02, 2005
    JOURNAL FREE ACCESS
    One of the airborne pollutants in wood products industry is formaldehyde, which may pose some health effects. Therefore this study is conducted to determine formaldehyde levels in 100 furniture-manufacturing workshops in Ankara and also to determine the symptoms, which may be related with formaldehyde exposure among the workers. Indoor formaldehyde levels ranged from 0.02 ppm to 2.22 ppm with a mean of 0.6 ± 0.3 ppm. Outdoor formaldehyde levels also ranged from 0.0 ppm to 0.08 ppm with a mean of 0.03 ± 0.03 ppm. Formaldehyde levels were higher in workplaces located at basement than in workplaces located at or above ground level (p < 0.01). An association was found between indoor formaldehyde levels and the types of fuel used (p < 0.05). The levels were higher in workplaces where only sawdust was used for heating, than in workplaces where wood, coal, and sawdust are used (p = 0.02). An association was found between runny nose and indoor formaldehyde levels (p = 0.03). Formaldehyde levels were lower in workplaces where employees had no symptoms than in those where employees had 4 or more symptoms (p = 0.02). Of 229 employees 57 subjects (24.9%) work under the formaldehyde levels of 0.75 ppm and above. Thus, approximately one fourth of the employees in workplaces are working in environments with formaldehyde levels exceeding those permitted by Occupational Safety and Health Administration (OSHA). The employees working in small-scale furniture workshops are at risk of formaldehyde exposure. Measures, such as improved ventilation, have to be taken in these workplaces, in order to decrease the formaldehyde levels.
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  • Osman Karakaya, Mustafa Saglam, Irfan Barutcu, Ali Metin Esen, Yucel O ...
    2005 Volume 207 Issue 2 Pages 165-170
    Published: 2005
    Released on J-STAGE: September 02, 2005
    JOURNAL FREE ACCESS
    Atrial rhythm disturbances, particularly atrial fibrillation (AF), are frequently encountered in trained athletes. P wave dispersion (PWD) is a recent electrocardiographic (ECG) marker that reflects velocity of atrial impulse propagation. However, it remains unknown whether the P wave duration and PWD are different between athletes and sedentary controls. In this study we therefore determined the P wave duration and PWD, markers for conduction abnormalities, in trained athletes and controls. Fifty athletes and sex and age-matched 40 healthy sedentary controls were included in the study. All of the athletes were the members of a local athletic college and they were regularly maintaining their sportive activities; the duration of athletic competition was 7.7 ± 3.3 years and the average athletic time was 10.1 ± 1.6 hours/week. The 12-lead surface ECG was obtained from each subject in the supine position. The P wave duration was measured, and the difference between the maximum and minimum P wave duration was defined as the PWD. Distribution of sex, age, body mass index, blood pressure was similar in athletic groups and controls. Heart rate was significantly lower in the athletes than in the controls (66 ± 7 vs 73 ± 9 beats/min, p < 0.05). Maximum and minimum P wave durations were not statistically different in athletic group and controls (115 ± 6 vs 114 ± 4 ms and 74 ± 8 vs 74 ± 7 ms, respectively). In addition, PWD did not differ significantly in both groups (41 ± 6 vs 40 ± 7 ms, respectively). Thus, athlete's heart is not associated with prolonged P wave duration and increased PWD, indicating that P wave duration or PWD could not be used as a predictor for AF developed in trained athletes.
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  • Suguru Watanabe, Takashi Suzuki, Souichirou Shizawa, Masato Endoh, Kou ...
    2005 Volume 207 Issue 2 Pages 171-179
    Published: 2005
    Released on J-STAGE: September 02, 2005
    JOURNAL FREE ACCESS
    Pulmonary vascular resistance drops sharply within a few minutes after birth for the survival of neonates. A majority of this resistance is caused by “pulmonary vascular bed” or vessel lacking smooth muscle cells. Heparin is known to promote proliferation and development of endothelial cells and to subsequently decrease their overall vascular resistance, but its detailed features remained unknown. Therefore, in this study we treated neonatal rabbits with heparin, protamine (antagonist of heparin), or saline, and evaluated histopathological features of vascular endothelial cells using two different types of computer assisted image analysis, i.e., CAS200 and NIH image. These two systems detected the percentage of vascular endothelial area per fields (VA) and CD31-positive area per total area of tissue following subtraction of background stain. CD31 was used as an endothelial cell marker. Heparin treated rabbits were associated with significant decrement of pulmonary/systemic artery pressure (Pp/Ps) (21.0 ± 6.0%) compared to protamine (29.9 ± 6.1%) or saline (29.4 ± 3.0%) treated animals. The values of VA obtained by the two image analyses (CAS200 and NIH image) were significantly increased in heparin treated animals (38.4 ± 3.2% determined by CAS200 and 24.0 ± 1.3% by NIH image) compared to protamine (30.2 ± 3.9% and 19.2 ± 1.8%) or saline (33.2 ± 1.5% and 20.8 ± 3.8%) treated animals on 14th day of treatment. The present study indicates that heparin accelerates pulmonary vascular bed development probably by increasing the number and volume of endothelial cells, which subsequently contributes to the decrease in pulmonary vascular resistance.
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